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Sample records for adult primary hepatocellular

  1. Primary prevention of hepatocellular carcinoma.

    PubMed

    Yu, S Z

    1995-01-01

    Hepatocellular carcinoma (HCC) is one of the major cancers in China. Accordingly, the mortality rates in 1990 (per 100,000) were 20.10 in certain cities and 24.32 in certain counties. More than 90% of HCC cases and 70% of controls were infected with the hepatitis B virus (HBV) (Odds Ratio (OR) = 10-50). In the same group of patients, 8-27% of those with HCC and 0-11% of the healthy controls were also infected with hepatitis C (HCV) (OR = 2.11-17.29). There appears to be some correlation between HBV markers and the OR. The government requires that 85% of infants be immunized with HBV vaccine. In 1992, there were 3 million infants inoculated with HB vaccines. Aflatoxins have been found as contaminants in food, particularly in corn, peanut oil, soya sauce and fermented soya beans. The intake of aflatoxin B1 (AFB1) by people of ten different villages correlated with HCC mortality rates (r = 0.55; P < 0.05). The concentration of AFB1-albumin adducts is an indicator of individual exposure to aflatoxins. These adducts are higher in hyperendemic HCC areas and cases. Most people have now changed their staple food and eat rice instead of corn. Six large epidemiological studies have confirmed that people who drink pond-ditch water experience higher HCC mortality rates than people who drink deep-well water. Recent research has found that the blue-green algal toxin microcystin (MCYST) was a contaminant of pond-ditch water. MCYST is a strong promoter of HCC and will induce severe intrahepatic haemorrhages and liver necrosis. More than 80% of people in Qidong County have already changed their sources of water from pond-ditches to deep wells. Therefore, a combined strategy of the prevention of hepatitis, control of crops and control of drinking water is advocated for the primary prevention of HCC in China.

  2. 77 FR 24959 - Scientific Information Request on Local Therapies for Unresectable Primary Hepatocellular Carcinoma

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-26

    ... Therapies for Unresectable Primary Hepatocellular Carcinoma AGENCY: Agency for Healthcare Research and... local, minimally invasive, medical devices for unresectable primary hepatocellular carcinoma (e.g... Comparative Effectiveness Review of Local Therapies for Unresectable Primary Hepatocellular Carcinoma,...

  3. Stereotactic Body Radiotherapy for Primary Hepatocellular Carcinoma

    SciTech Connect

    Andolino, David L.; Johnson, Cynthia S.; Maluccio, Mary; Kwo, Paul; Tector, A. Joseph; Zook, Jennifer; Johnstone, Peter A.S.; Cardenes, Higinia R.

    2011-11-15

    Purpose: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of primary hepatocellular carcinoma (HCC). Methods and Materials: From 2005 to 2009, 60 patients with liver-confined HCC were treated with SBRT at the Indiana University Simon Cancer Center: 36 Child-Turcotte-Pugh (CTP) Class A and 24 CTP Class B. The median number of fractions, dose per fraction, and total dose, was 3, 14 Gy, and 44 Gy, respectively, for those with CTP Class A cirrhosis and 5, 8 Gy, and 40 Gy, respectively, for those with CTP Class B. Treatment was delivered via 6 to 12 beams and in nearly all cases was prescribed to the 80% isodose line. The records of all patients were reviewed, and treatment response was scored according to Response Evaluation Criteria in Solid Tumors v1.1. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Local control (LC), time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were calculated according to the method of Kaplan and Meier. Results: The median follow-up time was 27 months, and the median tumor diameter was 3.2 cm. The 2-year LC, PFS, and OS were 90%, 48%, and 67%, respectively, with median TTP of 47.8 months. Subsequently, 23 patients underwent transplant, with a median time to transplant of 7 months. There were no {>=}Grade 3 nonhematologic toxicities. Thirteen percent of patients experienced an increase in hematologic/hepatic dysfunction greater than 1 grade, and 20% experienced progression in CTP class within 3 months of treatment. Conclusions: SBRT is a safe, effective, noninvasive option for patients with HCC {<=}6 cm. As such, SBRT should be considered when bridging to transplant or as definitive therapy for those ineligible for transplant.

  4. Hepatitis B virus infection and primary hepatocellular carcinoma.

    PubMed Central

    Feitelson, M

    1992-01-01

    For many years, epidemiological studies have demonstrated a strong link between chronic hepatitis B virus (HBV) infection and the development of primary hepatocellular carcinoma (PHC). Other hepatocarcinogens such as hepatitis C virus and aflatoxin also contribute to hepatocarcinogenesis either in conjunction with HBV infection or alone. Cellular and molecular biological studies are providing explanations for the HBV-PHC relationship, and models are now being formulated to further test the relative importance of various factors such as viral DNA integration, activation of oncogenes, genetic instability, loss of tumor suppressor genes, and trans-activating properties of HBV to the pathogenesis of PHC. Further research will probably define more than a single mechanism whereby chronic HBV infection results in PHC. PMID:1323384

  5. Brain tumor - primary - adults

    MedlinePlus

    ... tumor, relieve symptoms, and improve brain function or comfort. Surgery is often needed for most primary brain ... and pressure Anticonvulsants to reduce seizures Pain medicines Comfort measures, safety measures, physical therapy, and occupational therapy ...

  6. Primary hepatocellular lesions: imaging findings on state-of-the-art magnetic resonance imaging, with pathologic correlation.

    PubMed

    van den Bos, Indra C; Hussain, Shahid M; de Man, Robert A; Zondervan, Pieter E; Ijzermans, Jan N M; Krestin, Gabriel P

    2008-01-01

    Magnetic resonance imaging is routinely used for the workup of patients with focal or diffuse liver disease, including primary hepatocellular lesions, storage diseases, metastatic liver disease, and diseases of the hepatobiliary tree. The most important magnetic resonance imaging sequences used for diagnostic imaging of the liver consist of T1-weighted sequences, T2-weighted sequences, and at least the arterial and delayed phases of dynamic gadolinium-enhanced imaging. This article provides an overview of magnetic resonance imaging of primary hepatocellular lesions and will describe the following: (1) the classification and etiology of primary hepatocellular lesions, including focal nodular hyperplasia, hepatocellular adenoma, and hepatocellular carcinoma; (2) the stepwise carcinogenesis of hepatocellular carcinoma in cirrhosis on magnetic resonance imaging; and (3) the typical imaging findings of primary hepatocellular lesions on magnetic resonance imaging, with differential diagnoses. PMID:18436110

  7. PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

    ClinicalTrials.gov

    2016-03-01

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage D Adult Primary Liver Cancer (BCLC); Unspecified Adult Solid Tumor, Protocol Specific

  8. Multiple Primary Malignancies in Patients With Hepatocellular Carcinoma

    PubMed Central

    Xu, Wei; Liao, Wenjun; Ge, Penglei; Ren, Jinjun; Xu, Haifeng; Yang, Huayu; Sang, Xinting; Lu, Xin; Mao, Yilei

    2016-01-01

    Abstract Multiple primary malignancies (MPMs) are defined as 2 or more malignancies without subordinate relationship detected in different organs of an individual patient. Reports addressing MPM patients with hepatocellular carcinoma (HCC) are rare. We perform a 26-year follow-up study to investigate characteristics and prognosis of MPM patients associated with HCC due to the scarcity of relative researches. We retrospectively analyzed records of 40 patients who were diagnosed with MPM including HCC at the Departments of Surgery at Peking Union Medical College Hospital during 1989 to 2010. Their clinical characteristics and postoperative survival were compared with those of 448 patients who had HCC only during the study period. Among the 40 MPM patients, 11 were diagnosed synchronously and 29 metachronously. The most common extra-hepatic malignancies were lung cancer (15%), colorectal (12.5%), and thyroid carcinoma (12.5%). MPM patients had a negative hepatitis B virus infection rate (P = 0.013) and lower median alfa-fetoprotein (AFP) level (P = 0.001). Post-operative 1-, 3-, and 5-year overall survival (OS) rates for MPM patients were 82.5%, 64.5%, and 38.6% respectively, and showed no significant difference with those of HCC-only patients (84.7%, 54.2%, and 38.3% P = 0.726). During follow-up, 24 MPM patients died, including 17 (70.8%) who died of HCC-related causes. In univariate analysis, synchronous diagnosis, higher gamma glutamyltransferase (GGT) and/or AFP levels, tumor >5 cm and vascular invasion were significantly associated with shorter OS, but only tumor size was an independent OS factor in Cox modeling analysis. HCC should be considered as a potential second primary for all cancer survivors. Most MPM patients died of HCC-related causes and showed no significant difference in OS compared with HCC-only patients. Tumor size of HCC, rather than MPMs itself, was the only independent OS predictor for the MPM patients. PMID:27124050

  9. General Information about Adult Primary Liver Cancer

    MedlinePlus

    ... Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  10. Hepatocellular Carcinoma with Cervical Spine and Pelvic Bone Metastases Presenting as Unknown Primary Neoplasm.

    PubMed

    Hwang, Sea Won; Lee, Ji Eun; Lee, Jung Min; Hong, Sook Hee; Lee, Myung Ah; Chun, Hoo Geun; Chun, Ho Jong; Lee, Sung Hak; Jung, Eun Sun

    2015-07-01

    The occurrence of hepatocellular carcinoma (HCC) is closely associated with viral hepatitis or alcoholic hepatitis. Although active surveillance is ongoing in Korea, advanced or metastatic HCC is found at initial presentation in many patients. Metastatic HCC presents with a hypervascular intrahepatic tumor and extrahepatic lesions such as lung or lymph node metastases. Cases of HCC presenting as carcinoma of unknown primary have been rarely reported. The authors experienced a case of metastatic HCC in a patient who presented with a metastatic bone lesion but no primary intrahepatic tumor. This case suggests that HCC should be considered as a differential diagnosis when evaluating the primary origin of metastatic carcinoma.

  11. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma.

    PubMed

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-08-18

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed. PMID:27621765

  12. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma

    PubMed Central

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-01-01

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed.

  13. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma

    PubMed Central

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-01-01

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed. PMID:27621765

  14. Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma.

    PubMed

    Caparelli, Michael L; Roberts, Nathan J; Braverman, Timothy S; Stevens, Robert M; Broun, Edward R; Allamaneni, Shyam

    2016-08-18

    This report describes a patient that developed recurrent metastatic hepatocellular carcinoma (HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed.

  15. Assessment of oxidative metabolism in adults with hepatocellular carcinoma in the Sudan.

    PubMed Central

    Homeida, M M; Daneshmend, T K; Ali, E M; Yousif-Elkadaru, A G; Arbab, B M

    1986-01-01

    The hypothesis that an increased rate of oxidative metabolism may be an initiator or promoter of hepatocellular carcinoma was tested in vivo. Elimination of antipyrine (phenazone) was used as an index of the activity of microsomal mixed function oxidative enzymes. Plasma antipyrine kinetics were examined in 10 patients with hepatocellular carcinoma and in 10 normal Sudanese adults. The half life, volume of distribution and clearance of antipyrine in patients were 18.8 +/- 7.9 hours (mean +/- SD), 33.8 +/- 7.7 litres and 23.7 +/- 10.1 ml/min, respectively; and in normal adults were 20.3 +/- 8.8 hours, 40.1 +/- 10.4 litres and 25.7 +/- 12.0 ml/min, respectively. These differences were not significant. Antipyrine plasma clearance when corrected for weight was similar in the two groups. This study suggests that in a population at risk for hepatocellular carcinoma, the overall activity of mixed function oxidative enzymes is not an important determinant in selectively increasing this risk. PMID:3007307

  16. Whole-genome sequencing of matched primary and metastatic hepatocellular carcinomas

    PubMed Central

    2014-01-01

    Background To gain biological insights into lung metastases from hepatocellular carcinoma (HCC), we compared the whole-genome sequencing profiles of primary HCC and paired lung metastases. Methods We used whole-genome sequencing at 33X-43X coverage to profile somatic mutations in primary HCC (HBV+) and metachronous lung metastases (> 2 years interval). Results In total, 5,027-13,961 and 5,275-12,624 somatic single-nucleotide variants (SNVs) were detected in primary HCC and lung metastases, respectively. Generally, 38.88-78.49% of SNVs detected in metastases were present in primary tumors. We identified 65–221 structural variations (SVs) in primary tumors and 60–232 SVs in metastases. Comparison of these SVs shows very similar and largely overlapped mutated segments between primary and metastatic tumors. Copy number alterations between primary and metastatic pairs were also found to be closely related. Together, these preservations in genomic profiles from liver primary tumors to metachronous lung metastases indicate that the genomic features during tumorigenesis may be retained during metastasis. Conclusions We found very similar genomic alterations between primary and metastatic tumors, with a few mutations found specifically in lung metastases, which may explain the clinical observation that both primary and metastatic tumors are usually sensitive or resistant to the same systemic treatments. PMID:24405831

  17. Adult-onset liver disease and hepatocellular carcinoma in S-adenosylhomocysteine hydrolase deficiency

    PubMed Central

    Stender, Stefan; Chakrabarti, Rima S.; Xing, Chao; Gotway, Garrett; Cohen, Jonathan C.; Hobbs, Helen H.

    2016-01-01

    Background The etiology of liver disease remains elusive in some adults presenting with severe hepatic dysfunction. Methods and results Here we describe a woman of Pakistani descent who had elevated aminotransferases at age 23. She developed muscle weakness in her mid-20s, and was diagnosed with hepatocellular carcinoma at age 29. She died without a diagnosis at age 32 after having a liver transplant. Exome sequencing revealed that she was homozygous for a missense mutation (R49H) in AHCY, the gene encoding S-adenosylhomocysteine (SAH) hydrolase. SAH hydrolase catalyzes the final step in conversion of methionine to homocysteine and inactivating mutations in this enzyme cause a rare autosomal recessive disorder, SAH hydrolase deficiency, that typically presents in infancy. An asymptomatic 7-year old son of the proband is also homozygous for the AHCY-R49H mutation and has elevated serum aminotransferase levels, as well as markedly elevated serum levels of SAH, S-adenosylmethionine (SAM), and methionine, which are hallmarks of SAH hydrolase deficiency. Conclusion This report reveals several new aspects of SAH hydrolase deficiency. Affected women with SAH hydrolase deficiency can give birth to healthy children. SAH hydrolase deficiency can remain asymptomatic in childhood, and the disorder can be associated with early onset hepatocellular carcinoma. The measurement of serum amino acids should be considered in patients with liver disease or hepatocellular carcinoma of unknown etiology. PMID:26527160

  18. Expression of Girdin in primary hepatocellular carcinoma and its effect on cell proliferation and invasion.

    PubMed

    Cao, Ke; Lu, Can; Han, Shuang; Zou, Qiong; Li, Jingjing; Xie, Dingfang; He, Siqi; Yu, Li; Zhou, Jianda; Peng, Xiaowei; Cao, Peiguo

    2015-01-01

    Girdin has been proven to play a vital role in the process of proliferation, apoptosis, and invasion in various cancer cells, yet the underlying molecular mechanism in primary hepatocellular carcinoma (HCC) has not yet been clarified. Thereafter, we performed immunohistochemistry to detect the expression of Girdin in 40 primary HCC tissues and 30 matched adjacent tissues using hepatic carcinoma tissue microarray. Our data showed that the positive expression rate of Girdin in hepatocellular carcinoma tissues was 67.5%, higher than that found in adjacent tissues of 16.7% (P < 0.05). It closely correlates to tumor size, T stage, TNM stage and Edmondson-Steiner stage (P < 0.05) of HCC patients. After specific small interfering RNA of Girdin was transfected into HepG2 and Huh7.5.1 cells, the proliferation and invasion ability of tumor cells were significantly inhibited. In summary, we suggest that the oncogenic role of Girdin could provide new molecular target for the treatment of HCC.

  19. Primary care of adults with developmental disabilities

    PubMed Central

    Sullivan, William F.; Berg, Joseph M.; Bradley, Elspeth; Cheetham, Tom; Denton, Richard; Heng, John; Hennen, Brian; Joyce, David; Kelly, Maureen; Korossy, Marika; Lunsky, Yona; McMillan, Shirley

    2011-01-01

    Abstract Objective To update the 2006 Canadian guidelines for primary care of adults with developmental disabilities (DD) and to make practical recommendations based on current knowledge to address the particular health issues of adults with DD. Quality of evidence Knowledgeable health care providers participating in a colloquium and a subsequent working group discussed and agreed on revisions to the 2006 guidelines based on a comprehensive review of publications, feedback gained from users of the guidelines, and personal clinical experiences. Most of the available evidence in this area of care is from expert opinion or published consensus statements (level III). Main message Adults with DD have complex health issues, many of them differing from those of the general population. Good primary care identifies the particular health issues faced by adults with DD to improve their quality of life, to improve their access to health care, and to prevent suffering, morbidity, and premature death. These guidelines synthesize general, physical, behavioural, and mental health issues of adults with DD that primary care providers should be aware of, and they present recommendations for screening and management based on current knowledge that practitioners can apply. Because of interacting biologic, psychoaffective, and social factors that contribute to the health and well-being of adults with DD, these guidelines emphasize involving caregivers, adapting procedures when appropriate, and seeking input from a range of health professionals when available. Ethical care is also emphasized. The guidelines are formulated within an ethical framework that pays attention to issues such as informed consent and the assessment of health benefits in relation to risks of harm. Conclusion Implementation of the guidelines proposed here would improve the health of adults with DD and would minimize disparities in health and health care between adults with DD and those in the general population

  20. Diagnostic Challenges in Primary Hepatocellular Carcinoma: Case Reports and Review of the Literature

    PubMed Central

    Pazgan-Simon, Monika; Serafinska, Sylwia; Janocha-Litwin, Justyna; Simon, Krzysztof; Zuwala-Jagiello, Jolanta

    2015-01-01

    Hepatocellular carcinoma is the fifth most common malignancy and the third leading mortality cause worldwide. It typically develops secondarily to liver cirrhosis, due to hepatitis B or C infection, alcohol abuse, metabolic disease, and so forth. According to the American Association for the Study of Liver Diseases (AASLD) guidelines, which constitute diagnostic standards, the diagnosis of primary hepatocellular carcinoma (HCC) should be based on contrast-enhanced imaging. Lesion hyperenhancement should be observed throughout the arterial phase, followed by the washout during the venous phase. The diagnosis can also be based on the histopathological evaluation of liver biopsy specimen. Although the standards are clear, we often see patients with advanced HCC in clinical practice, who cannot be offered any effective treatment. Patients with chronic liver disease, presenting with inconclusive and changeable test results, constitute a separate problem. In such cases the diagnostic process is typically long-term and delayed. In this paper we present three case reports where the diagnosis could not be made promptly and the patients died as a result of a delayed diagnostic process. PMID:25922775

  1. Hepatocellular carcinoma cell lines retain the genomic and transcriptomic landscapes of primary human cancers

    PubMed Central

    Qiu, Zhixin; Zou, Keke; Zhuang, Liping; Qin, Jianjie; Li, Hong; Li, Chao; Zhang, Zhengtao; Chen, Xiaotao; Cen, Jin; Meng, Zhiqiang; Zhang, Haibin; Li, Yixue; Hui, Lijian

    2016-01-01

    Hepatocellular carcinoma (HCC) cell lines are useful in vitro models for the study of primary HCCs. Because cell lines acquire additional mutations in culture, it is important to understand to what extent HCC cell lines retain the genetic landscapes of primary HCCs. Most HCC cell lines were established during the last century, precluding comparison between cell lines and primary cancers. In this study, 9 Chinese HCC cell lines with matched patient-derived cells at low passages (PDCs) were established in the defined culture condition. Whole genome analyses of 4 HCC cell lines showed that genomic mutation landscapes, including mutations, copy number alterations (CNAs) and HBV integrations, were highly stable during cell line establishment. Importantly, genetic alterations in cancer drivers and druggable genes were reserved in cell lines. HCC cell lines also retained gene expression patterns of primary HCCs during in vitro culture. Finally, sequential analysis of HCC cell lines and PDCs at different passages revealed their comparable and stable genomic and transcriptomic levels if maintained within proper passages. These results show that HCC cell lines largely retain the genomic and transcriptomic landscapes of primary HCCs, thus laying the rationale for testing HCC cell lines as preclinical models in precision medicine. PMID:27273737

  2. Hepatocellular carcinoma cell lines retain the genomic and transcriptomic landscapes of primary human cancers.

    PubMed

    Qiu, Zhixin; Zou, Keke; Zhuang, Liping; Qin, Jianjie; Li, Hong; Li, Chao; Zhang, Zhengtao; Chen, Xiaotao; Cen, Jin; Meng, Zhiqiang; Zhang, Haibin; Li, Yixue; Hui, Lijian

    2016-06-07

    Hepatocellular carcinoma (HCC) cell lines are useful in vitro models for the study of primary HCCs. Because cell lines acquire additional mutations in culture, it is important to understand to what extent HCC cell lines retain the genetic landscapes of primary HCCs. Most HCC cell lines were established during the last century, precluding comparison between cell lines and primary cancers. In this study, 9 Chinese HCC cell lines with matched patient-derived cells at low passages (PDCs) were established in the defined culture condition. Whole genome analyses of 4 HCC cell lines showed that genomic mutation landscapes, including mutations, copy number alterations (CNAs) and HBV integrations, were highly stable during cell line establishment. Importantly, genetic alterations in cancer drivers and druggable genes were reserved in cell lines. HCC cell lines also retained gene expression patterns of primary HCCs during in vitro culture. Finally, sequential analysis of HCC cell lines and PDCs at different passages revealed their comparable and stable genomic and transcriptomic levels if maintained within proper passages. These results show that HCC cell lines largely retain the genomic and transcriptomic landscapes of primary HCCs, thus laying the rationale for testing HCC cell lines as preclinical models in precision medicine.

  3. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. Hepatocellular ...

  4. Treatment of primary brain tumours in adults.

    PubMed

    McNamara, Shanne

    This article considers the complexities of caring for patients with primary brain tumours. The incidence, classification and clinical signs and symptoms are outlined. Adult patients experience disabling effects as a result of a brain tumour, which is often accompanied by high morbidity and mortality rates. The various treatment options available are summarised. However, for many patients, there are limited curative treatment options and the main focus is palliative care. The nurse's contribution to care and support of these patients and their families is discussed, with the aim of improving their quality of life.

  5. A case of primary clear cell hepatocellular carcinoma in a non-cirrhotic liver: an immunohistochemical and ultrastructural study

    PubMed Central

    Clayton, Erica Fan; Furth, Emma Elizabeth; Ziober, Amy; Xu, Theodore; Yao, Yuan; Hwang, Pil Gyu; Bing, Zhanyong

    2012-01-01

    The clear cell variant of hepatocellular carcinoma is a rare entity, occurring at a frequency of less than 10% of hepatocellular carcinoma, with a female prevalence and usually associated with hepatitis C and cirrhosis. We reported a case of primary clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without history of hepatitis. Our examination included gross pathology, histopathology, immunohistochemistry, special stains, and electron microscopy evaluation. The tumor was composed of sheets of medium-to-large cells with foamy and reticulated cytoplasm and small-to-medium sized nuclei with variably prominent nucleoli. Oil red O stain showed abundant intracellular lipid. Periodic Acid-Schiff stain confirmed the presence of abundant glycogen deposition. Immunohistochemically the tumor cells were positive for Hep Par1, negative for epithelial membrane antigen, steroidogenic factor-1, HMB45, melan A, CK7 and CK20. Electron microscopy study was performed, which was first done in a clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without elevation of liver function tests. Ultrastructural evaluation of the clear cells showed scarce cellular organelles, cytoplasmic lipid vacuoles and swollen mitochondria. PMID:22826786

  6. Anti-human AFP variant monoclonal antibody in radioimmunodetection of primary hepatocellular carcinoma

    PubMed Central

    Liu, Yang; Wu, Meng-Chao; Chen, Han; Zhang, Bai-He; Qian, Guang-Xiang; Pan, Wen-Zhou; Qiang, Mei-Yu

    1997-01-01

    AIM: To investigate the affinity of AFP-R-LCA monoclonal antibody (AFP-R-LCA McAb) for AFP-positive primary hepatocellular carcinoma (HCC) cells. METHODS: AFP-R-LCA McAb was labeled by 131I. Eleven cases of HCC with AFP positivity, 6 with AFP negativity, and 4 with hepatitis B-related cirrhosis were investigated by radioimmunodetection. RESULTS: The 131I-AFP-R-LCA McAb immunoreacted with 9 of the HCC AFP-positive cases (9/11), but with none of the 6 AFP negative HCC cases or of the 4 cirrhosis patients. 131I-AFP-R-LCA McAb at a small dose (7.4 × 107 Bq/300 μg) was associated with no side effects as determined by the liver function test, prothrombin time (Pt) test and thyroid gland function test (P > 0.05). Two cases of AFP-positive HCC were not imaged because of large tumor size (diameter > 10 cm) and higher AFP concentration in serum (20000 μg/L). CONCLUSION: AFP-R-LCA McAb has a strong and special affinity to AFP-positive HCC cells and may be useful as a carrier for radioimmunodetection and radioimmunotherapy. PMID:27053873

  7. Hepatocellular Carcinoma associated with Extra-hepatic Primary Malignancy: its Secular change, Clinical Manifestations and Survival.

    PubMed

    Kee, Kwong Ming; Wang, Jing-Houng; Wang, Chih-Chi; Cheng, Yu-Fan; Lu, Sheng-Nan

    2016-01-01

    Clinical manifestations between hepatocellular carcinoma (HCC) and extra-hepatic primary malignancy (EHPM) are lack of large-scale study. We enrolled 14555 HCC patients between 1986 and 2013 retrospectively. The EHPM was classified as prior, synchronous and metachronous group based on before, within and after 6 months of HCC diagnosis, respectively. The incidence rate of EHPM is 3.91% (95% confidence interval [CI]: 3.60-4.23%). Urogenital cancers, kidney and bladder, were at unexpected higher ranks. Older in age, Child-Pugh A cirrhosis, negativity of HBsAg and anti-HCV, and earlier BCLC staging are independent factors associated with EHPM. The survival rates of EHPM improve over time and also better than HCC-alone. Cox proportional-hazards regression shows independent poor prognostic factors are age >60, male, AFP levels ≥400 ng/ml, positivity of HBsAg, Child-Pugh B vs. A, Non-metachronous group, respectively, treated with local ablation, transcatheter arterial embolization, radiotherapy and supportive care vs. surgery, respectively, TNM stage IIIA vs. I, and BCLC stages A, B, C and D vs. 0, respectively. Survival of EHPM improve could be explained by early diagnosis and improve treatment of cancers. PMID:27444261

  8. Recombinant soluble gp130 protein reduces DEN-induced primary hepatocellular carcinoma in mice

    PubMed Central

    Hong, Jing; Wang, Hang; Shen, Guoying; Lin, Da; Lin, Yanxue; Ye, Nanhui; Guo, Yashan; Li, Qiaoling; Ye, Nanhui; Deng, Chengjun; Meng, Chun

    2016-01-01

    IL-6 (interleukin 6) plays an important role in the development and growth of hepatocellular carcinoma (HCC) via both classic signaling and trans-signaling pathways. Soluble gp130 (sgp130) is known to be a natural inhibitor of the trans-signaling pathway. In the present study, our goal was to investigate whether recombinant sgp130 could suppress the initiation and progression of HCC in mouse models. Our results demonstrate that sgp130 induced an apoptosis of HepG2 cells and inhibited the clonogenicity of HepG2 in vitro. Moreover, the IL-6 trans-signaling pathway is significantly suppressed by sgp130 as reflected by the decrease in the level of STAT3 phosphorylation and other inflammatory factors both in vitro and in vivo. In the DEN-induced HCC mouse model, intravenous injection of sgp130 attenuated hepatic fibrosis at 16 weeks and reduced the initiation and progression of primary HCC at 36 weeks. Furthermore, our results also demonstrate that intravenous administration of sgp130 significantly suppressed the growth and metastasis of xenograft human HCC in NOD/SCID mice. PMID:27080032

  9. Hepatocellular Carcinoma associated with Extra-hepatic Primary Malignancy: its Secular change, Clinical Manifestations and Survival

    PubMed Central

    Kee, Kwong Ming; Wang, Jing-Houng; Wang, Chih-Chi; Cheng, Yu-Fan; Lu, Sheng-Nan

    2016-01-01

    Clinical manifestations between hepatocellular carcinoma (HCC) and extra-hepatic primary malignancy (EHPM) are lack of large-scale study. We enrolled 14555 HCC patients between 1986 and 2013 retrospectively. The EHPM was classified as prior, synchronous and metachronous group based on before, within and after 6 months of HCC diagnosis, respectively. The incidence rate of EHPM is 3.91% (95% confidence interval [CI]: 3.60–4.23%). Urogenital cancers, kidney and bladder, were at unexpected higher ranks. Older in age, Child-Pugh A cirrhosis, negativity of HBsAg and anti-HCV, and earlier BCLC staging are independent factors associated with EHPM. The survival rates of EHPM improve over time and also better than HCC-alone. Cox proportional-hazards regression shows independent poor prognostic factors are age >60, male, AFP levels ≥400 ng/ml, positivity of HBsAg, Child-Pugh B vs. A, Non-metachronous group, respectively, treated with local ablation, transcatheter arterial embolization, radiotherapy and supportive care vs. surgery, respectively, TNM stage IIIA vs. I, and BCLC stages A, B, C and D vs. 0, respectively. Survival of EHPM improve could be explained by early diagnosis and improve treatment of cancers. PMID:27444261

  10. Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma

    PubMed Central

    Liu, Hui; Li, Peng; Zhai, Yun; Qu, Chun-Feng; Zhang, Li-Jie; Tan, Yu-Fen; Li, Ning; Ding, Hui-Guo

    2010-01-01

    AIM: To evaluate the diagnostic value of glypican-3 (GPC3) in serum and liver for primary hepatocellular carcinoma (HCC). METHODS: Serum levels of GPC3 and α-fetoprotein (AFP) were measured in 75 patients with primary HCC and 32 patients with liver cirrhosis. Expression of GPC3 and AFP in 58 HCC and 12 cirrhotic specimens was detected with immunohistochemical staining. RESULTS: When the cut-off value of serum GPC3 was set at 300 ng/L, its sensitivity and specificity for HCC were 47.0% and 93.5%, respectively. Among the 14 patients with HCC at stage according to the Barcelona Clinic Liver Cancer staging system, the serum GPC3 level was higher than 300 ng/L in 50% (7/14) patients, the serum AFP level was not ≥ 400 μg/L in any patient. Combined serum AFP and GPC3 significantly increased the sensitivity to the diagnosis of HCC. The GPC3 expression was detected in cytoplasm of HCC cells but not in hepatocytes and bile ducts of benign tumors. Among the 58 HCC patients, the GPC3 was expressed in 100% (28/28) patients with their serum AFP level ≥ 400 μg/L, and in 90% (27/30) patients with their AFP level < 400 μg/L, respectively. The GPC3 was weakly or negatively expressed in all paracarcinomatous and cirrhotic tissue samples. AFP positive HCC cells were only found in 1 out of the 58 HCC patients. CONCLUSION: GPC3 protein is a sensitive and specific serum marker for diagnosis of early HCC. Its expression in liver tissues can be used to discriminate tumor cells from benign hepatic cells. PMID:20845507

  11. A Systematic Review of Des-γ-Carboxy Prothrombin for the Diagnosis of Primary Hepatocellular Carcinoma

    PubMed Central

    De, Ji; Shen, Yi; Qin, Jinyu; Feng, Li; Wang, Yiping; Yang, Li

    2016-01-01

    Abstract Determining the serum des-γ-carboxy-prothrombin (DCP) level is of great importance for the diagnosis of primary hepatocellular carcinoma (PHC). Although several studies have investigated the accuracy of diagnostic DCP tests for PHC, the results have been inconsistent. The aim of this study was to systematically evaluate DCP as a diagnostic standard for PHC. Several databases, including PubMed, EMBASE, MEDLINE (Ovid), the Chinese National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), WanFang Data, and the China Biological Medicine Database (CBM), were searched from the date of database inception until July 1, 2015 to collect published international and domestic studies of DCP in the diagnosis of PHC. Two investigators screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies. A total of 38 studies involving 11,124 cases were included (5298 cases in the PHC group and 5826 cases in the control group). A meta-analysis was then performed using Meta-Disc 1.4 and RevMan 5.2 software. The overall sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (−LR) of DCP for the detection of PHC were 0.66 (95% confidence interval [CI]: 0.65–0.68), 0.88 (95% CI: 0.87–0.90), 7.13 (95% CI: 5.73–8.87), and 0.33 (95% CI: 0.29–0.38), respectively. The area under the curve (AUC) of the summary receiver-operating characteristic curve (SROC) was 0.9002. In conclusion, DCP has moderate diagnostic utility for PHC. Owing to the heterogeneity and limitations of the included studies, the above conclusion requires further support from additional high-quality studies. PMID:27124038

  12. A Systematic Review of Des-γ-Carboxy Prothrombin for the Diagnosis of Primary Hepatocellular Carcinoma.

    PubMed

    De, Ji; Shen, Yi; Qin, Jinyu; Feng, Li; Wang, Yiping; Yang, Li

    2016-04-01

    Determining the serum des-γ-carboxy-prothrombin (DCP) level is of great importance for the diagnosis of primary hepatocellular carcinoma (PHC). Although several studies have investigated the accuracy of diagnostic DCP tests for PHC, the results have been inconsistent.The aim of this study was to systematically evaluate DCP as a diagnostic standard for PHC.Several databases, including PubMed, EMBASE, MEDLINE (Ovid), the Chinese National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), WanFang Data, and the China Biological Medicine Database (CBM), were searched from the date of database inception until July 1, 2015 to collect published international and domestic studies of DCP in the diagnosis of PHC. Two investigators screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies.A total of 38 studies involving 11,124 cases were included (5298 cases in the PHC group and 5826 cases in the control group). A meta-analysis was then performed using Meta-Disc 1.4 and RevMan 5.2 software. The overall sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (-LR) of DCP for the detection of PHC were 0.66 (95% confidence interval [CI]: 0.65-0.68), 0.88 (95% CI: 0.87-0.90), 7.13 (95% CI: 5.73-8.87), and 0.33 (95% CI: 0.29-0.38), respectively. The area under the curve (AUC) of the summary receiver-operating characteristic curve (SROC) was 0.9002. In conclusion, DCP has moderate diagnostic utility for PHC. Owing to the heterogeneity and limitations of the included studies, the above conclusion requires further support from additional high-quality studies.

  13. A Systematic Review of Des-γ-Carboxy Prothrombin for the Diagnosis of Primary Hepatocellular Carcinoma.

    PubMed

    De, Ji; Shen, Yi; Qin, Jinyu; Feng, Li; Wang, Yiping; Yang, Li

    2016-04-01

    Determining the serum des-γ-carboxy-prothrombin (DCP) level is of great importance for the diagnosis of primary hepatocellular carcinoma (PHC). Although several studies have investigated the accuracy of diagnostic DCP tests for PHC, the results have been inconsistent.The aim of this study was to systematically evaluate DCP as a diagnostic standard for PHC.Several databases, including PubMed, EMBASE, MEDLINE (Ovid), the Chinese National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), WanFang Data, and the China Biological Medicine Database (CBM), were searched from the date of database inception until July 1, 2015 to collect published international and domestic studies of DCP in the diagnosis of PHC. Two investigators screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies.A total of 38 studies involving 11,124 cases were included (5298 cases in the PHC group and 5826 cases in the control group). A meta-analysis was then performed using Meta-Disc 1.4 and RevMan 5.2 software. The overall sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (-LR) of DCP for the detection of PHC were 0.66 (95% confidence interval [CI]: 0.65-0.68), 0.88 (95% CI: 0.87-0.90), 7.13 (95% CI: 5.73-8.87), and 0.33 (95% CI: 0.29-0.38), respectively. The area under the curve (AUC) of the summary receiver-operating characteristic curve (SROC) was 0.9002. In conclusion, DCP has moderate diagnostic utility for PHC. Owing to the heterogeneity and limitations of the included studies, the above conclusion requires further support from additional high-quality studies. PMID:27124038

  14. Adult mouse model of early hepatocellular carcinoma promoted by alcoholic liver disease

    PubMed Central

    Ambade, Aditya; Satishchandran, Abhishek; Gyongyosi, Benedek; Lowe, Patrick; Szabo, Gyongyi

    2016-01-01

    AIM: To establish a mouse model of alcohol-driven hepatocellular carcinoma (HCC) that develops in livers with alcoholic liver disease (ALD). METHODS: Adult C57BL/6 male mice received multiple doses of chemical carcinogen diethyl nitrosamine (DEN) followed by 7 wk of 4% Lieber-DeCarli diet. Serum alanine aminotransferase (ALT), alpha fetoprotein (AFP) and liver Cyp2e1 were assessed. Expression of F4/80, CD68 for macrophages and Ly6G, MPO, E-selectin for neutrophils was measured. Macrophage polarization was determined by IL-1β/iNOS (M1) and Arg-1/IL-10/CD163/CD206 (M2) expression. Liver steatosis and fibrosis were measured by oil-red-O and Sirius red staining respectively. HCC development was monitored by magnetic resonance imaging, confirmed by histology. Cellular proliferation was assessed by proliferating cell nuclear antigen (PCNA). RESULTS: Alcohol-DEN mice showed higher ALTs than pair fed-DEN mice throughout the alcohol feeding without weight gain. Alcohol feeding resulted in increased ALT, liver steatosis and inflammation compared to pair-fed controls. Alcohol-DEN mice had reduced steatosis and increased fibrosis indicating advanced liver disease. Molecular characterization showed highest levels of both neutrophil and macrophage markers in alcohol-DEN livers. Importantly, M2 macrophages were predominantly higher in alcohol-DEN livers. Magnetic resonance imaging revealed increased numbers of intrahepatic cysts and liver histology confirmed the presence of early HCC in alcohol-DEN mice compared to all other groups. This correlated with increased serum alpha-fetoprotein, a marker of HCC, in alcohol-DEN mice. PCNA immunostaining revealed significantly increased hepatocyte proliferation in livers from alcohol-DEN compared to pair fed-DEN or alcohol-fed mice. CONCLUSION: We describe a new 12-wk HCC model in adult mice that develops in livers with alcoholic hepatitis and defines ALD as co-factor in HCC. PMID:27122661

  15. An inducible hepatocellular carcinoma model for preclinical evaluation of antiangiogenic therapy in adult mice.

    PubMed

    Runge, Anja; Hu, Junhao; Wieland, Matthias; Bergeest, Jan-Philip; Mogler, Carolin; Neumann, André; Géraud, Cyrill; Arnold, Bernd; Rohr, Karl; Komljenovic, Dorde; Schirmacher, Peter; Goerdt, Sergij; Augustin, Hellmut G

    2014-08-01

    The limited availability of experimental tumor models that faithfully mimic the progression of human tumors and their response to therapy remains a major bottleneck to the clinical translation and application of novel therapeutic principles. To address this challenge in hepatocellular carcinoma (HCC), one of the deadliest and most common cancers in the world, we developed and validated an inducible model of hepatocarcinogenesis in adult mice. Tumorigenesis was triggered by intravenous adenoviral delivery of Cre recombinase in transgenic mice expressing the hepatocyte-specific albumin promoter, a loxP-flanked stop cassette, and the SV40 large T-antigen (iAST). Cre recombinase-mediated excision of the stop cassette led to a transient viral hepatitis and resulted in multinodular tumorigenesis within 5 to 8 weeks. Tumor nodules with histologic characteristics of human HCC established a functional vasculature by cooption, remodeling, and angiogenic expansion of the preexisting sinusoidal liver vasculature with increasing signs of vascular immaturity during tumor progression. Treatment of mice with sorafenib rapidly resulted in the induction of vascular regression, inhibition of tumor growth, and enhanced overall survival. Vascular regression was characterized by loss of endothelial cells leaving behind avascular type IV collagen-positive empty sleeves with remaining pericytes. Sorafenib treatment led to transcriptional changes of Igf1, Id1, and cMet over time, which may reflect the emergence of potential escape mechanisms. Taken together, our results established the iAST model of inducible hepatocarcinogenesis as a robust and versatile preclinical model to study HCC progression and validate novel therapies. PMID:24906623

  16. Primary cerebral alveolar rhabdomyosarcoma in adult

    PubMed Central

    Pirillo, Vania; Cipriano Cecchi, Paolo; Tripodi, Massimo; Maier, Klaus; Rizzo, Paolo; Schwarz, Andreas

    2011-01-01

    Primary cerebral rhabdomyosarcomas are very rare and malignant tumors that occur predominantly in the posterior fossa of pediatric patients. We report a rare case of primary cerebral rhabdomyosarcoma located in the supratentorial compartment of a 51 year-old woman together with a review of the pertinent Literature especially regarding the histological diagnosis and pitfalls. PMID:21769325

  17. Comparative proteomic analysis of mouse livers from embryo to adult reveals an association with progression of hepatocellular carcinoma.

    PubMed

    Lee, Nikki P Y; Leung, Kar-wai; Cheung, Nicole; Lam, Brian Y; Xu, Michelle Z; Sham, Pak C; Lau, George K; Poon, Ronnie T P; Fan, Sheung Tat; Luk, John M

    2008-05-01

    To identify potential oncofetal biomarkers that distinguish hepatocellular carcinoma (HCC) from healthy liver tissues, we compared and analyzed the proteomic profiles of mouse livers at different developmental stages. Fetal (E13.5, E16.5), newborn (NB), postnatal (3-week) and adult (3-month) livers were isolated and profiled by 2-D PAGE. Statistical analysis using linear regression and false discovery rate (FDR) revealed that 361 protein spots showed significant changes. Unsupervised hierarchical tree analysis segregated the proteins into fetal, NB, and postnatal-adult clusters. Distinctive protein markers were identified by MALDI-TOF/MS and the corresponding mRNA profiles were further determined by Q-PCR. Fetal markers (hPCNA, hHSP7C, hHEM6) and postnatal-adult markers (hARGI1, hASSY, hBHMT, hFABPL) were selected for testing against a panel of seven human hepatocyte/HCC cell lines and 59 clinical specimens. The fetal proteins were found to be overexpressed in the metastatic HCC cell lines and the tumor tissues, whereas the postnatal-adult proteins were expressed in non-tumor tissues and normal hepatocytes. This "Ying-Yang" pattern, as orchestrated by distinct fetal and adult markers, is hypothesized to indicate the progressive change of the liver from a growing, less-differentiated organ into a functional metabolic center. Thus, embryogenesis and tumorigenesis share certain oncofetal markers and adult "hepatic" phenotypes are lost in HCC.

  18. Sorafenib combined with radiofrequency ablation in the treatment of a patient with renal cell carcinoma plus primary hepatocellular carcinoma.

    PubMed

    Gang, Guo; Hongkai, Yu; Xu, Zhang

    2015-01-01

    The combination of renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) is extremely rare, and the prognosis for patients with these two cancers is poor. In the past decade, molecular targeted therapy and radiofrequency ablation (RFA) have emerged and these treatments are now playing an increasingly important role in the management of patients with advanced primary RCC and HCC. In this case report, a 72-year-old male patient diagnosed as having RCC invading the renal vein and grade I-II HCC was treated with RFA and sorafenib (400 mg twice daily). After 3 months of this combination treatment, an evaluation of his target lesions showed stable disease (SD), and progression-free survival (PFS) times were 28 months weeks for RCC and 16 months weeks for HCC. Overall survival (OS) was 40 weeks. PMID:26881596

  19. Sorafenib combined with radiofrequency ablation in the treatment of a patient with renal cell carcinoma plus primary hepatocellular carcinoma.

    PubMed

    Gang, Guo; Hongkai, Yu; Xu, Zhang

    2015-01-01

    The combination of renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) is extremely rare, and the prognosis for patients with these two cancers is poor. In the past decade, molecular targeted therapy and radiofrequency ablation (RFA) have emerged and these treatments are now playing an increasingly important role in the management of patients with advanced primary RCC and HCC. In this case report, a 72-year-old male patient diagnosed as having RCC invading the renal vein and grade I-II HCC was treated with RFA and sorafenib (400 mg twice daily). After 3 months of this combination treatment, an evaluation of his target lesions showed stable disease (SD), and progression-free survival (PFS) times were 28 months weeks for RCC and 16 months weeks for HCC. Overall survival (OS) was 40 weeks.

  20. Complex segregation analysis of primary hepatocellular carcinoma in Chinese families: interaction of inherited susceptibility and hepatitis B viral infection.

    PubMed Central

    Shen, F M; Lee, M K; Gong, H M; Cai, X Q; King, M C

    1991-01-01

    Primary hepatocellular carcinoma (PHC) is extremely common in eastern China, where it is both associated with chronic infection with hepatitis B virus (HBV) and often familial. Complex segregation analysis of 490 extended families was undertaken with liability classes defined by age, sex, and HBV infection status. The maximum-likelihood model suggests that a recessive allele with population frequency approximately .25 yields lifetime risk of PHC, in the presence of both HBV infection and genetic susceptibility, of .84 for males and .46 for females. The model further predicts that, in the absence of genetic susceptibility, lifetime risk of PHC is .09 for HBV-infected males and .01 for HBV-infected females and that, regardless of genotype, it is virtually zero for uninfected persons. Complex segregation analysis therefore provides evidence for the interaction of genotype, environmental exposure, sex and age in determining the occurrence of PHC in this population. PMID:1648308

  1. [Primary retroperitoneal enteric cyst in an adult].

    PubMed

    Kondor, Ariella; Hajdu, Gábor; Zöllei, István; Bende, Mariann

    2005-06-01

    The posterior mediastinum is the usual location of enteric cysts. They can be located at any part of the posterior mediastinum adjacent to the oesophagus, but communication with that structure is rare. Approximately 60 percent of the cysts occur in infants less than one year of age, and symptoms of tracheal or oesophageal obstruction are common. The cysts usually contain clear, colorless mucoid fluid. The authors describe here a successfully treated enteric cyst with an unusual, retroperitoneal location, which presented in an adult.

  2. Sorting and biological characteristics analysis for side population cells in human primary hepatocellular carcinoma

    PubMed Central

    Jiang, Yegui; Gao, Hucheng; Liu, Mingdong; Mao, Qing

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cause of the tumor worldwide, its incidence is increasing year by year. This study aims to investigate the sorting and biological characteristics of side population (SP) cells. Human HCC tissues used were obtained from patients undergoing surgical resection. SP cells were sorted using flow cytometry. Cell cycle assay, apoptosis assay and colony formation assay were performed to detect cell proliferation and apoptosis. Invasion assay was employed to examine SP cell invasion. Tumorigenicity assay was used to evaluate tumorigenicity. HCC related microRNAs (miRNA) were analyzed using Micro-array analysis. Target genes were predicted using miRNA database. GO analsis was employed to predict target gene function. Apoptosis percentage was lower and cell viability was higher in SP cells than non-SP (NSP) cells. Colony forming ability of SP cells was significantly higher than NSP cells. Transwell assay positive cells in SP cells were higher significantly than NSP cells. Tumorigenicity of SP cells was higher significantly than NSP cells. 107 differentially expression miRNA were discovered, including 45 up-expressed miRNAs and 62 down-expressed miRNAs in SP cells. Up-regulated hsa-miR-193b-3p and hsa-miR-505-3p predict 25 and 35 target genes, and correlated with 4 and 42 GO terms, respectively. Down-regulated hsa-miR-200a-3p, hsa-miR-194-5p, hsa-miR-130b-3p predict 133, 48 and 127 target genes, and correlate with 10, 7 and 109 GO terms, respectively. In conclusion, proliferation, colony formation, anti-apoptosis, self-renewal capavility, invasive characteristic and tumorigenicity in SP cells isolated from HCC tissues was higher compared to NSP cells. Therefore, sorted SP cells could characterize with biological functions of cancer stem cells. PMID:27725897

  3. Primary care for adults on the autism spectrum.

    PubMed

    Nicolaidis, Christina; Kripke, Clarissa Calliope; Raymaker, Dora

    2014-09-01

    Autism spectrum disorder (ASD) is defined by differences in social communication and restricted, repetitive patterns of behavior, interests, or activities. Skills and challenges can change depending on environmental stimuli, supports, and stressors. Quality of life can be improved by the use of accommodations, assistive technologies, therapies to improve adaptive function or communication, caregiver training, acceptance, access, and inclusion. This article focuses on the identification of ASD in adults, referrals for services, the recognition of associated conditions, strategies and accommodations to facilitate effective primary care services, and ethical issues related to caring for autistic adults.

  4. Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma

    ClinicalTrials.gov

    2015-12-01

    Hepatocellular Carcinoma; Hepatoma; Liver Cancer, Adult; Liver Cell Carcinoma; Liver Cell Carcinoma, Adult; Cancer of Liver; Cancer of the Liver; Cancer, Hepatocellular; Hepatic Cancer; Hepatic Neoplasms; Hepatocellular Cancer; Liver Cancer; Neoplasms, Hepatic; Neoplasms, Liver

  5. Practice Patterns and Attitudes of Primary Care Providers and Barriers to Surveillance of Hepatocellular Carcinoma in Patients with Cirrhosis

    PubMed Central

    Dalton-Fitzgerald, Eimile; Tiro, Jasmin; Kandunoori, Pragathi; Halm, Ethan A.; Yopp, Adam; Singal, Amit G.

    2014-01-01

    Background & Aims Fewer than 20% of patients with cirrhosis undergo surveillance for hepatocellular carcinoma (HCC), so these tumors are often detected at late stages. Although primary care providers (PCPs) follow 60% of patients with cirrhosis in the US, little is known about their practice patterns for HCC surveillance. We investigated factors associated with adherence to guidelines for HCC surveillance by PCPs. Methods We conducted a web-based survey of all 131 PCPs at a large urban hospital. The survey was derived from validated surveys and pretested among providers; it included questions about provider and practice characteristics, self-reported rates of surveillance, surveillance test and frequency preference, and attitudes and barriers to HCC surveillance. Results We obtained a clinic-level response rate of 100% and provider-level response rate of 60%. Only 65% of respondents reported annual and 15% reported biannual surveillance of patients for HCC. Barriers to HCC surveillance included not being up-to-date with HCC guidelines (68% of PCPs), difficulties in communicating effectively with patients about HCC surveillance (56%), and more important issues to manage in clinic (52%). About half of PCPs (52%) reported using ultrasound or measurements of α-fetoprotein in surveillance; 96% said that this combination was effective in reducing HCC-related mortality. However, many providers incorrectly believed that clinical examination (45%), or levels of liver enzymes (59%) or α-fetoprotein alone (89%), were effective surveillance tools. Conclusions PCPs have misconceptions about tests to detect HCC that contribute to ineffective surveillance. Reported barriers to surveillance include suboptimal knowledge about guidelines, indicating a need for interventions, including provider education, to increase HCC surveillance effectiveness. PMID:25019694

  6. Sex-specific associations between birth weight and adult primary liver cancer in a large cohort of Danish children.

    PubMed

    Zimmermann, Esther; Berentzen, Tina L; Gamborg, Michael; Sørensen, Thorkild I A; Baker, Jennifer L

    2016-03-15

    Whether the prenatal period is critical for the development of adult primary liver cancer (PLC) is sparsely investigated. Recently, attention has been drawn to potential sex-differences in the early origins of adult disease. The association between birth weight and adult PLC, separately in men and women was investigated, using a large cohort of 217,227 children (51% boys), born from 1936 to 1980, from the Copenhagen School Health Records Register, and followed them until 2010 in national registers. Hazard ratios (95% confidence intervals) of PLC (30 years or older) were estimated by Cox regression models stratified by birth cohort. During 5.1 million person-years of follow-up, 185 men and 65 women developed PLC. Sex modified the association between birth weight and adult PLC (p values for interaction = 0.0005). Compared with a sex-specific reference group of birth weights between 3.25 and 3.75 kg, men with birth weights between 2.00 and 3.25 kg and 3.75-5.50 kg, had HRs of 1.48 (1.06-2.05) and 0.85 (0.56-1.28), respectively. Among women the corresponding HRs were 1.71 (0.90-3.29) and 3.43 (1.73-6.82). Associations were similar for hepatocellular carcinoma only, across year of birth, and after accounting for diagnoses of alcohol-related disorders, viral hepatitis and biliary cirrhosis. Prenatal exposures influenced the risk of adult PLC, and the effects at the high birth weight levels appeared to be sex-specific. These findings underscore the importance of considering sex-specific mechanisms in the early origins of adult PLC.

  7. Adult primary retroperitoneal cavernous hemangioma: a case report.

    PubMed

    He, Hang; Du, Zunguo; Hao, Sijie; Yao, Lie; Yang, Feng; Di, Yang; Li, Ji; Jiang, Yongjian; Jin, Chen; Fu, Deliang

    2012-01-01

    Primary retroperitoneal cavernous hemangioma (PRCH) in an adult is extremely rare. We report on the diagnosis and treatment of a patient with PRCH with subtle clinical features and atypical findings on imaging scans. A 38-year-old man was admitted to hospital with a 5-day history of epigastralgia after alcohol drinking. Using various imaging methods, we found a giant cyst-like retroperitoneal mass compressing the surrounding organs. Surgical resection of the tumor was performed, and the mass was found to be a cavernous hemangioma measuring 90 × 80 × 60 mm, with a thick fibrotic wall and extensive intracystic hemorrhage. Physicians should be aware that PRCH may mimic a cystic neoplasm, and that a large tumor size probably indicates intracystic hemorrhage. Surgical resection is a curative approach for PRCH.

  8. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2016-06-17

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  9. Contemporary management of primary immune thrombocytopenia in adults.

    PubMed

    Lakshmanan, S; Cuker, A

    2012-10-01

    Immune thrombocytopenia (ITP) comprises a syndrome of diverse disorders that have in common immune-mediated thrombocytopenia, but that differ with respect to pathogenesis, natural history and response to therapy. ITP may occur in the absence of an evident predisposing etiology (primary ITP) or as a sequela of a growing list of associated conditions (secondary ITP). Primary ITP remains a diagnosis of exclusion and must be differentiated from non-autoimmune etiologies of thrombocytopenia and secondary causes of ITP. The traditional objective of management is to provide a hemostatic platelet count (> 20-30 × 10(9) L(-1) in most cases) while minimizing treatment-related toxicity, although treatment goals should be tailored to the individual patient and clinical setting. Corticosteroids, supplemented with either intravenous immune globulin G or anti-Rh(D) as needed, are used as upfront therapy to stop bleeding and raise the platelet count acutely in patients with newly diagnosed or newly relapsed disease. Although most adults with primary ITP respond to first-line therapy, the majority relapse after treatment is tapered and require a second-line approach to maintain a hemostatic platelet count. Standard second-line options include splenectomy, rituximab and the thrombopoietin receptor agonists, romiplostim and eltrombopag. Studies that directly compare the efficacy, safety and cost-effectiveness of these approaches are lacking. In the absence of such data, we do not favor a single second-line approach for all patients. Rather, we consider the pros and cons of each option with our patients and engage them in the decision-making process.

  10. Efficacy and safety of the oxaliplatin-based chemotherapy in the treatment of advanced primary hepatocellular carcinoma

    PubMed Central

    Liu, Lin; Zheng, Ying-hui; Han, Li; Qin, Shu-Kui

    2016-01-01

    Abstract Background: Many clinical studies have demonstrated the survival benefits of oxaliplatin-based chemotherapy for advanced hepatocellular carcinoma patients. Therefore, we aim to evaluate the efficacy and safety of oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma by conducting a meta-analysis of prospective studies. Methods: A comprehensive literature search was performed using the PubMed, Cochrane Library, EMBASE, and Web of Science databases from their inception to June 2016. Only prospective studies evaluating oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma were selected. The main outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and main adverse events. Results: Ten prospective studies involving 525 patients were included. The pooled ORR, 1-year PFS, and OS were 14.4% (95% confidence interval [CI] 9.2–19.6%), 9.3% (95%CI 10–28%), and 35.7% (95%CI 27–44%), respectively, for oxaliplatin-based chemotherapy. The median PFS and OS were 4.7 and 9.4 months, respectively. The incidences of grade 3/4 toxicities of neutropenia, thrombopenia, anemia, neurotoxicity, diarrhea, and nausea/vomiting were 17.2%, 9.2%, 6.0%, 4.8%, 3.1%, and 1.8%, respectively. Subgroup analysis revealed that the pooled ORR was 13.9% (95%CI 6.8–21%) in Asian patients and 12.8% (95%CI 6.8–18.7%) in Western patients. For Asian patients, the median PFS and OS were 4.2 and 9.2 months, and the 1-year PFS and OS were 12.5% and 30.5%, respectively. For Western patients, the median PFS and OS were 4.7 and 9.5 months, and the 1-year PFS and OS were 19.6% and 42.4%, respectively. There were no significant differences in the ORR, 1-year PFS, and OS (P > 0.05) between Asian and Western patients. Conclusions: Oxaliplatin-based chemotherapy appears to be effective and safe for the treatment of advanced hepatocellular carcinoma. PMID:27749557

  11. Novel Imaging Diagnosis for Hepatocellular Carcinoma: Consensus from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014)

    PubMed Central

    Chen, Bang-Bin; Murakami, Takamichi; Shih, Tiffany Ting-Fang; Sakamoto, Michiie; Matsui, Osamu; Choi, Byung-Ihn; Kim, Myeong-Jin; Lee, Jeong Min; Yang, Ren-jie; Zeng, Meng-Su; Chen, Ran-Chou; Liang, Ja-Der

    2015-01-01

    Current novel imaging techniques in the diagnosis of hepatocellular carcinoma (HCC), with the latest evidence in this field, was discussed at the Asia-Pacific Primary Liver Cancer Expert (APPLE) meeting held in Taipei, Taiwan, in July 2014. Based on their expertise in a specific area of research, the novel imaging group comprised 12 participants from Japan, South Korea, Taiwan, and China and it included 10 abdominal radiologists, one hepatologist, and one pathologist. The expert participants discussed topics related to HCC imaging that were divided into four categories: (i) detection method, (ii) diagnostic method, (iii) evaluation method, and (iv) functional method. Consensus was reached on 10 statements; specific comments on each statement were provided to explain the rationale for the voting results and to suggest future research directions. PMID:26734577

  12. Rituximab use in adult primary glomerulopathy: where is the evidence?

    PubMed Central

    Mallat, Samir G; Itani, Houssam S; Abou-Mrad, Rana M; Abou Arkoub, Rima; Tanios, Bassem Y

    2016-01-01

    Rituximab is a chimeric anti-CD20 antibody that results in depletion of B-cell lymphocytes. It is currently used in the treatment of a variety of autoimmune diseases, in addition to CD20-positive lymphomas. The use of rituximab in the treatment of the adult primary glomerular diseases has emerged recently, although not yet established as first-line therapy in international guidelines. In patients with steroid-dependent minimal change disease or frequently relapsing disease, and in patients with idiopathic membranous nephropathy (IMN), several retrospective and prospective studies support the use of rituximab to induce remission, whereas in idiopathic focal and segmental glomerulosclerosis (FSGS), the use of rituximab has resulted in variable results. Evidence is still lacking for the use of rituximab in patients with immunoglobulin A nephropathy (IgAN) and idiopathic membranoproliferative glomerulonephritis (MPGN), as only few reports used rituximab in these two entities. Randomized controlled trials (RCTs) are warranted and clearly needed to establish the definitive role of rituximab in the management of steroid-dependent and frequently relapsing minimal change disease, IMN, both as first-line and second-line treatment, and in MPGN. We await the results of an ongoing RCT of rituximab use in IgAN. Although current evidence for the use of rituximab in patients with idiopathic FSGS is poor, more RCTs are needed to clarify its role, if any, in the management of steroid-resistant or steroid-dependent FSGS. PMID:27621641

  13. Rituximab use in adult primary glomerulopathy: where is the evidence?

    PubMed Central

    Mallat, Samir G; Itani, Houssam S; Abou-Mrad, Rana M; Abou Arkoub, Rima; Tanios, Bassem Y

    2016-01-01

    Rituximab is a chimeric anti-CD20 antibody that results in depletion of B-cell lymphocytes. It is currently used in the treatment of a variety of autoimmune diseases, in addition to CD20-positive lymphomas. The use of rituximab in the treatment of the adult primary glomerular diseases has emerged recently, although not yet established as first-line therapy in international guidelines. In patients with steroid-dependent minimal change disease or frequently relapsing disease, and in patients with idiopathic membranous nephropathy (IMN), several retrospective and prospective studies support the use of rituximab to induce remission, whereas in idiopathic focal and segmental glomerulosclerosis (FSGS), the use of rituximab has resulted in variable results. Evidence is still lacking for the use of rituximab in patients with immunoglobulin A nephropathy (IgAN) and idiopathic membranoproliferative glomerulonephritis (MPGN), as only few reports used rituximab in these two entities. Randomized controlled trials (RCTs) are warranted and clearly needed to establish the definitive role of rituximab in the management of steroid-dependent and frequently relapsing minimal change disease, IMN, both as first-line and second-line treatment, and in MPGN. We await the results of an ongoing RCT of rituximab use in IgAN. Although current evidence for the use of rituximab in patients with idiopathic FSGS is poor, more RCTs are needed to clarify its role, if any, in the management of steroid-resistant or steroid-dependent FSGS.

  14. Order-sensitive plasticity in adult primary auditory cortex

    PubMed Central

    Kilgard, Michael P.; Merzenich, Michael M.

    2002-01-01

    The neural response to a stimulus presented as part of a rapid sequence is often quite different from the response to the same stimulus presented in isolation. In primary auditory cortex (A1), although the most common effect of preceding stimuli is inhibitory, most neurons can also exhibit response facilitation if the appropriate spectral and temporal separation of sequence elements is presented. In this study, we investigated whether A1 neurons in adult animals can develop context-dependent facilitation to a novel acoustic sequence. After repeatedly pairing electrical stimulation of the basal forebrain with a three-element sequence (high frequency tone–low frequency tone– noise burst), 25% of A1 neurons exhibited facilitation to the low tone when preceded by the high tone, compared with only 5% in controls. In contrast, there was no increase in the percent of sites that showed facilitation for the reversed tone order (low preceding high). Nearly 60% of sites exhibited a facilitated response to the noise burst when preceded by the two tones. Although facilitation was greatest in response to the paired sequence, facilitation also generalized to related sequences that were either temporally distorted or missing one of the tones. Pairing basal forebrain stimulation with the acoustic sequence also caused a decrease in the time to peak response and an increase in population discharge synchrony, which was not seen after pairing simple tones, tone trains, or broadband stimuli. These results indicate that context-dependent facilitation and response synchronization can be substantially altered in an experience-dependent fashion and provide a potential mechanism for learning spectrotemporal patterns. PMID:11880653

  15. Nurse Practitioner Primary Care Competencies in Specialty Areas: Adult, Family, Gerontological, Pediatric, and Women's Health.

    ERIC Educational Resources Information Center

    Crabtree, M. Katherine; Stanley, Joan; Werner, Kathryn E.; Schmid, Emily

    This document presents the nurse practitioner primary care competencies that a national panel of representatives of nine national organizations of the five primary care nurse practitioner specialties--adult, family, gerontological, pediatric, and women's health--identified as necessary for entry-level primary care nurse practitioners. Section 1…

  16. Hepatocellular carcinoma.

    PubMed

    Llovet, Josep M; Zucman-Rossi, Jessica; Pikarsky, Eli; Sangro, Bruno; Schwartz, Myron; Sherman, Morris; Gores, Gregory

    2016-01-01

    Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies - resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate- and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches. PMID:27158749

  17. Radiosurgery Compared with External Radiation Therapy as a Primary Treatment in Spine Metastasis from Hepatocellular Carcinoma : A Multicenter, Matched-Pair Study

    PubMed Central

    Sohn, Seil; Sohn, Moon Jun; Kim, Sung Hwan; Kim, Jinhee; Park, Eunjung

    2016-01-01

    Objective The aim of this multicenter, matched-pair study was to compare the outcomes of stereotactic radiosurgery (SRS) and conventional external radiation therapy (RT) when used as a primary treatment in spine metastasis from hepatocellular carcinoma (HCC). Methods From 2005 to 2012, 28 patients underwent SRS as the primary treatment in spine metastasis from HCC. Based on sex, age, number of spine metastasis, Child-Pugh classification, interval from original tumor to spine metastasis, and year of treatment, 28 patients who underwent RT were paired. Outcomes of interest were pain relief, progression free survival, toxicities, and further treatment. Results The perioperative visual analog scale (VAS) decrease was larger in SRS group than in RT group, but the difference was not significant (3.7 vs. 2.8, p=0.13). When pain medication was adjusted, the number of patients with complete (n=6 vs.3) or partial (n=12 vs.13) relief was larger in SRS group than in RT group; however, the difference was not significant (p=0.83). There was no significant difference in progression free survival (p=0.48). In SRS group, 32.1% of patients had 1 or more toxicities whereas the percentage in RT group was 63.0%, a significant difference (p=0.04). Six SRS patients and 7 RT patients received further intervention at the treated segment. Conclusion Clinical and radiological outcome were not significantly different between the two treatments. Toxicities, however, were more prevalent in the RT group. PMID:26885284

  18. Consensus for Radiotherapy in Hepatocellular Carcinoma from The 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014): Current Practice and Future Clinical Trials.

    PubMed

    Park, Hee Chul; Yu, Jeong Il; Cheng, Jason Chia-Hsien; Zeng, Zhao Chong; Hong, Ji Hong; Wang, Michael Lian Chek; Kim, Mi Sook; Chi, Kwan Hwa; Liang, Po-Ching; Lee, Rheun-Chuan; Lau, Wan-Yee; Han, Kwang Hyub; Chow, Pierce Kah-Hoe; Seong, Jinsil

    2016-07-01

    A consensus meeting to develop practice guidelines and to recommend future clinical trials for radiation therapy (RT), including external beam RT (EBRT), and selective internal RT (SIRT) in hepatocellular carcinoma (HCC) was held at the 5th annual meeting of the Asia-Pacific Primary Liver Cancer Expert consortium. Although there is no randomized phase III trial evidence, the efficacy and safety of RT in HCC has been shown by prospective and retrospective studies using modern RT techniques. Based on these results, the committee came to a consensus on the utility and efficacy of RT in the management of HCC according to each disease stage as follows: in early and intermediate stage HCC, if standard treatment is not compatible, RT, including EBRT and SIRT can be considered. In locally advanced stage HCC, combined EBRT with transarterial chemoembolization or hepatic arterial infusion chemotherapy, and SIRT can be considered. In terminal stage HCC, EBRT can be considered for palliation of symptoms and reduction of morbidity caused by the primary tumor or its metastases. Despite the currently reported benefits of RT in HCC, the committee agreed that there is a compelling need for large prospective studies, including randomized phase III trial evidence evaluating the role of RT. Specifically studies evaluating the efficacy and safety of sequential combination of EBRT and SIRT are strongly recommended. PMID:27493892

  19. Consensus for Radiotherapy in Hepatocellular Carcinoma from The 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014): Current Practice and Future Clinical Trials

    PubMed Central

    Park, Hee Chul; Yu, Jeong Il; Cheng, Jason Chia-Hsien; Zeng, Zhao Chong; Hong, Ji Hong; Wang, Michael Lian Chek; Kim, Mi Sook; Chi, Kwan Hwa; Liang, Po-Ching; Lee, Rheun-Chuan; Lau, Wan-Yee; Han, Kwang Hyub; Chow, Pierce Kah-Hoe; Seong, Jinsil

    2016-01-01

    A consensus meeting to develop practice guidelines and to recommend future clinical trials for radiation therapy (RT), including external beam RT (EBRT), and selective internal RT (SIRT) in hepatocellular carcinoma (HCC) was held at the 5th annual meeting of the Asia-Pacific Primary Liver Cancer Expert consortium. Although there is no randomized phase III trial evidence, the efficacy and safety of RT in HCC has been shown by prospective and retrospective studies using modern RT techniques. Based on these results, the committee came to a consensus on the utility and efficacy of RT in the management of HCC according to each disease stage as follows: in early and intermediate stage HCC, if standard treatment is not compatible, RT, including EBRT and SIRT can be considered. In locally advanced stage HCC, combined EBRT with transarterial chemoembolization or hepatic arterial infusion chemotherapy, and SIRT can be considered. In terminal stage HCC, EBRT can be considered for palliation of symptoms and reduction of morbidity caused by the primary tumor or its metastases. Despite the currently reported benefits of RT in HCC, the committee agreed that there is a compelling need for large prospective studies, including randomized phase III trial evidence evaluating the role of RT. Specifically studies evaluating the efficacy and safety of sequential combination of EBRT and SIRT are strongly recommended. PMID:27493892

  20. Primary Care of Adult Women: Common Dermatologic Conditions.

    PubMed

    Ruiz de Luzuriaga, Arlene M; Mhlaba, Julie; Roman, Carly

    2016-06-01

    Dermatologic disease often presents in the primary care setting. Therefore, it is important for the primary care provider to be familiar with the presentation, diagnosis, and treatment of common skin conditions. This article provides an overview of acne, rosacea, melasma, vitiligo, alopecia, nonmelanoma, and melanoma skin cancer, dermatitis, and lichen sclerosus. PMID:27212088

  1. Primary feather molt of adult mourning doves in North and South Carolina

    USGS Publications Warehouse

    Haas, G.H.; Amend, S.R.

    1979-01-01

    Examination of 8,141 adult mourning doves (Zenaida macroura) in North and South Carolina revealed that substantial numbers complete primary feather molt in September. Adult mourning doves shed primaries at the rate of 1 per 14 days. No difference was found in this rate between sexes or among years, 1969-74. The initiation of molt differed from year to year, and female molt always preceded male molt. Available data show that southern doves complete primary molt a month earlier than northern doves. Therefore, age based on primary molt can be biased upward if all molt-complete wings from southern hunting samples are considered immature.

  2. Primary cilia regulate proliferation of amplifying progenitors in adult hippocampus: implications for learning and memory.

    PubMed

    Amador-Arjona, Alejandro; Elliott, Jimmy; Miller, Amber; Ginbey, Ashley; Pazour, Gregory J; Enikolopov, Grigori; Roberts, Amanda J; Terskikh, Alexey V

    2011-07-01

    Integration of new neurons into the adult hippocampus has been linked to specific types of learning. Primary cilia were found to be required for the formation of adult neural stem cells (NSCs) in the hippocampal dentate gyrus during development. However, the requirement of cilia in maintenance of adult NSCs is unknown. We developed a genetic mouse model in which fetal/perinatal brain development is unaffected, but adult hippocampal neurogenesis is constantly reduced by conditional ablation of primary cilia in adult GFAP(+) neural stem/progenitor cells. We found that this approach specifically reduces the number of hippocampal amplifying progenitors (also called type 2a cells) without affecting the number of radial NSCs (or type 1 cells). Constant reduction of adult hippocampal neurogenesis produced a delay rather than a permanent deficiency in spatial learning without affecting the retention of long-term memories. Decreased neurogenesis also altered spatial novelty recognition and hippocampus-independent cue conditioning. Here, we propose that adult hippocampal newborn neurons increase the efficiency of generating the new representations of spatial memories and that reduction of adult hippocampal neurogenesis may be biased toward cue-based strategies. This novel mouse model provides evidences that cognitive deficits associated with ciliary defects (ciliopathies) might be, in part, mediated by the deficiency of primary cilia in adult hippocampal stem/progenitor cells. PMID:21734285

  3. Primary cilia regulate proliferation of amplifying progenitors in adult hippocampus: implications for learning and memory.

    PubMed

    Amador-Arjona, Alejandro; Elliott, Jimmy; Miller, Amber; Ginbey, Ashley; Pazour, Gregory J; Enikolopov, Grigori; Roberts, Amanda J; Terskikh, Alexey V

    2011-07-01

    Integration of new neurons into the adult hippocampus has been linked to specific types of learning. Primary cilia were found to be required for the formation of adult neural stem cells (NSCs) in the hippocampal dentate gyrus during development. However, the requirement of cilia in maintenance of adult NSCs is unknown. We developed a genetic mouse model in which fetal/perinatal brain development is unaffected, but adult hippocampal neurogenesis is constantly reduced by conditional ablation of primary cilia in adult GFAP(+) neural stem/progenitor cells. We found that this approach specifically reduces the number of hippocampal amplifying progenitors (also called type 2a cells) without affecting the number of radial NSCs (or type 1 cells). Constant reduction of adult hippocampal neurogenesis produced a delay rather than a permanent deficiency in spatial learning without affecting the retention of long-term memories. Decreased neurogenesis also altered spatial novelty recognition and hippocampus-independent cue conditioning. Here, we propose that adult hippocampal newborn neurons increase the efficiency of generating the new representations of spatial memories and that reduction of adult hippocampal neurogenesis may be biased toward cue-based strategies. This novel mouse model provides evidences that cognitive deficits associated with ciliary defects (ciliopathies) might be, in part, mediated by the deficiency of primary cilia in adult hippocampal stem/progenitor cells.

  4. Primary Care for Adults with Down Syndrome: Adherence to Preventive Healthcare Recommendations

    ERIC Educational Resources Information Center

    Jensen, K. M.; Taylor, L. C.; Davis, M. M.

    2013-01-01

    Background: Due to significant medical improvements, persons with Down syndrome now live well into adulthood. Consequently, primary care for adults with Down syndrome needs to incorporate routine care with screening for condition-specific comorbidities. This study seeks to evaluate the adherence of primary care physicians to age- and…

  5. Prevalence and Predictors of Change in Adult-Child Primary Caregivers

    ERIC Educational Resources Information Center

    Szinovacz, Maximiliane E.; Davey, Adam

    2013-01-01

    Family caregiving research is increasingly contextual and dynamic, but few studies have examined prevalence and predictors of change in primary caregivers, those with the most frequent contact with healthcare professionals. We identified prevalence and predictors of 2-year change in primary adult-child caregivers. Data pooled from the 1992-2000…

  6. Guideline for primary care management of headache in adults

    PubMed Central

    Becker, Werner J.; Findlay, Ted; Moga, Carmen; Scott, N. Ann; Harstall, Christa; Taenzer, Paul

    2015-01-01

    Abstract Objective To increase the use of evidence-informed approaches to diagnosis, investigation, and treatment of headache for patients in primary care. Quality of evidence A comprehensive search was conducted for relevant guidelines and systematic reviews published between January 2000 and May 2011. The guidelines were critically appraised using the AGREE (Appraisal of Guidelines for Research and Evaluation) tool, and the 6 highest-quality guidelines were used as seed guidelines for the guideline adaptation process. Main message A multidisciplinary guideline development group of primary care providers and other specialists crafted 91 specific recommendations using a consensus process. The recommendations cover diagnosis, investigation, and management of migraine, tension-type, medication-overuse, and cluster headache. Conclusion A clinical practice guideline for the Canadian health care context was created using a guideline adaptation process to assist multidisciplinary primary care practitioners in providing evidence-informed care for patients with headache. PMID:26273080

  7. Primary Afferent Synapses on Developing and Adult Renshaw Cells

    PubMed Central

    Mentis, George Z.; Siembab, Valerie C.; Zerda, Ricardo; O’Donovan, Michael J.; Alvarez, Francisco J.

    2010-01-01

    The mechanisms that diversify adult interneurons from a few pools of embryonic neurons are unknown. Renshaw cells, Ia inhibitory interneurons (IaINs), and possibly other types of mammalian spinal interneurons have common embryonic origins within the V1 group. However, in contrast to IaINs and other V1-derived interneurons, adult Renshaw cells receive motor axon synapses and lack proprioceptive inputs. Here, we investigated how this specific pattern of connectivity emerges during the development of Renshaw cells. Tract tracing and immunocytochemical markers [parvalbumin and vesicular glutamate transporter 1 (VGLUT1)] showed that most embryonic (embryonic day 18) Renshaw cells lack dorsal root inputs, but more than half received dorsal root synapses by postnatal day 0 (P0) and this input spread to all Renshaw cells by P10–P15. Electrophysiological recordings in neonates indicated that this input is functional and evokes Renshaw cell firing. VGLUT1-IR bouton density on Renshaw cells increased until P15 but thereafter decreased because of limited synapse proliferation coupled with the enlargement of Renshaw cell dendrites. In parallel, Renshaw cell postsynaptic densities apposed to VGLUT1-IR synapses became smaller in adult compared with P15. In contrast, vesicular acetylcholine transporter-IR motor axon synapses contact embryonic Renshaw cells and proliferate postnatally matching Renshaw cell growth. Like other V1 neurons, Renshaw cells are thus competent to receive sensory synapses. However, after P15, these sensory inputs appear deselected through arrested proliferation and synapse weakening. Thus, Renshaw cells shift from integrating sensory and motor inputs in neonates to predominantly motor inputs in adult. Similar synaptic weight shifts on interneurons may be involved in the maturation of motor reflexes and locomotor circuitry. PMID:17182780

  8. Progress of primary feather molt of adult mourning doves in Missouri

    USGS Publications Warehouse

    Sadler, K.C.; Tomlinson, R.E.; Wight, H.M.

    1970-01-01

    The examination of 7,892 adult doves in Missouri between 1953 and 1965 showed that less than 2.5% of adult doves completed their molt before October 1. Adult doves of both sexes began molting their primary feathers during early June in Missouri and lost the last (tenth) primary during the latter half of October. Approximately 140-150 days were required to complete the molt. Thus, early-hatched immatures, which begin their primary molt 25-30 days after hatching, contributed the bulk of the wings with completed molts in September. By correctly classifying September samples of dove wings with a completed molt as young-of-the-year a more accurate young:adult ratio is obtained.

  9. Sero-epidemiology of Hepatitis B Surface Antigenaemia among Adult Nigerians with Clinical Features of Liver Diseases Attending a Primary-Care Clinic in a Resource-Constrained Setting of Eastern Nigeria

    PubMed Central

    Iloh, Gabriel Uche Pascal; Ikwudinma, Austin Obiora

    2013-01-01

    Background: Hepatitis-B infection is not commonly perceived as a serious medical problem in Nigeria. However, chronic hepatitis-B infection, which is a subject of global concern, may lead to lethal liver diseases. Aim: The study was to determine the sero-epidemiology of hepatitis-B surface antigenaemia among adult Nigerians with clinical features of liver diseases attending a primary-care clinic in a resource-constrained setting of Eastern Nigeria. Materials and Methods: A cross-sectional study was carried out on 140 adult Nigerians with clinical features of liver diseases at the primary-care clinic of Federal Medical Centre, Owerri. They made up three groups: 44 patients, 62 patients and 34 patients with clinical features of hepatitis, liver cirrhosis and hepatocellular carcinoma, respectively. Hepatitis-B surface antigen (HBsAg) was assayed using an immunochromatographic method. Demographic variables were collected. Results: The overall sero-positivity rate was 50.7%. The sero-positivity rates for these patients were 23.9%, 39.5% and 36.6% for hepatitis, liver cirrhosis and hepatocellular carcinoma, respectively. The age group 40-60 years (P = 0.048) and artisans (P = 0.019) were significantly infected. Abdominal swelling (86.4%) and ascites (67.1%) were the most common symptoms and signs, respectively. Conclusion: HBsAg prevalence was high and has significant association with age and occupation. PMID:23724405

  10. [Primary small bowel volvulus in a young adult].

    PubMed

    Pastor, J; Adámek, S; Polanecký, O

    2014-06-01

    The authors present a rare case of a young male patient with primary small bowel volvulus. They show the main points to be considered in clinical diagnosis of this kind of acute abdomen and the importance of CT scan in such cases.

  11. Primary Care for the Older Adult Patient: Common Geriatric Issues and Syndromes.

    PubMed

    Thompson, Katherine; Shi, Sandra; Kiraly, Carmela

    2016-06-01

    Older adults are the fastest growing segment of the US population and the majority of older adults are women. Primary care for the older adult patient requires a wide variety of skills, reflecting the complexity and heterogeneity of this patient population. Individualizing care through consideration of patients' goals, medical conditions, and prognosis is paramount. Quality care for the older adult patient requires familiarity with common geriatric syndromes, such as dementia, falls, and polypharmacy. In addition, developing the knowledge and communication skills necessary for complex care and end-of-life care planning is essential.

  12. Hepatocellular carcinoma: From diagnosis to treatment.

    PubMed

    Grandhi, Miral Sadaria; Kim, Amy K; Ronnekleiv-Kelly, Sean M; Kamel, Ihab R; Ghasebeh, Mounes A; Pawlik, Timothy M

    2016-06-01

    Primary liver cancer is the sixth most common cancer overall and the second most common cause of cancer mortality worldwide. Hepatocellular carcinoma accounts for up to 90% of all primary hepatic malignancies and represents a major international health problem. While surgical resection and transplantation are the cornerstone of therapy in early-stage hepatocellular carcinoma, locoregional therapy and sorafenib are beneficial in those with more advanced disease or those who are not surgical candidates. At times, the integration of both surgical and locoregional therapy may be necessary. Hence, hepatocellular carcinoma requires a multidisciplinary approach to determine the most appropriate treatment as well as the timing of various treatments for optimal outcomes. PMID:27312032

  13. Polygonal networks, "geodomes", of adult rat hepatocytes in primary culture.

    PubMed

    Mochizuki, Y; Furukawa, K; Mitaka, T; Yokoi, T; Kodama, T

    1988-01-01

    Polygonal networks, "geodomes", in cultured hepatocytes of adult rats were examined by both light and electron microscopy. On light microscopical examinations of specimens stained with Coomassie blue after the treatment with Triton X-100, the networks were detected 5 days after culture, which consisted of triangles arranged mainly in hexagonal patterns. They surrounded main cell body, looking like a headband, or were occasionally situated over nuclei, looking like a geodesic dome. Scanning electron microscopical observations after Triton treatment revealed that these structures were located underneath surface membrane. Transmission electron microscopical investigations revealed that the connecting fibers of networks consisted of microfilaments which radiated in a compact bundle from electron-dense vertices. PMID:3396075

  14. Spontaneous regression of hepatocellular carcinoma.

    PubMed Central

    Ayres, R C; Robertson, D A; Dewbury, K C; Millward-Sadler, G H; Smith, C L

    1990-01-01

    A 63 year old white woman presented with abdominal discomfort, anorexia, and weight loss. Investigations showed hepatocellular carcinoma with pulmonary metastases. The primary and secondary tumours resolved without specific treatment. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:2165992

  15. Surgery for Intermediate and Advanced Hepatocellular Carcinoma: A Consensus Report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014)

    PubMed Central

    Ho, Ming-Chih; Hasegawa, Kiyoshi; Chen, Xiao-Ping; Nagano, Hiroaki; Lee, Young-Joo; Chau, Gar-Yang; Zhou, Jian; Wang, Chih-Chi; Choi, Young Rok; Poon, Ronnie Tung-Ping; Kokudo, Norihiro

    2016-01-01

    Background The Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy does not recommended surgery for treating BCLC stage B and C hepatocellular carcinoma (HCC). However, numerous Asia-Pacific institutes still perform surgery for this patient group. This consensus report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting aimed to share opinions and experiences pertaining to liver resection for intermediate and advanced HCCs and to provide evidence to issue recommendations for surgery in this patient group. Summary Thirteen experts from five Asia-Pacific regions were invited to the meeting; 10 of them (Japan: 2, Taiwan: 3, South Korea: 2, Hong Kong: 1, and China: 2) voted for the final consensus. The discussion focused on evaluating the preoperative liver functional reserve and surgery for large tumors, multiple tumors, HCCs with vascular invasion, and HCCs with distant metastasis. The feasibility of future prospective randomized trials comparing surgery with transarterial chemoembolization for intermediate HCC and with sorafenib for advanced HCC was also discussed. The Child-Pugh score (9/10 experts) and indocyanine green retention rate at 15 min (8/10) were the most widely accepted methods for evaluating the preoperative liver functional reserve. All (10/10) experts agreed that portal hypertension, tumor size >5 cm, portal venous invasion, hepatic venous invasion, and extrahepatic metastasis are not absolute contraindications for the surgical resection of HCC. Furthermore, 9 of the 10 experts agreed that tumor resection may be performed for patients with >3 tumors. The limitations of surgery are associated with a poor liver functional reserve, incomplete tumor resection, and a high probability of recurrence. Key Messages Surgery provides significant survival benefits for Asian-Pacific patients with intermediate and advanced HCCs, particularly when the liver functional reserve is favorable. However, prospective randomized controlled trials

  16. Motivational interviewing for older adults in primary care: a systematic review.

    PubMed

    Purath, Janet; Keck, Annmarie; Fitzgerald, Cynthia E

    2014-01-01

    Chronic disease is now the leading cause of death and disability in United States. Many chronic illnesses experienced by older adults can be prevented or managed through behavior change, making patient counseling an essential component of disease prevention and management. Motivational Interviewing (MI), a type of conversational method, has been effective in eliciting health behavior changes in people in a variety of settings and may also be a useful tool to help older adults change. This review of the literature analyzes current research and describes potential biases of MI interventions that have been conducted in primary care settings with older adults. MI shows promise as a technique to elicit health behavior change among older adults. However, further study with this population is needed to evaluate efficacy of MI interventions in primary care settings.

  17. Personality Assessment Screener, Childhood Abuse, and Adult Partner Violence in African American Women Using Primary Care.

    PubMed

    Porcerelli, John H; Hurrell, Kristen; Cogan, Rosemary; Jeffries, Keturah; Markova, Tsveti

    2015-12-01

    This study assessed the relationship between psychopathology with the Personality Assessment Screener (PAS) and childhood physical and sexual abuse and adult physical and sexual partner violence in a primary care sample of 98 urban-dwelling African American women. Patients completed the PAS, the Childhood Trauma Questionnaire, and the Conflict Tactics Scale. The PAS total score significantly correlated with all measures of childhood and adult abuse. Stepwise regression analyses revealed that PAS element scores of Suicidal Thinking and Hostile Control significantly predicted a history of childhood physical abuse; Suicidal Thinking, Hostile Control, and Acting Out significantly predicted a history of childhood sexual abuse; Suicidal Thinking, Negative Affect, and Alienation significantly predicted current adult partner physical violence; and Psychotic Features, Alcohol Problems, and Anger Control significantly predicted current adult sexual partner violence. The PAS appears to be a useful measure for fast-paced primary care settings for identifying patients who need a more thorough assessment for abuse.

  18. Personality Assessment Screener, Childhood Abuse, and Adult Partner Violence in African American Women Using Primary Care.

    PubMed

    Porcerelli, John H; Hurrell, Kristen; Cogan, Rosemary; Jeffries, Keturah; Markova, Tsveti

    2015-12-01

    This study assessed the relationship between psychopathology with the Personality Assessment Screener (PAS) and childhood physical and sexual abuse and adult physical and sexual partner violence in a primary care sample of 98 urban-dwelling African American women. Patients completed the PAS, the Childhood Trauma Questionnaire, and the Conflict Tactics Scale. The PAS total score significantly correlated with all measures of childhood and adult abuse. Stepwise regression analyses revealed that PAS element scores of Suicidal Thinking and Hostile Control significantly predicted a history of childhood physical abuse; Suicidal Thinking, Hostile Control, and Acting Out significantly predicted a history of childhood sexual abuse; Suicidal Thinking, Negative Affect, and Alienation significantly predicted current adult partner physical violence; and Psychotic Features, Alcohol Problems, and Anger Control significantly predicted current adult sexual partner violence. The PAS appears to be a useful measure for fast-paced primary care settings for identifying patients who need a more thorough assessment for abuse. PMID:26374084

  19. Use of and interest in alternative therapies among adult primary care clinicians and adult members in a large health maintenance organization.

    PubMed

    Gordon, N P; Sobel, D S; Tarazona, E Z

    1998-09-01

    During spring 1996, random samples of adult primary care physicians, obstetrics-gynecology physicians and nurse practitioners, and adult members of a large northern California group practice model health maintenance organization (HMO) were surveyed by mail to assess the use of alternative therapies and the extent of interest in having them incorporated into HMO-delivered care. Sixty-one percent (n = 624) of adult primary care physicians, 70% (n = 157) of obstetrics-gynecology clinicians, and 50% (2 surveys, n = 1,507 and n = 17,735) of adult HMO members responded. During the previous 12 months, 25% of adults reported using and nearly 90% of adult primary care physicians and obstetrics-gynecology clinicians reported recommending at least 1 alternative therapy, primarily for pain management. Chiropractic, acupuncture, massage, and behavioral medicine techniques such as meditation and relaxation training were most often cited. Obstetrics-gynecology clinicians used herbal and homeopathic medicines more often than adult primary care physicians, primarily for menopause and premenstrual syndrome. Two thirds of adult primary care physicians and three fourths of obstetrics-gynecology clinicians were at least moderately interested in using alternative therapies with patients, and nearly 70% of young and middle-aged adult and half of senior adult members were interested in having alternative therapies incorporated into their health care. Adult primary care physicians and members were more interested in having the HMO cover manipulative and behavioral medicine therapies than homeopathic or herbal medicines.

  20. Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems.

    PubMed

    Shlomai, Amir; Schwartz, Robert E; Ramanan, Vyas; Bhatta, Ankit; de Jong, Ype P; Bhatia, Sangeeta N; Rice, Charles M

    2014-08-19

    Hepatitis B virus (HBV) chronically infects 400 million people worldwide and is a leading driver of end-stage liver disease and liver cancer. Research into the biology and treatment of HBV requires an in vitro cell-culture system that supports the infection of human hepatocytes, and accurately recapitulates virus-host interactions. Here, we report that micropatterned cocultures of primary human hepatocytes with stromal cells (MPCCs) reliably support productive HBV infection, and infection can be enhanced by blocking elements of the hepatocyte innate immune response associated with the induction of IFN-stimulated genes. MPCCs maintain prolonged, productive infection and represent a facile platform for studying virus-host interactions and for developing antiviral interventions. Hepatocytes obtained from different human donors vary dramatically in their permissiveness to HBV infection, suggesting that factors--such as divergence in genetic susceptibility to infection--may influence infection in vitro. To establish a complementary, renewable system on an isogenic background in which candidate genetics can be interrogated, we show that inducible pluripotent stem cells differentiated into hepatocyte-like cells (iHeps) support HBV infection that can also be enhanced by blocking interferon-stimulated gene induction. Notably, the emergence of the capacity to support HBV transcriptional activity and initial permissiveness for infection are marked by distinct stages of iHep differentiation, suggesting that infection of iHeps can be used both to study HBV, and conversely to assess the degree of iHep differentiation. Our work demonstrates the utility of these infectious systems for studying HBV biology and the virus' interactions with host hepatocyte genetics and physiology. PMID:25092305

  1. Mutations in CIZ1 cause adult-onset primary cervical dystonia

    PubMed Central

    Xiao, Jianfeng; Uitti, Ryan J.; Zhao, Yu; Vemula, Satya R.; Perlmutter, Joel S.; Wszolek, Zbigniew K.; Maraganore, Demetrius M.; Auburger, Georg; Leube, Barbara; Lehnhoff, Katja; LeDoux, Mark S.

    2012-01-01

    Objective Primary dystonia is usually of adult onset, can be familial, and frequently involves the cervical musculature. Our goal was to identify the causal mutation in a family with adult-onset, primary cervical dystonia. Methods Linkage and haplotype analyses were combined with solution-based whole-exome capture and massively parallel sequencing in a large Caucasian pedigree with adult-onset, primary cervical dystonia to identify a cosegregating mutation. High-throughput screening and Sanger sequencing were completed in 308 Caucasians with familial or sporadic adult-onset cervical dystonia and matching controls for sequence variants in this mutant gene. Results Exome sequencing led to the identification of an exonic splicing enhancer mutation in Exon 7 of CIZ1 (c.790A>G, p.S264G) which encodes CIZ1, Cip1-interacting zinc finger protein 1. CIZ1 is a p21Cip1/Waf1-interacting zinc finger protein expressed in brain and involved in DNA synthesis and cell-cycle control. Using a minigene assay, we showed that c.790A>G altered CIZ1 splicing patterns. The p.S264G mutation also altered the nuclear localization of CIZ1. Screening in subjects with adult-onset cervical dystonia identified two additional CIZ1 missense mutations (p.P47S and p.R672M). Interpretation Mutations in CIZ1 may cause adult-onset, primary cervical dystonia, possibly by precipitating neurodevelopmental abnormalities that manifest in adults and/or G1/S cell-cycle dysregulation in the mature central nervous system. PMID:22447717

  2. Screening for Suicide Risk in Adolescents, Adults, and Older Adults in Primary Care

    MedlinePlus

    ... Task Force learned about the potential benefits and harms of suicide screening by primary care clinicians: There ... not enough evidence to weigh the benefits and harms of screening the general population for suicide risk. ...

  3. Health Checks in Primary Care for Adults with Intellectual Disabilities: How Extensive Should They Be?

    ERIC Educational Resources Information Center

    Chauhan, U.; Kontopantelis, E.; Campbell, S.; Jarrett, H.; Lester, H.

    2010-01-01

    Background: Routine health checks have gained prominence as a way of detecting unmet need in primary care for adults with intellectual disabilities (ID) and general practitioners are being incentivised in the UK to carry out health checks for many conditions through an incentivisation scheme known as the Quality and Outcomes Framework (QOF).…

  4. Adult Antisocial Behavior and Affect Regulation among Primary Crack/Cocaine-Using Women

    ERIC Educational Resources Information Center

    Litt, Lisa Caren; Hien, Denise A.; Levin, Deborah

    2003-01-01

    The relationship between deficits in affect regulation and Adult Antisocial Behavior (ASB) in primary crack/cocaine-using women was explored in a sample of 80 inner-city women. Narrative early memories were coded for two components of affect regulation, Affect Tolerance and Affect Expression, using the Epigenetic Assessment Rating Scale (EARS;…

  5. Physician Perspectives on Providing Primary Medical Care to Adults with Autism Spectrum Disorders (ASD)

    ERIC Educational Resources Information Center

    Warfield, Marji Erickson; Crossman, Morgan K.; Delahaye, Jennifer; Der Weerd, Emma; Kuhlthau, Karen A.

    2015-01-01

    We conducted in-depth case studies of 10 health care professionals who actively provide primary medical care to adults with autism spectrum disorders. The study sought to understand their experiences in providing this care, the training they had received, the training they lack and their suggestions for encouraging more physicians to provide this…

  6. A Meta-Analysis of Adult-Rated Child Personality and Academic Performance in Primary Education

    ERIC Educational Resources Information Center

    Poropat, Arthur E.

    2014-01-01

    Background: Personality is reliably associated with academic performance, but personality measurement in primary education can be problematic. Young children find it difficult to accurately self-rate personality, and dominant models of adult personality may be inappropriate for children. Aims: This meta-analysis was conducted to determine the…

  7. Primary retroperitoneal teratoma in the adult: correlation of MRI features with CT and pathology.

    PubMed

    Bellin, M F; Duron, J J; Curet, P; Dion-Voirin, E; Grellet, J

    1991-01-01

    Primary benign teratoma of the retroperitoneum is a rare tumor in the adult population. Only one case with an MRI examination has been reported in the English literature. This paper describes the CT and MRI features of a retroperitoneal teratoma in a 24-year-old male and discusses the value of MRI in the diagnosis and the preoperative imaging of such a tumor.

  8. Prevalence of Epilepsy in Adults with Mental Retardation and Related Disabilities in Primary Care

    ERIC Educational Resources Information Center

    McDermott, Suzanne; Moran, Robert; Platt, Tan; Wood, Hope; Isaac, Terri; Dasari, Srikanth

    2005-01-01

    Two primary care practices were used to recruit adults with and without disability. Disability groups included autism, Down syndrome, cerebral palsy, and mental retardation. The patients without disability had an epilepsy prevalence rate of 1%. The prevalence of epilepsy within the disability groups was 13% for cerebral palsy, 13.6% for Down…

  9. Campylobacter fetus bacteremia with purulent pleurisy in a young adult with primary hypogammaglobulinemia.

    PubMed

    Yamagami, Keiko; Miyashita, Tomoko; Nakamura, Tomoyuki; Shirano, Michinori; Nakamura, Tadahiro; Kameda, Kazuaki; Nishijima, Masayoshi; Imanishi, Masahiro; Yang, Xi; Kanegane, Hirokazu

    2014-01-01

    A 24-year-old man presented with fever and pleural effusion predominantly containing lymphocytes. Cultures of the pleural effusion and blood revealed Campylobacter fetus, and laboratory studies showed a low serum level of immunoglobulin. The patient was diagnosed with C. fetus pleuritis, bacteremia and primary hypogammaglobulinemia, and subsequent treatment with meropenem and immunoglobulin improved his condition. Although the underlying cause of the primary hypogammaglobulinemia remains unclear, the patient's status improved under immunoglobulin replacement therapy. C. fetus pleuritis is a rare infectious disease usually observed in immunocompromised hosts. We herein describe the first report of C. fetus pleuritis in a young adult with primary hypogammaglobulinemia.

  10. Hepatocellular carcinoma.

    PubMed

    Buendia, Marie-Annick; Neuveut, Christine

    2015-02-01

    The hepatitis B virus (HBV) is a widespread human pathogen that causes liver inflammation, cirrhosis, and hepatocellular carcinoma (HCC). Recent sequencing technologies have refined our knowledge of the genomic landscape and pathogenesis of HCC, but the mechanisms by which HBV exerts its oncogenic role remain controversial. In a prevailing view, inflammation, liver damage, and regeneration may foster the accumulation of genetic and epigenetic defects leading to cancer onset. However, a more direct and specific contribution of the virus is supported by clinical and biological observations. Among genetically heterogeneous HCCs, HBV-related tumors display high genomic instability, which may be attributed to the ability of HBV to integrate its DNA into the host cell genome, provoking chromosomal alterations and insertional mutagenesis of cancer genes. The viral transactivator HBx may also participate in transformation by deregulating diverse cellular machineries. A better understanding of the complex mechanisms linking HBV to HCC will improve prevention and treatment strategies. PMID:25646384

  11. Prevention of Hepatocellular Carcinoma

    PubMed Central

    Schütte, Kerstin; Balbisi, Fathi; Malfertheiner, Peter

    2016-01-01

    The epidemiology of hepatocellular carcinoma (HCC) has significantly changed throughout the past decade and will continue to do so in the future as a consequence of effective primary prevention and treatment of virus-related liver diseases. However, other risk factors for HCC are constantly on the rise, including alcoholic liver disease and nonalcoholic fatty liver disease. The knowledge on these and further risk factors associated with an increased risk of HCC provide the opportunity and chance for the development and implementation of successful preventive strategies to decrease the worldwide burden of HCC. This mini-review gives a short overview on current strategies in primary, secondary, and tertiary prevention of HCC. PMID:27722155

  12. Initial manifestation of primary hyperoxaluria type I in adults-- recognition, diagnosis, and management.

    PubMed Central

    Kuiper, J J

    1996-01-01

    Primary hyperoxaluria type I may initially manifest as urolithiasis, renal insufficiency, or symptoms of systemic oxalosis. This hereditary disorder was fatal until effective therapies evolved during the past two decades. Difficulty in recognizing and diagnosing this disorder in adults is illustrated in a report of a patient eventually restored to good health by high-flux dialysis and combined renal and hepatic transplantation. I explore the molecular processes of the genetic defect and discuss clinical indicators of primary hyperoxaluria type I, manifestations of oxalosis, the pathogenesis of chronic oxalate nephropathy, and the diagnosis and management of this disease. Images Figure 2. Figure 3. Figure 4. PMID:8779202

  13. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q

    SciTech Connect

    Wirtz, M.K.; Samples, J.R.; Kramer, P.L.

    1997-02-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-on-set primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. 57 refs., 3 figs., 3 tabs.

  14. Adult cystic fibrosis patients' experiences of primary care consultations: a qualitative study

    PubMed Central

    Lowton, Karen; Ballard, Karen D

    2006-01-01

    Background ‘Expert patient’ programmes have been introduced in the UK as a new approach to chronic disease management for the 21st century. The average survival age of those with cystic fibrosis (CF) has steadily increased such that the majority of those with the condition now live into adulthood. Currently, specialist CF centres deliver the core of medical care, with primary care providing access to prescribed medicines, referral to other services, and care of non-CF needs, however, it is necessary to provide a more comprehensive service for adult CF patients, involving both specialist centres and primary care. To date, little is known about these expert patients' experiences of primary care. Aim To investigate how young adults with CF perceive and experience primary healthcare services. Design of study Qualitative study. Setting One specialist CF centre in southeast England. Method Interview study of 31 patients with CF, aged 18 years or over. Results Adults with CF consult in primary care on two distinct levels: as lay and expert patients. When consulting as experts, patients tend to operate as consumers of health care and perceive a satisfactory doctor–patient relationship to be influenced by three factors: GPs' understanding of how people live with CF, GPs' ability to prescribe certain specialist medications, and sensitive management of the cost of health care for adults with CF. A doctor–patient relationship based on trust and understanding is seen as desirable, but requires that these factors are addressed both by the GP and the patient. Conclusion Expert patient policy has focused on the role of patients with common chronic conditions in secondary and tertiary care, with little consideration of how adults with rare chronic illness and their GPs manage health problems that can be addressed in primary care. Enabling easy access to holistic care, as well as establishing successful trusting relationships with people with long-term rare conditions, is a

  15. Fundamental reform of payment for adult primary care: comprehensive payment for comprehensive care.

    PubMed

    Goroll, Allan H; Berenson, Robert A; Schoenbaum, Stephen C; Gardner, Laurence B

    2007-03-01

    Primary care is essential to the effective and efficient functioning of health care delivery systems, yet there is an impending crisis in the field due in part to a dysfunctional payment system. We present a fundamentally new model of payment for primary care, replacing encounter-based imbursement with comprehensive payment for comprehensive care. Unlike former iterations of primary care capitation (which simply bundled inadequate fee-for-service payments), our comprehensive payment model represents new investment in adult primary care, with substantial increases in payment over current levels. The comprehensive payment is directed to practices to include support for the modern systems and teams essential to the delivery of comprehensive, coordinated care. Income to primary physicians is increased commensurate with the high level of responsibility expected. To ensure optimal allocation of resources and the rewarding of desired outcomes, the comprehensive payment is needs/risk-adjusted and performance-based. Our model establishes a new social contract with the primary care community, substantially increasing payment in return for achieving important societal health system goals, including improved accessibility, quality, safety, and efficiency. Attainment of these goals should help offset and justify the costs of the investment. Field tests of this and other new models of payment for primary care are urgently needed. PMID:17356977

  16. [Hepatocellular carcinoma].

    PubMed

    Colombo, Massimo; Sangiovanni, Angelo

    2016-07-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer death and the first in patients with compensated cirrhosis. Chronic infection with hepatitis B and C, alcohol, smoking, exposure to aflatoxin and metabolic syndrome, associated with diabetes and obesity are the main etiological factors. Regardless of etiology, patients with cirrhosis stand as the category at higher risk of developing HCC, and indeed are the target of surveillance programs aimed to the early diagnosis of HCC, the only chance to reduce HCC-related mortality. This notwithstanding, International Scientific Societies have issued recommendations for the management of HCC, a significant number of patients are treated outside guidelines, due to several reasons. Among queries still unsolved, the impact of biological characterization of HCC, along with the biological profiling of patients at risk of developing HCC represent main challenges for the future. Treatment personalization and multimodal treatment being further challenges. This chapter summarizes the recommendations for surveillance, diagnosis and treatment of HCC and focus on future directions. PMID:27571469

  17. [Screening for attention deficit hyperactivity disorder in adult patients in primary care].

    PubMed

    Aragonès, Enric; Cañisá, Anna; Caballero, Antònia; Piñol-Moreso, Josep Lluís

    2013-05-01

    AIMS. To estimate the proportion of adult patients in primary care with a positive screening test for attention deficit hyper-activity disorder (ADHD) and to analyse their characteristics. PATIENTS AND METHODS. A cross-sectional descriptive study was performed in nine primary care clinics in the province of Tarragona. The sample consisted of 432 consecutive patients in primary care who visited for any reason, with ages ranging from 18 to 55 years. Screening for ADHD was carried out by means of the Adult ADHD Self-Report Scale (ASRS). Data about functional impact (Sheehan Disability Inventory) were obtained and a review of the patient records provided data concerning psychiatric comorbidity and the consumption of psychopharmaceuticals. RESULTS. The percentage of positive results in the screening tests was 19.9% (95% CI = 16.4-23.9%). Taking into account the sensitivity and specificity of the ASRS, the 'real' prevalence was estimated to be 12.5% (95% CI = 8.2-16.8%). None of these patients were diagnosed or treated for ADHD. Positive screening tests are associated with occupational, social and familial dysfunction, and greater perceived stress. There is also a higher level of comorbidity with affective disorders and substance abuse, as well as greater use of psychopharmaceuticals. CONCLUSIONS. Screening for ADHD in adult patients in primary care gives rise to a notably high proportion of positive screening test results, which suggests that there could be a significant prevalence of patients with ADHD. These data contrast with the absence of this diagnosis in the patient records. Further research is needed to determine the usefulness of the diagnosis of ADHD and the possible role that must be played by primary care.

  18. The distinction between juvenile and adult-onset primary open-angle glaucoma

    SciTech Connect

    Wiggs, J.L.; Haines, J.L.; Damji, K.F.

    1996-01-01

    Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light of the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.

  19. Genus Distichopora (Cnidaria, Hydrozoa): from primary cyclosystem to adult pore organisation

    NASA Astrophysics Data System (ADS)

    Puce, S.; Pica, D.; Brun, F.; Mancini, L.; Bavestrello, G.

    2012-09-01

    This investigation provides the first detailed description of the growth stages of two Distichopora species showing the formation of a primary cyclosystem and explaining the growth process leading from primary cyclosystem to adult pore organisation. The earliest observed stage is an oval calcareous disc from which, at a later stage, a primary cyclosystem raises up. Then, the addition of new gastropores and dactylopores leads to the pore rows typical of the genus. Using X-ray computed microtomography, we are able to visualise the dense canal network that permeates the coenosteum and envelops the gastropores and the dactylopores in all the observed growth stages. In both species, the thin canals surrounding the gastropores are responsible for the formation of the new gastropores that originate between the old ones, while the thin canals placed on the external side of the dactylopore rows produce the new dactylopores.

  20. Suicide Risk in Primary Care: Identification and Management in Older Adults

    PubMed Central

    Raue, Patrick J.; Ghesquiere, Angela R.; Bruce, Martha L.

    2014-01-01

    The National Strategy for Suicide Prevention (2012) has set a goal to reduce suicides by 20% within 5 years. Suicide rates are higher in older adults compared to most other age groups, and the majority of suicide completers have visited their primary care physician in the year before suicide. Primary care is an ideal setting to identify suicide risk and initiate mental health care. We review risk factors for late-life suicide; methods to assess for different levels of suicidality; and recent research developments regarding both effective assessment and management of suicide risk among older primary care patients. We highlight that broader scale screening of suicide risk may be considered in light of findings that suicidality can occur even in the absence of major risk factors like depression. We also highlight collaborative care models targeting suicide risk, and recent innovative interventions that aim to prevent the development of suicidal ideation and suicidal behavior. PMID:25030971

  1. Suicide risk in primary care: identification and management in older adults.

    PubMed

    Raue, Patrick J; Ghesquiere, Angela R; Bruce, Martha L

    2014-09-01

    The National Strategy for Suicide Prevention (2012) has set a goal to reduce suicides by 20% within 5 years. Suicide rates are higher in older adults compared to most other age groups, and the majority of suicide completers have visited their primary care physician in the year before suicide. Primary care is an ideal setting to identify suicide risk and initiate mental health care. We review risk factors for late-life suicide; methods to assess for different levels of suicidality; and recent research developments regarding both effective assessment and management of suicide risk among older primary care patients. We highlight that broader scale screening of suicide risk may be considered in light of findings that suicidality can occur even in the absence of major risk factors like depression. We also highlight collaborative care models targeting suicide risk, and recent innovative interventions that aim to prevent the development of suicidal ideation and suicidal behavior.

  2. Activating Older Adults With Serious Mental Illness for Collaborative Primary Care Visits

    PubMed Central

    Bartels, Stephen J.; Aschbrenner, Kelly A.; Rolin, Stephanie A.; Hendrick, Delia Cimpean; Naslund, John A.; Faber, Marjan J.

    2016-01-01

    Objective Persons with serious mental illness frequently receive inadequate medical care and are more likely to experience difficulty navigating the health care system compared with the general population. To address this gap in quality, we developed a program of peer co-led collaborative activation training for primary care (CAT-PC) designed to improve “patient activation” and person-centered care in primary care visits for middle-aged and older adults with serious mental illness and cardiovascular risk. This report presents pilot study feasibility and participant outcomes for CAT-PC. Method A pre-post pilot evaluation of CAT-PC included N = 17 adults (age ≥ 50) with serious mental illness and cardiovascular health risk conditions, and N = 6 primary care providers. CAT-PC consists of 9 weekly peer co-led patient education and skills training sessions and a 45-min video-based training for primary care providers. Pre-post measures included the Patient Activation Measure (PAM), Perceived Efficacy in Patient-Physician Interactions (PEPPI), Autonomy Preference Index (API) for preferred role in primary care encounters, and Social Skills Performance Assessment (SSPA) role-play test for medical visits. Results All 17 participants attended 5 or more sessions. Post-intervention improvement was found for patient activation and simulated performance of medical visit communication skills. Trends were observed for improved self-efficacy in provider interactions and greater preference for a more collaborative role in decision-making. Conclusions and Implications CAT-PC is a brief, peer co-led education and skills training intervention potentially improving patient activation in primary care encounters and providing an important missing component in emerging models of “patient-centered behavioral health homes” for this high-risk group. PMID:24219769

  3. Arthroscopic Treatment for Primary Septic Arthritis of the Hip in Adults

    PubMed Central

    2016-01-01

    Purpose. Primary septic arthritis is a rare differential diagnosis of acute hip pain in adults. Inspired by the success of all-arthroscopic treatment in pediatric patients, we developed a diagnostic and surgical pathway for our adult patients. Methods. Seven patients, average age 44 ± 13.7 years with acute hip pain since 4.4 ± 2.9 days in the average, were included. Septic arthritis was confirmed by joint aspiration and dissemination was excluded by MRI and standard radiographs. Surgical treatment consisted of immediate arthroscopic lavage using 4 portals for debridement, high-volume irrigation, partial synovectomy, and drainage. Results. Patients were treated in hospital for 12.4 ± 3.1 days (range 7–16 days). WBC and CRP returned to physiological levels. During the mean follow-up of 26.4 ± 19.4 months (range 13–66 months) no patient showed recurrence of infection. The 5 patients with an unimpaired hip joint prior to the infection had a mean modified Harris Hip Score of 94 ± 5.6 points (range 91–100) at final follow-up. Conclusions. Arthroscopic therapy using a minimally invasive approach with low perioperative morbidity for the treatment of primary septic arthritis of the adult hip is able to restore normal hip function in acute cases without dissemination of the infection. Level of Evidence. IV. PMID:27800188

  4. Primary Care Use before Cancer Diagnosis in Adolescents and Young Adults – A Nationwide Register Study

    PubMed Central

    Ahrensberg, Jette Møller; Fenger-Grøn, Morten; Vedsted, Peter

    2016-01-01

    Introduction Survival rates of cancer patients have generally improved in recent years. However, children and older adults seem to have experienced more significant clinical benefits than adolescents and young adults (AYAs). Previous studies suggest a prolonged diagnostic pathway in AYAs, but little is known about their pre-diagnostic healthcare use. This study investigates the use of primary care among AYAs during the two years preceding a cancer diagnosis. Methods The study is a retrospective population-based matched cohort study using Danish nationwide registry data. All persons diagnosed with cancer during 2002–2011 in the age group 15–39 years were included (N = 12,306); each participant was matched on gender, age and general practice with 10 randomly selected references (N = 123,060). The use of primary healthcare services (face-to-face contacts, blood tests and psychometric tests) was measured during the two years preceding the diagnosis (index date), and collected data were analysed in a negative binomial regression model. Results The cases generally increased their use of primary care already from 8 months before a cancer diagnosis, whereas a similar trend was not found for controls. The increase was observed for all cancer types, but it started at different times: 17 months before a diagnosis of CNS tumour, 12 months before a diagnosis of soft tissue sarcoma, 9 months before a diagnosis of lymphoma, 5–6 months before a diagnosis of leukaemia, bone tumour or GCT, and 3 months before a diagnosis of malignant melanoma. Conclusion The use of primary care among AYAs increase several months before a cancer diagnosis. The diagnostic intervals are generally short for malignant melanomas and long for brain tumours. A prolonged diagnostic pathway may indicate non-specific or vague symptomatology and low awareness of cancer among AYAs primary-care personnel. The findings suggest potential of faster cancer diagnosis in AYAs. PMID:27203083

  5. Hepatocellular carcinoma.

    PubMed

    Okuda, K

    2000-01-01

    Hepatocellular carcinoma (HCC) is increasing in many countries as a result of an increase in hepatitis C virus (HCV) infection since World War II. The epidemiology of HCC varies with the global region. There have been conflicting observations from different parts of the world concerning the frequency of HCC in patients who in the distant past had post-transfusion non-A, non-B hepatitis. The genetic basis of hepatocarcinogenesis is still poorly understood. In hepatitis B virus (HVB) associated HCC, codon 249 mutation in the p 53 gene seems more related to exposure to aflatoxin B1 than to hepatocarcinogenesis itself. HCC that occurs in children in high HBV endemic regions could be associated with germ-line mutations, but little information is available; not much is known about chemical hepatocarcinogens in the environment other than aflatoxins. The X gene of HBV seems to play an important role in HBV-associated hepatocarcinogenesis. There are preliminary observations on the molecular mechanism of HCV-associated HCC, such as HCV core protein inducing HCC in transgenic mice and the NS3 genome transforming NIH 3T3 cells. Pathological distinction between preneoplastic and very early transformed lesions still depends on classical morphology, and a more genetically oriented differential diagnosis is required. Clinical diagnosis based on modern imaging has improved greatly, but is still unsatisfactory in the differential diagnosis of preneoplastic and early transformed nodules, because the vasculature changes that occur within the nodule are not accurately discerned with the current imaging. Use of sensitive des-gamma-carboxy prothrombin (PIVKA II) assay, and lectin affinity chromatography separating HCC specific subspecies of AFP molecules with a more practical biochemical technique will further improve diagnosis. Early diagnosis and transplantation are the best treatment at the moment, but transplantation is not widely available because of the donor shortage. Despite

  6. Associations between adult attachment characteristics, medical burden, and life satisfaction among older primary care patients.

    PubMed

    Kirchmann, Helmut; Nolte, Tobias; Runkewitz, Kristin; Bayerle, Lisa; Becker, Simone; Blasczyk, Verena; Lindloh, Julia; Strauss, Bernhard

    2013-12-01

    We investigated whether attachment security, measured by the Adult Attachment Prototype Rating (AAPR), was correlated with life satisfaction, independent of sociodemographic characteristics, medical burden, and age-related coping strategies in a sample of 81 patients (69-73 years) recruited from the register of a general primary care practice. Furthermore, we examined whether patients classified as AAPR-secure reported better adjustment to medical burden in terms of higher life satisfaction than did insecure patients. Attachment security was independently related to life satisfaction. Moreover, the association between medical burden and lower life satisfaction was significantly stronger for insecure than for secure participants. Our findings indicate that interventions to improve attachment security or coping processes related to attachment could help older adults retain life satisfaction.

  7. Primary haematogenous osteomyelitis of the patella: a rare cause for anterior knee pain in an adult

    PubMed Central

    Kankate, R; Selvan, T

    2000-01-01

    Acute osteomyelitis of the patella is a very rare condition, which commonly affects children between the ages of 5-15 years. Primary haematogenous osteomyelitis in an adult usually occurs in patients with associated risk factors like intravenous drug abuse, HIV infection, and trauma. This report discusses a similar condition in a 46 year old women with no associated predisposing risk factors. The rarity of this condition and its atypical presentation should be borne in mind while treating an adult patient with anterior knee pain. Point tenderness over the patella should alert a physician to the possibility of osteomyelitis of the patella. The value of bone scan and computed tomography in the early stages to help diagnose this condition has been stressed. The literature has been reviewed and discussed briefly.


Keywords: haematogenous osteomyelitis; patella PMID:11060146

  8. Primary monolayer culture of adult mouse hepatocytes -- a model for the study of hepatotropic viruses.

    PubMed

    Arnheiter, H

    1980-01-01

    Primary monolayer cultures of adult mouse hepatocytes isolated by collagenase perfusion of the liver in situ were exposed to 2 hepatotropic viruses, an avian influenza A virus adapted to grow in mouse liver in vivo and a herpes simplex type I virus. Influenza virus infection led to lysis ofindividual hepatocytes and total monolayer destruction within 18 to 120 hours after infection according to the virus dose used. Virus replication was evidenced by assaying hepatocyte supernates for hemagglutinin and infectivity, by immunofluorescent staining and by electron microscopy. Herpes virus infection resulted in polykaryocyte formation followed by nuclear pycnosis and cell lysis. Virus replication was assayed by titration of supernate infectivity.

  9. Changes in the contralateral eye in uncomplicated persistent hyperplastic primary vitreous in adults.

    PubMed

    Awan, K J; Humayun, M

    1985-02-15

    In two adults (a 62-year-old man and a 71-year-old woman) uncomplicated full-blown unilateral persistent hyperplastic primary vitreous was diagnosed on the basis of characteristic clinical features and ultrasonography. In the contralateral uninvolved eyes, we found open-angle glaucoma, anomalous blood vessels along the entire circumference of the anterior chamber angle, band keratopathy, and heterochromia iridis. The axial length of one involved eye was about 0.85 mm larger than that of the uninvolved eye.

  10. Cost-Effectiveness of Eszopiclone for the Treatment of Adults with Primary Chronic Insomnia

    PubMed Central

    Snedecor, Sonya J.; Botteman, Marc F.; Bojke, Chris; Schaefer, Kendyl; Barry, Nadine; Pickard, A. Simon

    2009-01-01

    Study Objective: To assess the cost-effectiveness of treatment with eszopiclone for chronic primary insomnia in adults. Methods: A model using patient-level data from a 6-month, double-blind, placebo-controlled, clinical trial (n = 824), combined with data from a claims database and published literature, was used to assess the quality-adjusted life years (QALYs) gained and costs associated with eszopiclone versus placebo in adults with primary insomnia. Quality of life data were collected during the trial via the SF-36, from which preference-based utility scores were derived using published algorithms. Medical and absenteeism costs, estimated via a retrospective analysis of a claims and absenteeism database, were assigned to patients based on the degree of severity of their insomnia, assessed via the Insomnia Severity Index collected in the clinical trial. Presenteeism costs (lost productivity while at work) were estimated from responses to the Work Limitation Questionnaire collected during the trial. Six-month gains in QALYs and costs for each treatment group were calculated to derive cost-effectiveness ratios. Uncertainty was addressed via univariate and multivariate sensitivity analyses. Results: Over the 6-month period, eszopiclone use resulted in a net gain of 0.0137 QALYs over placebo at an additional cost of $67, resulting in an incremental cost per QALY gained of slightly less than $5,000. When absenteeism and presenteeism costs were excluded, the cost-effectiveness ratio increased to approximately $33,000 per QALY gained, which is below the commonly used threshold of $50,000 used to define cost-effectiveness. Extensive sensitivity analyses indicate the results are generally robust. Conclusion: Our model, based on efficacy data from a clinical trial, demonstrated eszopiclone was cost-effective for the treatment of primary insomnia in adults, especially when lost productivity costs were included. Citation: Snedecor SJ; Botteman MF; Bojke C; Schaefer K; Barry

  11. Origin of germ cells and formation of new primary follicles in adult human ovaries

    PubMed Central

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Upadhyaya, Nirmala B

    2004-01-01

    sophisticated adaptive mechanism created during the evolution of female reproduction. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. An essential mission of such follicular turnover might be elimination of spontaneous or environmentally induced genetic alterations of oocytes in resting primary follicles. PMID:15115550

  12. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review

    PubMed Central

    NEUNERT, C.; NOROOZI, N.; NORMAN, G.; BUCHANAN, G. R.; GOY, J.; NAZI, I.; KELTON, J. G.; ARNOLD, D. M.

    2016-01-01

    Summary Background The burden of severe bleeding in adults and children with immune thrombocytopenia (ITP) has not been established. Objectives To describe the frequency and severity of bleeding events in patients with ITP, and the methods used to measure bleeding in ITP studies. Patients/Methods We performed a systematic review of all prospective ITP studies that enrolled 20 or more patients. Two reviewers searched Medline, Embase, CINAHL and the Cochrane registry up to May 2014. Overall weighted proportions were estimated using a random effects model. Measurement properties of bleeding assessment tools were evaluated. Results We identified 118 studies that reported bleeding (n = 10 908 patients). Weighted proportions for intracerebral hemorrhage (ICH) were 1.4% for adults (95% confidence interval [CI], 0.9–2.1%) and 0.4% for children (95% CI, 0.2–0.7%; P < 0.01), most of whom had chronic ITP. The weighted proportion for severe (non-ICH) bleeding was 9.6% for adults (95% CI, 4.1–17.1%) and 20.2% for children (95% CI, 10.0–32.9%; P < 0.01) with newly-diagnosed or chronic ITP. Methods of reporting and definitions of severe bleeding were highly variable in primary studies. Two bleeding assessment tools (Buchanan 2002 for children; Page 2007 for adults) demonstrated adequate interrater reliability and validity in independent assessments. Conclusions ICH was more common in adults and tended to occur during chronic ITP; other severe bleeds were more common in children and occurred at all stages of disease. Reporting of non-ICH bleeding was variable across studies. Further attention to ITP-specific bleeding measurement in clinical trials is needed to improve standardization of this important outcome for patients. PMID:25495497

  13. The effect of increased primary schooling on adult women's HIV status in Malawi and Uganda: Universal Primary Education as a natural experiment.

    PubMed

    Behrman, Julia Andrea

    2015-02-01

    This paper explores the causal relationship between primary schooling and adult HIV status in Malawi and Uganda, two East African countries with some of the highest HIV infection rates in the world. Using data from the 2010 Malawi Demographic Health Survey and the 2011 Uganda AIDS Indicator Survey, the paper takes advantage of a natural experiment, the implementation of Universal Primary Education policies in the mid 1990s. An instrumented regression discontinuity approach is used to model the relationship between increased primary schooling and adult women's HIV status. Results indicate that a one-year increase in schooling decreases the probability of an adult woman testing positive for HIV by 0.06 (p < 0.01) in Malawi and by 0.03 (p < 0.05) in Uganda. These results are robust to a variety of model specifications. In a series of supplementary analyses a number of potential pathways through which such effects may occur are explored. Findings indicate increased primary schooling positively affects women's literacy and spousal schooling attainment in Malawi and age of marriage and current household wealth in Uganda. However primary schooling has no effect on recent (adult) sexual behavior.

  14. Primary and Specialty Medical Care Among Ethnically Diverse, Older Rural Adults With Type 2 Diabetes: The ELDER Diabetes Study

    ERIC Educational Resources Information Center

    Bell, Ronny A.; Quandt, Sara A.; Arcury, Thomas A.; Snively, Beverly M.; Stafford, Jeanette M.; Smith, Shannon L.; Skelly, Anne H.

    2005-01-01

    Purpose: Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes.…

  15. Primary and Specialty Medical Care among Ethnically Diverse, Older Rural Adults with Type 2 Diabetes: The ELDER Diabetes Study

    ERIC Educational Resources Information Center

    Bell, Ronny A.; Quandt, Sara A.; Arcury, Thomas A.; Snively, Beverly M.; Stafford, Jeanette M.; Smith, Shannon L.; Skelly, Anne H.

    2005-01-01

    Purpose: Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes.…

  16. A systematic review of motivational interviewing for weight loss among adults in primary care

    PubMed Central

    Barnes, R. D.; Ivezaj, V.

    2015-01-01

    Summary Motivational interviewing (MI) is a client-centred method of intervention focused on enhancing intrinsic motivation and behaviour change. A previous review of the literature and meta-analyses support the effectiveness of MI for weight loss. None of these studies, however, focused on the bourgeoning literature examining MI for weight loss among adults within primary care settings, which confers unique barriers to providing weight loss treatment. Further, the current review includes 19 studies not included in previous reviews or meta-analyses. We conducted a comprehensive review of PubMed, MI review papers, and citations from relevant papers. A total of 24 adult randomized controlled trials were identified. MI interventions typically were provided individually by a range of clinicians and compared with usual care. Few studies provided adequate information regarding MI treatment fidelity. Nine studies (37.5%) reported significant weight loss at post-treatment assessment for the MI condition compared with control groups. Thirteen studies (54.2%) reported MI patients achieving at least 5% loss of initial body weight. There is potential for MI to help primary care patients lose weight. Conclusions, however, must be drawn cautiously as more than half of the reviewed studies showed no significant weight loss compared with usual care and few reported MI treatment fidelity. PMID:25752449

  17. Utilization and perceptions of primary health care services in Australian adults with mental illness.

    PubMed

    Scott, David; Happell, Brenda

    2013-06-01

    Persons accessing inpatient mental health services generally experience reduced access to and quality of primary health care. The objective of this study was to compare health service utilization and perceptions, and receipt of specified health services, in Australian adults with and without a previous mental illness diagnosis. A cross-sectional survey was administered by computer-assisted telephone interviewing in 2011; the main outcome measures were receipt of services in the previous 12 months, satisfaction with health care services, and concerns regarding health care affordability. Participants included 1275 adults residing in Queensland, Australia; 292 (23%) participants reported a diagnosis of mental illness, largely depression and/or anxiety (87%). The mental illness group had higher scores for concerns regarding health care affordability (mean ranks 778 vs. 706, respectively; z=-2.90, P=0.004) and lower scores for perceptions of health care service quality and accessibility (mean ranks 631 vs. 701, respectively; z=-2.90, P=0.004). After adjustment for increased utilization of services, the mental illness group had an increased likelihood of having received only 5 of 19 services in the past 12 months (odds ratios: 1.54-1.71). Compared to those with no mental illness, Australians with a mental illness report increased dissatisfaction with health care affordability, accessibility, and quality, and generally have similar odds of primary care services per health care utilization despite being at significantly greater risk of chronic disease.

  18. Measuring health-related quality of life in adults with chronic conditions in primary care settings

    PubMed Central

    Hand, Carri

    2016-01-01

    Abstract Objective To describe health-related quality of life (HRQOL) conceptual frameworks, critically review 3 commonly used HRQOL scales relevant to adults with chronic conditions in primary care settings, and make recommendations for using HRQOL scales in primary care practice. Data sources Information was accessed regarding HRQOL conceptual and theoretical approaches. A comprehensive search strategy identified 3 commonly used scales that met the review criteria and evidence regarding use of the scales in adults with chronic conditions in community settings. Scale selection Scales were selected if they were designed for clinical use; were easy to administer; were generic and broad in content areas; and contained some individualized items. Scales were critiqued according to content development, theoretical basis, psychometric properties, scoring, feasibility, the concepts being measured, and the number of items that measured an individualized concept. Synthesis Early HRQOL approaches focused on health and functional status while recent approaches incorporate individualized concepts such as the person’s own values and the environment. The abbreviated World Health Organization Quality of Life Scale (WHOQOL-BREF), the 36-Item Short Form Health Survey (SF-36), and the Duke Health Profile were critiqued. All address physical, mental, and social domains, while the WHOQOL-BREF also addresses environment. Psychometric evidence supports use of the SF-36 and WHOQOL-BREF with this population. The SF-36 has the most evidence of responsiveness but has some floor and ceiling effects, while the WHOQOL-BREF does not appear to have floor or ceiling effects but has limited evidence of responsiveness. The WHOQOL-BREF has the highest proportion of individualized items. Conclusion Measurement of HRQOL in adults with chronic conditions can support patient management and contribute to primary care service evaluation. Scales that are based on a broad definition of health and that

  19. Primary blast injury-induced lesions in the retina of adult rats

    PubMed Central

    2013-01-01

    Background The effect of primary blast exposure on the brain is widely reported but its effects on the eye remains unclear. Here, we aim to examine the effects of primary blast exposure on the retina. Methods Adult male Sprague–Dawley rats were exposed to primary blast high and low injury and sacrificed at 24 h, 72 h, and 2 weeks post injury. The retina was subjected to western analysis for vascular endothelial growth factor (VEGF), aquaporin-4 (AQP4), glutamine synthethase (GS), inducible nitric oxide synthase (NOS), endothelial NOS, neuronal NOS and nestin expression; ELISA analysis for cytokines and chemokines; and immunofluorescence for glial fibrillary acidic protein (GFAP)/VEGF, GFAP/AQP4, GFAP/nestin, GS/AQP4, lectin/iNOS, and TUNEL. Results The retina showed a blast severity-dependent increase in VEGF, iNOS, eNOS, nNOS, and nestin expression with corresponding increases in inflammatory cytokines and chemokines. There was also increased AQP4 expression and retinal thickness after primary blast exposure that was severity-dependent. Finally, a significant increase in TUNEL+ and Caspase-3+ cells was observed. These changes were observed at 24 h post-injury and sustained up to 2 weeks post injury. Conclusions Primary blast resulted in severity-dependent pathological changes in the retina, manifested by the increased expression of a variety of proteins involved in inflammation, edema, and apoptosis. These changes were observed immediately after blast exposure and sustained up to 2 weeks suggesting acute and chronic injury mechanisms. These changes were most obvious in the astrocytes and Müller cells and suggest important roles for these cells in retina pathophysiology after blast. PMID:23819902

  20. Severe chronic primary neutropenia in adults: report on a series of 108 patients.

    PubMed

    Sicre de Fontbrune, Flore; Moignet, Aline; Beaupain, Blandine; Suarez, Felipe; Galicier, Lionel; Socié, Gérard; Varet, Bruno; Coppo, Paul; Michel, Marc; Pautas, Cécile; Oksenhendler, Eric; Lengline, Etienne; Terriou, Louis; Moreau, Philippe; Chantepie, Sylvain; Casadevall, Nicole; Michot, Jean Marie; Gardembas, Martine; Michallet, Mauricette; Croisille, Laure; Audrain, Marie; Bellanné-Chantelot, Christine; Donadieu, Jean; Lamy, Thierry

    2015-10-01

    Severe chronic primary neutropenia (CPN) is a rare entity, and long-term outcome and risk factors for infections in severe CPN adults have not been described to date. We report the characteristics and outcomes of 108 severe adult CPN patients enrolled in a multi-institutional observational study. Severe CPN adults were mostly female (78%), and median age at diagnosis was 28.3 years. Diagnosis was fortuitous in 62% of cases. The median absolute neutrophil count (ANC) at diagnosis was 0.4 × 10(9)/L, and median ANC without granulocyte colony-stimulating factor (G-CSF) during follow-up was 0.5 × 10(9)/L. Twenty-three of 66 (34.8%) evaluable patients had neutrophil autoantibodies, and 6 of 47 (12.8%) a T-cell clone. The presence of neutrophil autoantibodies or T-cell clone was not associated with any specific clinical or biological characteristics. No death or hematologic malignancies occurred, and 44 severe bacterial infections were reported in 27 patients with a median follow-up of 8.3 years. Fifty patients received G-CSF either sporadically (n = 24) or continuously (n = 26) and responded (96%). Nineteen patients received immunosuppressive therapies: overall response (OR) was 41%, and median duration of response was 3 months. At diagnosis, the only predictive factor for the occurrence of severe bacterial infections was an ANC count below 0.2 × 10(9)/L (OR, 0.76). Severe CPN in adults is characterized by a female predominance and a benign outcome with a low rate of severe bacterial infections and no secondary malignancies. G-CSF is efficient and well tolerated but is not required in a majority of patients. PMID:26261239

  1. Weight management services for adults--highlighting the role of primary care.

    PubMed

    Hassan, S J; O'Shea, D

    2012-01-01

    Ireland has the fourth highest prevalence of overweight and obese men in the European Union and the seventh highest prevalence among women. This study focuses on 777 referrals on the waiting list for Ireland's only fully funded hospital-based adult weight management service with special emphasis on the role of primary care in the referral process. Since our last review two years ago, we found that patients are now being referred at a younger age (mean 43 years). The mean BMI at referral has increased from 44 to 46. Five hundred and forty eight (70%) referrals were from primary care with males accounting for 163 (30%) of these, despite male obesity being more prevalent. Interestingly, as the distance from Dublin increased, the number of referrals decreased. Overall this is a concerning trend showing the increasing burden of obesity on a younger population and a health system inadequately equipped to deal with the problem. It also highlights the central role of the primary care physician in the timely and appropriate referral to optimise use of our available resources.

  2. Synchronous Fibrolamellar Hepatocellular Carcinoma and Auricular Myxoma

    PubMed Central

    González-Cantú, Yessica M.; Rodriguez-Padilla, Cristina; Tena-Suck, Martha Lilia; García de la Fuente, Alberto; Mejía-Bañuelos, Rosa María; Díaz Mendoza, Raymundo; Quintanilla-Garza, Samuel; Batisda-Acuña, Yolaester

    2015-01-01

    Synchronic occurrence of benign and malignant tumors is extremely rare. Fibrolamellar hepatocellular carcinoma represents 1% to 2% of all hepatocarcinomas, while myxomas represent about half of all the cases of primary tumors of the heart. We present the case of a 53-year-old woman with a left atrial myxoma that was surgically removed. Several weeks later, the patient returned to the hospital with abdominal pain. CT scan showed a mass in the left lobe of the liver that was resected and diagnosed as fibrolamellar hepatocellular carcinoma. As of this writing, the patient is healthy. PMID:26509093

  3. Synchronous Fibrolamellar Hepatocellular Carcinoma and Auricular Myxoma.

    PubMed

    González-Cantú, Yessica M; Rodriguez-Padilla, Cristina; Tena-Suck, Martha Lilia; García de la Fuente, Alberto; Mejía-Bañuelos, Rosa María; Díaz Mendoza, Raymundo; Quintanilla-Garza, Samuel; Batisda-Acuña, Yolaester

    2015-01-01

    Synchronic occurrence of benign and malignant tumors is extremely rare. Fibrolamellar hepatocellular carcinoma represents 1% to 2% of all hepatocarcinomas, while myxomas represent about half of all the cases of primary tumors of the heart. We present the case of a 53-year-old woman with a left atrial myxoma that was surgically removed. Several weeks later, the patient returned to the hospital with abdominal pain. CT scan showed a mass in the left lobe of the liver that was resected and diagnosed as fibrolamellar hepatocellular carcinoma. As of this writing, the patient is healthy.

  4. Angiotensin-Converting Enzyme Gene Polymophism in Adult Primary Focal Segmental Glomerulosclerosis

    PubMed Central

    Mohd, Rozita; Wahab, Zaimi Abdul; Cader, Rizna; Gafor, Halim A.; Radzi, Azizah Md; Shah, Shamsul Azhar; Tong, Norella Kong Chiew

    2014-01-01

    Background Primary focal segmental glomerulosclerosis (FSGS) accounts for a third of biopsy-proven primary glomerulonephritis in Malaysia. Pediatric studies have found the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene to be associated with renal disease progression. The aim of this study was to determine the prevalence of the ACE (I/D) genotypes in adult primary FSGS and its association with renal outcome on follow-up. Methods Prospective observational study involving primary FSGS patients was conducted. Biochemical and urine tests at the time of study were compared to the time of the diagnosis and disease progression analyzed. ACE gene polymorphism was identified using polymerase chain reaction amplification technique and categorized into II, ID and DD genotypes. Results Forty-five patients with a median follow-up of 3.8 years (interquartile range: 1.8 - 5.6) were recruited. The commonest genotype was II (n = 23, 51.1%) followed by ID (n = 19, 42.2%) and DD (n = 3, 6.7%). The baseline characteristics were comparable between the II and non-II groups at diagnosis and at study recruitment except that the median urine protein-creatinine index was significantly lower in the II group compared to the non-II group (0.02 vs. 0.04 g/mmol (P = 0.03). Regardless of genotypes, all parameters of renal outcome improved after treatment. Conclusion The II followed by ID genotypes were the predominant ACE gene alleles in our FSGS. Although the D allele has been reported to have a negative impact on renal outcome, treatment appeared to be more important than genotype in preserving renal function in this cohort. PMID:24883149

  5. Giant primary ossified cavernous hemangioma of the skull in an adult: A rare calvarial tumor

    PubMed Central

    Tyagi, Devendra K; Balasubramaniam, Srikant; Sawant, Hemant V

    2011-01-01

    Primary intraosseous cavernous hemangiomas (PICHs) of the cranium are rare benign vascular tumors that account for about 0.2 % of all bone tumors and 10 % of benign skull tumors. They generally present as osteolytic lesions with honeycomb pattern of calcification. Completely ossified cavernous hemangioma of the calvarium in an adult has not been reported previously. A 28-year-old female presented to us with a large right parietal skull mass that had been present since the last 15 years. Total resection of the lesion was performed. Pathological examination was suggestive of cavernous hemangioma of the skull bone. Cavernous hemangioma should be considered as one of the differential diagnosis in any case of bony swelling of the calvarium so that adequate preoperative planning can be made to minimize blood loss and subsequent morbidity. PMID:21897684

  6. Continual electric field stimulation preserves contractile function of adult ventricular myocytes in primary culture.

    PubMed

    Berger, H J; Prasad, S K; Davidoff, A J; Pimental, D; Ellingsen, O; Marsh, J D; Smith, T W; Kelly, R A

    1994-01-01

    To model with greater fidelity the electromechanical function of freshly isolated heart muscle cells in primary culture, we describe a technique for the continual electrical stimulation of adult myocytes at physiological frequencies for several days. A reusable plastic cover was constructed to fit standard, disposable 175-cm2 tissue culture flasks and to hold parallel graphite electrodes along the long axis of each flask, which treated a uniform electric field that resulted in a capture efficiency of ventricular myocytes of 75-80%. Computer-controlled amplifiers were designed to be capable of driving a number of flasks concurrently, each containing up to 4 x 10(6) myocytes, over a range of stimulation frequencies (from 0.1 to 7.0 Hz) with reversal of electrode polarity after each stimulus to prevent the development of pH gradients around each electrode. Unlike quiescent, unstimulated myocytes, the amplitude of contraction, and velocities of shortening and relaxation did not change in myocytes paced at 3-5 Hz for up to 72 h. The maintenance of normal contractile function in paced myocytes required mechanical contraction per se, since paced myocytes that remained quiescent due to the inclusion of 2.5 microM verapamil in the culture medium for 48 h also exhibited a decline in contractility when paced after verapamil removal. Similarly, pacing increased peak calcium current compared with quiescent cells that had not been paced. Thus myocyte contraction at physiological frequencies induced by continual uniform electric field stimulation in short-term primary culture in defining medium maintains some biophysical parameters of myocyte phenotype that are similar to those observed in freshly isolated adult ventricular myocytes.

  7. Occupational and environmental risk factors of adult primary brain cancers: a systematic review.

    PubMed

    Gomes, J; Al Zayadi, A; Guzman, A

    2011-04-01

    The incidence of brain neoplasm has been progressively increasing in recent years in the industrialized countries. One of the reasons for this increased incidence could be better access to health care and improved diagnosis in the industrialized countries. It also appears that Caucasians have a higher incidence than blacks or Hispanics or Asians. A number of risk factors have been identified and described including the genetic, ethnic and age-based factors. Certain occupational and environmental factors are also believed to influence the risk of primary adult brain tumors. Potential occupational and environmental factors include exposure to diagnostic and therapeutic radiations, electromagnetic radiation from cellular phones and other wireless devices, infectious agents, air pollution and residence near landfills and high-voltage power lines and jobs as firefighters, farmers, physician, chemists and jobs in industries such as petrochemical, power generation, synthetic rubber manufacturing, agricultural chemicals manufacturing. The purpose of this systematic review is to examine occupational and environmental risk factors of brain neoplasm. A range of occupational and environmental exposures are evaluated for significance of their relationship with adult primary brain tumors. On the basis of this review we suggest a concurrent evaluation of multiple risk factors both within and beyond occupational and environmental domains. The concurrent approach needs to consider better exposure assessment techniques, lifetime occupational exposures, genotypic and phenotypic characteristics and lifestyle and dietary habits. This approach needs to be interdisciplinary with contributions from neurologists, oncologists, epidemiologists and molecular biologists. Conclusive evidence that has eluded multitude of studies with single focus and single exposure needs to multifaceted and multidisciplinary. PMID:23022824

  8. Activity, inhibition, and induction of cytochrome P450 2J2 in adult human primary cardiomyocytes.

    PubMed

    Evangelista, Eric A; Kaspera, Rüdiger; Mokadam, Nahush A; Jones, J P; Totah, Rheem A

    2013-12-01

    Cytochrome P450 2J2 plays a significant role in the epoxidation of arachidonic acid to signaling molecules important in cardiovascular events. CYP2J2 also contributes to drug metabolism and is responsible for the intestinal clearance of ebastine. However, the interaction between arachidonic acid metabolism and drug metabolism in cardiac tissue, the main expression site of CYP2J2, has not been examined. Here we investigate an adult-derived human primary cardiac cell line as a suitable model to study metabolic drug interactions (inhibition and induction) of CYP2J2 in cardiac tissue. The primary human cardiomyocyte cell line demonstrated similar mRNA-expression profiles of P450 enzymes to adult human ventricular tissue. CYP2J2 was the dominant isozyme with minor contributions from CYP2D6 and CYP2E1. Both terfenadine and astemizole oxidation were observed in this cell line, whereas midazolam was not metabolized suggesting lack of CYP3A activity. Compared with recombinant CYP2J2, terfenadine was hydroxylated in cardiomyocytes at a similar K(m) value of 1.5 μM. The V(max) of terfenadine hydroxylation in recombinant enzyme was found to be 29.4 pmol/pmol P450 per minute and in the cells 6.0 pmol/pmol P450 per minute. CYP2J2 activity in the cell line was inhibited by danazol, astemizole, and ketoconazole in submicromolar range, but also by xenobiotics known to cause cardiac adverse effects. Of the 14 compounds tested for CYP2J2 induction, only rosiglitazone increased mRNA expression, by 1.8-fold. This cell model can be a useful in vitro model to investigate the role of CYP2J2-mediated drug metabolism, arachidonic acid metabolism, and their association to drug induced cardiotoxicity. PMID:24021950

  9. Primary atypical teratoid/rhabdoid tumor of the spine in an adult patient

    PubMed Central

    Li, Luyuan; Patel, Mohit; Nguyen, Ha Son; Doan, Ninh; Sharma, Abhishiek; Maiman, Dennis

    2016-01-01

    Background: Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive neoplasm of the central nervous system that generally arises intracranially in patients under 2 years of age. Primary spinal AT/RT in an adult is rare. Case Description: A 23-year-old female presented with left lower extremity sciatica attributed to a magnetic resonance imaging (MRI)-documented intradural mass between L2 and L4. The lesion was biopsied (was unresectable) and treated with high-dose chemotherapy (methotrexate, vincristine, cyclophosphamide, etoposide, and cisplatin) with autologous hematopoietic stem cells rescue, followed by 2 months of radiation therapy (36 Gy to craniospinal axis, 20 Gy to lumbar region) with concurrent temozolomide; the latter was discontinued after 3 weeks due to myelosuppression. Tumor relapsed 1 year later at C7–T1 level. She was started on oral metronomic therapy, and bevacizumab was added 2 months later. Three months later, a cervical MRI showed progression of the tumor, along with new lesions in the thoracic/lumbar spine plus intracranial punctate nodular tumors. Following resection of the C7/T1 lesion, she was started on palliative alisertib; a month later, a cranial computed tomography showed progression of her disease with hydrocephalus. Treatment was discontinued, and she expired 12 months after initial diagnosis. Conclusion: Primary spinal AT/RT in the adult patient is rare. The pathology is associated with early recurrence and a poor prognosis. Although potential benefits of metronomic chemotherapy and alisertib have been reported, the patient in this study did not favorably respond to these modalities. PMID:27069744

  10. A quality-of-life measure for adults with primary ciliary dyskinesia: QOL–PCD

    PubMed Central

    Behan, Laura; Dunn Galvin, Audrey; Alpern, Adrianne; Morris, Anjana M.; Carroll, Mary P.; Knowles, Michael R.; Leigh, Margaret W.; Quittner, Alexandra L.

    2015-01-01

    Primary ciliary dyskinesia (PCD) is characterised by chronic suppurative lung disease, rhino-sinusitis, hearing impairment and sub-fertility. We have developed the first multidimensional measure to assess health-related quality of life (HRQoL) in adults with PCD (QOL–PCD). Following a literature review and expert panel meeting, open-ended interviews with patients investigated the impact of PCD on HRQoL in the UK and North America (n=21). Transcripts were content analysed to derive saturation matrices. Items were rated for relevance by patients (n=49). Saturation matrices, relevance scores, literature review, evaluation of existing measures, and expert opinion contributed to development of a preliminary questionnaire. The questionnaire was refined following cognitive interviews (n=18). Open-ended interviews identified a spectrum of issues unique to adults with PCD. Saturation matrices confirmed comprehensive coverage of content. QOL–PCD includes 48 items covering the following seven domains: Physical Functioning, Emotional Functioning, Treatment Burden, Respiratory and Sinus Symptoms, Ears and Hearing, Social Functioning, and Vitality and Health Perceptions. Cognitive testing confirmed that content was comprehensive and the items were well-understood by respondents. Content validity and cognitive testing supported the items and structure. QOL–PCD has been translated into other languages and is awaiting psychometric testing. PMID:25976687

  11. Compound heterozygote mutations in SPG7 in a family with adult-onset primary lateral sclerosis

    PubMed Central

    Yang, Yi; Lynch, David R.; Lukas, Thomas; Ahmeti, Kreshnik; Sleiman, Patrick M.A.; Ryan, Eanna; Schadt, Kimberly A.; Newman, Jordan H.; Deng, Han-Xiang; Siddique, Nailah

    2016-01-01

    Objective: To identify the genetic defect for adult-onset primary lateral sclerosis (PLS) in a family with 5 patients. Methods: Whole-exome sequencing was performed to identify the shared genetic variants in 3 affected members in a PLS family with 5 affected individuals. Sanger sequencing was used for validation of the variants and for cosegregation analysis. Mitochondrial activity for both patients and unaffected siblings was measured using a SeaHorse metabolic analyzer. Results: Whole-exome sequencing and subsequent cosegregation analysis demonstrated that compound heterozygous missense variants L695P and I743T in SPG7 were the only mutations cosegregating with the disease in an autosomal recessive fashion in this family. The parents and siblings are genetically heterozygous and clinically unaffected. Functional studies suggested that the PLS-associated SPG7 mutants affect mitochondrial function when glucose is reduced. Conclusions: Compound heterozygote mutations in SPG7 are associated with adult-onset PLS, extending the spectrum of SPG7-linked neurologic diseases. Patients with the PLS phenotype should have genetic testing for paraplegin, especially when the condition is familial. PMID:27123479

  12. A quality-of-life measure for adults with primary ciliary dyskinesia: QOL-PCD.

    PubMed

    Lucas, Jane S; Behan, Laura; Dunn Galvin, Audrey; Alpern, Adrianne; Morris, Anjana M; Carroll, Mary P; Knowles, Michael R; Leigh, Margaret W; Quittner, Alexandra L

    2015-08-01

    Primary ciliary dyskinesia (PCD) is characterised by chronic suppurative lung disease, rhino-sinusitis, hearing impairment and sub-fertility. We have developed the first multidimensional measure to assess health-related quality of life (HRQoL) in adults with PCD (QOL-PCD).Following a literature review and expert panel meeting, open-ended interviews with patients investigated the impact of PCD on HRQoL in the UK and North America (n=21). Transcripts were content analysed to derive saturation matrices. Items were rated for relevance by patients (n=49). Saturation matrices, relevance scores, literature review, evaluation of existing measures, and expert opinion contributed to development of a preliminary questionnaire. The questionnaire was refined following cognitive interviews (n=18).Open-ended interviews identified a spectrum of issues unique to adults with PCD. Saturation matrices confirmed comprehensive coverage of content. QOL-PCD includes 48 items covering the following seven domains: Physical Functioning, Emotional Functioning, Treatment Burden, Respiratory and Sinus Symptoms, Ears and Hearing, Social Functioning, and Vitality and Health Perceptions. Cognitive testing confirmed that content was comprehensive and the items were well-understood by respondents.Content validity and cognitive testing supported the items and structure. QOL-PCD has been translated into other languages and is awaiting psychometric testing.

  13. Clinicopathological correlation and treatment response of primary focal segmental glomerulosclerosis in adults and adolescents

    PubMed Central

    Dhanapriya, J.; Dineshkumar, T.; Gopalakrishnan, N.; Sakthirajan, R.; Balasubramaniyan, T.

    2016-01-01

    The incidence of focal segmental glomerulosclerosis (FSGS) is approximately 10% in children <6 years, 20% in adolescents, and 20-25% in adults. A retrospective observational study was done to document clinicopathological correlation, treatment response, and risk factors in the progression of chronic kidney disease (CKD) of primary FSGS in adults and adolescents. A total of 170 patients were studied with a mean follow-up of 4.32 ± 1.2 years. FSGS not otherwise specified was the most common subtype (56%) followed by tip variant (24%). About 32% had complete remission (CR) at a mean time of 6.4 months, 23% had partial remission (PR) at a mean time of 5.7 months, and 45% had no response to steroids. Persistent nephrotic proteinuria at 3rd and 6th month and presence of interstitial fibrosis and tubular atrophy >30% in renal biopsy are the independent predictors of poor response to treatment. Presence of anemia, interstitial fibrosis, and tubular atrophy of >30% in renal biopsy and the absence of remission after treatment were the independent predictors of CKD progression. Overall renal survival was 78% at 3 years and 54% at 5 years. Renal survival difference with or without nephrotic proteinuria at onset was 39% and 69% at 5 years. Renal survival was higher in patients with normal renal function (66%) compared with those who had renal failure (42%) at 5 years. Renal survival at 5 years for CR was 69%, PR was 49%, and no remission was 42%.

  14. Changes in Young Adult Primary Care Under the Affordable Care Act

    PubMed Central

    Ford, Carol A.; French, Benjamin; Rubin, David M.

    2015-01-01

    Objectives. We sought to describe changes in young adults’ routine care and usual sources of care (USCs), according to provider specialty, after implementation of extended dependent coverage under the Affordable Care Act (ACA) in 2010. Methods. We used Medical Expenditure Panel Survey data from 2006 to 2012 to examine young adults’ receipt of routine care in the preceding year, identification of a USC, and USC provider specialties (pediatrics, family medicine, internal medicine, and obstetrics and gynecology). Results. The percentage of young adults who sought routine care increased from 42.4% in 2006 to 49.5% in 2012 (P < .001). The percentage identifying a USC remained stable at approximately 60%. Among young adults with a USC, there was a trend between 2006 and 2012 toward increasing percentages with pediatric (7.6% vs 9.1%) and family medicine (75.9% vs 80.9%) providers and declining percentages with internal medicine (11.5% vs 7.6%) and obstetrics and gynecology (5.0% vs 2.5%) providers. Conclusions. Efforts under the ACA to increase health insurance coverage had favorable effects on young adults’ use of routine care. Monitoring routine care use and USC choices in this group can inform primary care workforce needs and graduate medical education priorities across specialties. PMID:26447914

  15. Primary Care Providers’ Perspectives On Psychoactive Medication Disorders in Older Adults

    PubMed Central

    Payne, Monica; Gething, Megan; Moore, Alison A.; Reid, M. C.

    2011-01-01

    Background Compared to younger adults, older adults consume a disproportionate percentage of pain and sleep medications. Some studies have reported that psychoactive medication misuse and abuse in older populations is a significant problem. Objectives To understand primary care providers' (PCPs) perspectives regarding the extent and clinical presentations of misuse and abuse of psychoactive medications in older patients and to explore PCP’s perceived barriers to identifying affected individuals. Design Semi-structured focus groups with PCPs. Participants Seventeen physicians and five nurse practitioners from two ambulatory care practices serving older adults in New York City. Methods Six focus group discussions were audiotaped and transcribed. Two raters coded transcripts to identify recurring themes. Qualitative analysis software (QSR NVivo 8) was employed for data coding and sorting purposes. Results Although PCPs felt that only a small percentage of older patients were actively misusing or abusing their psychoactive medications (average estimate given by providers = 8%), PCPs felt that these patients placed significant time burdens on them. Perceived risk factors included psychiatric disorders, prior substance abuse history, and cognitive impairment, but many PCPs found it impossible to predict which patients were at increased risk. PCPs identified multiple barriers to identifying affected patients, including lack of communication (between provider and patient, provider and patient’s caregivers, and between different providers), nonspecific symptoms, and the lack of a clear definition of misuse and abuse. Conclusions The lack of a clear definition, absence of well-defined risk factors, and ambiguous clinical manifestations of psychoactive medication misuse and abuse present substantial barriers to diagnosis. A standard, age-appropriate definition could help PCPs to establish a diagnosis, clarify what constitutes appropriate psychoactive medication use

  16. Nutrition and Hepatocellular Cancer

    PubMed Central

    Schütte, Kerstin; Schulz, Christian; Malfertheiner, Peter

    2016-01-01

    Background Hepatocellular carcinoma (HCC) significantly contributes to the global burden of cancer. Liver cancer is the third most frequent cause of cancer-related death with HCC representing more than 90% of primary liver cancers. The majority of patients are not only affected by the malignant disease but do also suffer from chronic liver disease. Therefore, several factors impact on the prognosis of patients with HCC, including tumor-related factors, liver function and patient-related factors such as performance status and other comorbidities. The nutritional status is of high significance for the patients' performance status, the tolerance of tumor-targeting therapy and the prognosis of cancer of any type and is specially referenced in HCC. This overview is on current concepts on the role of nutritional factors in hepatocarcinogenesis and the role of nutrition in patients affected by HCC. Summary Nutritional status and composition of diet are relevant factors related to the risk of HCC. They also have an important role concerning the prognosis of patients with HCC. Besides risk factors, several macro- and micronutrient components have been found to be inversely correlated with the risk of HCC. To prevent disease progression to liver cirrhosis or HCC in patients with nonalcoholic steatohepatitis, it is crucial to optimize the metabolic state Key Message and Practical Implication Evidence from well-designed prospective interventional trials with the aim to reduce the HCC incidence or to prolong survival in patients with HCC based on nutritional modification is still to be generated. PMID:27403413

  17. Primary human adult lung epithelial cells in vitro: response to interferon-gamma and cytomegalovirus.

    PubMed Central

    Ibrahim, L; Dominguez, M; Yacoub, M

    1993-01-01

    Primary human adult lung epithelial cells (ALEC) were established in culture using the most distal parts of the lung to avoid the airways. Immunocytochemical peroxidase staining and semiquantitative flow cytometry were used to characterize the cells in conjunction with a panel of monoclonal antibodies (mAb). The cells showed a constitutive expression of major histocompatibility complex (MHC) class I antigens, patchy expression of intercellular adhesion molecule-1 (ICAM-1) and a weak patchy expression of MHC class II antigens (detected using immunocytochemical staining). Incubation of the primary ALEC with interferon-gamma (IFN-gamma) (250 U/ml) stimulated an up-regulation of the expression of these three antigens to varying degrees; expression of MHC class I antigens and ICAM-1 molecules showed an up-regulation at 10 hr after the start of the treatment, reaching a peak at 48 hr, maintaining it for the next 24 hr and then, steadily and progressively, losing it towards the end of the experiment at 96 hr. Expression of HLA-DR showed an up-regulation at 17 hr after the start of the treatment, reaching a peak at 72 hr and maintaining it for the next 24 hr. Cytomegalovirus (CMV) infection of ALEC in culture caused an up-regulation of expression of class I antigens and ICAM-1, but not DR. However, when the infected cells were incubated with IFN-gamma, an up-regulation in the expression of DR took place. Therefore, within the micro-environment of the transplanted lung the presence of cytokines (IFN-gamma) produced by infiltrating activated mononuclear cells, may render the lung epithelial cells capable of acting as antigen-presenting cells, expressing high levels of class I antigens, ICAM-1 and class II antigens, activating CD8 and CD4 cells thus playing a major part in the process of rejection of the lung allograft; themselves becoming a primary target in the process. Images Figure 1 Figure 2 PMID:8099565

  18. Primary care interventions to improve transition of youth with chronic health conditions from paediatric to adult healthcare: a systematic review

    PubMed Central

    Bhawra, Jasmin; Toulany, Alene; Cohen, Eyal; Moore Hepburn, Charlotte; Guttmann, Astrid

    2016-01-01

    Objective To determine effective interventions to improve primary care provider involvement in transitioning youth with chronic conditions from paediatric to adult care. Design Systematic review. Multiple electronic databases were searched including Ovid MEDLINE, EMBASE and Web of Science (from 1 January 1947 to 5 August 2015). Evidence quality was assessed using a 36-point scoring system for disparate study designs. Setting Studies with paediatric-to-adult transition programmes and interventions involving primary care providers or in primary care settings. Participants Youth aged 16 years and over. Outcomes Relevant outcomes were grouped into 3 main domains based on the Triple Aim Framework: experience of care, population health, cost. Results A total of 1888 unique citations were identified, yielding 3 studies for inclusion. Overall, primary care provider roles were not well defined. 2 studies used case managers to facilitate referrals to primary care, and the remaining study was the only 1 situated in a primary care setting. None of the studies examined transition in all 3 Triple Aim Framework domains. The most commonly reported outcomes were in the cost domain. Conclusions There is limited empiric evidence to guide primary care interventions to improve transition outcomes for youth with chronic conditions. Future research and policy should focus on developing and evaluating coordinated transition interventions to better integrate primary care for high need populations. PMID:27150188

  19. First-time primary caregivers' experience of caring for young adults with first-episode psychosis.

    PubMed

    McCann, Terence V; Lubman, Dan I; Clark, Eileen

    2011-03-01

    Becoming a career is associated with physical, emotional, and financial hardship, with caregivers often experiencing a maelstrom of emotions as they struggle to understand what has happened to their loved one. While the burden of caring for young people with first-episode psychosis (FEP) has been well documented, much less is known about how carers develop the strength and resilience to continue caring. This qualitative study aimed to understand the experience of 20 first-time primary caregivers of young adults with FEP. Most caregivers were female (85%, n = 17) and parents (85%, n = 17). The average length of involvement as a caregiver at an FEP service was 14.5 months. Six main themes were identified in the data, highlighting the carers' experience in supporting young adults with FEP. Caregiving is a burdensome responsibility and is characterized as a roller coaster and unpredictable experience. Caregivers often feel responsible for the young person's illness; however, eventually most come to terms with the changes that have occurred in the young person with FEP. As a consequence of the illness, the relationship between caregiver and care recipient frequently becomes closer and deeper, although it is important that they both maintain hope for the future. These findings provide important insights into the experiences of first-time caregivers of young people with FEP, with direct implications for improving the information and support given to caregivers by FEP services, as well as the development of interventions that effectively address the unique challenges caregivers face following the onset of FEP. PMID:19679716

  20. Insulin Resistance in Adult Primary Care Patients With a Surrogate Index, Guadalajara, Mexico, 2012

    PubMed Central

    Espinel-Bermúdez, María Claudia; Robles-Cervantes, José Antonio; del Sagrario Villarreal-Hernández, Liliana; Villaseñor-Romero, Juan Pablo; Hernández-González, Sandra Ofelia; González-Ortiz, Manuel; Martínez-Abundis, Esperanza; Pérez-Rubio, Karina Griselda

    2015-01-01

    Introduction Insulin resistance (IR) is a key molecular disorder related with diabetes mellitus, obesity, and cardiovascular disease. The objective of this study was to determine IR in adult primary care patients using the triglyceride/glucose (TyG) index [(Ln TG (mg/dL) × FG (mg/dL))/2]. Methods We conducted a cross-sectional secondary analysis and identified IR subjects according to the TyG index. Results There were 1500 patients included. Significant differences were found between the IR group versus the insulin-sensitive group, respectively: age (in years), 46.4 ± 9.34 versus 40.24 ± 11.27 (P < 0.001); fasting glucose (mg/dL), 99.87 ± 11.95 versus 84.62 ± 6.59 (P < 0.001); total cholesterol (mg/dL), 203.21 ± 37.38 versus 173.91 ± 33.99 (P < 0.001); triglycerides (mg/dL), 226.40 ± 96.66 versus 111.27 ± 23.44 (P < 0.001); uric acid (mg/dL), 6.09 ± 1.59 versus 4.77 ± 1.40 (P < 0.001); and TyG index, 4.96 ± 0.21 versus 4.48 ± 0.13 (P < 0.001). The cutoff of the TyG index for IR was 4.68 or greater. Conclusions The TyG index allows for early diagnosis of IR in primary health care. PMID:25503090

  1. Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy.

    PubMed

    Redei, E E; Andrus, B M; Kwasny, M J; Seok, J; Cai, X; Ho, J; Mohr, D C

    2014-09-16

    An objective, laboratory-based diagnostic tool could increase the diagnostic accuracy of major depressive disorders (MDDs), identify factors that characterize patients and promote individualized therapy. The goal of this study was to assess a blood-based biomarker panel, which showed promise in adolescents with MDD, in adult primary care patients with MDD and age-, gender- and race-matched nondepressed (ND) controls. Patients with MDD received cognitive behavioral therapy (CBT) and clinical assessment using self-reported depression with the Patient Health Questionnaire-9 (PHQ-9). The measures, including blood RNA collection, were obtained before and after 18 weeks of CBT. Blood transcript levels of nine markers of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1 and TLR7, differed significantly between participants with MDD (N=32) and ND controls (N=32) at baseline (q< 0.05). Abundance of the DGKA, KIAA1539 and RAPH1 transcripts remained significantly different between subjects with MDD and ND controls even after post-CBT remission (defined as PHQ-9 <5). The ROC area under the curve for these transcripts demonstrated high discriminative ability between MDD and ND participants, regardless of their current clinical status. Before CBT, significant co-expression network of specific transcripts existed in MDD subjects who subsequently remitted in response to CBT, but not in those who remained depressed. Thus, blood levels of different transcript panels may identify the depressed from the nondepressed among primary care patients, during a depressive episode or in remission, or follow and predict response to CBT in depressed individuals.

  2. Age–incidence patterns of primary CNS tumors in children, adolescents, and adults in England

    PubMed Central

    Arora, Ramandeep S.; Alston, Robert D.; Eden, Tim O.B.; Estlin, Edward J.; Moran, Anthony; Birch, Jillian M.

    2009-01-01

    Around 25% of all tumors in those 0–14 years of age and 9% in those 15–24 years of age involve the CNS. They are the most common cause of cancer-related deaths in both age groups. In adults 25–84 years of age, the proportion of CNS tumors is 2%; 5-year overall survival is 10%–15%; and survivors have considerable morbidity. Comprehensive up-to-date population-based incidence data on these tumors are lacking. We present incidence rates for primary CNS tumors based on data derived from the high-quality national cancer registration system in England. A total of 54,336 CNS tumors of malignant, benign, and uncertain behavior were registered across the whole of England from 1995 through 2003. The age-standardized rates for all ages (0–84 years) was 9.21 per 100,000 person-years. This is higher than previously reported for England because it includes nonmalignant CNS tumors and hence gives a more accurate picture of burden of disease. The age-standardized rates for those 0–14 years of age, 15–24 years of age, and 25–84 years of age were 3.56, 3.26, and 14.57 per 100,000 person-years, respectively. In this article, we describe the changing patterns in the epidemiology of primary CNS tumors in these three age groups with respect to sex, tumor behavior, and histology using the current WHO classification. This information will provide a reference for future studies nationally and internationally and make comparisons relevant and meaningful. PMID:19033157

  3. [A single metastasis in the carpal bones as the first clinical manifestation of a hepatocellular carcinoma].

    PubMed

    Corrales Pinzón, R; Alonso Sánchez, J M; de la Mano González, S; El Karzazi Tarazona, K

    2014-01-01

    Hepatocellular carcinoma is the most common primary tumor of the liver. Spreading outside the liver usually takes place in advanced stages of the disease, and bone is the third most common site of metastases. We present a case of hepatocellular carcinoma in which the first clinical manifestation was a single metastasis to the carpal bones. The interest of this case lies in the way this hepatocellular carcinoma manifested as well as in the unusual site of the metastasis.

  4. Misdiagnosis of primary pleomorphic rhabdomyosarcoma of the right thigh in a young adult: A case report

    PubMed Central

    Yu, Xiaolong; Yang, Yong; Zhang, Bin; Liu, Hucheng; Guo, Runsheng; Dai, Min

    2016-01-01

    Pleomorphic rhabdomyosarcoma (PRMS) is a rare type of soft tissue tumor accounting for <2% of all adult sarcomas. The present study describes a case of a 28-year-old male patient with primary PRMS of the right thigh. The patient was initially diagnosed with a schwannoma and underwent conservative therapy at a local hospital. At the 6-month follow-up, the patient reported a marked increase in the size of the mass. Finally, the patient underwent fine-needle aspiration and total tumor resection. The tumor measured 11×9×5 cm3 in size and was located in the vastus intermedius muscle. According to histological and immunohistochemical findings, a diagnosis of PRMS was confirmed by an expert pathology consultant. Postoperative follow-up at 3 months revealed no evidence of recurrent disease or residual side effects from therapy. However, it is imperative that such cases are closely monitored following surgery, in order to evaluate the long-term efficacy of the procedure, since misdiagnosis may increase the risk of recurrence and metastasis. The present case is noteworthy due to the misdiagnosis of PRMS, the large size of the mass and the young age of the patient. PMID:27588141

  5. A search for the primary abnormality in adult-onset type II citrullinemia

    SciTech Connect

    Kobayashi, Keiko; Shaheen, Nazma; Saheki, Takeyori ); Kumashiro, Ryukichi; Tanikawa, Kyuichi ); O'Brien, W.E.; Beaudet, A.L. )

    1993-11-01

    Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, the authors show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. The authors also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus. 29 refs., 1 fig., 3 tabs.

  6. Uncommon primary pelvic retroperitoneal masses in adults: a pattern-based imaging approach.

    PubMed

    Shanbhogue, Alampady K; Fasih, Najla; Macdonald, David B; Sheikh, Adnan M; Menias, Christine O; Prasad, Srinivasa R

    2012-01-01

    There is a broad spectrum of primary pelvic retroperitoneal masses in adults that demonstrate characteristic epidemiologic and histopathologic features and natural histories. These masses may be classified into five distinct subgroups using a pattern-based approach that takes anatomic distribution and certain imaging characteristics into account, allowing greater accuracy in their detection and characterization and helping to optimize patient management. The five groups are cystic (serous and mucinous epithelial neoplasms, pelvic lymphangioma, tailgut cyst, ancient schwannoma), vascular or hypervascular (solitary fibrous tumor, paraganglioma, pelvic arteriovenous malformation, Klippel-Trénaunay-Weber syndrome, extraintestinal GIST [gastrointestinal stromal tumor]), fat-containing (lipoma, liposarcoma, myelolipoma, presacral teratoma), calcified (calcified lymphocele, calcified rejected transplant kidney, rare sarcomas), and myxoid (schwannoma, plexiform neurofibroma, myxoma).Cross-sectional imaging modalities help differentiate the more common gynecologic neoplasms from more unusual masses. In particular, the tissue-specific multiplanar capability of high-resolution magnetic resonance imaging permits better tumor localization and internal characterization, thereby serving as a road map for surgery.

  7. Toxic effects of bortezomib on primary sensory neurons and Schwann cells of adult mice.

    PubMed

    Alé, Albert; Bruna, Jordi; Herrando, Mireia; Navarro, Xavier; Udina, Esther

    2015-05-01

    The proteasome inhibitor bortezomib is nowadays first line treatment for multiple myeloma. One of the most significant adverse events is peripheral neuropathy, mainly involving sensory nerve fibers that can lead to withdrawal of treatment. Here we develop an in vitro model to compare the effects of bortezomib on primary sensory neurons and Schwann cells of adult mice. We observed that sensory neurons were more susceptible to bortezomib, and their viability was reduced at a concentration of 6 nM, that only affected Schwann cell proliferation but not survival. At concentration higher than 8 nM Schwann cell viability was also compromised. Already at low concentrations, surviving neurons presented alterations in neurite outgrowth. Neurites were shorter and had dystrophic appearance, with alterations in neurofilament staining. However, neurites were able to regrow after removing bortezomib from the medium, thus indicating reversibility of the neurotoxicity. We confirmed in vivo that bortezomib produced alterations in neurofilaments at early stages of the treatment. After an accumulated dose of 2 mg/kg bortezomib, dorsal root ganglia neurons of treated animals showed accumulation of neurofilament in the soma. To evaluate if this accumulation was related with alterations in axonal transport, we tested the ability of sensory neurons to retrogradely transport a retrotracer applied at the distal nerve. Treated animals showed a lower amount of retrotracer in the soma 24 h after its application to the tibial nerve, therefore suggesting that axonal transport was affected by bortezomib.

  8. Secondary malignant neoplasms following radiotherapy for primary cancer in children and young adults.

    PubMed

    Harbron, Richard W; Feltbower, Richard G; Glaser, Adam; Lilley, John; Pearce, Mark S

    2014-04-01

    A study was conducted to investigate secondary malignant neoplasm (SMN) occurrence following radiotherapy (RT) for cancer in children and young adults, to examine the spatial distribution of SMNs in relation to the irradiated field, and to evaluate a possible role of bystander effects in SMN distribution. Forty-two SMNs were identified among 7257 subjects diagnosed with cancer while living in Yorkshire, UK. Thirty-two of these occurred in patients receiving RT. Distances between SMN locations and RT field edge were estimated along with dose at SMN site. Expected radiation-induced SMN frequency in remote tissues receiving less than 0.1 Gy was predicted using risk estimates based on atomic bombing data. After a median follow-up period of 7.58 years, patients treated with RT were at a nearly five-fold increased risk of developing a subsequent primary neoplasm than the general population in the 0-29 years age range. The most common type of secondary malignancy associated with RT was of the central nervous system (28%), followed by sarcoma (25%) and leukemia (19%). Considering only solid SMNs developing 5 years or more from treatment, the spatial distribution showed a strong pattern of proximity to the irradiated field, with 68% occurring in-field or within 8 cm of the field edge. The SMN frequency in distant tissues receiving doses of less than 0.1 Gy was low but compatible with local absorbed dose.

  9. [Primary immune thrombocytopenia in adults in Mexico: national characteristics and the relation to international literature].

    PubMed

    Meillón-García, Luis Antonio; García-Chávez, Jaime; Gómez-Almaguer, David; Gutiérrez-Espíndola, Guillermo R; Martínez-Murillo, Carlos

    2014-01-01

    In order to identify the clinical approach of a sample of Mexican hematologists for primary immune thrombocytopenia (ITP) in adults in Mexico, we applied an electronic survey via the internet to identify common practices for the diagnosis and treatment of ITP and draw a comparison between the information from these hematologists with international guidelines or the international literature. The results were analyzed using measures of central tendency. The sample was 21 medical hematologists, predominantly from Mexico City (average age: 51.4 years). A total of 66.7% of the surveyed physicians use international guidelines to make therapeutic decisions, and 43% defined ITP including the numerical concept (< 100 x 10(9)/l). We found some differences between requested clinical exams and tests indicated by the guidelines. In first-line treatment (except emergency), 91% of the participants start with prednisone and 24% use dexamethasone. Danazol is used in persistent ITP by most (41%) of the specialists. In second-line treatment, 67% would indicate splenectomy. Some differences were found between clinical practice of the hematologists in Mexico versus guidelines recommendations.

  10. Sleep time and pattern of adult individuals in primary care in an Asian urbanized community

    PubMed Central

    Tan, Ngiap Chuan; Tan, Mui Suan; Hwang, Siew Wai; Teo, Chia Chia; Lee, Zhi Kang Niccol; Soh, Jing Yao Jonathan; Koh, Yi Ling Eileen; How, Choon How

    2016-01-01

    Abstract Sleep norms vary between individuals, being affected by personal, communal, and socioeconomic factors. Individuals with sleep time which deviate from the population norm are at risks of adverse mental, cardiovascular, and metabolic health. Sleep-related issues are common agenda for consultation in primary care. This study aimed to determine the sleep time, pattern, and behavior of multiethnic Asian individuals who attended public primary care clinics in an urban metropolitan city-state. Standardized questionnaires were assistant-administered to adult Asian individuals who visited 2 local public primary care clinics in north-eastern and southern regions of Singapore. The questionnaire included questions on demographic characteristics, self-reported sleep time, patterns, and behavior and those originated from the American National Sleep Foundation Sleep Diary. The data were collated, audited, rectified, and anonymized before being analyzed by the biostatistician. Individuals with 7 h sleep time or longer were deemed getting adequate sleep. Chi-squared or Fisher exact test was used to test the association between the demographic and behavioral variables and sleep time. Next, regression analysis was performed to identify key factors associated with their sleep time. A total of 350 individuals were recruited, with higher proportion of those of Chinese ethnicity reporting adequate sleep. Almost half (48.1%) of those who slept <7 h on weekdays tended to sleep ≥7 h on weekends. More individuals who reported no difficulty falling asleep, had regular sleep hours and awakening time, tended to sleep adequately. Those who slept with children, studied, read leisurely, used computer or laptops in their bedrooms, drank caffeinated beverages or smoked had inadequate sleep. Those who perceived sufficient sleep and considered 8 h as adequate sleep time had weekday and weekend sleep adequacy. Sleep time varied according to ethnicity, employment status, personal

  11. Screening for hepatocellular carcinoma.

    PubMed

    Merican, I

    1996-03-01

    Hepatocellular carcinoma (HCC) is one of the commonest cancers in Asian males. In Malaysia, it is one of the ten most common cancers amongst the male population. Most of our patients with HCC present to us rather late and almost all die within 4 months of diagnosis. HCC occurs more commonly in patients with cirrhosis associated with hepatitis B and C infections. Screening for HCC can lead to early detection of small tumours (< 5 cm) that are more amenable to surgical resection, resulting in improved survival rates. The average 5-year survival rate for those who have undergone surgical resection is 68% (range, 22-73%). Better results are obtained with the smaller tumours (< 2 cm in diameter). Patients with chronic hepatitis B and C infection especially those who are > 45 years of age, who have concomitant cirrhosis or have a family history of HCC should be examined every 3-6 months with periodic serum alpha-fetoprotein (AFP) measurements and abdominal ultrasound examinations. Abdominal ultrasound is useful in the detection of small tumours. While mass screening for HCC is not cost-effective in countries of low incidence of HCC, screening of high risk groups may be justified in countries with a high endemicity of HBV infection. Screening for HCC in Japan, Taiwan and China appears to yield better results than those in the West. Nonetheless, primary prevention with mass hepatitis B vaccination and blood donor screening for anti-HCV is expected to make a much greater impact in the control of HCC in the years to come.

  12. Hepatocellular carcinoma: a review

    PubMed Central

    Balogh, Julius; Victor, David; Asham, Emad H; Burroughs, Sherilyn Gordon; Boktour, Maha; Saharia, Ashish; Li, Xian; Ghobrial, R Mark; Monsour, Howard P

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT) or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an aggressive cancer that occurs in the setting of cirrhosis and commonly presents in advanced stages. HCC can be prevented if there are appropriate measures taken, including hepatitis B virus vaccination, universal screening of blood products, use of safe injection practices, treatment and education of alcoholics and intravenous drug users, and initiation of antiviral therapy. Continued improvement in both surgical and nonsurgical approaches has demonstrated

  13. Economic burden to primary informal caregivers of hospitalized older adults in Mexico: a cohort study

    PubMed Central

    2013-01-01

    Background The burden of out of pocket spending for the Mexican population is high compared to other countries. Even patients insured by social security institutions have to face the cost of health goods, services or nonmedical expenses related to their illness. Primary caregivers, in addition, experience losses in productivity by taking up responsibilities in care giving activities. This situation represents a mayor economic burden in an acute care setting for elderly population. There is evidence that specialized geriatric services could represent lower overall costs in these circumstances and could help reduce these burdens. The aim of this study was to investigate economic burden differences in caregivers of elderly patients comparing two acute care services (Geriatric and Internal Medicine). Specifically, economic costs associated with hospitalization of older adults in these two settings by evaluating health care related out of pocket expenditures (OOPE), non-medical OOPE and indirect costs. Methods A comparative analysis of direct and indirect costs in hospitalised elderly patients (60-year or older) and their primary informal caregivers in two health care settings, using a prospective cohort was performed. Economic burden was measured by out of pocket expenses and indirect costs (productivity lost) due to care giving activities. The analysis included a two-part model, the first one allowing the estimation of the probability of observing any health care related and non-medical OOPE; and the second one, the positive observations or expenditures. Results A total of 210 subjects were followed during their hospital stay. Of the total number of subjects 95% reported at least one non-medical OOPE, being daily transportation the most common expense. Regarding medical OOPE, medicines were the most common expense, and the mean numbers of days without income were 4.12 days. Both OOPE and indirect costs were significantly different between type of services, with less

  14. Transcranial direct current stimulation of the primary motor cortex improves word-retrieval in older adults

    PubMed Central

    Meinzer, Marcus; Lindenberg, Robert; Sieg, Mira M.; Nachtigall, Laura; Ulm, Lena; Flöel, Agnes

    2014-01-01

    Language facilitation by transcranial direct current stimulation (tDCS) in healthy individuals has generated hope that tDCS may also allow improving language impairment after stroke (aphasia). However, current stimulation protocols have yielded variable results and may require identification of residual language cortex using functional magnetic resonance imaging (fMRI), which complicates incorporation into clinical practice. Based on previous behavioral studies that demonstrated improved language processing by motor system pre-activation, the present study assessed whether tDCS administered to the primary motor cortex (M1) can enhance language functions. This proof-of-concept study employed a sham-tDCS controlled, cross-over, within-subject design and assessed the impact of unilateral excitatory (anodal) and bihemispheric (dual) tDCS in 18 healthy older adults during semantic word-retrieval and motor speech tasks. Simultaneous fMRI scrutinized the neural mechanisms underlying tDCS effects. Both active tDCS conditions significantly improved word-retrieval compared to sham-tDCS. The direct comparison of activity elicited by word-retrieval vs. motor-speech trials revealed bilateral frontal activity increases during both anodal- and dual-tDCS compared to sham-tDCS. This effect was driven by more pronounced deactivation of frontal regions during the motor-speech task, while activity during word-retrieval trials was unaffected by the stimulation. No effects were found in M1 and secondary motor regions. Our results show that tDCS administered to M1 can improve word-retrieval in healthy individuals, thereby providing a rationale to explore whether M1-tDCS may offer a novel approach to improve language functions in aphasia. Functional magnetic resonance imaging revealed neural facilitation specifically during motor speech trials, which may have reduced switching costs between the overlapping neural systems for lexical retrieval and speech processing, thereby resulting in

  15. Primary Mature Cystıc Teratoma Mimickıng an Adrenal Mass in an Adult Male Patient

    PubMed Central

    Ener, Kemal; Aldemir, Mustafa; Isik, Evren; Irkkan, Cigdem; Kayigil, Onder

    2014-01-01

    Teratomas are bizarre neoplasms derived from embryonic tissues that are typically found only in the gonadal and sacrococcygeal regions of adults. Primary retroperitoneal teratomas are rare and present challenging management options. We report a case of a unilateral primary retroperitoneal mature cystic teratoma mimicking an adrenal mass in a 54-year-old male patient. Complete resection of the adrenal mass was performed by the flank approach by using the 11th rib resection. Because of the risk of malignancy, follow-up radiographic studies were performed to ensure the oncologic efficacy of resection. The patient has been free of recurrence for longer than 12 months. PMID:24578814

  16. Hepatocellular adenoma: An update.

    PubMed

    Vijay, Adarsh; Elaffandi, Ahmed; Khalaf, Hatem

    2015-11-01

    Hepatocellular adenomas (HCA) are rare benign liver tumors. Recent technological advancements have helped in the early identification of such lesions. However, precise diagnosis of hepatocellular incidentalomas remains challenging. Studies at the molecular level have provided new insights into the genetics and pathophysiology of these lesions. These in turn have raised questions over their existing management modalities. However, the rarity of the tumor still restricts the quality of evidence available for current recommendations and guidelines. This article provides a comprehensive review on the etiology, molecular biology, patho-physiology, clinical manifestations, and complications associated with HCA. It also elaborates on the genetic advancements, existing diagnostic tools and current guidelines for management for such lesions.

  17. Adapting evidence-based, cognitive-behavioral interventions for anxiety for use with adults in integrated primary care settings.

    PubMed

    Shepardson, Robyn L; Funderburk, Jennifer S; Weisberg, Risa B

    2016-06-01

    Evidence-based treatments for adult patients with anxiety are greatly needed within primary care settings. Psychotherapy protocols, including those for cognitive-behavioral therapy (CBT), are often disorder-specific and were developed for specialty mental health settings, rendering them infeasible in primary care. Behavioral health consultants (BHCs) integrated into primary care settings are uniquely positioned to provide anxiety treatment. However, due to the dearth of empirically supported brief treatments for anxiety, BHCs are tasked with adapting existing treatments for use in primary care, which is quite challenging due to the abbreviated format and population-based approach to care. CBT protocols are highly effective in the treatment of anxiety and fit well with the self-management emphasis of integrated primary care. We review the rationale and procedure for 6 evidence-based CBT intervention techniques (psycho-education, mindfulness and acceptance-based behavioral techniques, relaxation training, exposure, cognitive restructuring, and behavioral activation) that can be adapted for use in the brief format typical of integrated primary care. We offer tips based on our clinical experience, highlight resources (e.g., handouts, websites, apps), and discuss 2 case examples to aid BHCs in their everyday practice. Our goal is to provide BHCs with practical knowledge that will facilitate the use of evidence-based interventions to improve the treatment of anxiety in primary care settings. (PsycINFO Database Record PMID:27064434

  18. FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases

    PubMed Central

    Zannoni, Gian Franco; Improta, Giuseppina; Petrillo, Marco; Pettinato, Angela; Scambia, Giovanni; Fraggetta, Filippo

    2016-01-01

    Granulosa cell tumors (GCTs) of the ovary are uncommon neoplasms, accounting for ~5% of all malignant ovarian tumors. GCTs are a relatively homogeneous group of tumors, categorized into two distinct subtypes, juvenile GCT and adult GCT (AGCT), likely arising from a limited set of molecular events usually involving the disruption of pathways that regulate granulosa cell proliferation. In the present study, the presence of forkheadbox L2 (FOXL2) c.402C>G mutation was investigated in a series of 42 samples of primary and metastatic AGCT of the ovary. The samples consisted of 37 primary and 5 metastatic ovarian AGCTs from 37 patients. FOXL2 mutational status was evaluated using a pyrosequencing approach on 2.5-µm sections of formalin-fixed paraffin-embedded tissue. FOXL2 c.402C>G mutation was found in 33/37 (89.2%) primary AGCTs and in 4/5 (80.0%) metastases, with the molecular status of the metastases recapitulating that of the primary tumors (4 mutated cases and 1 wild-type case). Overall, FOXL2 mutation is present in the majority of primary and metastatic AGCTs, and could be used as a valid tool in the diagnosis of the disease and in cases of metastatic lesions from an unknown primary origin. Moreover the concordance of FOXL2 molecular status in primary and associated metastases suggests its early appearance and genomic stability in AGCT tumorigenesis. PMID:27446412

  19. Prevalence, diagnosis, and disease course of pertussis in adults with acute cough: a prospective, observational study in primary care

    PubMed Central

    Teepe, Jolien; Broekhuizen, Berna DL; Ieven, Margareta; Loens, Katherine; Huygen, Kris; Kretzschmar, Mirjam; de Melker, Hester; Butler, Chris C; Little, Paul; Stuart, Beth; Coenen, Samuel; Goossens, Herman; Verheij, Theo JM

    2015-01-01

    Background Most cases of adult pertussis probably remain undiagnosed. Aim To explore the prevalence, diagnosis, and disease course of acute pertussis infection in adult patients presenting with acute cough. Design and setting Prospective observational study between 2007 and 2010 in primary care in 12 European countries. Method Adults presenting with acute cough (duration of ≤28 days) were included. Bordetella pertussis infection was determined by polymerase chain reaction (from nasopharyngeal flocked swabs and sputa) and by measurement of immunoglobulin G antibodies to pertussis toxin (PT) in venous blood at day 28. An antibody titre to PT of ≥125 IU/ml or PCR positive result in a respiratory sample defined recent infection. Patients completed a symptom diary for 28 days. Results Serum and/or respiratory samples were obtained in 3074 patients. Three per cent (93/3074) had recent B. pertussis infection. Prior cough duration >2 weeks discriminated to some extent between those with and without pertussis (adjusted odds ratio 1.89, 95% confidence interval = 1.17 to 3.07; P = 0.010). Median cough duration after presentation was 17 and 12 days in patients with and without pertussis, respectively (P = 0.008). Patients with pertussis had longer duration of phlegm production (P = 0.010), shortness of breath (P = 0.037), disturbed sleep (P = 0.013) and interference with normal activities or work (P = 0.033) after presentation. Conclusion Pertussis infection plays a limited role among adults presenting with acute cough in primary care, but GPs should acknowledge the possibility of pertussis in uncomplicated lower respiratory tract infection. As in children, pertussis also causes prolonged symptoms in adults. However, pertussis is difficult to discern from other acute cough syndromes in adults at first presentation. PMID:26412843

  20. Primary adult human astrocytes as an ex vivo vehicle for beta-glucuronidase delivery in the brain.

    PubMed

    Serguera, C; Sarkis, C; Ridet, J L; Colin, P; Moullier, P; Mallet, J

    2001-06-01

    Astrocytes are a good candidate cell type for brain transplantation: They are endogenous to the CNS, they have efficient secretory machinery, and they play a major role in neuronal support. We assessed the potential of genetically modified primary adult human astrocytes as vehicles for the delivery of secreted molecules in the mammalian CNS. We report that such cells can be efficiently transduced by a recombinant adenoviral vector carrying the human beta-glucuronidase cDNA (Ad/CMV*beta-glu) and that the transduced astrocytes produce large amounts of the enzyme. Released beta-glucuronidase could be captured, in vitro, by primary neurons and astrocytes and by a neuroblastoma cell line and beta-glucuronidase-deficient fibroblasts. Following grafting into the mouse striatum, adult human astrocytes survived and expressed the transgene for at least 8 weeks. Moreover, the dosage of beta-glucuronidase activity within the grafted brains revealed high enzymatic levels at a long distance from the graft. These experiments document the grafting of engineered primary adult human astrocytes, allowing the release of a secreted therapeutic factor throughout the brain.

  1. Systematic Review of Interventions to Improve the Provision of Information for Adults with Primary Brain Tumors and Their Caregivers

    PubMed Central

    Langbecker, Danette; Janda, Monika

    2014-01-01

    Background: Adults with primary brain tumors and their caregivers have significant information needs. This review assessed the effect of interventions to improve information provision for adult primary brain tumor patients and/or their caregivers. Methods: We included randomized or non-randomized trials testing educational interventions that had outcomes of information provision, knowledge, understanding, recall, or satisfaction with the intervention, for adults diagnosed with primary brain tumors and/or their family or caregivers. PubMed, MEDLINE, EMBASE, and Cochrane Reviews databases were searched for studies published between 1980 and June 2014. Results: Two randomized controlled, 1 non-randomized controlled, and 10 single group pre–post trials enrolled more than 411 participants. Five group, four practice/process change, and four individual interventions assessed satisfaction (12 studies), knowledge (4 studies), and information provision (2 studies). Nine studies reported high rates of satisfaction. Three studies showed statistically significant improvements over time in knowledge and two showed greater information was provided to intervention than control group participants, although statistical testing was not performed. Discussion: The trials assessed intermediate outcomes such as satisfaction, and only 4/13 reported on knowledge improvements. Few trials had a randomized controlled design and risk of bias was either evident or could not be assessed in most domains. PMID:25667919

  2. Adult Visual Experience Promotes Recovery of Primary Visual Cortex from Long-Term Monocular Deprivation

    ERIC Educational Resources Information Center

    Fischer, Quentin S.; Aleem, Salman; Zhou, Hongyi; Pham, Tony A.

    2007-01-01

    Prolonged visual deprivation from early childhood to maturity is believed to cause permanent visual impairment. However, there have been case reports of substantial improvement of binocular vision in human adults following lifelong visual impairment or deprivation. These observations, together with recent findings of adult ocular dominance…

  3. An Update of the Mayo Clinic Cohort of Patients With Adult Primary Central Nervous System Vasculitis

    PubMed Central

    Salvarani, Carlo; Brown, Robert D.; Christianson, Teresa; Miller, Dylan V.; Giannini, Caterina; Huston, John; Hunder, Gene G.

    2015-01-01

    Abstract Primary central nervous system vasculitis (PCNSV) is an uncommon condition in which lesions are limited to vessels of the brain and spinal cord. Because the clinical manifestations are not specific, the diagnosis is often difficult, and permanent disability and death are frequent outcomes. This study is based on a cohort of 163 consecutive patients with PCNSV who were examined at the Mayo Clinic over a 29-year period from 1983 to 2011. The aim of the study was to define the characteristics of these patients, which represents the largest series in adults reported to date. A total of 105 patients were diagnosed by angiographic findings and 58 by biopsy results. The patients diagnosed by biopsy more frequently had at presentation cognitive dysfunction, greater cerebrospinal fluid total protein concentrations, less frequent cerebral infarcts, and more frequent leptomeningeal gadolinium-enhanced lesions on magnetic resonance imaging (MRI), along with less mortality and disability at last follow-up. The patients diagnosed by angiograms more frequently had at presentation hemiparesis or a persistent neurologic deficit or stroke, more frequent infarcts on MRI and an increased mortality. These differences were mainly related to the different size of the vessels involved in the 2 groups. Although most patients responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide and tended to improve during the follow-up period, an overall increased mortality rate was observed. Relapses occurred in one-quarter of the patients and were less frequent in patients treated with prednisone and cyclophosphamide compared with those treated with prednisone alone. The mortality rate and degree of disability at last follow-up were greater in those with increasing age, cerebral infarctions on MRI, angiographic large vessel involvement, and diagnosis made by angiography alone, but were lower in those with gadolinium-enhanced lesions on MRI and in those with

  4. Sorafenib Tosylate in Treating Patients With Liver Cancer Who Have Undergone a Liver Transplant

    ClinicalTrials.gov

    2015-03-25

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer

  5. Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care

    PubMed Central

    Peat, G; McCarney, R; Croft, P

    2001-01-01

    BACKGROUND—Osteoarthritis is the single most common cause of disability in older adults, and most patients with the condition will be managed in the community and primary care.
AIM—To discuss case definition of knee osteoarthritis for primary care and to summarise the burden of the condition in the community and related use of primary health care in the United Kingdom.
DESIGN—Narrative review.
METHOD—A literature search identified studies of incidence and prevalence of knee pain, disability, and radiographic osteoarthritis in the general population, and data related to primary care consultations. Findings from UK studies were summarised with reference to European and international studies.
RESULTS—During a one year period 25% of people over 55 years have a persistent episode of knee pain, of whom about one in six in the UK and the Netherlands consult their general practitioner about it in the same time period. The prevalence of painful disabling knee osteoarthritis in people over 55 years is 10%, of whom one quarter are severely disabled.
CONCLUSION—Knee osteoarthritis sufficiently severe to consider joint replacement represents a minority of all knee pain and disability suffered by older people. Healthcare provision in primary care needs to focus on this broader group to impact on community levels of pain and disability.

 PMID:11156538

  6. FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after Neoadjuvant Therapy in Adult Primary Bone Sarcomas

    DOE PAGES

    Benz, Matthias R.; Czernin, Johannes; Tap, William D.; Eckardt, Jeffrey J.; Seeger, Leanne L.; Allen-Auerbach, Martin S.; Dry, Sarah M.; Phelps, Michael E.; Weber, Wolfgang A.; Eilber, Fritz C.

    2010-01-01

    Purpose . Tmore » he aim of this study was to prospectively evaluate whether FDG-PET allows an accurate assessment of histopathologic response to neoadjuvant treatment in adult patients with primary bone sarcomas. Methods . Twelve consecutive patients with resectable, primary high grade bone sarcomas were enrolled prospectively. FDG-PET/CT imaging was performed prior to the initiation and after completion of neoadjuvant treatment. Imaging findings were correlated with histopathologic response. Results . Histopathologic responders showed significantly more pronounced decreases in tumor FDG-SUVmax from baseline to late follow up than non-responders ( 64 ± 19 % versus 29 ± 30 %, resp.; P = .03 ). Using a 60% decrease in tumor FDG-uptake as a threshold for metabolic response correctly classified 3 of 4 histopathologic responders and 7 of 8 histopathologic non-responders as metabolic responders and non-responders, respectively (sensitivity, 75%; specificity, 88%). Conclusion . These results suggest that changes in FDG-SUVmax at the end of neoadjuvant treatment can identify histopathologic responders and non-responders in adult primary bone sarcoma patients.« less

  7. A review of primary care interventions to improve health outcomes in adult survivors of adverse childhood experiences.

    PubMed

    Korotana, Laurel M; Dobson, Keith S; Pusch, Dennis; Josephson, Trevor

    2016-06-01

    Research has consistently demonstrated a link between the experience of adverse childhood experiences (ACEs) and adult health conditions, including mental and physical health problems. While a focus on the prevention or mitigation of adversity in childhood is an important direction of many programs, many individuals do not access support services until adulthood, when health problems may be fairly engrained. It is not clear which interventions have the strongest evidence base to support the many adults who present to services with a history of ACEs. The current review examines the evidence base for psychosocial interventions for adults with a history of ACEs. The review focuses on interventions that may be provided in primary care, as that is the setting where most patients will first present and are most likely to receive treatment. A systematic review of the literature was completed using PsycInfo and PubMed databases, with 99 studies identified that met inclusion and exclusion criteria. These studies evaluated a range of interventions with varying levels of supportive evidence. Overall, cognitive-behavioral therapies (CBT) have the most evidence for improving health problems - in particular, improving mental health and reducing health-risk behaviors - in adults with a history of ACEs. Expressive writing and mindfulness-based therapies also show promise, whereas other treatments have less supportive evidence. Limitations of the current literature base are discussed and research directions for the field are provided. PMID:27179348

  8. Evaluation of health care services provided for older adults in primary health care centers and its internal environment

    PubMed Central

    Alhamdan, Adel A.; Alshammari, Sulaiman A.; Al-Amoud, Maysoon M.; Hameed, Tariq A.; Al-Muammar, May N.; Bindawas, Saad M.; Al-Orf, Saada M.; Mohamed, Ashry G.; Al-Ghamdi, Essam A.; Calder, Philip C.

    2015-01-01

    Objectives: To evaluate the health care services provided for older adults by primary health care centers (PHCCs) in Riyadh, Kingdom of Saudi Arabia (KSA), and the ease of use of these centers by older adults. Methods: Between October 2013 and January 2014, we conducted a descriptive cross-sectional study of 15 randomly selected PHCCs in Riyadh City, KSA. The evaluation focused on basic indicators of clinical services offered and factors indicative of the ease of use of the centers by older adults. Evaluations were based upon the age-friendly PHCCs toolkit of the World Health Organization. Results: Coverage of basic health assessments (such as blood pressure, diabetes, and blood cholesterol) was generally good. However, fewer than half of the PHCCs offered annual comprehensive screening for the common age-related conditions. There was no screening for cancer. Counseling on improving lifestyle was provided by most centers. However, there was no standard protocol for counseling. Coverage of common vaccinations was poor. The layout of most PHCCs and their signage were good, except for lack of Braille signage. There may be issues of access of older adults to PHCCs through lack of public transport, limited parking opportunities, the presence of steps, ramps, and internal stairs, and the lack of handrails. Conclusions: Clinical services and the internal environment of PHCCs can be improved. The data will be useful for health-policy makers to improve PHCCs to be more age-friendly. PMID:26318467

  9. A review of primary care interventions to improve health outcomes in adult survivors of adverse childhood experiences.

    PubMed

    Korotana, Laurel M; Dobson, Keith S; Pusch, Dennis; Josephson, Trevor

    2016-06-01

    Research has consistently demonstrated a link between the experience of adverse childhood experiences (ACEs) and adult health conditions, including mental and physical health problems. While a focus on the prevention or mitigation of adversity in childhood is an important direction of many programs, many individuals do not access support services until adulthood, when health problems may be fairly engrained. It is not clear which interventions have the strongest evidence base to support the many adults who present to services with a history of ACEs. The current review examines the evidence base for psychosocial interventions for adults with a history of ACEs. The review focuses on interventions that may be provided in primary care, as that is the setting where most patients will first present and are most likely to receive treatment. A systematic review of the literature was completed using PsycInfo and PubMed databases, with 99 studies identified that met inclusion and exclusion criteria. These studies evaluated a range of interventions with varying levels of supportive evidence. Overall, cognitive-behavioral therapies (CBT) have the most evidence for improving health problems - in particular, improving mental health and reducing health-risk behaviors - in adults with a history of ACEs. Expressive writing and mindfulness-based therapies also show promise, whereas other treatments have less supportive evidence. Limitations of the current literature base are discussed and research directions for the field are provided.

  10. [Role of the general practitioner or primary care physician in the management of adult congenital heart disease].

    PubMed

    Thambo, Jean-Benoît

    2013-03-01

    Congenital heart diseases are the most common inborn defect, occurring approximately 0.8% according to the last European Union count. This rate is stable for decades. Nowadays, up to 90% of children born with congenital heart diseases underwent surgical correction and reach adulthood, gratefully to the surgery and interventional cardiology advances, in conjunction to the post-surgery and following cares improvement. Both of this facts results to a growing population of adults with congenital heart diseases, actually exceeding the infant population. This arising population will lead general practitioners and primary care physicians to face more often this kind of patient. The needed cares are specifics, regarding the typical evolutions of this pathologies, as well as because congenital heart diseases wil impact other pathologies or usual cares. The need of an extended knowledge of the adult patients with congenital heart diseases is clearly emerging, and should lead the whole medical corps to work in close network. PMID:23687765

  11. Roles of primary care physicians in managing bipolar disorders in adults.

    PubMed

    Awaluddin, A; Jali, N; Bahari, R; Jamil, Z; Haron, N

    2015-01-01

    Management of bipolar disorder (BD) is challenging due to its multiple and complex facets of presentations as well as various levels of interventions. There is also limitation of treatment accessibility especially at the primary care level. Local evidence-based clinical practice guidelines address the importance of integrated care of BD at various levels. Primary care physicians hold pertinent role in maintaining remission and preventing relapse by providing systematic monitoring of people with BD. Pharmacological treatment in particular mood stabilisers remain the most effective management with psychosocial interventions as adjunct. This paper highlights the role of primary care physicians in the management of BD.

  12. [The primary study of articulation effect on the adults with cleft palate undergoing palatopharyngoplasty

    PubMed

    Yang, Y; Yao, L H; Wang, G M; Yu, C Q

    1997-03-01

    A retrospective study was performed in 15 adults with cleft palate who operated with palato-pharyngoplasty.Using frequency spectrum analyser to describe their Chinese vowel frequency spectrum curve character.Their articulation effect after sugery was analyzed.The result shows:The excellent rate of the articulation on effect appears 46.67%.The author believes that:the palato-pharyngoplasty can be utilized as a manner to cure the adults with cleft palate and the advanced effect is needed to be continuously studied. PMID:15159955

  13. The effect of pharmacist-led interventions in optimising prescribing in older adults in primary care: A systematic review

    PubMed Central

    Riordan, David O; Walsh, Kieran A; Galvin, Rose; Sinnott, Carol; Kearney, Patricia M; Byrne, Stephen

    2016-01-01

    Objective: To evaluate studies of pharmacist-led interventions on potentially inappropriate prescribing among community-dwelling older adults receiving primary care to identify the components of a successful intervention. Data sources: An electronic search of the literature was conducted using the following databases from inception to December 2015: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, MEDLINE (through Ovid), Trip, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews, ISI Web of Science, ScienceDirect, ClinicalTrials.gov, metaRegister of Controlled Trials, ProQuest Dissertations & Theses Database (Theses in Great Britain, Ireland and North America). Review methods: Studies were included if they were randomised controlled trials or quasi-randomised studies involving a pharmacist-led intervention compared to usual/routine care which aimed to reduce potentially inappropriate prescribing in older adults in primary care. Methodological quality of the included studies was independently assessed. Results: A comprehensive literature search was conducted which identified 2193 studies following removal of duplicates. Five studies met the inclusion criteria. Four studies involved a pharmacist conducting a medication review and providing feedback to patients or their family physician. One randomised controlled trial evaluated the effect of a computerised tool that alerted pharmacists when elderly patients were newly prescribed potentially inappropriate medications. Four studies were associated with an improvement in prescribing appropriateness. Conclusion: Overall, this review demonstrates that pharmacist-led interventions may improve prescribing appropriateness in community-dwelling older adults. However, the quality of evidence is low. The role of a pharmacist working as part of a multidisciplinary primary care team requires further investigation to optimise prescribing in this group of patients. PMID

  14. Hepatocellular adenoma: An update

    PubMed Central

    Vijay, Adarsh; Elaffandi, Ahmed; Khalaf, Hatem

    2015-01-01

    Hepatocellular adenomas (HCA) are rare benign liver tumors. Recent technological advancements have helped in the early identification of such lesions. However, precise diagnosis of hepatocellular incidentalomas remains challenging. Studies at the molecular level have provided new insights into the genetics and pathophysiology of these lesions. These in turn have raised questions over their existing management modalities. However, the rarity of the tumor still restricts the quality of evidence available for current recommendations and guidelines. This article provides a comprehensive review on the etiology, molecular biology, patho-physiology, clinical manifestations, and complications associated with HCA. It also elaborates on the genetic advancements, existing diagnostic tools and current guidelines for management for such lesions. PMID:26557953

  15. How Adults' Access to Outpatient Physician Services Relates to the Local Supply of Primary Care Physicians in the Rural Southeast

    PubMed Central

    Pathman, Donald E; Ricketts, Thomas C; Konrad, Thomas R

    2006-01-01

    Objective To examine how access to outpatient medical care varies with local primary care physician densities across primary care service areas (PCSAs) in the rural Southeast, for adults as a whole and separately for the elderly and poor. Data Sources Access data from a 2002 to 2003 telephone survey of 4,311 adults living in 298 PCSAs within 150 rural counties in eight Southeastern states were linked geographically with physician practice location data from the American Medical and American Osteopathic Associations and population data from the U.S. Census. Study Design In a cross-sectional study design, we used a series of logistic regression models to assess how 26 measures of various aspects of access to outpatient physician services varied for subjects arranged into five groups based on the population-per-physician ratios of the PCSAs where they lived. Principal Findings Among adults as a whole, more individuals reported traveling over 30 minutes for outpatient care in PCSAs with more than 3,500 people per physician than in PCSAs with fewer than 1,500 people per physician (39.1 versus 18.5 percent, p<.001) and more reported travel difficulties. Otherwise, PCSA density of primary care physicians was unrelated to reported barriers to care, unrelated to people's satisfaction with care, and unrelated to indicators of people's use of services. Use rates of six recommended preventive health services varied in no consistent direction with physician densities. Among the elderly, only the proportion traveling over 30 minutes for care was greater in areas with lowest physician densities. Among subjects covered under Medicaid or uninsured, lower local physician densities were associated with longer travel time, difficulties with travel and reaching one's physician by phone, and two areas of dissatisfaction with care. Conclusions For adults as a whole in the rural South and for the elderly there, low local primary care physician densities are associated with travel

  16. The Role of National Adult Education Centre in Curriculum Development in Somalia in Selected Government Primary Adult Schools of Mogadisho. African Studies in Curriculum Development and Evaluation, No. 109.

    ERIC Educational Resources Information Center

    Bahar, Ismail F. S.

    A study of curriculum development in Somalia focused on the role of the National Adult Education Centre (NAEC) and involvement of teachers and inspectors. The sample consisted of 80 Mogadisho primary adult school teachers. Information sources were related literature, teacher questionnaires, and unstructured interviews with school inspectors,…

  17. Primary Prevention for Mental Health: A Stress Inoculation Training Course for Functioning Adults.

    ERIC Educational Resources Information Center

    Schiraldi, Glenn R.; Brown, Stephen L.

    2001-01-01

    Describes a college course that taught preventive mental health skills to adults by exploring diverse cognitive-behavioral skills that facilitate coping, are preventive in nature, and are suitable for learning by healthy individuals in educational settings. It focused on anger management, anxiety and worry management, self-esteem enhancement,…

  18. Presentation of hepatocellular antigens

    PubMed Central

    Grakoui, Arash; Crispe, Ian Nicholas

    2016-01-01

    The liver is an organ in which antigen-specific T-cell responses manifest a bias toward immune tolerance. This is clearly seen in the rejection of allogeneic liver transplants, and multiple other phenomena suggest that this effect is more general. These include tolerance toward antigens introduced via the portal vein, immune failure to several hepatotropic viruses, the lack of natural liver-stage immunity to malaria parasites, and the frequent metastasis of cancers to the liver. Here we review the mechanisms by which T cells engage with hepatocellular antigens, the context in which such encounters occur, and the mechanisms that act to suppress a full T-cell response. While many mechanisms play a role, we will argue that two important processes are the constraints on the cross-presentation of hepatocellular antigens, and the induction of negative feedback inhibition driven by interferons. The constant exposure of the liver to microbial products from the intestine may drive innate immunity, rendering the local environment unfavorable for specific T-cell responses through this mechanism. Nevertheless, tolerance toward hepatocellular antigens is not monolithic and under specific circumstances allows both effective immunity and immunopathology. PMID:26924525

  19. Environmental Exposures and Hepatocellular Carcinoma

    PubMed Central

    Wu, Hui-Chen

    2013-01-01

    Infection with hepatitis B and/or hepatitis C virus is a well-established risk factor for the development of hepatocellular carcinoma (HCC). However, it is now clear that certain occupational, environmental, and lifestyle factors also play a role in cancer development. Among these factors are smoking, alcohol consumption, workplace exposure to vinyl chloride, and exposure to polycylic aromatic hydrocarbons and aflatoxins. There is also evidence that several other chemical and infectious agents have a role in inducing HCC in humans. Epidemiologic studies and the use of biomarkers have provided essential data to demonstrate the importance of some of these factors in human risk, while animal studies have suggested that other chemicals may also play a role. Although immunization against hepatitis B virus infection remains the primary method of preventing HCC in regions of the world where this virus is a primary etiologic agent, there is currently no vaccine for hepatitis C virus. Thus, limiting exposure to other known risk factors remains an important mechanism in preventing HCC. PMID:26357611

  20. The Impact of Checking the Health of Adults with Intellectual Disabilities on Primary Care Consultation Rates, Health Promotion and Contact with Specialists

    ERIC Educational Resources Information Center

    Felce, David; Baxter, Helen; Lowe, Kathy; Dunstan, Frank; Houston, Helen; Jones, Glyn; Grey, Jill; Felce, Janet; Kerr, Michael

    2008-01-01

    Background: Studies have found that health checking in primary care led to the identification of previously unrecognized morbidity among adults with intellectual disabilities. The aim here was to evaluate whether health checking stimulated increased consultation with the general practitioner or another member of the primary care team, increased…

  1. Primary Cutaneous Lymphoma-Associated Pseudoepitheliomatous Hyperplasia Masquerading as Squamous Cell Carcinoma in a Young Adult.

    PubMed

    Ansari, Mahsa; Azmoodeh Ardalan, Farid; Najafi, Masoumeh; Goodarzi, Azadeh; Ghanadan, Alireza

    2015-12-01

    Primary cutaneous anaplastic large cell lymphoma is a T-cell malignancy with atypical CD30 positive lymphocytes. Pseudoepitheliomatous hyperplasia is an uncommon finding in primary cutaneous anaplastic large cell lymphoma, and may mimic squamous cell carcinoma as pseudomalignancy. Careful attention of a pathologist to correct diagnosis of pseudoepitheliomatous hyperplasia and its underlying causes will help physicians to avoid inappropriate management. Here, we present a 22-year-old man referred to our hospital with a solitary nodule persistent on his forearm which was diagnosed as squamous cell carcinoma in the first biopsy. The lesion recurred after two months and histopathologic and immunohistochemistry examination revealed anaplastic large cell lymphoma with florid pseudoepitheliomatous hyperplasia which masquerading as well-differentiated squamous cell carcinoma. Diagnosis of pseudoepitheliomatous hyperplasia must guide the pathologist to search for underlying causes, such as primary cutaneous lymphoma. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and this can result in inappropriate diagnosis and management. PMID:26749237

  2. Adult Primary Spinal Epidural Extraosseous Ewing's Sarcoma: A Case Report and Review of the Literature

    PubMed Central

    Thomas, Cheddhi; Modrek, Aram S.; Bayin, N. Sumru; Snuderl, Matija; Schiff, Peter B.

    2016-01-01

    Background. Extraosseous Ewing's sarcoma in the spinal epidural space is a rare malignancy, especially in adults. Case Presentation. A 40-year-old male presented with back pain and urinary hesitancy. MRI revealed a thoracic extradural mass with no osseous involvement. He underwent surgery for gross total resection of the mass, which was diagnosed as Ewing's sarcoma. He was subsequently treated with chemoradiotherapy. He remains disease-free 1 year after surgery. Review of the literature indicated only 45 previously reported cases of spinal epidural extraosseous Ewing's sarcoma in adults. Conclusions. Extraosseous Ewing's sarcoma in the spinal epidural space is a rare clinical entity that should be included in the differential for spinal epidural masses. Its treatment is multidisciplinary but frequently requires surgical intervention due to compressive neurologic symptoms. Gross total resection appears to correlate with improved outcomes. PMID:27610254

  3. Adult Primary Spinal Epidural Extraosseous Ewing's Sarcoma: A Case Report and Review of the Literature.

    PubMed

    Bustoros, Mark; Thomas, Cheddhi; Frenster, Joshua; Modrek, Aram S; Bayin, N Sumru; Snuderl, Matija; Rosen, Gerald; Schiff, Peter B; Placantonakis, Dimitris G

    2016-01-01

    Background. Extraosseous Ewing's sarcoma in the spinal epidural space is a rare malignancy, especially in adults. Case Presentation. A 40-year-old male presented with back pain and urinary hesitancy. MRI revealed a thoracic extradural mass with no osseous involvement. He underwent surgery for gross total resection of the mass, which was diagnosed as Ewing's sarcoma. He was subsequently treated with chemoradiotherapy. He remains disease-free 1 year after surgery. Review of the literature indicated only 45 previously reported cases of spinal epidural extraosseous Ewing's sarcoma in adults. Conclusions. Extraosseous Ewing's sarcoma in the spinal epidural space is a rare clinical entity that should be included in the differential for spinal epidural masses. Its treatment is multidisciplinary but frequently requires surgical intervention due to compressive neurologic symptoms. Gross total resection appears to correlate with improved outcomes. PMID:27610254

  4. A genetic platform to model sarcomagenesis from primary adult mesenchymal stem cells

    PubMed Central

    Guarnerio, Jlenia; Riccardi, Luisa; Taulli, Riccardo; Maeda, Takahiro; Wang, Guocan; Hobbs, Robin M.; Song, Min Sup; Sportoletti, Paolo; Bernardi, Rosa; Bronson, Roderick T.; Castillo-Martin, Mireia; Cordon-Cardo, Carlos; Lunardi, Andrea; Pandolfi, Pier Paolo

    2015-01-01

    The regulatory factors governing adult mesenchymal stem cells (MSCs) physiology and their tumorigenic potential are still largely unknown, which substantially delays the identification of effective therapeutic approaches for the treatment of aggressive and lethal form of MSC-derived mesenchymal tumors, such as undifferentiated sarcomas. Here we have developed a novel platform to screen and quickly identify genes and pathways responsible for adult MSCs transformation, modeled undifferentiated sarcoma in vivo, and, ultimately, tested the efficacy of targeting the identified oncopathways. Importantly, by taking advantage of this new platform, we demonstrate the key role of an aberrant LRF-DLK1-SOX9 pathway in the pathogenesis of undifferentiated sarcoma with important therapeutic implications. PMID:25614485

  5. Adult Primary Spinal Epidural Extraosseous Ewing's Sarcoma: A Case Report and Review of the Literature

    PubMed Central

    Thomas, Cheddhi; Modrek, Aram S.; Bayin, N. Sumru; Snuderl, Matija; Schiff, Peter B.

    2016-01-01

    Background. Extraosseous Ewing's sarcoma in the spinal epidural space is a rare malignancy, especially in adults. Case Presentation. A 40-year-old male presented with back pain and urinary hesitancy. MRI revealed a thoracic extradural mass with no osseous involvement. He underwent surgery for gross total resection of the mass, which was diagnosed as Ewing's sarcoma. He was subsequently treated with chemoradiotherapy. He remains disease-free 1 year after surgery. Review of the literature indicated only 45 previously reported cases of spinal epidural extraosseous Ewing's sarcoma in adults. Conclusions. Extraosseous Ewing's sarcoma in the spinal epidural space is a rare clinical entity that should be included in the differential for spinal epidural masses. Its treatment is multidisciplinary but frequently requires surgical intervention due to compressive neurologic symptoms. Gross total resection appears to correlate with improved outcomes.

  6. Comparative effects of contraction and angiotensin II on growth of adult feline cardiocytes in primary culture

    NASA Technical Reports Server (NTRS)

    Wada, H.; Zile, M. R.; Ivester, C. T.; Cooper, G. 4th; McDermott, P. J.

    1996-01-01

    The purposes of this study were 1) to determine whether angiotensin II causes growth of adult feline cardiocytes in long-term culture, 2) to compare the growth effects of angiotensin II with those resulting from electrically stimulated contraction, and 3) to determine whether the anabolic effects of contraction are exerted via the angiotensin type 1 receptor. Adult feline cardiocytes were cultured on laminin-coated trays in a serum-free medium. Cardiocytes were either electrically stimulated to contract (1 Hz, 5-ms pulse duration, alternating polarity) or were nonstimulated and quiescent. Quiescent cells were studied as controls and after treatment with angiotensin II (10(-8) M), losartan (10(-6) M; an angiotensin type 1-receptor antagonist), or angiotensin II plus losartan. Contracting cells were studied in the presence and absence of angiotensin II or losartan. In quiescent cardiocytes, angiotensin II treatment on day 7 significantly increased protein synthesis rates by 22% and protein content per cell by 17%. The effects of angiotensin II were completely blocked by losartan. Electrically stimulated contraction on days 4 and 7 in culture significantly increased protein synthesis rate by 18 and 38% and protein content per cell by 19 and 46%, respectively. Angiotensin II treatment did not further increase protein synthesis rate or protein content in contracting cardiocytes. Furthermore, losartan did not block the anabolic effects of contraction on protein synthesis rates or protein content. In conclusion, angiotensin II can exert a modest anabolic effect on adult feline cardiocytes in culture. In contracting feline cardiocytes, angiotensin II has no effect on growth. Growth caused by electrically stimulated contraction occurs more rapidly and is greater in magnitude than that caused by angiotensin II. Growth of contracting adult feline cardiocytes is not dependent on activation of the angiotensin receptor.

  7. A Systematic Review of Depression Treatments in Primary Care for Latino Adults

    ERIC Educational Resources Information Center

    Cabassa, Leopoldo J.; Hansen, Marissa C.

    2007-01-01

    Objective: A systematic literature review of randomized clinical trials (RCTs) assessing depression treatments in primary care for Latinos is conducted. The authors rate the methodological quality of studies, examine cultural and linguistic adaptations, summarize clinical outcomes and cost-effectiveness findings, and draw conclusions for improving…

  8. Real-life management of primary immune thrombocytopenia (ITP) in adult patients and adherence to practice guidelines.

    PubMed

    Lozano, María Luisa; Revilla, N; Gonzalez-Lopez, T J; Novelli, S; González-Porras, J R; Sánchez-Gonzalez, B; Bermejo, N; Pérez, S; Lucas, F J; Álvarez, M T; Arilla, M J; Perera, M; do Nascimento, J; Campos, R M; Casado, L F; Vicente, V

    2016-06-01

    Very few data exist on the management of adult patients diagnosed with primary immune thrombocytopenia (ITP). The objectives of this study were to describe the diagnostic and treatment patterns for ITP and to compare the findings to recent ITP guidelines. We retrospectively analyzed the medical records of adult ITP patients diagnosed with primary ITP between January 2011 and June 2012 and examined whether management strategies were consistent or not with eight recent guideline-recommended practices. Overall, median age at the diagnosis of the disease (n = 101) was 58 years and median platelet count 12 × 10(9)/L with 75.2 % of patients having symptoms of ITP. The study perceived two major shortcomings in the diagnostic approach: (1) failure to perform peripheral blood film examination in 22.8 % of patients, a test that is mandatory by all guidelines, and (2) ordinary bone marrow assessment in more than half of the patients at diagnosis (50.5 %), a test not routinely recommended by guidelines. Low appropriateness in therapeutic management of patients included (1) unjustified use of intravenous immunoglobulin in the absence of bleeding in 54.8 % of patients and (2) splenectomy not being deferred until 6-12 months from diagnosis (median 161 days). Data also reflect a trend towards the early use of thrombopoietin receptor agonists in the treatment of patients who are refractory to any first-line therapy. We have recognized important areas of inapropriateness in the diagnostic and therapeutic management of adult ITP patients. Compliance with established guidelines should be encouraged in order to improve patient outcomes. PMID:27098812

  9. Comparison of quadriceps strength and handgrip strength in their association with health outcomes in older adults in primary care.

    PubMed

    Chan, On Ying A; van Houwelingen, Anne H; Gussekloo, Jacobijn; Blom, Jeanet W; den Elzen, Wendy P J

    2014-01-01

    Sarcopenia is thought to play a major role in the functional impairment that occurs with old age. In clinical practice, sarcopenia is often determined by measuring handgrip strength. Here, we compared the lower limb quadriceps strength to the handgrip strength in their association with health outcomes in older adults in primary care. Our study population consisted of older adults (n = 764, 68.2% women, median age 83) that participated in the Integrated Systemic Care for Older People (ISCOPE) study. Participants were visited at baseline to measure quadriceps strength and handgrip strength. Data on health outcomes were obtained at baseline and after 12 months (including life satisfaction, disability in daily living, GP contact-time and hospitalization). Quadriceps strength and handgrip strength showed a weak association (β = 0.42 [95% CI 0.33-0.50]; R (2) = 0.17). Quadriceps strength and handgrip strength were independently associated with health outcomes at baseline, including quality of life, disability in daily living, GP contact-time, hospitalization, and gait speed. Combined weakness of the quadriceps and handgrip distinguished a most vulnerable subpopulation that presented with the poorest health outcomes. At follow-up, handgrip strength showed an association with quality of life (β = 0.05; P = 0.002) and disability in daily living (β = -0.5; P = 0.004). Quadriceps weakness did not further contribute to the prediction of the measured health outcomes. We conclude that quadriceps strength is only moderately associated with handgrip strength in an older population and that the combination of quadriceps strength and handgrip strength measurements may aid in the identification of older adults in primary care with the poorest health outcomes. In the prediction of poor health outcomes, quadriceps strength measurements do not show an added value to the handgrip strength.

  10. Primary and Specialty Medical Care Among Ethnically Diverse, Older Rural Adults With Type 2 Diabetes: The ELDER Diabetes Study

    PubMed Central

    Bell, Ronny A.; Quandt, Sara A.; Arcury, Thomas A.; Snively, Beverly M.; Stafford, Jeanette M.; Smith, Shannon L.; Skelly, Anne H.

    2006-01-01

    Purpose Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes. Methods Data were drawn from a cross-sectional face-to-face survey of randomly selected African American (n = 220), Native American (n = 181), and white (n = 297) Medicare beneficiaries ≥65 years old with diabetes in 2 rural counties in central North Carolina. Participants were asked about utilization of a primary care doctor and of specialists (nutritionist, diabetes specialist, eye doctor, bladder specialist, kidney specialist, heart specialist, foot specialist) in the past year. Findings Virtually all respondents (99.0%) reported having a primary care doctor and seeing that doctor in the past year. About 42% reported seeing a doctor for diabetes-related care. On average, participants reported seeing 2 specialists in the past year, and 54% reported seeing >1 specialist. Few reported seeing a diabetes specialist (5.7%), nutritionist (10.9%), or kidney specialist (17.5%). African Americans were more likely than others to report seeing a foot specialist (P<.01), while men were more likely than women to have seen a bladder specialist (P =.02), kidney specialist (P =.001), and heart specialist (P =.004), after adjusting for potential confounders. Predictors of the number of specialists seen include gender, education, poverty status, diabetes medication use, and self-rated health. Conclusions These data indicate low utilization of specialty diabetes care providers across ethnic groups and reflect the importance of primary care providers in diabetes care in rural areas. PMID:16092292

  11. Challenges in Identifying and Managing Attention-Deficit/Hyperactivity Disorder in Adults in the Primary Care Setting: A Review of the Literature

    PubMed Central

    Mattingly, Gregory

    2010-01-01

    Objective: To examine how to screen for and establish a correct diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults and to identify the outcomes associated with untreated ADHD. Data Sources: PubMed was searched using the key words ADHD, adult, diagnosis, and primary care from the years 1999 to 2009. Study Selection: This search produced 50 publications. Data Extraction: Publications were screened for data specific to the diagnosis or management of adult patients with ADHD in the primary care setting. Data Synthesis: The estimated prevalence of ADHD in adults throughout the United States is 4.4% or approximately 10 million adults. Adults with ADHD by definition must experience impairment from the symptoms of ADHD in at least 2 areas of their life. Despite significant impairment, only 1 in 10 adults with ADHD have received ADHD treatment within the past year. Given the high rates of undertreatment, primary care physicians, who provide much of the general adult mental health care in the United States, are increasingly charged with making the diagnosis of ADHD in adults. ADHD symptoms are often masked by comorbid psychiatric conditions or patient adaptations such as choice of occupation. One of the ADHD assessment tools, a short 6-item screener, can simplify identification and management of ADHD in adults and help identify which patients may require further evaluation. Conclusions: Primary care physicians should consult with other members of the health care community such as psychiatrists and psychologists when necessary, but should also develop a level of comfort with diagnosing and treating ADHD. PMID:21494335

  12. Corticosteroid Risk Function of Severe Infection in Primary Immune Thrombocytopenia Adults. A Nationwide Nested Case-Control Study.

    PubMed

    Moulis, Guillaume; Palmaro, Aurore; Sailler, Laurent; Lapeyre-Mestre, Maryse

    2015-01-01

    Corticosteroid (CS)-related infection risk in immune thrombocytopenia (ITP) is unknown. The aim of this study was to assess the adjusted CS risk function of severe infection in persistent or chronic primary ITP adults. We designed a nested case-control study in the FAITH cohort. This cohort is built through the French national health insurance database named SNIIRAM and includes all treated incident persistent or chronic primary ITP adults in France (ENCePP n°4574). Patients who entered the FAITH cohort between 2009 and 2012 were eligible (n = 1805). Cases were patients with infection as primary diagnosis code during hospitalization. Index date was the date of first hospitalization for infection. A 2:1 matching was performed on age and entry date in the cohort. Various CS exposure time-windows were defined: current user, exposure during the 1/3/6 months preceding index date and from the entry date. CS doses were converted in prednisone equivalent (PEQ). The cumulative CS doses were averaged in each time-window to obtain daily PEQ dosages. Each CS exposure definition was assessed using multivariate conditional regression models. During the study period, 161 cases (9 opportunistic) occurred. The model with the best goodness of fit was CS exposure during the month before the index date (OR: 2.48, 95% CI: 1.61-3.83). The dose-effect relation showed that the risk existed from averaged daily doses ≥5 mg PEQ (vs. <5 mg: 2.09, 95% CI: 1.17-3.71). The risk of infection was mainly supported by current or recent exposure to CS, even with low doses.

  13. Corticosteroid Risk Function of Severe Infection in Primary Immune Thrombocytopenia Adults. A Nationwide Nested Case-Control Study

    PubMed Central

    Moulis, Guillaume; Palmaro, Aurore; Sailler, Laurent; Lapeyre-Mestre, Maryse

    2015-01-01

    Corticosteroid (CS)-related infection risk in immune thrombocytopenia (ITP) is unknown. The aim of this study was to assess the adjusted CS risk function of severe infection in persistent or chronic primary ITP adults. We designed a nested case-control study in the FAITH cohort. This cohort is built through the French national health insurance database named SNIIRAM and includes all treated incident persistent or chronic primary ITP adults in France (ENCePP n°4574). Patients who entered the FAITH cohort between 2009 and 2012 were eligible (n = 1805). Cases were patients with infection as primary diagnosis code during hospitalization. Index date was the date of first hospitalization for infection. A 2:1 matching was performed on age and entry date in the cohort. Various CS exposure time-windows were defined: current user, exposure during the 1/3/6 months preceding index date and from the entry date. CS doses were converted in prednisone equivalent (PEQ). The cumulative CS doses were averaged in each time-window to obtain daily PEQ dosages. Each CS exposure definition was assessed using multivariate conditional regression models. During the study period, 161 cases (9 opportunistic) occurred. The model with the best goodness of fit was CS exposure during the month before the index date (OR: 2.48, 95% CI: 1.61–3.83). The dose-effect relation showed that the risk existed from averaged daily doses ≥5 mg PEQ (vs. <5 mg: 2.09, 95% CI: 1.17–3.71). The risk of infection was mainly supported by current or recent exposure to CS, even with low doses. PMID:26559054

  14. Corticosteroid Risk Function of Severe Infection in Primary Immune Thrombocytopenia Adults. A Nationwide Nested Case-Control Study.

    PubMed

    Moulis, Guillaume; Palmaro, Aurore; Sailler, Laurent; Lapeyre-Mestre, Maryse

    2015-01-01

    Corticosteroid (CS)-related infection risk in immune thrombocytopenia (ITP) is unknown. The aim of this study was to assess the adjusted CS risk function of severe infection in persistent or chronic primary ITP adults. We designed a nested case-control study in the FAITH cohort. This cohort is built through the French national health insurance database named SNIIRAM and includes all treated incident persistent or chronic primary ITP adults in France (ENCePP n°4574). Patients who entered the FAITH cohort between 2009 and 2012 were eligible (n = 1805). Cases were patients with infection as primary diagnosis code during hospitalization. Index date was the date of first hospitalization for infection. A 2:1 matching was performed on age and entry date in the cohort. Various CS exposure time-windows were defined: current user, exposure during the 1/3/6 months preceding index date and from the entry date. CS doses were converted in prednisone equivalent (PEQ). The cumulative CS doses were averaged in each time-window to obtain daily PEQ dosages. Each CS exposure definition was assessed using multivariate conditional regression models. During the study period, 161 cases (9 opportunistic) occurred. The model with the best goodness of fit was CS exposure during the month before the index date (OR: 2.48, 95% CI: 1.61-3.83). The dose-effect relation showed that the risk existed from averaged daily doses ≥5 mg PEQ (vs. <5 mg: 2.09, 95% CI: 1.17-3.71). The risk of infection was mainly supported by current or recent exposure to CS, even with low doses. PMID:26559054

  15. Non-viral causes of hepatocellular carcinoma

    PubMed Central

    Blonski, Wojciech; Kotlyar, David S; Forde, Kimberly A

    2010-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and represents an international public health concern as one of the most deadly cancers worldwide. The main etiology of HCC is chronic infection with hepatitis B and hepatitis C viruses. However, there are other important factors that contribute to the international burden of HCC. Among these are obesity, diabetes, non-alcoholic steatohepatitis and dietary exposures. Emerging evidence suggests that the etiology of many cases of HCC is in fact multifactorial, encompassing infectious etiologies, comorbid conditions and environmental exposures. Clarification of relevant non-viral causes of HCC will aid in preventative efforts to curb the rising incidence of this disease. PMID:20677332

  16. Suicide risk in older adults: evaluating models of risk and predicting excess zeros in a primary care sample.

    PubMed

    Cukrowicz, Kelly C; Jahn, Danielle R; Graham, Ryan D; Poindexter, Erin K; Williams, Ryan B

    2013-11-01

    Research is needed that examines theory-based risk factors for suicide in older adults. The interpersonal theory of suicide (Joiner, 2005; Van Orden et al., 2010) provides specific hypotheses regarding variables that contribute to the development and variability in death ideation and suicide ideation; however, data suggest that older adults may not report suicide ideation in research settings or to treatment providers even when they experience it (Heisel et al., 2006). The purpose of this study was to test theory-based predictions regarding variables that contribute to death ideation (i.e., a passive wish to die) and suicide ideation in older adults. This study introduces the application of zero-inflated negative binomial regression (ZINB) to the study of suicidal behavior. ZINB was used to test theory-based predictions, while also testing a hypothesis regarding variables associated with denial of suicide ideation among participants who endorsed risk factors associated with suicide risk. Participants included 239 adults aged 60 and older recruited from primary care clinics who completed a variety of self-report instruments. The results of this study indicated that perceived burdensomeness and hopelessness were significantly associated with variability in death ideation. Additional results indicated that elevated scores on thwarted belonging, the interaction between perceived burdensomeness and hopelessness, and the interaction between thwarted belonging and perceived burdensomeness were associated with a significant reduction in the probability of a participant being a suicide ideator. These results offer substantial support for the interpersonal theory of suicide. The implications of these findings are discussed. PMID:24364604

  17. Predictors of treatment satisfaction among older adults with anxiety in a primary care psychology program.

    PubMed

    Hundt, Natalie E; Armento, Maria E A; Porter, Bennett; Cully, Jeffrey A; Kunik, Mark E; Stanley, Melinda

    2013-04-01

    Increasing numbers of patients are treated in integrated primary care mental health programs. The current study examined predictors of satisfaction with treatment in patients from a randomized clinical trial of late-life generalized anxiety disorder (GAD) in primary care. Higher treatment satisfaction was associated with receiving CBT rather than enhanced usual care. Treatment credibility, treatment expectancies, social support, and improvements in depression and anxiety symptoms predicted higher treatment satisfaction in the total sample. In the CBT group, only credibility and adherence with treatment predicted satisfaction. This suggests that older patients receiving CBT who believe more strongly in the treatment rationale and follow the therapist's recommendations more closely are likely to report satisfaction at the end of treatment. In addition, this study found that adherence mediated the relationship between treatment credibility and treatment satisfaction. In other words, patients' perceptions that the treatment made sense for them led to greater treatment adherence which then increased their satisfaction with treatment. PMID:23434724

  18. Primary retroperitoneal teratoma in an adult: ultrasonographic, computer tomographic and magnetic resonance imaging demonstrations.

    PubMed

    Hirano, S; Kawaguchi, S; Mikawa, I; Karino, T; Kitagawa, K; Saito, K

    1988-11-01

    A 25-year-old male patient with a primary retroperitoneal teratoma is described. The chief complaint was right hypochondralgia during exercise for seven days. Various diagnostic imagings disclosed an expansive, heterogeneous and fat-rich mass associated with multiple cystic lesions in the right suprarenal fossa. Sagittal, transaxial and coronal magnetic resonance imaging scan visualized the extent and character of the tumor very clearly. Histological examination of the tumor removed through a thoracoabdominal approach showed cystic teratoma with out malignant transformations.

  19. Office-Based Case Finding for Chronic Obstructive Pulmonary Disease in Older Adults in Primary Care.

    PubMed

    Lee, Linda; Patel, Tejal; Hillier, Loretta M; Milligan, James

    2016-01-01

    Background. Chronic Obstructive Pulmonary Disease (COPD) is underdiagnosed in primary care. Aim. To explore the utility of proactive identification of COPD in patients 75 years of age and older in a Canadian primary care setting. Methods. Canadian Thoracic Society (CTS) screening questions were administered to patients with a smoking history of 20 pack-years or more; those with a positive screen were referred for postbronchodilator spirometry. Results. A total of 107 patients (21%), of 499 screened, had a 20-pack-year smoking history; 105 patients completed the CTS screening. Forty-four (42%) patients were positive on one or more questions on the screening; significantly more patients with a previous diagnosis of COPD (64%) were positive on the CTS compared to those without a previous diagnosis of COPD (30%). Of those who were not previously diagnosed with COPD (N = 11), four (36%) were newly diagnosed with COPD. Conclusion. A systematic two-stage method of screening for COPD, using CTS screening questions followed by spirometric confirmation, is feasible in the context of a busy primary care setting. More research is needed to assess the value of restricting screening to patients with a smoking history of 20 pack-years and on the sensitivity and specificity of these measures. PMID:27445513

  20. Primary Care Opportunities to Prevent Unintentional Home Injuries: A Focus on Children and Older Adults

    PubMed Central

    McDonald, Eileen M.; Mack, Karin; Shields, Wendy C.; Lee, Robin P.; Gielen, Andrea C.

    2016-01-01

    Unintentional injuries are a persistent public health problem in the United States. A new health care landscape has the potential to create a clinical environment that fosters greater involvement by health care providers in injury prevention. The aim of this article is to provide evidence supporting the need for engagement by primary care providers in unintentional home injury prevention along with examples of how this could be accomplished. We know a great deal about what population groups are at risk for certain types of injuries. We also know that many injuries can be prevented through policies, programs, and resources that ensure safe environments and promote safe behaviors. For example, the Centers for Disease Control and Prevention’s STEADI (Stopping Elderly Accidents, Deaths, and Injuries) initiative comprises clinical decision support tools and educational materials for health care providers. Two effective interventions that have demonstrated a reduction in falls among children are the redesign of baby walkers (engineering) and the mandated use of window guards (enforcement). Primary care clinicians can play a key role in promoting their patient’s safety. Taken collectively, a focused attention on preventing unintentional home injuries by primary care providers can contribute to the reduction of injuries and result in optimal health for all. PMID:27141210

  1. Office-Based Case Finding for Chronic Obstructive Pulmonary Disease in Older Adults in Primary Care

    PubMed Central

    Lee, Linda

    2016-01-01

    Background. Chronic Obstructive Pulmonary Disease (COPD) is underdiagnosed in primary care. Aim. To explore the utility of proactive identification of COPD in patients 75 years of age and older in a Canadian primary care setting. Methods. Canadian Thoracic Society (CTS) screening questions were administered to patients with a smoking history of 20 pack-years or more; those with a positive screen were referred for postbronchodilator spirometry. Results. A total of 107 patients (21%), of 499 screened, had a 20-pack-year smoking history; 105 patients completed the CTS screening. Forty-four (42%) patients were positive on one or more questions on the screening; significantly more patients with a previous diagnosis of COPD (64%) were positive on the CTS compared to those without a previous diagnosis of COPD (30%). Of those who were not previously diagnosed with COPD (N = 11), four (36%) were newly diagnosed with COPD. Conclusion. A systematic two-stage method of screening for COPD, using CTS screening questions followed by spirometric confirmation, is feasible in the context of a busy primary care setting. More research is needed to assess the value of restricting screening to patients with a smoking history of 20 pack-years and on the sensitivity and specificity of these measures. PMID:27445513

  2. Violence victimization after HIV infection in a US probability sample of adult patients in primary care.

    PubMed Central

    Zierler, S; Cunningham, W E; Andersen, R; Shapiro, M F; Nakazono, T; Morton, S; Crystal, S; Stein, M; Turner, B; St Clair, P; Bozzette, S A

    2000-01-01

    OBJECTIVES: This study estimated the proportion of HIV-infected adults who have been assaulted by a partner or someone important to them since their HIV diagnosis and the extent to which they reported HIV-seropositive status as a cause of the violence. METHODS: Study participants were from a nationally representative probability sample of 2864 HIV-infected adults who were receiving medical care and were enrolled in the HIV Costs and Service Utilization Study. All interviews (91% in person, 9% by telephone) were conducted with computer-assisted personal interviewing instruments. Interviews began in January 1996 and ended 15 months later. RESULTS: Overall, 20.5% of the women, 11.5% of the men who reported having sex with men, and 7.5% of the heterosexual men reported physical harm since diagnosis, of whom nearly half reported HIV-seropositive status as a cause of violent episodes. CONCLUSIONS: HIV-related care is an appropriate setting for routine assessment of violence. Programs to cross-train staff in antiviolence agencies and HIV care facilities need to be developed for men and women with HIV infection. PMID:10667181

  3. Infections of neonatal and adult mice with murine CMV HaNa1 strain upon oronasal inoculation: New insights in the pathogenesis of natural primary CMV infections.

    PubMed

    Xiang, Jun; Zhang, Shunchuan; Nauwynck, Hans

    2016-01-01

    In healthy individuals, naturally acquired infections of human cytomegalovirus (HCMV) are generally asymptomatic. Animal models mimicking the natural primary HCMV infections in infants and adults are scarce. Here, neonatal and adult BALB/c mice were inoculated oronasally with a Belgian isolate HaNa1 of murine cytomegalovirus (MCMV). None of the mice showed clinical symptoms. In neonatal mice, a typical systemic infection occurred. In adult mice, viral replication was restricted to the nasal mucosa and submandibular glands. Infectious virus was not detected in trachea, oral mucosa, pharynx, esophagus, small intestines of both neonatal and adult mice at all time points. Nose was demonstrated to be the entry site. Double immunofluorescence staining showed that in nose infected cells were olfactory neurons and sustentacular cells in olfactory epithelium and were macrophages and dendritic cells in nasopharynx-associated lymphoid tissues (NALT). Neonatal and adult mice developed similar antibody response pattern, though former magnitude was lower. In summary, we have established intranasal (without anesthesia) infections of neonatal and adult mice with murine CMV HaNa1 strain, which mimic the range and extent of virus replication during natural primary HCMV infections in healthy infants and adults. These findings might bring new insights in the pathogenesis of natural primary CMV infections. PMID:26474525

  4. Primary Intra-Abdominal Rhabdomyosarcoma in an Adult: an Unusual Presentation and Review of Literature.

    PubMed

    Yadav, Sanjay Kumar; Sinha, Dipendra Kumar; Ahmed, Aftab; Azhar, T; Sinha, Mini

    2015-06-01

    Rhabdomyosarcomas, the commonest soft tissue sarcoma in paediatric age group, represent 5-10 % of all solid tumors in childhood. These tumors are rare in adult population. There are sporadic case reports of intra-abdominal rhabdomyosarcoma, but mostly in paediatric age group. Here we are reporting an unsual case of intra abdominal rhabdomyosarcoma in an elderly which presented with acute intestinal obstruction. CECT abdomen showed a solid mass in retroperitoneum compressing adjacent bowel loops. Upon emergency exploratory laparotomy a hard mass was found to be compressing the ascending colon and infiltrating into duodenum, pancreas and liver. No specific organ of origin could be identified. Biopsy was taken, as the mass was unresectable and ileostomy was done. Histopthological examination revealed embryonal rhabdomyosarcoma. Rarity of this disease and unusual presentation prompted us to report this case. PMID:26405418

  5. Adult-onset nemaline myopathy in a dog presenting with persistent atrial standstill and primary hypothyroidism.

    PubMed

    Nakamura, R K; Russell, N J; Shelton, G D

    2012-06-01

    A nine-year-old neutered female mixed breed dog presented for evaluation following a five-day history of lethargy, inappetence, weakness, abdominal distension and generalised muscle atrophy. Persistent vatrial standstill with a junctional rhythm was identified on electrocardiogram. Echocardiogram identified moderate dilation of all cardiac chambers and mild thickening of the mitral and tricuspid valves. Serology was negative for Neospora caninum and Toxoplasma gondii. Permanent pacemaker implantation was performed in addition to endomyocardial and skeletal muscle biopsies. Cryosections from the biceps femoris muscle showed numerous nemaline rod bodies while endomyocardial biopsies were possibly consistent with end-stage myocarditis. Rod bodies have rarely been reported in the veterinary literature. To the authors' knowledge, this is the first report of adult-onset nemaline rod myopathy and hypothyroidism with concurrent cardiac disease in a dog. PMID:22647214

  6. Characterizing Adults Receiving Primary Medical Care in New York City: Implications for Using Electronic Health Records for Chronic Disease Surveillance

    PubMed Central

    Romo, Matthew L.; Lurie-Moroni, Elizabeth; Perlman, Sharon E.; Newton-Dame, Remle; Thorpe, Lorna E.; McVeigh, Katharine H.

    2016-01-01

    Introduction Electronic health records (EHRs) from primary care providers can be used for chronic disease surveillance; however, EHR-based prevalence estimates may be biased toward people who seek care. This study sought to describe the characteristics of an in-care population and compare them with those of a not-in-care population to inform interpretation of EHR data. Methods We used data from the 2013–2014 New York City Health and Nutrition Examination Survey (NYC HANES), considered the gold standard for estimating disease prevalence, and the 2013 Community Health Survey, and classified participants as in care or not in care, on the basis of their report of seeing a health care provider in the previous year. We used χ2 tests to compare the distribution of demographic characteristics, health care coverage and access, and chronic conditions between the 2 populations. Results According to the Community Health Survey, approximately 4.1 million (71.7%) adults aged 20 or older had seen a health care provider in the previous year; according to NYC HANES, approximately 4.7 million (75.1%) had. In both surveys, the in-care population was more likely to be older, female, non-Hispanic, and insured compared with the not-in-care population. The in-care population from the NYC HANES also had a higher prevalence of diabetes (16.7% vs 6.9%; P < .001), hypercholesterolemia (35.7% vs 22.3%; P < .001), and hypertension (35.5% vs 26.4%; P < .001) than the not-in-care population. Conclusion Systematic differences between in-care and not-in-care populations warrant caution in using primary care data to generalize to the population at large. Future efforts to use primary care data for chronic disease surveillance need to consider the intended purpose of data collected in these systems as well as the characteristics of the population using primary care. PMID:27126554

  7. UNIQUE GENOMIC PROFILE OF FIBROLAMELLAR HEPATOCELLULAR CARCINOMA

    PubMed Central

    Cornella, Helena; Alsinet, Clara; Sayols, Sergi; Zhang, Zhongyang; Hao, Ke; Cabellos, Laia; Hoshida, Yujin; Villanueva, Augusto; Thung, Swan; Ward, Stephen C.; Rodriguez-Carunchio, Leonardo; Vila-Casadesús, Maria; Imbeaud, Sandrine; Lachenmayer, Anja; Quaglia, Alberto; Nagorney, David M.; Minguez, Beatriz; Carrilho, Flair; Roberts, Lewis R.; Waxman, Samuel; Mazzaferro, Vincenzo; Schwartz, Myron; Esteller, Manel; Heaton, Nigel D.; Zucman-Rossi, Jessica; Llovet, Josep M.

    2015-01-01

    Background & Aims Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer that develops in children and young adults without cirrhosis. Little is known about its pathogenesis, and it can only be treated with surgery. We performed an integrative genomic analysis of a large series of patients with FLC to identify associated genetic factors. Methods Using 78 clinically annotated FLC samples, we performed whole-transcriptome (n=58), single-nucleotide polymorphism array (n=41), and next-generation sequencing (n=48) analyses; we also assessed the prevalence of the DNAJB1–PRKACA fusion transcript associated with this cancer (n=73). We performed class discovery using non-negative matrix factorization, and functional annotation using gene set enrichment analyses, nearest template prediction, ingenuity pathway analyses, and immunohistochemistry. The genomic identification of significant targets in cancer algorithm was used to identify chromosomal aberrations, MuTect and VarScan2 were used to identify somatic mutations, and the random survival forest was used to determine patient prognoses. Findings were validated in an independent cohort. Results Unsupervised gene expression clustering revealed 3 robust molecular classes of tumors: the proliferation class (51% of samples) had altered expression of genes that regulate proliferation and mTOR signaling activation; the inflammation class (26% of samples) had altered expression of genes that regulate inflammation and cytokine production; and the unannotated class (23% of samples) had a gene expression signature not previously associated with liver tumors. Expression of genes that regulate neuroendocrine function, as well has histologic markers of cholangiocytes and hepatocytes, were detected in all 3 classes. FLCs had few copy number variations; the most frequent were focal amplification at 8q24.3 (in 12.5% of samples) and deletions at 19p13 (in 28% of samples) and 22q13.32 (in 25% of samples). The DNAJB1

  8. Adoption of Evidence-Based Fall Prevention Practices in Primary Care for Older Adults with a History of Falls

    PubMed Central

    Phelan, Elizabeth A.; Aerts, Sally; Dowler, David; Eckstrom, Elizabeth; Casey, Colleen M.

    2016-01-01

    A multifactorial approach to assess and manage modifiable risk factors is recommended for older adults with a history of falls. Limited research suggests that this approach does not routinely occur in clinical practice, but most related studies are based on provider self-report, with the last chart audit of United States practice published over a decade ago. We conducted a retrospective chart review to assess the extent to which patients aged 65+ years with a history of repeated falls or fall-related health-care use received multifactorial risk assessment and interventions. The setting was an academic primary care clinic in the Pacific Northwest. Among the 116 patients meeting our inclusion criteria, 48% had some type of documented assessment. Their mean age was 79 ± 8 years; 68% were female, and 10% were non-white. They averaged six primary care visits over a 12-month period subsequent to their index fall. Frequency of assessment of fall-risk factors varied from 24% (for home safety) to 78% (for vitamin D). An evidence-based intervention was recommended for identified risk factors 73% of the time, on average. Two risk factors were addressed infrequently: medications (21%) and home safety (24%). Use of a structured visit note template independently predicted assessment of fall-risk factors (p = 0.003). Geriatrics specialists were more likely to use a structured note template (p = 0.04) and perform more fall-risk factor assessments (4.6 vs. 3.6, p = 0.007) than general internists. These results suggest opportunities for improving multifactorial fall-risk assessment and management of older adults at high fall risk in primary care. A structured visit note template facilitates assessment. Given that high-risk medications have been found to be independent risk factors for falls, increasing attention to medications should become a key focus of both public health educational efforts and fall prevention in primary care practice. PMID:27660753

  9. Adoption of Evidence-Based Fall Prevention Practices in Primary Care for Older Adults with a History of Falls

    PubMed Central

    Phelan, Elizabeth A.; Aerts, Sally; Dowler, David; Eckstrom, Elizabeth; Casey, Colleen M.

    2016-01-01

    A multifactorial approach to assess and manage modifiable risk factors is recommended for older adults with a history of falls. Limited research suggests that this approach does not routinely occur in clinical practice, but most related studies are based on provider self-report, with the last chart audit of United States practice published over a decade ago. We conducted a retrospective chart review to assess the extent to which patients aged 65+ years with a history of repeated falls or fall-related health-care use received multifactorial risk assessment and interventions. The setting was an academic primary care clinic in the Pacific Northwest. Among the 116 patients meeting our inclusion criteria, 48% had some type of documented assessment. Their mean age was 79 ± 8 years; 68% were female, and 10% were non-white. They averaged six primary care visits over a 12-month period subsequent to their index fall. Frequency of assessment of fall-risk factors varied from 24% (for home safety) to 78% (for vitamin D). An evidence-based intervention was recommended for identified risk factors 73% of the time, on average. Two risk factors were addressed infrequently: medications (21%) and home safety (24%). Use of a structured visit note template independently predicted assessment of fall-risk factors (p = 0.003). Geriatrics specialists were more likely to use a structured note template (p = 0.04) and perform more fall-risk factor assessments (4.6 vs. 3.6, p = 0.007) than general internists. These results suggest opportunities for improving multifactorial fall-risk assessment and management of older adults at high fall risk in primary care. A structured visit note template facilitates assessment. Given that high-risk medications have been found to be independent risk factors for falls, increasing attention to medications should become a key focus of both public health educational efforts and fall prevention in primary care practice.

  10. Adoption of Evidence-Based Fall Prevention Practices in Primary Care for Older Adults with a History of Falls.

    PubMed

    Phelan, Elizabeth A; Aerts, Sally; Dowler, David; Eckstrom, Elizabeth; Casey, Colleen M

    2016-01-01

    A multifactorial approach to assess and manage modifiable risk factors is recommended for older adults with a history of falls. Limited research suggests that this approach does not routinely occur in clinical practice, but most related studies are based on provider self-report, with the last chart audit of United States practice published over a decade ago. We conducted a retrospective chart review to assess the extent to which patients aged 65+ years with a history of repeated falls or fall-related health-care use received multifactorial risk assessment and interventions. The setting was an academic primary care clinic in the Pacific Northwest. Among the 116 patients meeting our inclusion criteria, 48% had some type of documented assessment. Their mean age was 79 ± 8 years; 68% were female, and 10% were non-white. They averaged six primary care visits over a 12-month period subsequent to their index fall. Frequency of assessment of fall-risk factors varied from 24% (for home safety) to 78% (for vitamin D). An evidence-based intervention was recommended for identified risk factors 73% of the time, on average. Two risk factors were addressed infrequently: medications (21%) and home safety (24%). Use of a structured visit note template independently predicted assessment of fall-risk factors (p = 0.003). Geriatrics specialists were more likely to use a structured note template (p = 0.04) and perform more fall-risk factor assessments (4.6 vs. 3.6, p = 0.007) than general internists. These results suggest opportunities for improving multifactorial fall-risk assessment and management of older adults at high fall risk in primary care. A structured visit note template facilitates assessment. Given that high-risk medications have been found to be independent risk factors for falls, increasing attention to medications should become a key focus of both public health educational efforts and fall prevention in primary care practice. PMID:27660753

  11. Primary hyperoxaluria in an adult male: A rare cause of end-stage kidney disease yet potentially fatal if misdiagnosed.

    PubMed

    El-Reshaid, Kamel; Al-Bader, Dalal; Madda, John P

    2016-05-01

    Primary hyperoxaluria is an autosomal recessive disorder due to a deficiency in the activity of the peroxisomal hepatic enzyme alanine-glyoxylate aminotransferase. It is a common cause of urolithiasis and end-stage kidney disease in children contrary to the adult phenotypic presentation which is considered a mild disorder with occasional urolithiasis. In this case report, we describe a 25-year-old man who presented with advanced and irreversible kidney failure within three months following strenuous physical training in the police academy. He had nephrocalcinosis and stones in one kidney. Diagnosis was confirmed by establishing the existence of extensive tubular and interstitial crystal deposition in his kidneys and molecular genetic testing. The case illustrates the need to establish an early diagnosis of this disorder to prevent the need for combined liver and kidney transplantation. PMID:27215260

  12. Unusual Presentation of Hepatocellular Carcinoma into Right iliac fossa: A Rare Entity

    PubMed Central

    Periyasamy, Karthikumaran

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most common primary malignant hepatic tumour. Hepatocellular carcinoma presenting itself or extending into the right iliac fossa (RIF) is a very rare entity. We report on a rare case of hepatocellular carcinoma in a 60-year-old lady, presented with a mobile mass in the lower abdomen without cirrhosis, with normal α-feto protein levels (AFP) or any known risk factors for liver disease. HCC in this case was unusual in its presentation both in the patient as well as a disease. PMID:26672490

  13. Unusual Presentation of Hepatocellular Carcinoma into Right iliac fossa: A Rare Entity.

    PubMed

    Uthamalingam, Murali; Periyasamy, Karthikumaran

    2015-11-01

    Hepatocellular carcinoma (HCC) is the most common primary malignant hepatic tumour. Hepatocellular carcinoma presenting itself or extending into the right iliac fossa (RIF) is a very rare entity. We report on a rare case of hepatocellular carcinoma in a 60-year-old lady, presented with a mobile mass in the lower abdomen without cirrhosis, with normal α-feto protein levels (AFP) or any known risk factors for liver disease. HCC in this case was unusual in its presentation both in the patient as well as a disease.

  14. HEALTH LITERACY, MEDICATION ADHERENCE, AND BLOOD PRESSURE LEVEL AMONG HYPERTENSIVE OLDER ADULTS TREATED AT PRIMARY HEALTH CARE CENTERS.

    PubMed

    Wannasirikul, Phitchayaphat; Termsirikulchai, Lakkhana; Sujirarat, Dusit; Benjakul, Sarunya; Tanasugarn, Chanuantong

    2016-01-01

    We conducted this study to explore the causal relationships between health literacy, individual characteristics, literacy, culture and society, cognitive ability, medication adherence, and the blood pressure levels of hypertensive older adults receiving health care services at Primary Health Care Centers in Sa Kaeo Province, Thailand. Six hundred hypertensive older adults had their blood pressure level recorded and were interviewed using questionnaires. Structural Equation Modeling (SEM) was used to determine the effect size, both direct and indirect, among factors. Almost half (48.7%) of studied subjects had inadequate health literacy, 98.3% had good medication adherence, and 80% had good blood pressure levels. The highest effect size on health literacy was literacy, followed by cognitive ability, and culture and society. Medication adherence was affected directly and indirectly by cognitive ability, literacy, and culture and society. Health literacy had not only a direct effect on medication adherence but was also the mediator. Finally, the highest effect size on blood pressure level was critical and communicative health literacy. These findings suggest that health literacy should be considered in the Health Literacy Program of the National Public Health Policy and Plan, Ministry of Public Health. PMID:27086432

  15. HEALTH LITERACY, MEDICATION ADHERENCE, AND BLOOD PRESSURE LEVEL AMONG HYPERTENSIVE OLDER ADULTS TREATED AT PRIMARY HEALTH CARE CENTERS.

    PubMed

    Wannasirikul, Phitchayaphat; Termsirikulchai, Lakkhana; Sujirarat, Dusit; Benjakul, Sarunya; Tanasugarn, Chanuantong

    2016-01-01

    We conducted this study to explore the causal relationships between health literacy, individual characteristics, literacy, culture and society, cognitive ability, medication adherence, and the blood pressure levels of hypertensive older adults receiving health care services at Primary Health Care Centers in Sa Kaeo Province, Thailand. Six hundred hypertensive older adults had their blood pressure level recorded and were interviewed using questionnaires. Structural Equation Modeling (SEM) was used to determine the effect size, both direct and indirect, among factors. Almost half (48.7%) of studied subjects had inadequate health literacy, 98.3% had good medication adherence, and 80% had good blood pressure levels. The highest effect size on health literacy was literacy, followed by cognitive ability, and culture and society. Medication adherence was affected directly and indirectly by cognitive ability, literacy, and culture and society. Health literacy had not only a direct effect on medication adherence but was also the mediator. Finally, the highest effect size on blood pressure level was critical and communicative health literacy. These findings suggest that health literacy should be considered in the Health Literacy Program of the National Public Health Policy and Plan, Ministry of Public Health.

  16. Acceptance and commitment therapy program for distressed adults with a primary brain tumor: a case series study.

    PubMed

    Kangas, Maria; McDonald, Skye; Williams, Janet R; Smee, Robert I

    2015-10-01

    Research has indicated that adults diagnosed with a primary brain tumor (BT) are susceptible to experiencing anxiety and depressive problems post-diagnosis. However, there is a notable paucity of psychological interventions which have been tested with adult BT patients. An acceptance and commitment therapy (ACT)-based manualized program was developed for anxious and/or depressed BT patients. The preliminary efficacy of this program was initially tested using a proof-of-concept study design based on a case series of four clinically distressed BT patients. Three of the four participants no longer met criteria for anxiety and/or depressive disorders at post-therapy, and these effects were maintained at 3 months of follow-up. The fourth participant, who had a premorbid psychiatric history, experienced a stabilization of anxiety and depressive symptoms. Given the current dearth of studies which have tested psychological interventions for distressed BT survivors, these preliminary findings have promising clinical utility. However, the efficacy of psychological interventions tailored for clinically distressed BT patients needs to be further tested using larger-scale controlled trial designs.

  17. Audit and comprehensive health assessment programme in the primary healthcare of adults with intellectual disability: a pilot study.

    PubMed

    Lennox, N G; Green, M; Diggens, J; Ugoni, A

    2001-06-01

    International research has demonstrated significant shortcomings in the health of adults with intellectual disability (ID). Because general practitioners (GPs) are the main providers of primary healthcare for this population, strategies to improve general practice care are an important aspect of rectifying these shortcomings. The present pilot study aimed to determine the effect of various interventions on health maintenance activities and to assess their acceptability to GPs, with a view to informing larger scale studies. The GPs were recruited through an earlier questionnaire-based postal survey. The GPs identified all their adult patients with ID, then obtained consent for participation from three patients randomly selected by the investigators. The GPs completed two self-evaluation forms and case note audits 12 months apart, read a synopsis of the relevant literature provided by the researchers, and completed a comprehensive health assessment (CHA) of their three patients. Forty-five GPs agreed to participate in the CHA programme (CHAP), and 15 completed the project. Thirty-eight patients completed the project. The number of patient-GP dyads who completed the project was too small to demonstrate statistically significant changes in health issues over time. The GPs found that the synopsis of the literature was the best intervention for increasing knowledge and was also the most practical to use in general practice. The CHAP was the intervention that prompted the most action from the GP which would not have been undertaken otherwise. The CHAP appeared to provide a superior review process compared to the other interventions used in the present study. The numbers of health maintenance activities found to be overdue and the number of health issues detected as a result of the process were considerable. The CHAP served as a communication tool and an educative instrument, providing a basis for future studies and strategies to improve the general practice care of adults

  18. Primary hypertrophic osteoarthropathy (incomplete form) in young adults: a case report and review of literature

    PubMed Central

    Nayak, Hemanta K; Rajkumar, Vangipuram Deepak; Kumar, Naresh; Kar, Premashis

    2012-01-01

    Hypertrophic osteoarthropathy is characterised by digital clubbing and periosteal reaction of long bones. Most cases are associated with malignancy or other conditions such as congenital heart disease, liver cirrhosis, pulmonary fibrosis, biliary atresia and inflammatory bowel diseases. We report a middle-aged man found to have 15-year history of clubbing of the fingers and toes on his routine check-up for dyspepsia. Skiagram of hand joints showed periosteal apposition without any periosteal reaction of long bones. The search for a secondary cause of clubbing remained negative. The primary or idiopathic form is rare and has a good prognosis and has to be differentiated from secondary form. He was eradicated successfully with Pylori kit for his antral predominant Helicobacter-induced gastritis. PMID:23242097

  19. Primary adrenal teratoma: Clinical characteristics and retroperitoneal laparoscopic resection in five adults

    PubMed Central

    LI, SHUQIANG; LI, HANZHONG; JI, ZHIGANG; YAN, WEIGANG; ZHANG, YUSHI

    2015-01-01

    Primary adrenal teratoma is extremely rare. To investigate the clinical characteristics and further enrich the limited knowledge on its diagnosis and treatment, the present study retrospectively analyzed the detailed clinical data of five patients with primary adrenal teratomas treated in the Peking Union Medical College Hospital (Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China) between March 2009 and February 2014. The five patients were female, aged from 16 to 51 years (mean, 36.0±16.3 years), with solitary lesions that were incidentally found on routine physical examinations. The tumor size ranged from 2.4 to 9.0 cm (mean, 6.0±2.7 cm). Ultrasonography revealed a mixed echo in four patients, and computed tomography showed mixed density masses with fat components and calcification in three patients. Adrenal-related endocrine tests were normal in all five patients, and no abnormalities were found in the three patients who underwent somatostatin receptor scintigraphy examination. All patients were treated with retroperitoneal laparoscopic surgery, with no complications, and the resected tumors were identified as mature cystic teratomas pathologically. To date, the patients have been followed up for 4–60 months post-operatively, with no recurrence. In conclusion, this rare adrenal teratoma is an occult entity to which reproductive females are susceptible. The tumor exhibits no typical clinical manifestations or adrenal-related laboratory abnormalities, and the pre-operative diagnosis mainly relies on imaging characteristics of a heterogeneous lesion containing fat components with scattered and marginal calcifications. The preferred treatment is retroperitoneal laparoscopic surgery, and the prognosis is good. PMID:26722254

  20. Pain measurement as part of primary healthcare of adult patients with sickle cell disease

    PubMed Central

    Signorelli, Andreza Aparecida Felix; Ribeiro, Sonia Beatriz Felix; Moraes-Souza, Helio; de Oliveira, Lucas Felix; Ribeiro, João Batista; da Silva, Sheron Hellen; de Oliveira, Daniel Fachinelli Felix; Ribeiro, Matheus Fernando Felix

    2013-01-01

    Objective The aim of this exploratory, cross-sectional study was to evaluate pain in sickle cell disease patients and aspects related to primary healthcare. Methods Data were obtained through home interviews. The assessment instruments (body diagram, Numerical Pain Scale, McGill Pain Questionnaire) collected information on the underlying disease and on pain. Data were analyzed using the Statistical Package for Social Sciences program for Windows. Associations between the subgroups of sickle cell disease patients (hemoglobin SS, hemoglobin SC, sickle β-thalassemia and others) and pain were analyzed using contingency tables and non-parametric tests of association (classic chi-square, Fisher's and Kruskal-Wallis) with a level of 5% (p-value < 0.05) being set for the rejection of the null hypothesis. Results Forty-seven over 18-year-old patients with sickle cell disease were evaluated. Most were black (78.7%) and female (59.6%) and the mean age was 30.1 years. The average number of bouts of pain annually was 7.02; pain was predominantly reported by individuals with sickle cell anemia (hemoglobin SS). The intensity of pain (Numeric Pain Scale) was 5.5 and the quantitative index (McGill) was 35.9. This study also shows that patients presented a high frequency of moderately painful crises in their own homes. Conclusion According to these facts, it is essential that pain related to sickle cell disease is properly identified, quantified, characterized and treated at the three levels of healthcare. In primary healthcare, accurate measurement of pain combined with better care may decrease acute painful episodes and consequently minimize tissue damage, thus improving the patient's overall health. PMID:24106446

  1. [Early detection of chronic liver disease in primary care in the apparently health adult population].

    PubMed

    Caballería, Llorenç; Torán, Pere

    2012-12-01

    Liver diseases are highly prevalent and are a major health problem as they progress to more severe forms. In the west, cirrhosis and primitive liver cancer are among the first 10 causes of death in adults. Moreover, chronic liver inflammation, irrespective of cause, is usually asymptomatic. Consequently diagnosis tends to be established when the disease is in the advanced stages and is thus irreversible and with few treatment possibilities. Therefore, ideally, diagnosis would be established in the initial phases of chronic liver inflammation, which would allow the natural history of the disease to be altered by either halting or delaying progression. To date, physicians have been guided by alterations in liver function tests to identify the etiology of liver disease or-depending on the severity of involvement-the presence of liver disease. Abdominal ultrasound findings can also reveal alterations suggesting the presence of chronic liver disease. However, in the last few years, noninvasive methods have been designed. These include serological markers (direct and indirect) of fibrosis and radiological tests (especially elastography) based on measuring liver elasticity, which allow noninvasive quantification of the degree of fibrous tissue in the liver. The use of noninvasive methods may be highly useful in the early detection of liver diseases.

  2. Tai Chi Chuan for the Primary Prevention of Stroke in Middle-Aged and Elderly Adults: A Systematic Review

    PubMed Central

    Zheng, Guohua; Liu, Feiwen; Li, Shuzhen; Tao, Jing; Chen, Lidian

    2015-01-01

    Background. Stroke is a major healthcare problem with serious long-term disability and is one of the leading causes of death in the world. Prevention of stroke is considered an important strategy. Methods. Seven electronic databases were searched. Results. 36 eligible studies with a total of 2393 participants were identified. Primary outcome measures, TCC exercise combined with other intervention had a significant effect on decreasing the incidence of nonfatal stroke (n = 185, RR = 0.11, 95% CI 0.01 to 0.85, P = 0.03) and CCD (n = 125, RR = 0.33, 95% CI 0.11 to 0.96, P = 0.04). For the risk factors of stroke, pooled analysis demonstrated that TCC exercise was associated with lower body weight, BMI, FBG level, and decreasing SBP, DBP, plasma TC, and LDL-C level regardless of the intervention period less than half a year or more than one year and significantly raised HDL-C level in comparison to nonintervention. Compared with other treatments, TCC intervention on the basis of the same other treatments in patients with chronic disease also showed the beneficial effect on lowering blood pressure. Conclusion. The present systematic review indicates that TCC exercise is beneficially associated with the primary prevention of stroke in middle-aged and elderly adults by inversing the high risk factors of stroke. PMID:25784950

  3. Validity of symptom and clinical measures of asthma severity for primary outpatient assessment of adult asthma.

    PubMed Central

    Ng, T P

    2000-01-01

    BACKGROUND: Symptom and pulmonary function measures of asthma severity are used for severity classification in practice guidelines. However, there is limited methodological evidence in support of their validity and utility. AIM: To validate initial symptom and forced expiratory volume (FEV1) measures of asthma severity with the subsequent risks of exacerbations resulting in emergency room (ER) visits, hospitalisation, and sickness absence from work. In addition, symptom-based measures of change in asthma severity were also evaluated against the concurrent risks of asthma exacerbations. METHOD: A cohort of 361 adult asthmatic patients in general outpatient clinics was studied. At initial interview, frequencies of asthmatic symptoms and nocturnal exacerbations, FEV1, and a severity score combining these measures, were recorded. At re-interview in the third year, the frequencies of asthma exacerbations resulting in ER visits, hospitalisation, and sickness absence, and a self-assessed global measure of change in severity and serially-assessed change in symptom frequencies, were measured. RESULTS: All individual symptom and FEV1 measures were strongly related to the subsequent risks of ER visits, hospitalisation, and sick absence. A severity score of more than 3 (moderate to severe asthma) and self-assessed change in asthma severity were most strongly and significantly associated with greatly increased risks of all outcomes. Individual symptoms and FEV1 measures alone did not show high sensitivities, but the severity score combining these measures gave much more satisfactory validity. Perhaps not surprisingly, self-assessed change in asthma appeared to give the most satisfactory validity. CONCLUSION: These results support the validity and clinical utility of a simple clinical score based on symptom and FEV1 measures, and self-assessed measure of change in severity, for risk classification in contemporary clinical practice guidelines. PMID:10695059

  4. Sexual violence against adult women primary care attenders in east London.

    PubMed Central

    Coid, Jeremy; Petruckevitch, Ann; Chung, Wai-Shan; Richardson, Jo; Moorey, Stirling; Cotter, Sarah; Feder, Gene S

    2003-01-01

    BACKGROUND: Sexual violence against women is common. The prevalence appears to be higher in north America than Europe. However, not all surveys have differentiated the experience of forced sex by a current or former partner. Few women are thought to report these experiences to their general practitioner (GP). AIM: To measure the prevalence of rape, sexual assault, and forced sexual intercourse by a partner among women attending general practices, to test the association between these experiences of sexual violence and demographic factors, and to assess the acceptability to women of screening for sexual violence by GPs. DESIGN OF STUDY: Cross-sectional survey. METHOD: A self-administered questionnaire survey of 1207 women aged over 15 years was carried out in 13 general practices in Hackney, east London. RESULTS: Eight per cent (95% confidence interval [CI] = 6.2 to 9.6) of women have experienced rape, 9% (95% CI = 7.0 to 10.6) another type of sexual assault, and 16% (95% CI = 13.6 to 18.1) forced sex by a partner in adulthood: 24% (95% CI = 21.2 to 26.5) have experienced one or more of these types of sexual violence. Experiences of sexual violence demonstrated high levels of lifetime co-occurrence. Women forced to have sex by partners experienced the most severe forms of domestic violence. One in five women would object to routine questioning about being raped and/or sexually assaulted, and one in nine about being forced to have sex by a partner. CONCLUSION: Experiences of sexual violence are common in the lives of adult women in east London, and they represent a significant public health problem. Those women who have one experience appear to be at risk of being victims again. A substantial minority object to routine questions about sexual violence. PMID:14702905

  5. Cutaneous metastases of hepatocellular carcinoma.

    PubMed

    Lazaro, M; Serrano, M L; Allende, I; Ratón, J A; Acebo, E; Diaz-Perez, J L

    2009-12-01

    Cutaneous metastases are an unusual finding that may present as the first sign of an internal neoplasia. A case of cutaneous metastases of hepatocellular carcinoma, which may often involve other organs but very rarely metastases to the skin, is reported.

  6. Prospective assessment of quality of life in adult patients with primary brain tumors in routine neurooncology practice.

    PubMed

    Budrukkar, Ashwini; Jalali, Rakesh; Dutta, Debnarayan; Sarin, Rajiv; Devlekar, Rashmi; Parab, Sachin; Kakde, Anagha

    2009-12-01

    The aim of this article is to evaluate and assess the impact of various factors on quality of life (QOL) in adult patients with primary brain tumors seen consecutively in routine neurooncology practice. Two hundred and fifty-seven adult patients, after undergoing surgical intervention and histologically proven primary brain neoplasms were registered in the NeuroOncology Clinic at our centre during 1 full calendar year. The study included detailed neurological assessment, evaluation of QOL using EORTC questionnaire (QLQ-30) and specific Brain Cancer module (BN 20). In the present analysis, QOL scores before starting adjuvant treatment were measured and impact of patient and tumor related factors were analyzed. Baseline global QOL data of all patients (available in 243) was relatively low including in all histological tumor types. Physical function, role function, emotion function, cognitive and social function scores were 80, 78, 65.7, 70 and 70.5 (higher values better), respectively. Domains of future uncertainty, visual disorder, motor deficit, communication deficit, headache, seizures and drowsiness scores were 19.6, 18.2, 28.5, 30.7, 21, 31.8 and 16 (lower values better), respectively. Elderly patients had poorer global score (21 points difference; p = 0.161). Patients with lower performance status (KPS < 70) had a lower global QOL (KPS >or= 80 vs. primary brain tumours before starting adjuvant therapy have

  7. Disease characteristics and outcomes in younger adults with primary and secondary myelofibrosis.

    PubMed

    Beauverd, Yan; Alimam, Samah; McLornan, Donal P; Radia, Deepti H; Harrison, Claire N

    2016-10-01

    Myelofibrosis (MF) is a rare haematopoietic disorder, commonly diagnosed in the 6th decade: less than 20% are diagnosed before the age of 50 years. In this retrospective study we included all patients given a diagnosis of World Health Organization-defined primary or secondary MF when aged ≤50 years. Forty-three patients with a median age of 43 years were included. Median follow up was 44 months. Twenty-two (51%) harboured the JAK2 V617F mutation, 18/43 (42%) CALR, 0/43 (0%) MPL mutations and 3/43 (7%) were 'Triple Negative' (TN). At the time of diagnosis, no significant differences existed in haematological and clinical phenotypes between JAK2, CALR and TN patients. The frequency of splenomegaly was greater (P = 0·047) in the JAK2-mutated group compared to CALR-mutated patients. In the whole cohort, the 5-year probability of developing anaemia, thrombocytopenia and marked leucocytosis was 24%, 10% and 13% respectively. Finally, the cumulative incidence of thrombotic events and progression to acute myeloid leukaemia was 1% and 0·5% patient-year respectively. No death was reported during the follow-up. These findings suggest that MF in younger patients may have a more indolent course when compared to older patients.

  8. Emphysema in an adult with galactosialidosis linked to a defect in primary elastic fiber assembly.

    PubMed

    Lehman, Anna; Mattman, Andre; Sin, Don; Pare, Peter; Zong, Zheyuan; d'Azzo, Alessandra; Campos, Yvan; Sirrs, Sandra; Hinek, Aleksander

    2012-05-01

    Galactosialidosis is a lysosomal storage disorder caused by loss of function of protective protein cathepsin A, which leads to secondary deficiencies of β-galactosidase and neuraminidase-1. Emphysema has not been previously reported as a possible complication of this disorder, but we now describe this condition in a 41-year-old, non-smoking male. Our patient did not display deficiency in α-1-antitrypsin, the most common cause of emphysema in non-smokers, which brings about disseminated elastolysis. We therefore hypothesized that loss of cathepsin A activity was responsible because of previously published evidence showing it is prerequisite for normal elastogenesis. We now present experimental evidence to support this theory by demonstrating impaired primary elastogenesis in cultures of dermal fibroblasts from our patient. The obtained data further endorse our previous finding that functional integrity of the cell surface-targeted molecular complex of cathepsin A, neuraminidase-1 and the elastin-binding protein (spliced variant of β-galactosidase) is prerequisite for the normal assembly of elastic fibers. Importantly, we also found that elastic fiber production was increased after exposure either to losartan, spironolactone, or dexamethasone. Of immediate clinical relevance, our data suggest that surviving patients with galactosialidosis should have periodic assessment of their pulmonary function. We also encourage further experimental exploration of therapeutic potential of the afore-mentioned elastogenesis-stimulating drugs for the alleviation of pathological processes in galactosialidosis that could be mechanistically linked to impaired deposition of elastic fibers.

  9. Prevalence of undifferentiated fever in adults of Rawalpindi having primary dengue fever.

    PubMed

    Zafar, Humaira; Hayyat, Abbas; Akhtar, Naeem; Rizwan, Syeda Fatima

    2013-06-01

    The objectives of the study were to highlight early subclinical presentation of dengue viral infection (DVI) as an undifferentiated febrile illness. The descriptive cross-sectional study was carried out at Microbiology Department, Rawalpindi Medical College from March to September 2009. Stratified random sampling was used to select subjects from various urban and rural areas of Rawalpindi, and Serum IgG anti-dengue antibodies were detected by using 3rd generation enzyme-linked immunosorbent assay (ELISA). Out of the total 240 subjects, 69 (28.75%) were found to be positive for anti-dengue IgG antibodies. Of the positive cases, 41 (59.4%) - comprising 31 (44.9%) urban residents - and 10 (14.4%) rural residents presented with a previous history of undifferentiated fever (p<0.05). It was concluded that primary DVI can present as subclinical form in healthy population residing in rural and urban areas of Rawalpindi, which is an alarming situation indicating the spread of disease in the study area.

  10. Risk of Shingles in Adults with Primary Sjogren’s Syndrome and Treatments: A Nationwide Population-Based Cohort Study

    PubMed Central

    Chen, Jen-Yin; Wang, Li-Kai; Feng, Ping-Hsun; Chu, Chin-Chen; Cheng, Tain-Junn; Weng, Shih-Feng; Wu, Su-Zhen; Lu, Tsung-Hsueh; Chang, Chia-Yu

    2015-01-01

    Background Primary Sjögren's syndrome (pSS) is associated with immunological dysfunctions—a well-known risk factor of shingles. This study aimed to examine the incidence and risk of shingles in adults with pSS and pharmacological treatments. Methods This retrospective population-based cohort study was conducted using National Health Insurance claims data. Using propensity scores, 4,287 pSS adult patients and 25,722-matched cohorts by age, gender, selected comorbidities and Charlson comorbidity index scores were identified. Kaplan-Meier analysis and Cox regression were conducted to compare the differences in developing shingles. In pSS, oral and eye dryness are treated with substitute agents. Extraglandular features are often treated with pharmacological drugs including steroids and immunosuppressants. pSS patients were grouped as follows: no pharmacological drugs, steroids alone; immunosuppressants alone; combined therapies. Results During the follow-up, 463 adults with pSS (10.80%) and 1,345 control cohorts (5.23%) developed shingles. The cumulative incidence of shingles in pSS patients (18.74/1,000 patient-years) was significantly higher than controls (8.55/1,000 patient-years). The adjusted hazard ratio (HR) of shingles was 1.69 (95% confidence interval (CI) 1.50–1.90). In age-subgroup analyses, incidences of shingles in pSS increased with age and peaked in pSS patients aged ≧60; however, adjusted HRs decreased with age. Compared to control cohorts with no drugs, adjusted HRs for shingles in pSS patients were ranked from high to low as: combined therapies (4.14; 95% CI 3.14–5.45) > immunosuppressants alone (3.24; 95% CI 2.36–4.45) > steroids alone (2.54; 95% CI 2.16–2.97) > no pharmacological drugs (2.06; 95% CI 1.76–2.41). Rates of shingles-associated hospitalization and postherpetic neuralgia were 5.62% and 24.41%, both of which were significantly higher than those (2.60%; 13.01%) in the control cohorts. Conclusions Adults with pSS were at

  11. Exclusion of one pedigree affected by adult onset primary open angle glaucoma from linkage to the juvenile glaucoma locus on chromosome 1q21-q31.

    PubMed Central

    Avramopoulos, D; Kitsos, G; Economou-Petersen, E; Grigoriadou, M; Vassilopoulos, D; Papageorgiou, C; Psilas, K; Petersen, M B

    1996-01-01

    A locus for autosomal dominant juvenile onset primary open angle glaucoma (POAG) was recently assigned to chromosome region 1q21-q31. In the present study, a large Greek family with autosomal dominant adult onset POAG was investigated using microsatellite markers. Exclusion of linkage of the adult onset POAG gene to the region D1S194-D1S191 was obtained in this pedigree. Therefore, the data provide evidence that juvenile and adult onset POAG are genetically distinct disease entities. PMID:9004141

  12. Microvascular invasion in hepatocellular carcinoma

    PubMed Central

    Ünal, Emre; İdilman, İlkay Sedakat; Akata, Deniz; Özmen, Mustafa Nasuh; Karçaaltıncaba, Muşturay

    2016-01-01

    Microvascular invasion is a crucial histopathologic prognostic factor for hepatocellular carcinoma. We reviewed the literature and aimed to draw attention to clinicopathologic and imaging findings that may predict the presence of microvascular invasion in hepatocellular carcinoma. Imaging findings suggesting microvascular invasion are disruption of capsule, irregular tumor margin, peritumoral enhancement, multifocal tumor, increased tumor size, and increased glucose metabolism on positron emission tomography-computed tomography. In the presence of typical findings, microvascular invasion may be predicted. PMID:26782155

  13. Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases.

    PubMed

    Engstrom, Anna; Wang, Hao; Xia, Zhengui

    2015-08-01

    Adult hippocampal neurogenesis is the process whereby adult neural precursor cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate adult-born, functional neurons in the hippocampus. This process is modulated by various extracellular and intracellular stimuli, and the adult-born neurons have been implicated in hippocampus-dependent learning and memory. However, studies on how neurotoxic agents affect this process and the underlying mechanisms are limited. The goal of this study was to determine whether lead, a heavy metal, directly impairs critical processes in adult neurogenesis and to characterize the underlying signaling pathways using primary cultured SGZ-aNPCs isolated from adult mice. We report here that lead significantly increases apoptosis and inhibits proliferation in SGZ-aNPCs. In addition, lead significantly impairs spontaneous neuronal differentiation and maturation. Furthermore, we found that activation of the c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase signaling pathways are important for lead cytotoxicity. Our data suggest that lead can directly act on adult neural stem cells and impair critical processes in adult hippocampal neurogenesis, which may contribute to its neurotoxicity and adverse effects on cognition in adults.

  14. A retrospective clinical study of 98 adult idiopathic primary intraventricular hemorrhage cases

    PubMed Central

    Guo, Rui; Ma, Lu; Shrestha, Bal Krishna; Yu, Zhiyuan; Li, Hao; You, Chao

    2016-01-01

    Abstract The aim of the study is to define the clinical features, risk factors, treatment and prognosis of idiopathic primary intraventricular hemorrhage (IPIVH). We retrospectively collected the data of consecutively admitted patients who were diagnosed and treated for IPIVH in our hospital from January 2010 to December 2014. The clinical information, treatment, and prognosis at the 6-month follow-up were analyzed. Among the 3798 cases of spontaneous intracranial hemorrhage (ICH), 98 IPIVH (2.58%) patients were recruited for the study. The study population consisted of 60 males and 38 females, with an average age (± standard deviation, SD) of 51.20 ± 15.48 years. The initial symptoms were headache (75 cases) and impaired consciousness (23 cases). The surgical treatments included hematoma evacuation under a microscope or an endoscope in 8 cases (8.16%), external ventricular drainage (EVD) in 11 cases (11.22%), lumbar drainage (LD) in 10 cases (10.20%), and a combination of EVD and LD in 11 cases (11.22%). In total, 4 patients died in the hospital (4.08%). At the 6-month follow-up, 73 patients (74.49%) had an improved outcome (modified Rankin scale [mRS] < 3), and 21 patients (21.43%) had a poor outcome (mRS ≥ 3 points) at the end of the 6-month follow-up. IPIVH is rare in clinical practice, and hypertension is the most common risk factor. Furthermore, the treatment of IPIVH is still controversial. Hematoma evacuation under a microscope or an endoscope, EVD, LD and a combination of EVD and LD could be surgical options for the treatment of IPIVH patients. The outcomes for IPIVH patients could be relatively favorable with individualized treatment. PMID:27759637

  15. The Role of Radiotherapy and Chemotherapy in the Treatment of Primary Adult High Grade Gliomas: Assessment of Patients for These Treatment Approaches and the Common Immediate Side Effects

    PubMed Central

    Philip-Ephraim, E. E.; Eyong, K. I.; Williams, U. E.; Ephraim, R. P.

    2012-01-01

    Gliomas are the commonest primary brain tumours in adults. They are usually classified and graded according to the criteria by the World Health Organisation. High-grade gliomas are the most malignant primary brain tumours. Conventional therapies include surgery, radiotherapy, and chemotherapy. The tumours often demonstrate high levels of resistance to these conventional therapies, and in spite of treatment advances the prognosis remains poor. PMID:23304556

  16. Hepatocellular Carcinoma (HCC)

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.

    Hepatocellular carcinoma (HCC) is considered to be one of the most common malignancies worldwide, and the most common one in Africa and Asia. Over the last decade, a rising incidence of up to 10-15/100,000 per population has been seen in the Western world, with an estimate of 250,000 deaths and more than a million worldwide per year. By the year 2010, the World Health Organization expects that HCC will be the leading cause of cancer mortality surpassing lung cancer. This increasing incidence is most likely related to an increasing prevalence of chronic hepatitis C (HC) and B (HB) virus infections and other diseases inducing chronic inflammation (Befeler and Di Bisceglie 2002; Llovet et al. 2003).

  17. Diagnosis of hepatocellular carcinoma

    PubMed Central

    Di Bisceglie, Adrian M.

    2005-01-01

    Hepatocellular carcinoma (HCC) is responsible for a large proportion of cancer deaths worldwide. HCC is frequently diagnosed after the development of clinical deterioration at which time survival is measured in months. Long-term survival requires detection of small tumors, often present in asymptomatic individuals, which may be more amenable to invasive therapeutic options. Surveillance of high-risk individuals for HCC is commonly performed using the serum marker alfa-fetoprotein (AFP) often in combination with ultrasonography. Various other serologic markers are currently being tested to help improve surveillance accuracy. Diagnosis of HCC often requires more sophisticated imaging modalities such as CT scan and MRI, which have multiphasic contrast enhancement capabilities. Serum AFP used alone can be helpful if levels are markedly elevated, which occurs in fewer than half of cases at time of diagnosis. Confirmation by liver biopsy can be performed under circumstances when the diagnosis of HCC remains unclear. PMID:18333158

  18. Effectiveness of multicomponent interventions in primary healthcare settings to promote continuous smoking cessation in adults: a systematic review

    PubMed Central

    Martín Cantera, Carlos; Puigdomènech, Elisa; Ballvé, Jose Luis; Arias, Olga Lucía; Clemente, Lourdes; Casas, Ramon; Roig, Lydia; Pérez-Tortosa, Santiago; Díaz-Gete, Laura; Granollers, Sílvia

    2015-01-01

    Objective The objective of the present review is to evaluate multicomponent/complex primary care (PC) interventions for their effectiveness in continuous smoking abstinence by adult smokers. Design A systematic review of randomised and non-randomised controlled trials was undertaken. Eligibility criteria for included studies Selected studies met the following criteria: evaluated effects of a multicomponent/complex intervention (with 2 or more intervention components) in achieving at least 6-month abstinence in adult smokers who visited a PC, biochemical confirmation of abstinence, intention-to-treat analysis and results published in English/Spanish. Methods We followed PRISMA statement to report the review. We searched the following data sources: MEDLINE, Web of Science, Scopus (from inception to February 2014), 3 key journals and a tobacco research bulletin. The Scottish Intercollegiate Guidelines Network checklists were used to evaluate methodological quality. Data selection, evaluation and extraction were done independently, using a paired review approach. Owing to the heterogeneity of interventions in the studies included, a meta-analysis was not conducted. Results Of 1147 references identified, 9 studies were selected (10 204 participants, up to 48 months of follow-up, acceptable methodological quality). Methodologies used were mainly individual or group sessions, telephone conversations, brochures or quit-smoking kits, medications and economic incentives for doctors and no-cost medications for smokers. Complex interventions achieved long-term continuous abstinence ranging from 7% to 40%. Behavioural interventions were effective and had a dose–response effect. Both nicotine replacement and bupropion therapy were safe and effective, with no observed differences. Conclusions Multicomponent/complex interventions in PC are effective and safe, appearing to achieve greater long-term continuous smoking cessation than usual care and counselling alone. Selected

  19. Public Stigma towards Older Adults with Depression: Findings from the São Paulo-Manaus Elderly in Primary Care Study

    PubMed Central

    Kester, Rachel; Braga, Patrícia Emília; Peluso, Érica T. P.; Blay, Sérgio L.; R. Menezes, Paulo; E. Ribeiro, Euler

    2016-01-01

    This study investigates three domains of public stigma (perceived negative reactions, perceived discrimination, and dangerousness) against older adults with depression. The sample comprised of older adults registered with primary care clinics (n = 1,291) and primary health care professionals (n = 469) from São Paulo and Manaus, Brazil. Participants read a vignette describing a 70-year-old individual (Mary or John) with a depressive disorder and answered questions measuring stigma. The prevalence of the three stigma domains was between 30.2 and 37.6% among older participants from São Paulo and between 27.6 and 35.4% among older participants from Manaus. Older adults from both cities reported similar prevalence of perceived stigma. Key factors associated with stigmatizing beliefs among older participants were reporting depressive symptoms, having physical limitations, and identifying the case of the vignette as a case of mental disorder. Among health professionals, the prevalence of the three stigma domains was between 19.8 and 34.8% in São Paulo and 30.2 and 44.6% in Manaus. The key factor associated with stigma among primary health care professionals was city, with consistently higher risk in Manaus than in São Paulo. Findings confirm that public stigma against older adults in Brazil is common. It is important to educate the public and primary health care providers in Brazil on stigma related to mental illness in order to reduce barriers to adequate mental health treatment. PMID:27352293

  20. Public Stigma towards Older Adults with Depression: Findings from the São Paulo-Manaus Elderly in Primary Care Study.

    PubMed

    Scazufca, Marcia; P de Paula Couto, Maria Clara; Huang, Hsiang; Kester, Rachel; Braga, Patrícia Emília; Peluso, Érica T P; Blay, Sérgio L; R Menezes, Paulo; E Ribeiro, Euler

    2016-01-01

    This study investigates three domains of public stigma (perceived negative reactions, perceived discrimination, and dangerousness) against older adults with depression. The sample comprised of older adults registered with primary care clinics (n = 1,291) and primary health care professionals (n = 469) from São Paulo and Manaus, Brazil. Participants read a vignette describing a 70-year-old individual (Mary or John) with a depressive disorder and answered questions measuring stigma. The prevalence of the three stigma domains was between 30.2 and 37.6% among older participants from São Paulo and between 27.6 and 35.4% among older participants from Manaus. Older adults from both cities reported similar prevalence of perceived stigma. Key factors associated with stigmatizing beliefs among older participants were reporting depressive symptoms, having physical limitations, and identifying the case of the vignette as a case of mental disorder. Among health professionals, the prevalence of the three stigma domains was between 19.8 and 34.8% in São Paulo and 30.2 and 44.6% in Manaus. The key factor associated with stigma among primary health care professionals was city, with consistently higher risk in Manaus than in São Paulo. Findings confirm that public stigma against older adults in Brazil is common. It is important to educate the public and primary health care providers in Brazil on stigma related to mental illness in order to reduce barriers to adequate mental health treatment. PMID:27352293

  1. Public Stigma towards Older Adults with Depression: Findings from the São Paulo-Manaus Elderly in Primary Care Study.

    PubMed

    Scazufca, Marcia; P de Paula Couto, Maria Clara; Huang, Hsiang; Kester, Rachel; Braga, Patrícia Emília; Peluso, Érica T P; Blay, Sérgio L; R Menezes, Paulo; E Ribeiro, Euler

    2016-01-01

    This study investigates three domains of public stigma (perceived negative reactions, perceived discrimination, and dangerousness) against older adults with depression. The sample comprised of older adults registered with primary care clinics (n = 1,291) and primary health care professionals (n = 469) from São Paulo and Manaus, Brazil. Participants read a vignette describing a 70-year-old individual (Mary or John) with a depressive disorder and answered questions measuring stigma. The prevalence of the three stigma domains was between 30.2 and 37.6% among older participants from São Paulo and between 27.6 and 35.4% among older participants from Manaus. Older adults from both cities reported similar prevalence of perceived stigma. Key factors associated with stigmatizing beliefs among older participants were reporting depressive symptoms, having physical limitations, and identifying the case of the vignette as a case of mental disorder. Among health professionals, the prevalence of the three stigma domains was between 19.8 and 34.8% in São Paulo and 30.2 and 44.6% in Manaus. The key factor associated with stigma among primary health care professionals was city, with consistently higher risk in Manaus than in São Paulo. Findings confirm that public stigma against older adults in Brazil is common. It is important to educate the public and primary health care providers in Brazil on stigma related to mental illness in order to reduce barriers to adequate mental health treatment.

  2. Hepatocellular carcinoma: epidemiology, biology, diagnosis, and therapies.

    PubMed

    Gomes, Marcos António; Priolli, Denise Gonçalves; Tralhão, José Guilherme; Botelho, Maria Filomena

    2013-01-01

    Hepatocellular carcinoma is the fifth most common cancer in men and the seventh in women, as is diagnosed in more than half a million individuals worldwide every year. In Portugal, its incidence and mortality rates are low compared to other types of cancers. In Brazil, in the city of São Paulo, according to data released by the Brazilian Unified Health System (Sistema Único de Saúde - SUS), the incidence of primary liver cancer was 2.07/100,000 inhabitants. Although the vast majority of cases (85%) mainly affect developing countries, especially where infection by hepatitis B virus (HBV) is endemic, the incidence in developed countries is increasing. This pathology is associated with several risk factors, not only environmental but also genetic, generating an increasing interest in attaining a better understanding of this disease, which is still associated with very late diagnosis and poor prognosis. Of the available treatments, few patients benefit from their scanty advantages, increasingly stimulating research of new forms of treatment against this disease. This review aimed to briefly but fully identify risk factors, molecular and biochemical pathways, pathophysiology, diagnosis, and possible clinical approaches of hepatocellular carcinoma.

  3. Development of The Johns Hopkins University School of Nursing Adult/Geriatric Primary Care Nurse Practitioner Program in HIV Prevention, Treatment, and Care.

    PubMed

    Farley, Jason E; Stewart, Jennifer; Kub, Joan; Cumpsty-Fowler, Carolyn; Lowensen, Kelly; Becker, Kathleen

    2016-01-01

    In response to the call to create an AIDS Education and Training Center for Nurse Practitioner Education by the Health Resources and Services Administration, The Johns Hopkins University School of Nursing embarked on a transformative curriculum overhaul to integrate HIV prevention, treatment, and care into the Adult/Geriatric Nurse Practitioner Program. A six-step process outlined in the Curriculum Development for Medical Education was followed. A pilot cohort of Adult/Geriatric Nurse Practitioner students were enrolled, including 50% primary care setting and 50% HIV-focused primary care through a 12-month HIV continuity clinic experience. Through this pilot, substantive changes to the program were adopted. Programmatic outcomes were not compromised with the modification in clinical hours. The model of a 12-month HIV continuity clinical experience reduced the number of required preceptors. This model has important implications for the HIV workforce by demonstrating successful integration of HIV and primary care training for nurse practitioners.

  4. Vasopressin inhibits type-I collagen and albumin gene expression in primary cultures of adult rat hepatocytes

    SciTech Connect

    Chojkier, M.; Brenner, D.A.; Leffert, H.L.

    1989-06-05

    The mechanisms that regulate collagen gene expression in hepatic cells are poorly understood. Accelerated Ca2+ fluxes are associated with inhibiting collagen synthesis selectively in human fibroblasts. In suspension cultures of isolated hepatocytes, the Ca2+ agonist vasopressin increases cytosolic levels of free Ca2+. However, whether vasopressin's interactions with plasma membrane V1 receptors attenuate hepatic collagen production is unknown. We investigated this problem by studying vasopressin's effects on collagen synthesis and Ca2+ efflux in long-term primary cultures of differentiated and proliferation-competent adult rat hepatocytes. Twelve-day-old quiescent cultures were exposed to test substances and labeled with (5-3H)proline. Determinations of radioactivity in collagenase-sensitive and collagenase-resistant proteins were used to calculate the relative levels of collagen production. Synthetic (8-arg)vasopressin stimulated 45Ca2+ efflux within 1 min and inhibited hepatocyte collagen production within 3 h by 50%; overall rates of protein synthesis were not affected significantly. In cultures labeled with (35S)methionine, vasopressin also decreased the levels of newly synthesized and secreted albumin, but not fibrinogen, detected in specific immunoprecipitates analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Northern blot analyses using specific (32P)cDNA probes revealed 70% decreases in hybridizable levels of collagen alpha 1(I) mRNA in hepatocyte cultures treated with either vasopressin or Ca2+ ionophore A23187; hybridizable levels of albumin mRNA also fell approximately 50% following vasopressin treatment.

  5. Treatment Strategies of Adult Primary Focal Segmental Glomerulosclerosis: A Systematic Review Focusing on the Last Two Decades

    PubMed Central

    Beer, Arno; Mayer, Gert

    2016-01-01

    Adult primary focal segmental glomerulosclerosis (FSGS) remains a therapeutic challenge for the treating physician. With the advent of novel immunosuppressive measures, our arsenal of therapeutic options increased considerably. The aim of this review was to summarize reports published over the last two decades which reported on treatment outcome. Most reports included patients with a steroid-resistant (SR) disease course, yet the cohort with the highest unmet need, since persistent nephrotic range proteinuria is associated with a poor renal prognosis and portends a high risk of developing end-stage renal disease. While in first-line treatment, steroid treatment remains the recommended standard with an overall remission rate of 50% and higher, optimal treatment strategies for steroid-dependent/multirelapsing (SD/MR) and SR patients have to be defined. In both entities, calcineurin inhibitors showed good efficacy, while mycophenolate mofetil was less effective in SR cases compared to those with SD/MR. The same was true for rituximab, a monoclonal antibody targeting B-cells. In resistant cases, addition of extracorporeal treatment options or treatment with alkylating agents may be considered. To shape the future for treatment of FSGS, international collaborations to conduct larger clinical trials are needed to identify potential novel efficacious immunosuppressive or immunomodulatory therapies. PMID:27144166

  6. Sleep time and pattern of adult individuals in primary care in an Asian urbanized community: A cross-sectional study.

    PubMed

    Tan, Ngiap Chuan; Tan, Mui Suan; Hwang, Siew Wai; Teo, Chia Chia; Lee, Zhi Kang Niccol; Soh, Jing Yao Jonathan; Koh, Yi Ling Eileen; How, Choon How

    2016-08-01

    Sleep norms vary between individuals, being affected by personal, communal, and socioeconomic factors. Individuals with sleep time which deviate from the population norm are at risks of adverse mental, cardiovascular, and metabolic health. Sleep-related issues are common agenda for consultation in primary care. This study aimed to determine the sleep time, pattern, and behavior of multiethnic Asian individuals who attended public primary care clinics in an urban metropolitan city-state.Standardized questionnaires were assistant-administered to adult Asian individuals who visited 2 local public primary care clinics in north-eastern and southern regions of Singapore. The questionnaire included questions on demographic characteristics, self-reported sleep time, patterns, and behavior and those originated from the American National Sleep Foundation Sleep Diary. The data were collated, audited, rectified, and anonymized before being analyzed by the biostatistician. Individuals with 7 h sleep time or longer were deemed getting adequate sleep. Chi-squared or Fisher exact test was used to test the association between the demographic and behavioral variables and sleep time. Next, regression analysis was performed to identify key factors associated with their sleep time.A total of 350 individuals were recruited, with higher proportion of those of Chinese ethnicity reporting adequate sleep. Almost half (48.1%) of those who slept <7 h on weekdays tended to sleep ≥7 h on weekends. More individuals who reported no difficulty falling asleep, had regular sleep hours and awakening time, tended to sleep adequately. Those who slept with children, studied, read leisurely, used computer or laptops in their bedrooms, drank caffeinated beverages or smoked had inadequate sleep. Those who perceived sufficient sleep and considered 8 h as adequate sleep time had weekday and weekend sleep adequacy.Sleep time varied according to ethnicity, employment status, personal behavior, and

  7. Sleep time and pattern of adult individuals in primary care in an Asian urbanized community: A cross-sectional study.

    PubMed

    Tan, Ngiap Chuan; Tan, Mui Suan; Hwang, Siew Wai; Teo, Chia Chia; Lee, Zhi Kang Niccol; Soh, Jing Yao Jonathan; Koh, Yi Ling Eileen; How, Choon How

    2016-08-01

    Sleep norms vary between individuals, being affected by personal, communal, and socioeconomic factors. Individuals with sleep time which deviate from the population norm are at risks of adverse mental, cardiovascular, and metabolic health. Sleep-related issues are common agenda for consultation in primary care. This study aimed to determine the sleep time, pattern, and behavior of multiethnic Asian individuals who attended public primary care clinics in an urban metropolitan city-state.Standardized questionnaires were assistant-administered to adult Asian individuals who visited 2 local public primary care clinics in north-eastern and southern regions of Singapore. The questionnaire included questions on demographic characteristics, self-reported sleep time, patterns, and behavior and those originated from the American National Sleep Foundation Sleep Diary. The data were collated, audited, rectified, and anonymized before being analyzed by the biostatistician. Individuals with 7 h sleep time or longer were deemed getting adequate sleep. Chi-squared or Fisher exact test was used to test the association between the demographic and behavioral variables and sleep time. Next, regression analysis was performed to identify key factors associated with their sleep time.A total of 350 individuals were recruited, with higher proportion of those of Chinese ethnicity reporting adequate sleep. Almost half (48.1%) of those who slept <7 h on weekdays tended to sleep ≥7 h on weekends. More individuals who reported no difficulty falling asleep, had regular sleep hours and awakening time, tended to sleep adequately. Those who slept with children, studied, read leisurely, used computer or laptops in their bedrooms, drank caffeinated beverages or smoked had inadequate sleep. Those who perceived sufficient sleep and considered 8 h as adequate sleep time had weekday and weekend sleep adequacy.Sleep time varied according to ethnicity, employment status, personal behavior, and

  8. [External radiotherapy for hepatocellular carcinoma].

    PubMed

    Girard, N; Mornex, F

    2011-02-01

    For a long time radiotherapy has been excluded from the therapeutic strategy for hepatocellular carcinoma, given its significant toxicity on the non-tumoral liver parenchyma. Conformal radiation is a recent advance in the field of radiotherapy, allowing dose escalation and combination with other therapeutic options for hepatocellular carcinoma, including trans-arterial chemo-embolization. Conformal radiotherapy is associated with interesting features, especially in cirrhotic patients: wide availability, non-invasiveness, possibility to target multiple localizations anywhere within the liver parenchyma, and favorable tolerance profile even in patients with cirrhosis and/or in a poor medical condition. Recently, radiation delivery has been optimized through several technical developments: respiratory gating and intensity-modulated radiotherapy, which allow a better focalization of the ballistics, stereotactic techniques and proton-beam radiotherapy, whose availability is currently limited in Europe. Given the high response rates of hepatocellular carcinoma to radiation, conformal radiotherapy may be regarded as a curative-intent treatment for hepatocellular carcinoma, similar to surgery and per-cutaneous techniques. Yet the impact of radiotherapy has to be evaluated in randomized trials to better integrate in the complex therapeutic algorithm of hepatocellular carcinoma.

  9. Hepatocellular carcinoma in India.

    PubMed

    Bhattacharyya, Gouri Shankar; Babu, K Govind; Malhotra, Hemant; Ranade, Anantbhushan A; Murshed, Shaiqua; Datta, Debasis

    2013-12-01

    Cancers of the liver are one of the commonest cancers that occur in the world, the commonest of which is the hepatocellular carcinoma (HCC). It is considered to be the 5th commonest cancer in the world. In the areas that are endemic for hepatitis B and C, it is extremely common. Unfortunately, India which is an endemic zone for hepatitis B, there has been no comprehensive analyzed data for HCC. Incidence of HCC in India occurs at two peaks, one at a young age between 40 to 55 years and another above 60 years. Eighty per cent of all HCCs occurring in India occur with cirrhosis of liver in the background and 60% of all these cases are hepatitis B positive carriers. Symptoms are reflective of late presentation with advanced disease. Surgery, the only curative modulus available, unfortunately is not possible in 95% of HCC patients. Majority of the patients are treated with palliative and supportive care and life spans are limited. Sorafenib is used in a small section of patients. Characterization of HCC with molecular sub-typing is the need of the hour.

  10. Genetic heterogeneity of hepatocellular carcinoma

    SciTech Connect

    Unsal, H.; Isselbacher, K.J. ); Yakicier, C.; Marcais, C.; Ozturk, M. ); Kew, M. ); Volkmann, M. ); Zentgraf, H. )

    1994-01-18

    The authors studied 80 hepatocellular carcinomas from three continents for p53 gene (TP53) mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in tumors from Mozambique but not in tumors from South Africa, China, and Germany. Independent of geographic origin, most tumors were positive for HBV sequences. X gene coding sequences of HBV were detected in 78% of tumors, whereas viral sequences in the surface antigen- and core antigen-encoding regions were present in less than 35% of tumors. These observations indicate that hepatocellular carcinomas are genetically heterogeneous. Mozambican-types of hepatocellular carcinomas are characterized by a high incidence of p53 mutations related to aflatoxins. In other tumors, the rarity of p53 mutations combined with the frequent presence of viral X gene coding sequences suggests a possible interference of HBV with the wild-type p53 function.

  11. The Population Impact and Cost-Effectiveness of Statins for Primary Prevention in Adults 75 and Older in the United States

    PubMed Central

    Odden, Michelle C.; Pletcher, Mark J.; Coxson, Pamela G.; Thekkethala, Divya; Guzman, David; Heller, David; Goldman, Lee; Bibbins-Domingo, Kirsten

    2015-01-01

    BACKGROUND Over 40% of adults 75 and older are taking statins, yet there is little evidence to guide primary prevention in this population. OBJECTIVE To project the population impact and cost-effectiveness of statin therapy in adults aged 75 years and older. DESIGN Forecasting study using the Cardiovascular Disease Policy Model, a Markov model. DATA SOURCE Trial, cohort, and nationally-representative data sources. TARGET POPULATION U.S. adults aged 75–94 years. TIME HORIZON 10 years. PERSPECTIVE Health care system. INTERVENTION Statins for primary prevention based on: 1) Low density lipoprotein cholesterol ≥4.91 mmol/L (190 mg/dL), 2) ≥4.14 mmol/L (160 mg/dL), 3) ≥3.36 mmol/L (130 mg/dL), 4) diabetes, 5) 10-year risk score ≥7.5% (treat all). OUTCOME MEASURES Myocardial infarction (MI), coronary heart disease (CHD) death, disability adjusted life years, costs RESULT OF BASE-CASE ANALYSIS All adults aged 75 and older in NHANES have a 10-year risk score >7.5%. If statins have no effect on functional limitation or cognitive impairment, all primary prevention strategies would prevent MIs and CHD deaths and be cost effective. The broadest strategy, treatment of all adults aged 75–94 years would result in 8 million additional users, and prevent 105,000 (4.3%) incident MIs and 68,000 (2.3%) CHD deaths at an incremental cost per disability adjusted life year of $25,200. RESULT OF SENSITIVITY ANALYSIS An increased relative risk of functional limitation or mild cognitive impairment in the range of 1.10 to 1.30 could offset the cardiovascular benefits. LIMITATIONS Limited trial evidence targeting primary prevention in adults 75 and older. CONCLUSIONS At effectiveness similar to trial findings, statins are projected to be cost-effective for primary prevention in adults age 75–94 years; however, even a small increase in geriatric specific side effects could offset the cardiovascular benefit. Improved data on the potential benefits and harms of statins are needed to

  12. Undiagnosed Hepatocellular Carcinoma Presenting as Nasal Metastases

    PubMed Central

    Mohammed, Hassen; Sheikh, Rashid; Rahman, Waheed; Sheta, Sally; Dogan, Zeynel

    2015-01-01

    Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with up to half of cases suffering from extrahepatic metastasis in the later stages of the disease. Commonly reported and encountered metastatic sites include the lymph nodes, lung, bone, and adrenal glands. This is an effort to throw a spotlight on a rare case of metastatic HCC which presented to us as two distinct lesions in the nose. It focuses on the presentation and the steps that were taken to reach this rare and unusual diagnosis. It sparks interest from a clinical and histopathology perspective. Our cynosure is the findings of the case coupled with a probe on the possible routes of spread of HCC to sinonasal region. PMID:26618018

  13. A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome 1q

    SciTech Connect

    Morissette, J.; Plante, M.; Raymond, V.

    1995-06-01

    Primary open-angle glaucoma (POAG), which causes progressive loss of the visual fields, was subdivided into two groups according to age at onset: (1) chronic open-angle glaucoma (COAG) diagnosed after 40 years and (2) juvenile open-angle glaucoma (JOAG) diagnosed between 3 years of age and early adulthood. A JOAG gene (GLC1A) was recently mapped to chromosome 1q. We studied 142 members of a huge multigenerational French Canadian family affected with autosomal dominant POAG. Either JOAG or COAG was diagnosed with ocular hypertension (OHT), which may lead to POAG. To localize a common disease gene that might be responsible for both glaucoma subsets, we performed linkage analysis considering JOAG and COAG under the same phenotypic category. JOAG/COAG was tightly linked to seven microsatellite markers on chromosome 1q23-q25; a maximum lod score of 6.62 was obtained with AF-M278ye5. To refine the disease locus, we exploited a recombination mapping strategy based on a unique founder effect. The same characteristic haplotype, composed of 14 markers spanning 12 cM between loci D1S196 and D1S212, was recognized in all persons affected by JOAG, COAG, or OHT, but it did not occur in unaffected spouses and in normal family members >35 years of age, except for three obligatory carriers. Key combination events confined the disease region within a 9-cM interval between loci D1S445 and D1S416/D1S480. These observations demonstrate that the GLC1A gene is responsible for both adult-onset and juvenile glaucomas and suggest that the JOAG and COAG categories within this family may be part of a clinical continuum artificially divided at age 40 years. 49 refs., 4 figs., 2 tabs.

  14. Developing the Botswana Primary Care Guideline: an integrated, symptom-based primary care guideline for the adult patient in a resource-limited setting

    PubMed Central

    Tsima, Billy M; Setlhare, Vincent; Nkomazana, Oathokwa

    2016-01-01

    Background Botswana’s health care system is based on a primary care model. Various national guidelines exist for specific diseases. However, most of the guidelines address management at a tertiary level and often appear nonapplicable for the limited resources in primary care facilities. An integrated symptom-based guideline was developed so as to translate the Botswana national guidelines to those applicable in primary care. The Botswana Primary Care Guideline (BPCG) integrates the care of communicable diseases, including HIV/AIDS and noncommunicable diseases, by frontline primary health care workers. Methods The Department of Family Medicine, Faculty of Medicine, University of Botswana, together with guideline developers from the Knowledge Translation Unit (University of Cape Town) collaborated with the Ministry of Health to develop the guideline. Stakeholder groups were set up to review specific content of the guideline to ensure compliance with Botswana government policy and the essential drug list. Results Participants included clinicians, academics, patient advocacy groups, and policymakers from different disciplines, both private and public. Drug-related issues were identified as necessary for implementing recommendations of the guideline. There was consensus by working groups for updating the essential drug list for primary care and expansion of prescribing rights of trained nurse prescribers in primary care within their scope of practice. An integrated guideline incorporating common symptoms of diseases seen in the Botswana primary care setting was developed. Conclusion The development of the BPCG took a broad consultative approach with buy in from relevant stakeholders. It is anticipated that implementation of the BPCG will translate into better patient outcomes as similar projects elsewhere have done. PMID:27570457

  15. Mandible metastasis of hepatocellular carcinoma.

    PubMed

    Niedzielska, Iwona; Langowska-Adamczyk, Helena; Pajak, Jacek; Kajor, Maciej; Niedzielski, Zbigniew; Gołka, Dariusz

    2004-01-01

    Metastases to oral cavity are very uncommon. We present a case of hepatocellular carcinoma (HCC) metastasis to the jaw. The x-ray examination and clinical picture of the lesion were not characteristic. The gingival metastasis may mimic other benign and malignant conditions which affect jaw and therefore the histopathological examination is necessary to make an ultimate diagnosis.

  16. Integrated care as a means to improve primary care delivery for adults and adolescents in the developing world: a critical analysis of Integrated Management of Adolescent and Adult Illness (IMAI)

    PubMed Central

    2014-01-01

    Background More than three decades after the 1978 Declaration of Alma-Ata enshrined the goal of ‘health for all’, high-quality primary care services remain undelivered to the great majority of the world’s poor. This failure to effectively reach the most vulnerable populations has been, in part, a failure to develop and implement appropriate and effective primary care delivery models. This paper examines a root cause of these failures, namely that the inability to achieve clear and practical consensus around the scope and aims of primary care may be contributing to ongoing operational inertia. The present work also examines integrated models of care as a strategy to move beyond conceptual dissonance in primary care and toward implementation. Finally, this paper examines the strengths and weaknesses of a particular model, the World Health Organization’s Integrated Management of Adolescent and Adult Illness (IMAI), and its potential as a guidepost toward improving the quality of primary care delivery in poor settings. Discussion Integration and integrated care may be an important approach in establishing a new paradigm of primary care delivery, though overall, current evidence is mixed. However, a number of successful specific examples illustrate the potential for clinical and service integration to positively impact patient care in primary care settings. One example deserving of further examination is the IMAI, developed by the World Health Organization as an operational model that integrates discrete vertical interventions into a comprehensive delivery system encompassing triage and screening, basic acute and chronic disease care, basic prevention and treatment services, and follow-up and referral guidelines. IMAI is an integrated model delivered at a single point-of-care using a standard approach to each patient based on the universal patient history and physical examination. The evidence base on IMAI is currently weak, but whether or not IMAI itself

  17. The evolving epidemiology of hepatocellular carcinoma: a global perspective.

    PubMed

    Wallace, Michael C; Preen, David; Jeffrey, Gary P; Adams, Leon A

    2015-06-01

    Primary liver cancer, the majority of which are hepatocellular carcinomas, is now the second leading cause of cancer death worldwide. Hepatocellular carcinoma is a unique cancer that typically arises in the setting of chronic liver disease at a rate dependent upon the complex interplay between the host, disease and environmental factors. Infection with chronic hepatitis B or C virus is currently the dominant risk factor worldwide. However, changing lifestyle and environmental factors in western countries plus rising neonatal hepatitis B vaccination rates and decreasing exposure to dietary aflatoxins in developing countries are driving an evolution of the epidemiology of this cancer. An understanding of this change is crucial in combating the rising incidence currently being seen in western regions and will underpin the efforts to reduce the mortality rates associated with this cancer.

  18. Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma.

    PubMed Central

    Lavaissiere, L; Jia, S; Nishiyama, M; de la Monte, S; Stern, A M; Wands, J R; Friedman, P A

    1996-01-01

    To characterize genes that become upregulated with malignant transformation of human hepatocytes, a library of monoclonal antibodies was produced against the FOCUS hepatocellular carcinoma cell line. Antibody FB-50 reacted with an antigen that was highly expressed in 4 of 10 primary hepatocellular carcinomas, in all 20 cholangiocarcinomas we studied, and in a variety of transformed cell lines. This antigen was also highly expressed in neoplastic epithelial cells of breast and colon carcinomas in contrast to its low level of expression in normal hepatocytes and in non-neoplastic epithelial cells. Among the normal adult tissues studied, high levels were observed only in proliferating trophoblastic cells of the placenta and in adrenal glands. A 636-bp partial cDNA, isolated from a gamma GT11 expression library generated with HepG2 human hepatoblastoma cells, and a complete cDNA, generated by reverse transcriptase-PCR, identified the antigen as the human form of aspartyl(asparaginyl)beta-hydroxylase. This enzyme catalyzes posttranslational hydroxylation of beta carbons of specific aspartyl and asparaginyl residues in EGF-like domains of certain proteins. Analyses of extracts prepared from several human tumor cell lines compared to their normal tissue counterparts indicate that the increase in hydroxylase, approximately 10-fold, is controlled at the level of transcription and the protein is expressed in an enzymatically active form. In similar analyses, comparing hepatocellular carcinomas to adjacent uninvolved liver from five patients, enzymatic activity was much higher in the tumor tissue from the four patients whose immunoblots revealed increased hydroxylase protein in the malignant tissue. EGF repeats in the extracellular domain of Notch or its homologs contain the consensus sequence for hydroxylation. Deletion mutants lacking this domain are gain-of-function mutants, suggesting that the domain modulates signal transduction by the cytoplasmic domain. While the

  19. 3-Tesla MRI Response to TACE in HCC (Liver Cancer)

    ClinicalTrials.gov

    2016-08-22

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

  20. [Tumor markers for hepatocellular carcinoma].

    PubMed

    Tateishi, Ryosuke; Enooku, Kenichiro; Shiina, Shuichiro; Koike, Kazuhiko

    2012-05-01

    Three tumor markers for hepatocellular carcinoma (HCC) are available in Japan: alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonists-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3). Although AFP has drawbacks in its specificity, it is widely utilized in treatment evaluation and prognosis prediction. PIVKA-II is a unique marker that does not correlate with AFP value and can predict microvascular invasion. AFP-L3 is a highly specific marker and strong predictor of poor prognosis. These three markers are indispensable in every aspect of clinical practice of hepatocellular carcinoma including surveillance, diagnosis, treatment evaluation, and prognosis prediction.

  1. Age-friendly primary health care: an assessment of current service provision for older adults in Hong Kong.

    PubMed

    Woo, Jean; Mak, Benise; Yeung, Fannie

    2013-01-01

    There has been no study evaluating whether primary care services are sufficiently oriented towards the older population in Hong Kong, particularly those with increasing frailty. Since primary care is a key first interface in promotion and maintenance of health in older people, an assessment of the age-friendliness of service provisions is of critical importance in optimizing the health of aging populations. The age-friendliness of primary care services for older people was assessed using focus groups of elderly people and also of service providers who care for them. Discussion content was based on the WHO guidelines for age-friendly primary care in the following areas: Information, education and training, community-based health care management systems, and the physical environment. Desirable improvements were identified in all domains. The findings underscore the need for wider dissemination of health care needs of older people in the primary care setting.

  2. [Current management of hepatocellular carcinoma].

    PubMed

    Ruiz, I; Féray, C

    2015-10-01

    Hepatocellular carcinoma is the major complication of chronic liver diseases and particularly of cirrhosis whatever its etiology. Once encountered mainly in the endemic countries of hepatitis B and C, the incidence of hepatocellular carcinoma (6/100,000) is parallel to the global development of diabetes, overweight and alcohol consumption. Little progress has been made for this cancer, whose mortality is 100 % at 10 years. Liver transplantation is the only truly curative treatment (survival more than 50 % at 10 years) since it allows the eradication of hepatocellular carcinoma and its essential cause, cirrhotic liver. This is the only possible therapy when liver function is impaired. It has little impact since in the richest countries, less than 10 % of cases can be transplanted. Surgical resection and percutaneous destruction methods (uni- and multipolar radiofrequency, microwave, cryotherapy, electroporation) are the preferred treatments (survival less than 50 % at 5 years) but are only applicable for moderate tumour masses and in the absence of adjuvant therapy, are effective only in the medium term. Most patients received chemoembolization through hepatic artery, whose action is modest. Radiotherapy is widely used in Asia but almost non-existent in Western countries in this indication. Sorafenib is the only effective drug but its impact is modest. Therapies combining two modalities (embolization and radiotherapy; embolization and radiofrequency) seem promising and deserve wider testing. Screening and monitoring of cirrhosis is probably the major measure for potentially curative therapies. PMID:26337474

  3. Vaccination coverage against 2009 seasonal influenza in chronically ill children and adults: analysis of population registries in primary care in Madrid (Spain).

    PubMed

    Rodríguez-Rieiro, Cristina; Domínguez-Berjón, Ma Felicitas; Esteban-Vasallo, María D; Sánchez-Perruca, Luis; Astray-Mochales, Jenaro; Fornies, Domingo Iniesta; Ordoñez, Dolores Barranco; Jiménez-García, Rodrigo

    2010-08-31

    Using electronic clinical records in primary care (ECRPC) of the entire population living in the Autonomous Community of Madrid, Spain (5,102,568 persons) as a data source, this study aimed to ascertain seasonal anti-influenza vaccination coverage in the chronically ill at-risk children (aged 6 months to 14 years) and adults (15-59 years). Of the total population aged 6 months to 59 years with a medical card in the Autonomous Community of Madrid, 10.3% (n=528,095 patients) had a chronic condition for which anti-influenza vaccination was indicated. In children with chronic conditions, coverage was 27.1% and it was particularly high among diabetics (41.1%) and particularly low in children with "other pulmonary conditions" (15.2%). In adults with chronic conditions, coverage was 22.1% and in patients with diagnosed heart failure coverage reached 39.1%; with the lowest coverage was observed in patients suffering neuromuscular diseases (12.8%). The factors associated with vaccination among children and adults suffering a chronic condition included: having been vaccinated during the previous campaign, national origin (lower among immigrants), and having more than one chronic condition. In conclusion, our study shows that vaccination coverage for 2009 seasonal influenza in children and adults with chronic conditions living in Madrid (Spain) was less than acceptable.

  4. Antigen selection for future anti-Trichuris vaccines: a comparison of cytokine and antibody responses to larval and adult antigen in a primary infection.

    PubMed

    Dixon, H; Johnston, C E; Else, K J

    2008-09-01

    Trichuriasis, caused by the whipworm Trichuris trichiura, is endemic in tropical and subtropical areas, affecting approximately 1 billion people. Child anthelminthic treatment programmes are being implemented but repeated treatments are costly, may prevent the development of acquired immunity and can lead to the development of drug resistant parasites. Thus, the development of a vaccine which would lead to the acquisition of immunity at an earlier age and reduce community faecal egg output would be beneficial. Development of subunit vaccines requires the identification of protective antigens and their formulation in a suitable adjuvant. Trichuris muris is an antigenically similar laboratory model for T. trichiura. Subcutaneous vaccination with adult excretory-secretory products (ES) protects susceptible mouse strains from T. muris. Larval stages may contain novel and more relevant antigens which when incorporated in a vaccine induce worm expulsion earlier in infection than the adult worm products. This study finds negligible difference in the cellular and humoral immune response to T. muris adult and third stage larva(e) (L3) ES during a primary T. muris infection, but identifies high molecular weight proteins in both adult and L3 ES as potential vaccine candidates.

  5. Antigen selection for future anti-Trichuris vaccines: a comparison of cytokine and antibody responses to larval and adult antigen in a primary infection.

    PubMed

    Dixon, H; Johnston, C E; Else, K J

    2008-09-01

    Trichuriasis, caused by the whipworm Trichuris trichiura, is endemic in tropical and subtropical areas, affecting approximately 1 billion people. Child anthelminthic treatment programmes are being implemented but repeated treatments are costly, may prevent the development of acquired immunity and can lead to the development of drug resistant parasites. Thus, the development of a vaccine which would lead to the acquisition of immunity at an earlier age and reduce community faecal egg output would be beneficial. Development of subunit vaccines requires the identification of protective antigens and their formulation in a suitable adjuvant. Trichuris muris is an antigenically similar laboratory model for T. trichiura. Subcutaneous vaccination with adult excretory-secretory products (ES) protects susceptible mouse strains from T. muris. Larval stages may contain novel and more relevant antigens which when incorporated in a vaccine induce worm expulsion earlier in infection than the adult worm products. This study finds negligible difference in the cellular and humoral immune response to T. muris adult and third stage larva(e) (L3) ES during a primary T. muris infection, but identifies high molecular weight proteins in both adult and L3 ES as potential vaccine candidates. PMID:18565148

  6. Rate of bleeding-related episodes in adult patients with primary immune thrombocytopenia: a retrospective cohort study using a large administrative medical claims database in the US

    PubMed Central

    Altomare, Ivy; Cetin, Karynsa; Wetten, Sally; Wasser, Jeffrey S

    2016-01-01

    Background Immune thrombocytopenia (ITP) is a rare disorder characterized by low platelet counts and an increased tendency to bleed. The goal of ITP therapy is to treat or prevent bleeding. Actual rates of bleeding are unknown. Clinical trial data may not reflect real-world bleeding rates because of the inclusion of highly refractory patients and more frequent use of rescue therapy. Methods We used administrative medical claims data in the US to examine the occurrence of bleeding-related episodes (BREs) – a composite end point including bleeding and/or rescue therapy use – in adults diagnosed with primary ITP (2008–2012). BRE rates were calculated overall and by ITP phase and splenectomy status. Patients were followed from ITP diagnosis until death, disenrollment from the health plan, or June 30, 2013, whichever came first. Results We identified 6,651 adults diagnosed with primary ITP over the study period (median age: 53 years; 59% female). During 13,064 patient-years of follow-up, 3,768 patients (57%) experienced ≥1 BRE (1.08 BREs per patient-year; 95% confidence interval: 1.06–1.10). The majority (58%) of BREs consisted of rescue therapy use only. Common bleeding types were gastrointestinal hemorrhage, hematuria, ecchymosis, and epistaxis. Intracranial hemorrhage was reported in 74 patients (1%). Just over 7% of patients underwent splenectomy. Newly diagnosed and splenectomized patients had elevated BRE rates. Conclusion We provide current real-world estimates of BRE rates in adults with primary ITP. The majority of ITP patients experienced ≥1 BRE, and over half were defined by rescue therapy use alone. This demonstrates the importance of examining both bleeding and rescue therapy use to fully assess disease burden. PMID:27382333

  7. Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review.

    PubMed

    Lee, Edward Wolfgang; Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

    2016-01-01

    Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma. PMID:27390539

  8. Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

    PubMed Central

    Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

    2016-01-01

    Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma. PMID:27390539

  9. Prescribing Exercise for Older Adults: A Needs Assessment Comparing Primary Care Physicians, Nurse Practitioners, and Physician Assistants

    ERIC Educational Resources Information Center

    Dauenhauer, Jason A.; Podgorski, Carol A.; Karuza, Jurgis

    2006-01-01

    To inform the development of educational programming designed to teach providers appropriate methods of exercise prescription for older adults, the authors conducted a survey of 177 physicians, physician assistants, and nurse practitioners (39% response rate). The survey was designed to better understand the prevalence of exercise prescriptions,…

  10. Differences in Childhood Sexual Abuse Experience between Adult Hispanic and Anglo Women in a Primary Care Setting

    ERIC Educational Resources Information Center

    Katerndahl, David A.; Burge, Sandra K.; Kellogg, Nancy; Parra, Juan M.

    2005-01-01

    The literature on racial and ethnic factors in childhood sexual abuse is limited. The purpose of this exploratory study was to document Hispanic-Anglo differences in childhood sexual abuse experiences and assess whether these differences may be explained by socio-demographic and family environmental differences. Adult Hispanic (n = 69) and Anglo…

  11. Cognitive Behavioral Treatment for Older Adults with Generalized Anxiety Disorder: A Therapist Manual for Primary Care Settings

    ERIC Educational Resources Information Center

    Stanley, Melinda A.; Diefenbach, Gretchen J.; Hopko, Derek R.

    2004-01-01

    At least four academic clinical trials have demonstrated the utility of cognitive behavior therapy (CBT) for older adults with generalized anxiety disorder (GAD). These data may not generalize, however, to more heterogeneous and functionally impaired patients and the medical settings in which they typically receive care. A recent pilot project…

  12. Possible risk factors for primary adult onset dystonia: a case-control investigation by the Italian Movement Disorders Study Group

    PubMed Central

    Defazio, G.; Berardelli, A.; Abbruzzese, G.; Lepore, V.; Coviello, V.; Acquistapace, D.; Capus, L.; Carella, F.; De Berardinis, M. T.; Galardi, G.; Girlanda, P.; Maurri, S.; Albanese, A.; Bertolasi, L.; Liguori, R.; Rossi, A.; Santoro, L.; Tognoni, G.; Livrea, P.

    1998-01-01

    OBJECTIVES—Little is known about the aetiology of idiopathic adult onset dystonia. The Italian Movement Disorders Study Group promoted a case-control study on some hypothetical risk factors including past medical events, life events, life habits, occupational hazards, and family hystory of dystonia, parkinsonism, and tremor.
METHODS—Cases affected by idiopathic adult onset dystonia (age at symptom onset >20 years, duration of disease >one year and adult onset dystonia, whereas hypertension and cigarette smoking exerted a protective effect. The findings also suggested a positive association between local body injury—for example, previous ocular diseases and neck or trunk trauma—and dystonia of the same body part.
CONCLUSIONS—The results support the idea that environmental and genetic factors may both be important in the aetiology of adult onset dystonia, and suggest aetiological clues worthy of further analytical investigation.

 PMID:9436723

  13. Medication Use among Australian Adults with Intellectual Disability in Primary Healthcare Settings: A Cross-Sectional Study

    ERIC Educational Resources Information Center

    Doan, Tan N.; Lennox, Nicholas G.; Taylor-Gomez, Miriam; Ware, Robert S.

    2013-01-01

    Background: There is concern about widespread medication use by people with intellectual disability (ID), especially psychotropic and anticonvulsant agents. However, there is sparse information on prescribing patterns in Australia. Method: This cross-sectional study was conducted between 2000 and 2002 among adults with ID who live in the community…

  14. [Diagnostics and treatment of hepatocellular adenomas].

    PubMed

    Klompenhouwer, A J; de Man, R A; Thomeer, M G J; Doukas, M; IJzermans, J N M

    2016-01-01

    - Hepatocellular adenomas are essentially benign tumours of the liver that occur mostly in women of reproductive age. - The four different subtypes described, which can be distinguished both radiologically and histopathologically, are: steatotic, inflammatory, β-catenin mutated and unclassified adenomas. These subtypes differ in the risk of complications.- Contrast-enhanced liver MRI is the best method for diagnostics and characterization of hepatocellular adenomas. - Possible complications include bleeding, rupture, and malignant degeneration of the hepatocellular adenoma. These complications are rare in adenomas < 5 cm. - Men with hepatocellular adenomas are at higher risk for malignant degeneration. - In women, lifestyle changes (cessation of oral contraceptive and weight reduction) can cause regression of the adenoma, which can prevent the necessity for liver surgery. - In pregnant women there is a risk of growth of hepatocellular adenoma. It is, therefore, it is recommended to check the tumour in pregnant women every 6-12 weeks using ultrasound. PMID:27650020

  15. Primary care-based educational interventions to decrease risk factors for metabolic syndrome for adults with major psychotic and/or affective disorders: a systematic review

    PubMed Central

    2013-01-01

    Background Individuals with major psychotic and/or affective disorders are at increased risk for developing metabolic syndrome due to lifestyle- and treatment-related factors. Numerous pharmacological and non-pharmacological interventions have been tested in inpatient and outpatient mental health settings to decrease these risk factors. This review focuses on primary care-based non-pharmacological (educational or behavioral) interventions to decrease metabolic syndrome risk factors in adults with major psychotic and/or affective disorders. Methods The authors conducted database searches of PsychINFO, MEDLINE and the Cochrane Database of Systematic Reviews, as well as manual searches and gray literature searches to identify included studies. Results The authors were unable to identify any studies meeting a priori inclusion criteria because there were no primary care-based studies. Conclusions This review was unable to demonstrate effectiveness of educational interventions in primary care. Interventions to decrease metabolic syndrome risk have been demonstrated to be effective in mental health and other outpatient settings. The prevalence of mental illness in primary care settings warrants similar interventions to improve health outcomes for this population. PMID:24369749

  16. Imaging Features of Primary Tumors and Metastatic Patterns of the Extraskeletal Ewing Sarcoma Family of Tumors in Adults: A 17-Year Experience at a Single Institution

    PubMed Central

    Huh, Jimi; Park, Seong Joon; Kim, Hyoung Jung; Lee, Jong Seok; Ha, Hyun Kwon; Tirumani, Sree Harsha; Ramaiya, Nikhil H.

    2015-01-01

    Objective To comprehensively analyze the spectrum of imaging features of the primary tumors and metastatic patterns of the Extraskeletal Ewing sarcoma family of tumors (EES) in adults. Materials and Methods We performed a computerized search of our hospital's data-warehouse from 1996 to 2013 using codes for Ewing sarcoma and primitive neuroectodermal tumors as well as the demographic code for ≥ 18 years of age. We selected subjects who were histologically confirmed to have Ewing sarcoma of extraskeletal origin. Imaging features of the primary tumor and metastatic disease were evaluated for lesion location, size, enhancement pattern, necrosis, margin, and invasion of adjacent organs. Results Among the 70 patients (mean age, 35.8 ± 15.6 years; range, 18-67 years) included in our study, primary tumors of EES occurred in the soft tissue and extremities (n = 20), abdomen and pelvis (n = 18), thorax (n = 14), paravertebral space (n = 8), head and neck (n = 6), and an unknown primary site (n = 4). Most primary tumors manifested as large and bulky soft-tissue masses (mean size, 9.0 cm; range, 1.3-23.0 cm), frequently invading adjacent organs (45.6%) and showed heterogeneous enhancement (73.7%), a well-defined (66.7%) margin, and partial necrosis/cystic degeneration (81.9%). Notably, 29 patients had metastatic disease detected at their initial diagnosis. The most frequent site of metastasis was lymph nodes (75.9%), followed by bone (31.0%), lung (20.7%), abdominal solid organs (13.8%), peritoneum (13.8%), pleura (6.9%), and brain (3.4%). Conclusion Primary tumors of EES can occur anywhere and mostly manifest as large and bulky, soft-tissue masses. Lymph nodes are the most frequent metastasis sites. PMID:26175577

  17. Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells.

    PubMed

    Oikawa, Tsunekazu; Wauthier, Eliane; Dinh, Timothy A; Selitsky, Sara R; Reyna-Neyra, Andrea; Carpino, Guido; Levine, Ronald; Cardinale, Vincenzo; Klimstra, David; Gaudio, Eugenio; Alvaro, Domenico; Carrasco, Nancy; Sethupathy, Praveen; Reid, Lola M

    2015-01-01

    The aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs), cancers occurring increasingly in children to young adults, is poorly understood. We present a transplantable tumour line, maintained in immune-compromised mice, and validate it as a bona fide model of hFL-HCCs by multiple methods. RNA-seq analysis confirms the presence of a fusion transcript (DNAJB1-PRKACA) characteristic of hFL-HCC tumours. The hFL-HCC tumour line is highly enriched for cancer stem cells as indicated by limited dilution tumourigenicity assays, spheroid formation and flow cytometry. Immunohistochemistry on the hFL-HCC model, with parallel studies on 27 primary hFL-HCC tumours, provides robust evidence for expression of endodermal stem cell traits. Transcriptomic analyses of the tumour line and of multiple, normal hepatic lineage stages reveal a gene signature for hFL-HCCs closely resembling that of biliary tree stem cells--newly discovered precursors for liver and pancreas. This model offers unprecedented opportunities to investigate mechanisms underlying hFL-HCCs pathogenesis and potential therapies.

  18. Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells.

    PubMed

    Oikawa, Tsunekazu; Wauthier, Eliane; Dinh, Timothy A; Selitsky, Sara R; Reyna-Neyra, Andrea; Carpino, Guido; Levine, Ronald; Cardinale, Vincenzo; Klimstra, David; Gaudio, Eugenio; Alvaro, Domenico; Carrasco, Nancy; Sethupathy, Praveen; Reid, Lola M

    2015-01-01

    The aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs), cancers occurring increasingly in children to young adults, is poorly understood. We present a transplantable tumour line, maintained in immune-compromised mice, and validate it as a bona fide model of hFL-HCCs by multiple methods. RNA-seq analysis confirms the presence of a fusion transcript (DNAJB1-PRKACA) characteristic of hFL-HCC tumours. The hFL-HCC tumour line is highly enriched for cancer stem cells as indicated by limited dilution tumourigenicity assays, spheroid formation and flow cytometry. Immunohistochemistry on the hFL-HCC model, with parallel studies on 27 primary hFL-HCC tumours, provides robust evidence for expression of endodermal stem cell traits. Transcriptomic analyses of the tumour line and of multiple, normal hepatic lineage stages reveal a gene signature for hFL-HCCs closely resembling that of biliary tree stem cells--newly discovered precursors for liver and pancreas. This model offers unprecedented opportunities to investigate mechanisms underlying hFL-HCCs pathogenesis and potential therapies. PMID:26437858

  19. Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells

    PubMed Central

    Oikawa, Tsunekazu; Wauthier, Eliane; Dinh, Timothy A.; Selitsky, Sara R.; Reyna-Neyra, Andrea; Carpino, Guido; Levine, Ronald; Cardinale, Vincenzo; Klimstra, David; Gaudio, Eugenio; Alvaro, Domenico; Carrasco, Nancy; Sethupathy, Praveen; Reid, Lola M.

    2015-01-01

    The aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs), cancers occurring increasingly in children to young adults, is poorly understood. We present a transplantable tumour line, maintained in immune-compromised mice, and validate it as a bona fide model of hFL-HCCs by multiple methods. RNA-seq analysis confirms the presence of a fusion transcript (DNAJB1-PRKACA) characteristic of hFL-HCC tumours. The hFL-HCC tumour line is highly enriched for cancer stem cells as indicated by limited dilution tumourigenicity assays, spheroid formation and flow cytometry. Immunohistochemistry on the hFL-HCC model, with parallel studies on 27 primary hFL-HCC tumours, provides robust evidence for expression of endodermal stem cell traits. Transcriptomic analyses of the tumour line and of multiple, normal hepatic lineage stages reveal a gene signature for hFL-HCCs closely resembling that of biliary tree stem cells—newly discovered precursors for liver and pancreas. This model offers unprecedented opportunities to investigate mechanisms underlying hFL-HCCs pathogenesis and potential therapies. PMID:26437858

  20. Single nucleotide polymorphism (SNP) analysis demonstrates a significant association of tumour necrosis factor-alpha (TNFA) with primary immune thrombocytopenia among Caucasian adults.

    PubMed

    Sarpatwari, Ameet; Bussel, James B; Ahmed, Momin; Erqou, Sebhat; Semple, John W; Newland, Adrian C; Bennett, Dimitri; Pharoah, Paul; Provan, Drew

    2011-07-01

    T-helper 1 polarization in patients with primary immune thrombocytopenia (ITP) is well documented. However, the genetic contribution to this imbalance remains unclear. To address this question, we selected six candidate single nucleotide polymorphisms within cytokine or cytokine receptor genes for association testing among Caucasian adults. Patients from the United Kingdom Adult ITP Registry were gender-matched (1:3) with healthy controls from the Wellcome Trust Case Control Consortium. Variants IL10 -819 c>t, TNFA -308 g>a, TGFB1 -509 c>t, IL1A -889 c>t, IL10 -592 c>t, and IL4R q576r were measured in cases and retrieved for controls from the European Genome-phenome Archive. Associations were evaluated using logistic regression models. In total, 206 patients with primary ITP were matched with 618 controls. A significant per allele odds ratio of 1·34 (95% confidence interval, 1·03-1·75; P = 0·03) was observed for TNFA -308 g>a, implicating an increased disease susceptibility among Caucasian carriers of the rare allele.

  1. Induction of benzo(a)pyrene metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin in primary cultures of adult rat hepatocytes: regulation by vitamin A

    SciTech Connect

    Steward, A.R.

    1982-01-01

    In order to develop a cellular model for studying mechanisms of enzyme induction and the effects of this induction on xenobiotic metabolism and cytotoxicity, the induction of benzo(a)pyrene (BaP) metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated in primary hepatocyte cultures prepared from adult male rats and maintained in chemically-defined medium containing hormones. A derepression of induction was observed during the first 3 days in culture. Addition of 0.8 to 2.0 ..mu..g/ml of retinol acetate (RA) prevented about half of the derepression of induction occurring between 36 and 60 h in culture. Horse serum (10%) also blocked up to half of the observed derepression. Serum, however, also led to a 40% reduction in the partitioning of (/sup 3/H)TCDD from the medium into the hepatocytes. The derepresion of MFO induction in primary adult hepatocyte cultures may occur partly as a result of a deficiency of retinol. RA is hypothesized to slow the time course of induction by reducing the rate of protein turnover. RA may also partially block the shift in the dose-response curve for induction by TCDD by maintaining the normal metabolic regulation of the cytosolic receptor for TCDD. Addition of a physiological level of RA to the culture medium may therefore help to maintain the hepatocytes at a level of genetic expression more nearly representative of the intact liver.

  2. Effectiveness of Nurse-Practitioner-Delivered Brief Motivational Intervention for Young Adult Alcohol and Drug Use in Primary Care in South Africa: A Randomized Clinical Trial

    PubMed Central

    Mertens, Jennifer R.; Ward, Catherine L.; Bresick, Graham F.; Broder, Tina; Weisner, Constance M.

    2014-01-01

    Aims: To assess the effectiveness of brief motivational intervention for alcohol and drug use in young adult primary care patients in a low-income population and country. Methods: A randomized controlled trial in a public-sector clinic in Delft, a township in the Western Cape, South Africa recruited 403 patients who were randomized to either single-session, nurse practitioner-delivered Brief Motivational Intervention plus referral list or usual care plus referral list, and followed up at 3 months. Results: Although rates of at-risk alcohol use and drug use did not differ by treatment arm at follow-up, patients assigned to the Brief Motivational Intervention had significantly reduced scores on ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) for alcohol—the most prevalent substance. Conclusion: Brief Motivational Intervention may be effective at reducing at-risk alcohol use in the short term among low-income young adult primary care patients; additional research is needed to examine long-term outcomes. PMID:24899076

  3. Transhemangioma Ablation of Hepatocellular Carcinoma

    SciTech Connect

    Pua, Uei

    2012-12-15

    Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

  4. Oncogenic viruses and hepatocellular carcinoma.

    PubMed

    Ben Ari, Ziv; Weitzman, Ella; Safran, Michal

    2015-05-01

    About 80% of hepatocellular carcinoma (HCC) is caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections especially in the setting of established cirrhosis or advanced fibrosis, making HCC prevention a major goal of antiviral therapy. HCC tumors are highly complex and heterogeneous resulting from the aberrant function of multiple molecular pathways. The roles of HCV or HBV in promoting HCC development are still either directly or indirectly are still speculative, but the evidence for both effects is compelling. In patients with chronic hepatitis viral infection, cirrhosis is not a prerequisite for tumorigenesis.

  5. Targeted Therapy for Hepatocellular Carcinoma.

    PubMed

    Ohri, Nitin; Kaubisch, Andreas; Garg, Madhur; Guha, Chandan

    2016-10-01

    Hepatocellular cancer (HCC) is a leading cause of cancer death worldwide, and most patients who are diagnosed with HCC are ineligible for curative local therapy. The targeted agent sorafenib provides modest survival benefits in the setting of advanced disease. Novel systemic treatment options for HCC are sorely needed. In this review, we identify and categorize the drugs and targets that are in various phases of testing for use against HCC. We also focus on the potential for combining these agents with radiotherapy. This would help identify directions for future study that are likely to yield positive findings and improve outcomes for patients with HCC. PMID:27619254

  6. The Impact of Adult Mortality on Primary School Enrollment in Northwestern Tanzania. Africa Region Human Development Working Paper Series.

    ERIC Educational Resources Information Center

    Ainsworth, Martha; Beegle, Kathleen; Koda, Godlike

    The AIDS epidemic is making orphans out of many African children and threatens to reverse hard-won gains in raising school enrollments. The average gross primary enrollment ration (GPER) the number of children enrolled as a percent of the total number of children of school age was only 77% for Sub-Saharan Africa in 1996. The countries are hard-hit…

  7. Adult immunization

    PubMed Central

    Mehta, Bharti; Chawla, Sumit; Kumar Dharma, Vijay; Jindal, Harashish; Bhatt, Bhumika

    2014-01-01

    Vaccination is recommended throughout life to prevent vaccine-preventable diseases and their sequel. The primary focus of vaccination programs has historically been directed to childhood immunizations. For adults, chronic diseases have been the primary focus of preventive and medical health care, though there has been increased emphasis on preventing infectious diseases. Adult vaccination coverage, however, remains low for most of the routinely recommended vaccines. Though adults are less susceptible to fall prey to traditional infectious agents, the probability of exposure to infectious agents has increased manifold owing to globalization and increasing travel opportunities both within and across the countries. Thus, there is an urgent need to address the problem of adult immunization. The adult immunization enterprise is more complex, encompassing a wide variety of vaccines and a very diverse target population. There is no coordinated public health infrastructure to support an adult immunization program as there is for children. Moreover, there is little coordination among adult healthcare providers in terms of vaccine provision. Substantial improvement in adult vaccination is needed to reduce the health consequences of vaccine-preventable diseases among adults. Routine assessment of adult patient vaccination needs, recommendation, and offer of needed vaccines for adults should be incorporated into routine clinical care of adults. PMID:24128707

  8. Outcome and molecular characteristics of adolescent and young adult patients with newly diagnosed primary glioblastoma: a study of the Society of Austrian Neurooncology (SANO)

    PubMed Central

    Leibetseder, Annette; Ackerl, Michael; Flechl, Birgit; Wöhrer, Adelheid; Widhalm, Georg; Dieckmann, Karin; Kreinecker, Sabine-Spiegl; Pichler, Josef; Hainfellner, Johannes; Preusser, Matthias; Marosi, Christine

    2013-01-01

    Background Young age is a favorable prognostic factor for patients with glioblastoma multiforme (GBM). We reviewed the outcomes and molecular tumor characteristics of adolescent and young adult patients with GBM treated in 2 Austrian centers. Patients and Methods Data on patients with histologically proven primary GBM diagnosed from 18 through 40 years of age were retrospectively analyzed. All patients were treated with standard first-line therapy. The primary end points were overall survival (OS) and time to progression (TTP). IDH1-R132H mutation status was analyzed using immunohistochemistry, and MGMT promoter methylation was assessed using methylation-specific polymerase chain reaction. Results We included 70 patients (36 men and 34 women) with a median age of 33 years. IDH1-R132H mutations were detected in 22 (39.3%) of 56 cases and MGMT promoter methylation in 33 (61.1%) of 54 cases with available tissue samples. In patients with wild-type IDH, median TTP was 8.2 months and median OS was 24 months, compared with 18 months and 44 months, respectively, observed in patients with mutated IDH. Neither IDH1 nor MGMT status showed a statistically significant association with TTP or OS. Of note, the social and economical situation of the young patients with GBM was alarming, because only 17% succeeded in staying employed after receiving the diagnosis. Conclusions We found a high frequency of IDH1 mutations and MGMT promoter methylation among young adult patients with primary GBM that may contribute to the generally favorable outcome associated with young age. The social and economic coverage of patients with glioma remains an unsolved socio-ethical problem. PMID:23223340

  9. Hepatocellular carcinoma: modern image-guided therapies.

    PubMed

    Puppala, Sapna; Patel, Rafiuddin; Yap, Ki Sing; Patel, Jai; Wah, Tze; Snoddon, Andrew

    2016-03-01

    The most common primary malignancy of the liver and the third leading cause of cancer mortality worldwide is hepatocellular carcinoma (HCC), which presents a major global health problem due to its increasing incidence. Most cases of HCC are secondary to either infection (hepatitis B or C) or cirrhosis (alcohol being the most common cause). Clinical presentation is variable and the tumour can be an incidental finding. Treatment options for HCC and prognosis are dependent on many factors but most importantly tumour size and staging. The last two decades have revolutionised the treatment of HCC using image-guided techniques. The concepts of imaging and image-guided techniques are still young and not well described in standard textbooks and hence an up to date review article is essential. The clinical subspecialities may lack familiarity with image-guided techniques but are responsible for management of these patients before and after the treatment by interventional radiologists. This article reviews current image-guided techniques, evidence and outcomes and provides educational highlights and question and answers. The article provides an overview in a simple understandable manner to enable readers from various levels of practice and training to benefit from and apply in their practice. PMID:26787919

  10. Liver-Directed Radiotherapy for Hepatocellular Carcinoma

    PubMed Central

    Keane, Florence K.; Wo, Jennifer Y.; Zhu, Andrew X.; Hong, Theodore S.

    2016-01-01

    Background The incidence of hepatocellular carcinoma (HCC) continues to increase world-wide. Many patients present with advanced disease with extensive local tumor or vascular invasion and are not candidates for traditionally curative therapies such as orthotopic liver transplantation (OLT) or resection. Radiotherapy (RT) was historically limited by its inability to deliver a tumoricidal dose; however, modern RT techniques have prompted renewed interest in the use of liver-directed RT to treat patients with primary hepatic malignancies. Summary The aim of this review was to discuss the use of external beam RT in the treatment of HCC, with particular focus on the use of stereotactic body radiotherapy (SBRT). We review the intricacies of SBRT treatment planning and delivery. Liver-directed RT involves accurate target identification, precise and reproducible patient immobilization, and assessment of target and organ motion. We also summarize the published data on liver-directed RT, and demonstrate that it is associated with excellent local control and survival rates, particularly in patients who are not candidates for OLT or resection. Key Messages Modern liver-directed RT is safe and effective for the treatment of HCC, particularly in patients who are not candidates for OLT or resection. Liver-directed RT, including SBRT, depends on accurate target identification, precise and reproducible patient immobilization, and assessment of target and organ motion. Further prospective studies are needed to fully delineate the role of liver-directed RT in the treatment of HCC. PMID:27493895

  11. Potentiality of immunotherapy against hepatocellular carcinoma.

    PubMed

    Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Uemura, Yasushi; Nakatsura, Tetsuya

    2015-09-28

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options remain limited for advanced HCC, and as a result prognosis continues to be poor. Current therapeutic options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising, novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here, we summarize the various types of HCC immunotherapy and argue that the new-found field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies, such as tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer immunotherapy, have demonstrated safety and feasibility in HCC patients. Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this challenge will place immunotherapy at the forefront of HCC treatment, possibly in the near future.

  12. Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey

    PubMed Central

    Cotrim, Helma P.; Oliveira, Claudia P.; Coelho, Henrique Sérgio M.; Alvares-da-Silva, Mario R.; Nabuco, Leticia; Parise, Edison Roberto; Ivantes, Claúdia; Martinelli, Ana LC; Galizzi-Filho, João; Carrilho, Flair J.

    2016-01-01

    OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>20 g/day) and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases' 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul). The mean age was 67±11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3), in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, ≥3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in patients with and

  13. Intracellular signaling and hepatocellular carcinoma.

    PubMed

    Iakova, Polina; Timchenko, Lubov; Timchenko, Nikolai A

    2011-02-01

    Liver cancer is the fifth most common cancer and the third most common cause of cancer related death in the world. The recent development of new techniques for the investigations of global change in the gene expression, signaling pathways and wide genome binding has provided novel information for the mechanisms underlying liver cancer progression. Although these studies identified gene expression signatures in hepatocellular carcinoma, the early steps of the development of hepatocellular carcinomas (HCC) are not well understood. The development of HCC is a multistep process which includes the progressive alterations of gene expression leading to the increased proliferation and to liver cancer. This review summarizes recent progress in the identification of the key steps of the development of HCC with the focus on early events of carcinogenesis and on the role of translational and epigenetic alterations in the development of HCC. Quiescent stage of the liver is supported by several tumor suppressor proteins including p53, Rb and C/EBPα. Studies with chemical models of liver carcinogenesis and with human HCC have shown that the elevation of gankyrin is responsible for the elimination of these three proteins at early steps of carcinogenesis. Later stages of progression of the liver cancer are associated with alterations in many signaling pathways including translation which leads to epigenetic silencing/activation of many genes. Particularly, recent reports suggest a critical role of histone deacetylase 1, HDAC1, in the development of HCC through the interactions with transcription factors such as C/EBP family proteins. PMID:20850540

  14. Tailored weight loss intervention in obese adults within primary care practice: rationale, design, and methods of Choose to Lose.

    PubMed

    Hartman, Sheri J; Risica, Patricia M; Gans, Kim M; Marcus, Bess H; Eaton, Charles B

    2014-07-01

    Although there are efficacious weight loss interventions that can improve health and delay onset of diabetes and hypertension, these interventions have not been translated into clinical practice. The primary objective of this study is to evaluate the effectiveness and cost effectiveness of a tailored lifestyle intervention in primary care patients. Patients were recruited by their primary care physicians and eligible participants were randomized to an enhanced intervention or standard intervention. All participants met with a lifestyle counselor to set calorie and physical activity goals and to discuss behavioral strategies at baseline, 6 and 12 months. During the first year, enhanced intervention participants receive monthly counseling phone calls to assist in attaining and maintaining their goals. Enhanced intervention participants also receive weekly mailings consisting of tailored and non-tailored print materials and videos focusing on weight loss, physical activity promotion and healthy eating. The second year focuses on maintenance with enhanced intervention participants receiving tailored and non-tailored print materials and videos regularly throughout the year. Standard intervention participants receive five informational handouts on weight loss across the two years. This enhanced intervention that consists of multiple modalities of print, telephone, and video with limited face-to-face counseling holds promise for being effective for encouraging weight loss, increasing physical activity and healthy eating, and also for being cost effective and generalizable for wide clinical use. This study will fill an important gap in our knowledge regarding the translation and dissemination of research from efficacy studies to best practices in clinical settings. PMID:24937016

  15. Tailored weight loss intervention in obese adults within primary care practice: rationale, design, and methods of Choose to Lose.

    PubMed

    Hartman, Sheri J; Risica, Patricia M; Gans, Kim M; Marcus, Bess H; Eaton, Charles B

    2014-07-01

    Although there are efficacious weight loss interventions that can improve health and delay onset of diabetes and hypertension, these interventions have not been translated into clinical practice. The primary objective of this study is to evaluate the effectiveness and cost effectiveness of a tailored lifestyle intervention in primary care patients. Patients were recruited by their primary care physicians and eligible participants were randomized to an enhanced intervention or standard intervention. All participants met with a lifestyle counselor to set calorie and physical activity goals and to discuss behavioral strategies at baseline, 6 and 12 months. During the first year, enhanced intervention participants receive monthly counseling phone calls to assist in attaining and maintaining their goals. Enhanced intervention participants also receive weekly mailings consisting of tailored and non-tailored print materials and videos focusing on weight loss, physical activity promotion and healthy eating. The second year focuses on maintenance with enhanced intervention participants receiving tailored and non-tailored print materials and videos regularly throughout the year. Standard intervention participants receive five informational handouts on weight loss across the two years. This enhanced intervention that consists of multiple modalities of print, telephone, and video with limited face-to-face counseling holds promise for being effective for encouraging weight loss, increasing physical activity and healthy eating, and also for being cost effective and generalizable for wide clinical use. This study will fill an important gap in our knowledge regarding the translation and dissemination of research from efficacy studies to best practices in clinical settings.

  16. Sex Differences in Biopsychosocial Correlates of Binge Eating Disorder: A Study of Treatment-Seeking Obese Adults in Primary Care Setting

    PubMed Central

    Udo, Tomoko; McKee, Sherry A.; White, Marney A.; Masheb, Robin M.; Barnes, Rachel D.; Grilo, Carlos M.

    2013-01-01

    Objective Although community-based studies suggest equivalent levels of physical and psychological impairment by BED in men and women, men with binge eating disorder (BED) are still underrepresented in clinical studies. This study aimed to provide a comprehensive analysis of sex differences in biopsychosocial correlates of treatment-seeking obese patients with BED in primary care. Method One-hundred-ninety obese adults (26% men) were recruited in primary care settings for a treatment study for obesity and BED. Results Very few significant sex differences were found in the developmental history and in current levels of eating-disorder features, as well as psychosocial factors. Women reported significantly earlier age at onset of overweight and dieting, and greater frequency of dieting. Men reported more frequent strenuous exercise. Men were more likely than women to meet criteria for metabolic syndrome (MetS); men were more likely to show clinically elevated levels of triglycerides, blood pressure, and fasting glucose levels. Conclusion Despite few sex differences in behavioral and psychosocial factors, metabolic problems associated with obesity were more common among treatment-seeking obese men with BED than women. The findings highlight the importance of including men in clinical studies of BED, and active screening of BED in obese men at primary care settings. PMID:23969142

  17. Tailored weight loss intervention in obese adults within primary care practice: Rationale, design, and methods of Choose to Lose

    PubMed Central

    Hartman, Sheri J.; Risica, Patricia M.; Gans, Kim M.; Marcus, Bess H.; Eaton, Charles B.

    2014-01-01

    Although there are efficacious weight loss interventions that can improve health and delay onset of diabetes and hypertension, these interventions have not been translated into clinical practice. The primary objective of this study is to evaluate the effectiveness and cost effectiveness of a tailored lifestyle intervention in primary care patients. Patients were recruited by their primary care physicians and eligible participants were randomized to an enhanced intervention or augmented usual care. All participants met with a lifestyle counselor to set calorie and physical activity goals and to discuss behavioral strategies at baseline, 6 and 12 months. During the first year, enhanced intervention participants receive monthly counseling phone calls to assist in attaining and maintaining their goals. Enhanced intervention participants also receive weekly mailings consisting of tailored and non-tailored print materials and videos focusing on weight loss, physical activity promotion and healthy eating. The second year focuses on maintenance with enhanced intervention participants receiving tailored and non-tailored print materials and videos regularly throughout the year. Augmented usual care participants receive five informational handouts on weight loss across the two years. This enhanced intervention that consists of multiple modalities of print, telephone, and video with limited face-to-face counseling holds promise for being effective for encouraging weight loss, increasing physical activity and healthy eating, and also for being cost effective and generalizable for wide clinical use. This study will fill an important gap in our knowledge regarding the translation and dissemination of research from efficacy studies to best practices in clinical settings. PMID:24937016

  18. Cardiac arrhythmias as the initial manifestation of adult primary Sjögren's syndrome: a case report and literature review.

    PubMed

    Liang, Minrui; Bao, Liwen; Xiong, Nanqing; Jin, Bo; Ni, Huanchun; Zhang, Jinjin; Zou, Hejian; Luo, Xinping; Li, Jian

    2015-09-01

    Two middle-aged female patients presenting with heart palpitation and electrocardiogram revealed complex cardiac arrhythmias. A review of systems was positive for dry mouth and transient arthralgia, while laboratory and instrumental tests enabled us to make the diagnosis of primary Sjögren's syndrome (pSS). Cardiac electrophysiology revealed atrioventricular node dysfunction and impaired intraventricular conduction. Prednisone therapy induced a significant improvement in symptoms and electrocardiographic readings. The diagnosis of pSS should be considered in a patient presenting with complex cardiac arrhythmias.

  19. Concentrations of unmetabolized folic acid and primary folate forms in plasma after folic acid treatment in older adults.

    PubMed

    Obeid, Rima; Kirsch, Susanne H; Kasoha, Mariz; Eckert, Rudolf; Herrmann, Wolfgang

    2011-05-01

    Folate deficiency can cause age-related disease. Folic acid (FA) has been used in studies aiming at disease prevention. Recently, unmetabolized FA in plasma raised public health concerns; but numerous studies used FA for disease prevention. Concentrations of the folate forms FA, 5-methyltetrahydrofolate (5-MTHF), and tetrahydrofolate (THF) were measured before and after 3-week placebo or FA 5 mg, vitamin B6 40 mg, and cyanocobalamin 2 mg per day administrated to 74 older adults (median age, 82 years). Concentrations of 5-MTHF and total homocysteine (tHcy) (r = -0.392) and S-adenosylmethionine (r = 0.329) were correlated at baseline. Twenty-six percent of the elderly subjects had unmetabolized FA in plasma at the start, and concentrations of FA were increased after 3 weeks of FA treatment (median FA = 0.08 nmol/L at baseline and 15.3 nmol/L at the end of the treatment in the vitamin group). Folic acid caused a 10- and a 5-fold increase in 5-MTHF and THF, respectively, and lowered tHcy (median tHcy = 17.2 μmol/L at baseline vs 9.0 μmol/L after treatment). Concentrations of unmetabolized FA were positively related to those of 5-MTHF and THF. People showed wide variations in folate forms at baseline, but these were reduced after FA treatment. Folic acid given to older adults is mostly converted to THF and 5-MTHF and lowered concentrations of tHcy, but caused a substantial increase in unmetabolized FA in the plasma.

  20. Aetiological role of viral and bacterial infections in acute adult lower respiratory tract infection (LRTI) in primary care

    PubMed Central

    Creer, D D; Dilworth, J P; Gillespie, S H; Johnston, A R; Johnston, S L; Ling, C; Patel, S; Sanderson, G; Wallace, P G; McHugh, T D

    2006-01-01

    Background Lower respiratory tract infections (LRTI) are a common reason for consulting general practitioners (GPs). In most cases the aetiology is unknown, yet most result in an antibiotic prescription. The aetiology of LRTI was investigated in a prospective controlled study. Methods Eighty adults presenting to GPs with acute LRTI were recruited together with 49 controls over 12 months. Throat swabs, nasal aspirates (patients and controls), and sputum (patients) were obtained and polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT‐PCR) assays were used to detect Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, influenza viruses (AH1, AH3 and B), parainfluenza viruses 1–3, coronaviruses, respiratory syncytial virus, adenoviruses, rhinoviruses, and enteroviruses. Standard sputum bacteriology was also performed. Outcome was recorded at a follow up visit. Results Potential pathogens were identified in 55 patients with LRTI (69%) and seven controls (14%; p<0.0001). The identification rate was 63% (viruses) and 26% (bacteria) for patients and 12% (p<0.0001) and 6% (p = 0.013), respectively, for controls. The most common organisms identified in the patients were rhinoviruses (33%), influenza viruses (24%), and Streptococcus pneumoniae (19%) compared with 2% (p<0.001), 6% (p = 0.013), and 4% (p = 0.034), respectively, in controls. Multiple pathogens were identified in 18 of the 80 LRTI patients (22.5%) and in two of the 49 controls (4%; p = 0.011). Atypical organisms were rarely identified. Cases with bacterial aetiology were clinically indistinguishable from those with viral aetiology. Conclusion Patients presenting to GPs with acute adult LRTI predominantly have a viral illness which is most commonly caused by rhinoviruses and influenza viruses. PMID:16227331

  1. A task shifting approach to primary mental health care for adults in South Africa: human resource requirements and costs for rural settings.

    PubMed

    Petersen, Inge; Lund, Crick; Bhana, Arvin; Flisher, Alan J

    2012-01-01

    BACKGROUND A recent situational analysis suggests that post-apartheid South Africa has made some gains with respect to the decentralization and integration of mental health into primary health care. However, service gaps within and between provinces remain, with rural areas particularly underserved. Aim This study aims to calculate and cost a hypothetical human resource mix required to populate a framework for district adult mental health services. This framework embraces the concept of task shifting, where dedicated low cost mental health workers at the community and clinic levels supplement integrated care. METHOD The expected number and cost of human resources was based on: (a) assumptions of service provision derived from existing services in a sub-district demonstration site and a literature review of evidence-based packages of care in low- and middle-income countries; and (b) assumptions of service needs derived from other studies. RESULTS For a nominal population of 100 000, minimal service coverage estimates of 50% for schizophrenia, bipolar affective disorder, major depressive disorder and 30% for post-traumatic stress disorder and maternal depression would require that the primary health care staffing package include one post for a mental health counsellor or equivalent and 7.2 community mental health worker posts. The cost of these personnel amounts to £28 457 per 100 000 population. This cost can be offset by a reduction in the number of other specialist and non-specialist health personnel required to close service gaps at primary care level. CONCLUSION The adoption of the concept of task shifting can substantially reduce the expected number of health care providers otherwise needed to close mental health service gaps at primary health care level in South Africa at minimal cost and may serve as a model for other middle-income countries.

  2. General Information about Liver (Hepatocellular) Cancer

    MedlinePlus

    ... condition or to keep cancer from starting. General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer ... PDQ Screening and Prevention Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  3. Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection

    PubMed Central

    Bowlus, Christopher L

    2016-01-01

    Primary biliary cholangitis (PBC), previously known as primary biliary “cirrhosis”, is a rare autoimmune liver disease characterized by the hallmark autoantibodies to mitochondrial antigens and immune-mediated destruction of small bile duct epithelial cells leading to cholestasis and cirrhosis. Surprisingly, while immune modulators have not been effective in the treatment of PBC, supplementation with the hydrophilic bile acid (BA) ursodeoxycholic acid (UDCA) has been demonstrated to slow the disease progression. However, a significant minority of PBC patients do not have a complete response to UDCA and remain at risk of continued disease progression. Although the mechanisms of action are not well understood, UDCA provided proof of concept for BA therapy in PBC. Obeticholic acid (OCA), a novel derivative of the human BA chenodeoxycholic acid, is a potent agonist of the nuclear hormone receptor farnesoid X receptor, which regulates BA synthesis and transport. A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC. PMID:27621676

  4. Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection.

    PubMed

    Bowlus, Christopher L

    2016-01-01

    Primary biliary cholangitis (PBC), previously known as primary biliary "cirrhosis", is a rare autoimmune liver disease characterized by the hallmark autoantibodies to mitochondrial antigens and immune-mediated destruction of small bile duct epithelial cells leading to cholestasis and cirrhosis. Surprisingly, while immune modulators have not been effective in the treatment of PBC, supplementation with the hydrophilic bile acid (BA) ursodeoxycholic acid (UDCA) has been demonstrated to slow the disease progression. However, a significant minority of PBC patients do not have a complete response to UDCA and remain at risk of continued disease progression. Although the mechanisms of action are not well understood, UDCA provided proof of concept for BA therapy in PBC. Obeticholic acid (OCA), a novel derivative of the human BA chenodeoxycholic acid, is a potent agonist of the nuclear hormone receptor farnesoid X receptor, which regulates BA synthesis and transport. A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC. PMID:27621676

  5. Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection

    PubMed Central

    Bowlus, Christopher L

    2016-01-01

    Primary biliary cholangitis (PBC), previously known as primary biliary “cirrhosis”, is a rare autoimmune liver disease characterized by the hallmark autoantibodies to mitochondrial antigens and immune-mediated destruction of small bile duct epithelial cells leading to cholestasis and cirrhosis. Surprisingly, while immune modulators have not been effective in the treatment of PBC, supplementation with the hydrophilic bile acid (BA) ursodeoxycholic acid (UDCA) has been demonstrated to slow the disease progression. However, a significant minority of PBC patients do not have a complete response to UDCA and remain at risk of continued disease progression. Although the mechanisms of action are not well understood, UDCA provided proof of concept for BA therapy in PBC. Obeticholic acid (OCA), a novel derivative of the human BA chenodeoxycholic acid, is a potent agonist of the nuclear hormone receptor farnesoid X receptor, which regulates BA synthesis and transport. A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC.

  6. Cross-sectional study of older adults with type 2 diabetes mellitus in two rural public primary healthcare facilities in Malaysia.

    PubMed

    Ooi, C P; Loke, S C; Zaiton, A; Tengku-Aizan, H; Zaitun, Y

    2011-06-01

    Knowledge of the characteristics of older adults with type 2 diabetes mellitus (T2DM) is indispensible for improvement of their care. A cross-sectional study in two rural public primary healthcare centres in Malaysia identified 170 actively engaged older patients with T2DM, with suboptimal glycaemic control and frequent hypoglycaemia. The prevalence of multiple co-morbidities, complications of T2DM, high cardiovascular risk, neurological, musculoskeletal and visual deficits suggested high risk of disabilities and dependency but not yet disabled. This short window for interventions presents as an opportunity for development of a more comprehensive approach extending beyond glycaemia control to risk management, preventing functional loss and continuity of social participation.

  7. Are decreases in drug use risk associated with reductions in HIV sex risk behaviors among adults in an urban hospital primary care setting?

    PubMed

    Walter, Angela Wangari; Cheng, Debbie M; Lloyd-Travaglini, Christine A; Samet, Jeffrey H; Bernstein, Judith; Saitz, Richard

    2016-12-01

    Drug use is associated with increased sexual risk behaviors. We examined whether decreases in drug use risk are associated with reduction in HIV-related sex risk behaviors among adults. Data was from a cohort of participants (n = 574) identified by drug use screening in a randomized trial of brief intervention for drug use in an urban primary care setting. Inverse probability of treatment weighted (IPTW) logistic regression models were used to examine the relationship between decreases in drug use risk and sex-related HIV risk behavior reduction from study entry to six months. Weights were derived from propensity score modeling of decreases in drug use risk as a function of potential confounders. Thirty seven percent of the study participants (213/574) reported a decrease in drug use risk, and 7% (33/505) reported decreased sex-related HIV risk behavior at the six-month follow-up point. We did not detect a difference in reduction of risky sexual behaviors for those who decreased drug use risk (unadjusted: OR 1.32, 95% CI 0.65-2.70; adjusted OR [AOR] 1.12, 95% CI 0.54-2.36). Adults who screened positive for high drug use risk had greater odds of reducing sex risk behavior in unadjusted analyses OR 3.71, 95% CI 1.81-7.60; but the results were not significant after adjusting for confounding AOR 2.50, 95% CI 0.85-7.30). In this primary care population, reductions in HIV sex risk behaviors have complex etiologies and reductions in drug use risk do not appear to be an independent predictor of them. PMID:27570734

  8. Obesity and Its Cardio-metabolic Co-morbidities Among Adult Nigerians in a Primary Care Clinic of a Tertiary Hospital in South-Eastern, Nigeria

    PubMed Central

    Iloh, Gabriel Uche Pascal; Ikwudinma, Austin Obiora; Obiegbu, Nnadozie Paul

    2013-01-01

    Background: Obesity once thought the medical problem of affluent countries now exist in Nigeria and has been described as a time bomb for the future explosion in the frequency of cardio-metabolic diseases. The most deleterious health consequences of obesity are on the cardiovascular system and associated disorder of lipid and glucose homeostasis. Aim: This study was designed to determine the magnitude of obesity and its cardio-metabolic co-morbidities among adult Nigerians in a primary care clinic of a tertiary hospital South-Eastern, Nigeria. Materials and Methods: A cross-sectional study carried out on 2391 adult Nigerians who were assessed for obesity using body mass index (BMI) criterion. 206 patients who had BMI ≥30kg/m2 were screened for cardio-metabolic co-morbidities. The data collected included basic demographic variables, weight, height, blood pressure; fasting plasma glucose and lipid profile. Results: The prevalence of obesity was 8.6%. Grade I obesity (67.5%) was the most common pattern; others included grade II obesity (23.3%) and grade III obesity (9.2%). Hypertension (42.7%) was the most common cardio-metabolic morbidity. Others included low HDL-cholesterol (22.8%), diabetes mellitus (15.1%), high triglyceride (12.6%), high total cholesterol (9.2%), and high LDL-cholesterol (6.8%). Conclusion: Obesity and its cardio-metabolic morbidities exist among the study population. Anthropometric determination of obesity and screening for its associated cardio-metabolic co-morbidities should constitute clinical targets for intervention in primary care clinics. PMID:24479038

  9. An Atypical Age-Specific Pattern of Hepatocellular Carcinoma in Peru: A Threat for Andean Populations

    PubMed Central

    Loli, Sebastian; Moura, Julien; Zimic, Mirko; Deharo, Eric; Ruiz, Eloy

    2013-01-01

    Background In South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country. Methods A retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin. Results Surprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics. Conclusions The analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population. PMID:23840771

  10. A new cluster-based oversampling method for improving survival prediction of hepatocellular carcinoma patients.

    PubMed

    Santos, Miriam Seoane; Abreu, Pedro Henriques; García-Laencina, Pedro J; Simão, Adélia; Carvalho, Armando

    2015-12-01

    Liver cancer is the sixth most frequently diagnosed cancer and, particularly, Hepatocellular Carcinoma (HCC) represents more than 90% of primary liver cancers. Clinicians assess each patient's treatment on the basis of evidence-based medicine, which may not always apply to a specific patient, given the biological variability among individuals. Over the years, and for the particular case of Hepatocellular Carcinoma, some research studies have been developing strategies for assisting clinicians in decision making, using computational methods (e.g. machine learning techniques) to extract knowledge from the clinical data. However, these studies have some limitations that have not yet been addressed: some do not focus entirely on Hepatocellular Carcinoma patients, others have strict application boundaries, and none considers the heterogeneity between patients nor the presence of missing data, a common drawback in healthcare contexts. In this work, a real complex Hepatocellular Carcinoma database composed of heterogeneous clinical features is studied. We propose a new cluster-based oversampling approach robust to small and imbalanced datasets, which accounts for the heterogeneity of patients with Hepatocellular Carcinoma. The preprocessing procedures of this work are based on data imputation considering appropriate distance metrics for both heterogeneous and missing data (HEOM) and clustering studies to assess the underlying patient groups in the studied dataset (K-means). The final approach is applied in order to diminish the impact of underlying patient profiles with reduced sizes on survival prediction. It is based on K-means clustering and the SMOTE algorithm to build a representative dataset and use it as training example for different machine learning procedures (logistic regression and neural networks). The results are evaluated in terms of survival prediction and compared across baseline approaches that do not consider clustering and/or oversampling using the

  11. Primary mesenteric lymphangioma in a young adult with intestinal malrotation and ‘counter-clockwise barber pole sign’

    PubMed Central

    Singh, Neha; Singh, Ragini; Maheswari, Udbhav; Aga, Pallavi

    2013-01-01

    Mesenteric lymphangiomas are uncommon benign lesions that usually occur in isolation but rarely may be associated with gastrointestinal (GI) malrotation. Malrotation may cause chronic and recurrent volvulus leading to chronic venous congestion and lymphatic engorgement. Interference with lymphatic drainage may result in formation of a lymphangioma or a chylous mesenteric cyst. In our case, mesenteric lymphangioma was present with partial malrotation of small and large bowel. There was no radiological and surgical evidence of volvulus, favouring the hypothesis that lymphangioma may be a primary congenital association of GI malrotation. Another interesting finding was the counter-clockwise twisting of the superior mesenteric vein around the superior mesenteric artery which has been reported only seven times in the literature. PMID:23761495

  12. Hepatocellular carcinoma: A comprehensive review

    PubMed Central

    Waller, Lisa P; Deshpande, Vrushak; Pyrsopoulos, Nikolaos

    2015-01-01

    Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals with chronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival. PMID:26609342

  13. Molecular Pathogenesis of Hepatocellular Carcinoma

    PubMed Central

    Ho, Daniel Wai-Hung; Lo, Regina Cheuk-Lam; Chan, Lo-Kong; Ng, Irene Oi-Lin

    2016-01-01

    The pathogenesis of hepatocellular carcinoma (HCC) is a multistep process involving the progressive accumulation of molecular alterations pinpointing different molecular and cellular events. The next-generation sequencing technology is facilitating the global and systematic evaluation of molecular landscapes in HCC. There is emerging evidence supporting the importance of cancer metabolism and tumor microenvironment in providing a favorable and supportive niche to expedite HCC development. Moreover, recent studies have identified distinct surface markers of cancer stem cell (CSC) in HCC, and they also put forward the profound involvement of altered signaling pathways and epigenetic modifications in CSCs, in addition to the concomitant drug resistance and metastasis. Taken together, multiple key genetic and non-genetic factors, as well as liver CSCs, result in the development and progression of HCC. PMID:27781201

  14. [Hepatocellular Carcinoma: therapeutic options 2015].

    PubMed

    Schultheiß, Michael; Bettinger, Dominik; Neeff, Hannes P; Brunner, Thomas B; Thimme, Robert

    2015-07-01

    The incidence of hepatocellular carcinoma (HCC), a common neoplasm, is rising and the prognosis is poor. Many factors have to be taken into account when deciding on the best mode of therapy, like tumor size and number, liver function, sequelae of portal hypertension or other comorbidities. These factors are reflected in the Barcelona Clinic Liver Cancer (BCLC) classification. Resection, radiofrequency ablation (RFA) and liver transplantation can be seen as curative therapies for the early and localized HCC. For the intermediate state of the HCC, there are other therapeutic modalities in therapy available: transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT, rarer occasions), off label: stereotactic body radiation therapy (SBRT). At the moment, Sorafenib is the only option in treating advanced stages of HCC. Alternative treatment strategies, like e.g. immunological therapies, are being investigated. PMID:26182255

  15. Cytoreductive surgery for hepatocellular carcinoma.

    PubMed

    Lau, W Y; Leung, T W; Leung, K L; Ho, S; Leung, N; Chan, M; Lin, J; Li, A K

    1994-06-01

    A prospective study was conducted on 26 patients for cytoreductive surgery of inoperable hepatocellular carcinoma. These patients underwent cytoreduction with liver resection, cryosurgery, microwave tissue coagulation and/or absolute alcohol injection. In-hospital mortality was 7.7%. The symptomatic relief and quality of survival were excellent. The median survival of patients after cytoreduction was 10.0 months and the survival was much better than those of 26 patients matched by sex, age, tumour size, Child-Pugh grading and Karnofsky scores who received systemic chemotherapy during the same period of the study (log rank test, P = 0.0001). There was no statistical difference between the survival curves of those patients who received (19 patients) and those who did not receive (7 patients) additional treatment by chemotherapy or selective internal radiation therapy after cytoreduction. This suggests that the gained survival benefit could have been derived mainly from the cytoreductive surgery rather than the additional treatments.

  16. Hepatocellular carcinoma and industrial epidemics

    PubMed Central

    Braillon, Alain; Dubois, Gérard

    2011-01-01

    Worldwide, the burden of the non viral causes of hepatocellular carcinoma (HCC) is usually underestimated. Clearly industrial goods, tobacco, alcohol and processed foods are the agents of new epidemics in modern times which far outscore the burden of infectious agents on morbidity and mortality. Smoking, a dose-related contributing factor for HCC, receives too little attention in clinical practice. In France, tobacco, hepatitis B and C virus and alcohol are the main risk factors for HCC mortality (33%, 31% and 26%, respectively). In developing countries, where tobacco consumption is dramatically increasing, this epidemic may soon surpass hepatitis B. Obesity and diabetes are the contributing factors too. The role of industrial processed foods in the increase of the prevalence of obesity and diabetes cannot be ignored. PMID:21734811

  17. Experimental models of hepatocellular carcinoma☆

    PubMed Central

    Newell, Philippa; Villanueva, Augusto; Friedman, Scott L.; Koike, Kazuhiko; Llovet, Josep M.

    2010-01-01

    Hepatocellular carcinoma (HCC) is a common and deadly cancer whose pathogenesis is incompletely understood. Comparative genomic studies from human HCC samples have classified HCCs into different molecular subgroups; yet, the unifying feature of this tumor is its propensity to arise upon a background of inflammation and fibrosis. This review seeks to analyze the available experimental models in HCC research and to correlate data from human populations with them in order to consolidate our efforts to date, as it is increasingly clear that different models will be required to mimic different subclasses of the neoplasm. These models will be instrumental in the evaluation of compounds targeting specific molecular pathways in future preclinical studies. PMID:18314222

  18. Tumor markers for hepatocellular carcinoma

    PubMed Central

    ZHAO, YAN-JIE; JU, QIANG; LI, GUAN-CHENG

    2013-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high rate of morbidity and mortality. HCC affects approximately one million individuals annually worldwide, with the incidence equal to the mortality rate. In 2008, HCC was listed as the third most lethal cancer. Thus, early diagnosis is crucial for improving the survival rate for patients. α-fetoprotein (AFP) together with iconography and pathology detection are commonly used in the clinical early diagnosis of liver cancer. However, the specificity and sensitivity of AFP used in screening for liver cancer are not satisfactory. Athough the development of molecular biology has led to the identification of new tumor markers, including proteantigens, cytokines, enzymes and isoenzymes, as well as related genes that can be used in the treatment and prognosis of liver cancer, more tumor markers are required for effective early diagnosis of diseases and monitoring of the curative effect. PMID:24649215

  19. Risk of second primary malignancies in a population-based study of adult patients with essential thrombocythemia

    PubMed Central

    Shrestha, Rajesh; Giri, Smith; Pathak, Ranjan; Bhatt, Vijaya Raj

    2016-01-01

    AIM To determine the risk of second primary malignancy (SPM) and survival of patients with essential thrombocythemia (ET). METHODS We identified all patients with ET diagnosed during 2001 to 2011 from the Surveillance, Epidemiology and End Results (SEER) 18 database. Actuarial and relative survival methods were used to calculate the survival statistics. We utilized the SEER 13 database to calculate SPM. We used multiple primary standardized incidence ratio (SIR) session of the SEER*Stat software (version 8.1.5) to calculate SIR and excess risk of SPM for ET patients. RESULTS Age standardized five-year cause-specific survival was greater for patients < 50 years vs those ≥ 50 years (99.4% vs 93.5%, P < 0.01). Five-year cause-specific survival was lower for men vs women (70.2% vs 79.7%). A total of 201 patients (2.46%) developed SPM at a median age of 75 years. SPMs occurred at an observed/expected (O/E) ratio of 1.26 (95%CI: 1.09-1.45, P = 0.002) with an absolute excess risk (AER) of 37.44 per 10000 population. A significantly higher risk was noted for leukemia (O/E 3.78; 95%CI: 2.20-6.05, P < 0.001; AER 11.28/10000). CONCLUSION ET patients have an excellent cause-specific five-year survival but are at an increased risk of SPM, particularly leukemia, which may contribute to excess deaths. PMID:27579252

  20. Multilayer nanofilms as substrates for hepatocellular applications.

    PubMed

    Wittmer, Corinne R; Phelps, Jennifer A; Lepus, Christin M; Saltzman, William M; Harding, Martha J; Van Tassel, Paul R

    2008-10-01

    Multilayer nanofilms, formed by the layer-by-layer (LbL) adsorption of positively and negatively charged polyelectrolytes, are promising substrates for tissue engineering. We investigate here the attachment and function of hepatic cells on multilayer films in terms of film composition, terminal layer, rigidity, charge, and presence of biofunctional species. Human hepatocellular carcinoma (HepG2) cells, adult rat hepatocytes (ARH), and human fetal hepatoblasts (HFHb) are studied on films composed of the polysaccharides chitosan (CHI) and alginate (ALG), the polypeptides poly(l-lysine) (PLL) and poly(l-glutamic acid) (PGA), and the synthetic polymers poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS). The influence of chemical cross-linking following LbL assembly is also investigated. We find HepG2 to reach confluence after 7 days of culture on only 2 of 18 candidate multilayer systems: (PAH-PSS)(n) (i.e. nPAH-PSS bilayers) and cross-linked (PLL-ALG)(n)-PLL. Cross-linked PLL-ALG and PLL-PGA films support attachment and function of ARH, independently of the terminal layer, provided collagen is adsorbed to the top of the film. (PAH-PSS)(n), cross-linked (PLL-ALG)(n), and cross-linked (PLL-PGA)(n)-PLL films all support attachment, layer confluence, and function of HFHb, with the latter film promoting the greatest level of function at 8 days. Overall, film composition, terminal layer, and rigidity are key variables in promoting attachment and function of hepatic cells, while film charge and biofunctionality are somewhat less important. These studies reveal optimal candidate multilayer biomaterials for human liver tissue engineering applications.

  1. Depression or anxiety and all-cause mortality in adults with atrial fibrillation – A cohort study in Swedish primary care

    PubMed Central

    Wändell, Per; Carlsson, Axel C.; Gasevic, Danijela; Wahlsträm, Lars; Sundquist, Jan; Sundquist, Kristina

    2016-01-01

    Objective Our aim was to study depression and anxiety in atrial fibrillation (AF) patients as risk factors for all-cause mortality in a primary care setting. Methods The study population included adults (n = 12 283) of 45 years and older diagnosed with AF in 75 primary care centres in Sweden. The association between depression or anxiety and all-cause mortality was explored using Cox regression analysis, with hazard ratios (HRs) and 95% confidence intervals (95% CIs). Analyses were conducted in men and women, adjusted for age, educational level, marital status, neighborhood socio-economic status (SES), change of neighborhood status and anxiety or depression, respectively, and cardiovascular co-morbidities. As a secondary analysis, background factors and their association with depression or anxiety were explored. Results The risk of all-cause mortality was higher among men with depression compared to their counterparts without depression even after full adjustment (HR = 1.28, 95% CI 1.08–1.53). For anxiety among men and anxiety or depression among women with AF, no associations were found. Cerebrovascular disease was more common among depressed AF patients. Conclusions Increased awareness of the higher mortality among men with AF and subsequent depression is called for. We suggest a tight follow-up and treatment of both ailments in clinical practice. PMID:26758363

  2. Potential prescription patterns and errors in elderly adult patients attending public primary health care centers in Mexico City

    PubMed Central

    Corona-Rojo, José Antonio; Altagracia-Martínez, Marina; Kravzov-Jinich, Jaime; Vázquez-Cervantes, Laura; Pérez-Montoya, Edilberto; Rubio-Poo, Consuelo

    2009-01-01

    Introduction Six out of every 10 elderly persons live in developing countries. Objective To analyze and assess the drug prescription patterns and errors in elderly outpatients attending public health care centers in Mexico City, Mexico. Materials and methods A descriptive and retrospective study was conducted in 2007. Fourteen hundred prescriptions were analyzed. Prescriptions of ambulatory adults aged >70 years who were residents of Mexico City for at least two years were included. Prescription errors were divided into two groups: (1) administrative and legal, and (2) pharmacotherapeutic. In group 2, we analyzed drug dose strength, administration route, frequency of drug administration, treatment length, potential drug–drug interactions, and contraindications. Variables were classified as correct or incorrect based on clinical literature. Variables for each drug were dichotomized as correct (0) or incorrect (1). A Prescription Index (PI) was calculated by considering each drug on the prescription. SPSS statistical software was used to process the collected data (95% confidence interval; p <0.05). Results The drug prescription pattern in elderly outpatients shows that 12 drugs account for 70.72% (2880) of prescribed drugs. The most prescribed drugs presented potential pharmacotherapeutic errors (as defined in the present study). Acetylsalicylic acid–captopril was the most common potential interaction (not clinically assessed). Potential prescription error was high (53% of total prescriptions). Most of the prescription errors were due to omissions of dosage, administration route, and length of treatment and may potentially cause harm to the elderly outpatients. Conclusions A high number of potential prescription errors were found, mainly due to omissions. The drug prescription pattern of the study population is mainly constituted by 12 drugs. The results indicate that prescription quality depends on the number of prescribed drugs per prescription (p < 0

  3. Boerhaave's syndrome as the primary manifestation of adult eosinophilic esophagitis. Two case reports and a review of the literature.

    PubMed

    Lucendo, A J; Friginal-Ruiz, A B; Rodríguez, B

    2011-02-01

    Eosinophilic esophagitis (EoE) has been associated with an increased risk of esophageal mucosal tears induced by vomiting to dislodge impacted food or following endoscopic procedures. However, Boerhaave's syndrome or transmural perforation of the organ resulting from vomiting induced to dislodge impacted food has rarely been reported. In this article, we present two male adult patients with long-term esophageal symptoms who suffered from Boerhaave's syndrome after the impaction of food in the esophagus. Both patients required surgical management because of clinical and radiological signs of perforation. This rare complication of EoE has been documented in 11 other reports, predominantly affecting young men in whom EoE had not been previously diagnosed, despite the majority having esophageal symptoms and a history of atopy. There are only two published cases of esophageal perforation that presented in children, which were managed conservatively. Our two patients and 4 out of the 11 described in literature required surgery because of esophageal perforation. Our two cases involved closure of the perforation, while in three published reports, perforation resulted in a partial or complete esophagectomy. No cases have been published on Boerhaave's syndrome caused by EoE that ended in fatalities. It is important to note that esophageal perforation caused by vomiting is a potentially severe complication of EoE that is being increasingly described in literature. Therefore, patients with non-traumatic Boerhaave's syndrome should be assessed for EoE, especially if they are young men who have a prior history of dysphagia and allergic manifestations.

  4. Age differences in the purr call distinguished by units in the adult guinea pig primary auditory cortex.

    PubMed

    Grimsley, J M S; Palmer, A R; Wallace, M N

    2011-07-01

    Many communication calls contain information about the physical characteristics of the calling animal. During maturation of the guinea pig purr call the pitch becomes lower as the fundamental frequency progressively decreases from 476 to 261 Hz on average. Neurons in the primary auditory cortex (AI) often respond strongly to the purr and we postulated that some of them are capable of distinguishing between purr calls of different pitch. Consequently four pitch-shifted versions of a single call were used as stimuli. Many units in AI (79/182) responded to the purr call either with an onset response or with multiple bursts of firing that were time-locked to the phrases of the call. All had a characteristic frequency ≤5 kHz. Both types of unit altered their firing rate in response to pitch-shifted versions of the call. Of the responsive units, 41% (32/79) had a firing rate locked to the stimulus envelope that was at least 50% higher for one version of the call than any other. Some (14/32) had a preference that could be predicted from their frequency response area while others (18/32) were not predictable. We conclude that about 18% of stimulus-driven cells at the low-frequency end of AI are very sensitive to age-related changes in the purr call.

  5. Hepatocellular carcinoma: epidemiology and risk factors

    PubMed Central

    Kew, Michael C

    2014-01-01

    Hepatocellular carcinoma is one of the major malignant tumors in the world today. The number of new cases of the tumor increases year by year, and hepatocellular carcinoma almost always runs a fulminant course and carries an especially grave prognosis. It has a low resectability rate and a high recurrence rate after surgical intervention, and responds poorly to anticancer drugs and radiotherapy. Hepatocellular carcinoma does not have a uniform geographical distribution: rather, very high incidences occur in Eastern and Southeastern Asia and in sub-Saharan Black Africans. In these regions and populations, the tumor shows a distinct shift in age distribution toward the younger ages, seen to greatest extent in sub-Saharan Black Africans. In all populations, males are more commonly affected. The most common risk factors for hepatocellular carcinoma in resource-poor populations with a high incidence of the tumor are chronic hepatitis B virus infection and dietary exposure to the fungal hepatocarcinogen aflatoxin B1. These two causative agents act either singly or synergistically. Both the viral infection and exposure to the fungus occur from early childhood, and the tumor typically presents at an early age. Chronic hepatitis C virus infection is an important cause of hepatocellular carcinoma in resource-rich countries with a low incidence of the tumor. The infection is acquired in adulthood and hepatocellular carcinoma occurs later than it does with hepatitis B virus-induced tumors. In recent years, obesity and the metabolic syndrome have increased markedly in incidence and importance as a cause of hepatocellular carcinoma in some resource-rich regions. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. Excessive iron accumulation in hereditary hemochromatosis and dietary iron overload in the Black African population and membranous obstruction of the inferior cava

  6. Quality of life and hepatocellular carcinoma

    PubMed Central

    Khubchandani, Sapna; Iyer, Renuka

    2014-01-01

    Hepatocellular carcinoma (HCC) is a common and rapidly fatal cancer ranking third among the leading causes of cancer-related deaths. Potentially curative therapies like surgery, transplant and ablation are not an option for most patients as they are often diagnosed when the disease is advanced. Liver directed therapy and oral targeted therapies are used in these patients to prolong life and palliate symptoms of the cancer and associated liver failure. Overall survival remains poor and hence health-related quality of life (HRQoL) is of paramount importance in these patients. As novel therapies are developed to improve outcomes, a comprehensive knowledge of available tools to assess impact on QoL is needed. Hence we reviewed all the studies in HCC patients published within the last 13 years from 2001-2013 which assessed HRQoL as a primary or secondary endpoint. A total of 45 studies and 4 meta-analysis were identified. Commonly used tools were European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) (15 studies) and the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire (FACT-Hep) (14 studies). Of the 45 publications which incorporated HRQoL as end-point only 24 were clinical trials, 17/24 (71%) assessed systemic therapies while 7/24 (29%) assessed liver-directed therapies. Majority of the publications (trials + retrospective reviews) that had HRQoL as an endpoint in HCC patients were studies evaluating liver-directed therapies (23/45 or >50%). We discuss the measures included in the tools, their interpretation, and summarize existing QoL data that will help design future HCC trials. PMID:25083303

  7. Metastatic hepatocellular carcinoma in a juvenile rhesus macaque (Macaca mulatta).

    PubMed

    Laing, Steven T; Lemoy, Marie J; Sammak, Rebecca L; Tarara, Ross P

    2013-10-01

    Neoplasia in juvenile (younger than 5 y) rhesus macaques has been estimated to represent only approximately 1.4% of all occurrences of spontaneous neoplasia. Here we report an unusual case of a 3.75-y-old primiparous female rhesus macaque that was euthanized due to poor prognosis associated with progressive anemia, marked hepatomegaly, and radiographic evidence of meta- static neoplasia. Postmortem examination revealed an invasive, hemorrhagic hepatic mass that effaced approximately 70% of the liver parenchyma and had evidence of metastatic spread to multiple abdominal organs, the lungs, and the pituitary gland. Neoplastic polygonal cells lined large necrohemorrhagic cavities and exhibited marked anisocytosis and anisokaryosis, with frequent multinucleate cells. There was no desmoplasia associated with the primary neoplasm or metastases. Immunohistochemical studies revealed the neoplastic cells to be diffusely reactive with pancytokeratin, cytokeratin 7, and cytokeratin 8/18 antibodies and rarely reactive with carcinoembryonic antigen antibodies. The cells did not react with vimentin, S100, CD31, or factor VIII antibodies. Tumor morphology and immunophenotype led to the diagnosis of anaplastic hepatocellular carcinoma. This report represents the first known case of metastatic liver neoplasia in a rhesus macaque. The young age of this animal and the aggressive nature of the neoplasm are highly unusual and reminiscent of adolescent onset hepatocellular carcinoma in humans.

  8. Spontaneous Hepatocellular Carcinoma after the Combined Deletion of Akt Isoforms.

    PubMed

    Wang, Qi; Yu, Wan-Ni; Chen, Xinyu; Peng, Xiao-Ding; Jeon, Sang-Min; Birnbaum, Morris J; Guzman, Grace; Hay, Nissim

    2016-04-11

    Akt is frequently hyperactivated in human cancers and is targeted for cancer therapy. However, the physiological consequences of systemic Akt isoform inhibition were not fully explored. We showed that while combined Akt1 and Akt3 deletion in adult mice is tolerated, combined Akt1 and Akt2 deletion induced rapid mortality. Akt2(-/-) mice survived hepatic Akt1 deletion but all developed spontaneous hepatocellular carcinoma (HCC), which is associated with FoxO-dependent liver injury and inflammation. The gene expression signature of HCC-bearing livers is similar to aggressive human HCC. Consistently, neither Akt1(-/-) nor Akt2(-/-) mice are resistant to diethylnitrosamine-induced hepatocarcinogenesis, and Akt2(-/-) mice display a high incidence of lung metastasis. Thus, in contrast to other cancers, hepatic Akt inhibition induces liver injury that could promote HCC. PMID:26996309

  9. Responses of neurons in the middle temporal visual area after long-standing lesions of the primary visual cortex in adult new world monkeys.

    PubMed

    Collins, Christine E; Lyon, David C; Kaas, Jon H

    2003-03-15

    The retinotopic organization of the middle temporal visual area (MT) was determined in six adult owl monkeys and one adult marmoset 69 d to 10 months after lesions of the dorsolateral primary visual cortex (V1). The lesions removed were limited to extensive parts of the representation of the lower visual quadrant in V1. Microelectrodes were used to record from neurons at numerous sites in MT to determine whether parts of MT normally devoted to the lower visual quadrant (1) were unresponsive to visual stimuli, (2) acquired responsiveness to inputs from intact portions of V1, or (3) became responsive to some other visually driven input such as a relay from the superior colliculus via the pulvinar to MT. All monkeys (n = 6) with moderate to moderately large lesions had unresponsive portions of MT even after 10 months of recovery. These unresponsive regions were retinotopically equivalent to the removed parts of V1 in normal animals. Thus, there was no evidence for an alternative source of activation. In addition, these results indicate that any retinotopic reorganization of MT based on inputs from intact portions of V1 was not extensive, yet neurons near the margins of responsive cortex may have acquired new receptive fields, and the smallest 5 degrees lesion of V1 failed to produce an unresponsive zone. Deprived portions of MT were not remarkably changed in histological appearance in cytochrome oxidase, Nissl, and Wisteria floribunda agglutinin preparations. Nevertheless, some reduction in myelin staining and other histological changes were suggested. We conclude that MT is highly dependent on V1 for activation in these monkeys, and alternative sources do not become effective over months when normal activation is absent. Additionally, remaining V1 inputs have only a limited capacity to expand their activation territory into deprived portions of MT.

  10. Association between Body Mass Index and All-Cause Mortality in Hypertensive Adults: Results from the China Stroke Primary Prevention Trial (CSPPT)

    PubMed Central

    Yang, Wei; Li, Jian-Ping; Zhang, Yan; Fan, Fang-Fang; Xu, Xi-Ping; Wang, Bin-Yan; Xu, Xin; Qin, Xian-Hui; Xing, Hou-Xun; Tang, Gen-Fu; Zhou, Zi-Yi; Gu, Dong-Feng; Zhao, Dong; Huo, Yong

    2016-01-01

    The association between elevated body mass index (BMI) and risk of death has been reported in many studies. However, the association between BMI and all-cause mortality for hypertensive Chinese adults remains unclear. We conducted a post-hoc analysis using data from the China Stroke Primary Prevention Trial (CSPPT). Cox regression analysis was performed to determine the significance of the association of BMI with all-cause mortality. During a mean follow-up duration of 4.5 years, 622 deaths (3.0%) occurred among the 20,694 participants aged 45–75 years. A reversed J-shaped relationship was observed between BMI and all-cause mortality. The hazard ratios (HRs) for underweight (<18.5 kg/m2), overweight (24.0–27.9 kg/m2), and obesity (≥28.0 kg/m2) were calculated relative to normal weight (18.5–23.9 kg/m2). The summary HRs were 1.56 (95% CI, 1.11–2.18) for underweight, 0.78 (95% CI 0.64–0.95) for overweight and 0.64 (95% CI, 0.48–0.85) for obesity. In sex-age-specific analyses, participants over 60 years of age had optimal BMI in the obesity classification and the results were consistent in both males and females. Relative to normal weight, underweight was associated with significantly higher mortality. Excessive weight was not associated with increased risk of mortality. Chinese hypertensive adults had the lowest mortality in grade 1 obesity. PMID:27338470

  11. A Small Motor Cortex Lesion Abolished Ocular Dominance Plasticity in the Adult Mouse Primary Visual Cortex and Impaired Experience-Dependent Visual Improvements.

    PubMed

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Greifzu, Franziska; Löwel, Siegrid

    2015-01-01

    It was previously shown that a small lesion in the primary somatosensory cortex (S1) prevented both cortical plasticity and sensory learning in the adult mouse visual system: While 3-month-old control mice continued to show ocular dominance (OD) plasticity in their primary visual cortex (V1) after monocular deprivation (MD), age-matched mice with a small photothrombotically induced (PT) stroke lesion in S1, positioned at least 1 mm anterior to the anterior border of V1, no longer expressed OD-plasticity. In addition, in the S1-lesioned mice, neither the experience-dependent increase of the spatial frequency threshold ("visual acuity") nor of the contrast threshold ("contrast sensitivity") of the optomotor reflex through the open eye was present. To assess whether these plasticity impairments can also occur if a lesion is placed more distant from V1, we tested the effect of a PT-lesion in the secondary motor cortex (M2). We observed that mice with a small M2-lesion restricted to the superficial cortical layers no longer expressed an OD-shift towards the open eye after 7 days of MD in V1 of the lesioned hemisphere. Consistent with previous findings about the consequences of an S1-lesion, OD-plasticity in V1 of the nonlesioned hemisphere of the M2-lesioned mice was still present. In addition, the experience-dependent improvements of both visual acuity and contrast sensitivity of the open eye were severely reduced. In contrast, sham-lesioned mice displayed both an OD-shift and improvements of visual capabilities of their open eye. To summarize, our data indicate that even a very small lesion restricted to the superficial cortical layers and more than 3mm anterior to the anterior border of V1 compromised V1-plasticity and impaired learning-induced visual improvements in adult mice. Thus both plasticity phenomena cannot only depend on modality-specific and local nerve cell networks but are clearly influenced by long-range interactions even from distant brain regions.

  12. A Small Motor Cortex Lesion Abolished Ocular Dominance Plasticity in the Adult Mouse Primary Visual Cortex and Impaired Experience-Dependent Visual Improvements.

    PubMed

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Greifzu, Franziska; Löwel, Siegrid

    2015-01-01

    It was previously shown that a small lesion in the primary somatosensory cortex (S1) prevented both cortical plasticity and sensory learning in the adult mouse visual system: While 3-month-old control mice continued to show ocular dominance (OD) plasticity in their primary visual cortex (V1) after monocular deprivation (MD), age-matched mice with a small photothrombotically induced (PT) stroke lesion in S1, positioned at least 1 mm anterior to the anterior border of V1, no longer expressed OD-plasticity. In addition, in the S1-lesioned mice, neither the experience-dependent increase of the spatial frequency threshold ("visual acuity") nor of the contrast threshold ("contrast sensitivity") of the optomotor reflex through the open eye was present. To assess whether these plasticity impairments can also occur if a lesion is placed more distant from V1, we tested the effect of a PT-lesion in the secondary motor cortex (M2). We observed that mice with a small M2-lesion restricted to the superficial cortical layers no longer expressed an OD-shift towards the open eye after 7 days of MD in V1 of the lesioned hemisphere. Consistent with previous findings about the consequences of an S1-lesion, OD-plasticity in V1 of the nonlesioned hemisphere of the M2-lesioned mice was still present. In addition, the experience-dependent improvements of both visual acuity and contrast sensitivity of the open eye were severely reduced. In contrast, sham-lesioned mice displayed both an OD-shift and improvements of visual capabilities of their open eye. To summarize, our data indicate that even a very small lesion restricted to the superficial cortical layers and more than 3mm anterior to the anterior border of V1 compromised V1-plasticity and impaired learning-induced visual improvements in adult mice. Thus both plasticity phenomena cannot only depend on modality-specific and local nerve cell networks but are clearly influenced by long-range interactions even from distant brain regions

  13. Challenges of advanced hepatocellular carcinoma.

    PubMed

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-09-14

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  14. Challenges of advanced hepatocellular carcinoma

    PubMed Central

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

  15. Targeted therapies in hepatocellular carcinoma.

    PubMed

    Bronte, F; Bronte, G; Cusenza, S; Fiorentino, E; Rolfo, C; Cicero, G; Bronte, E; Di Marco, V; Firenze, A; Angarano, G; Fontana, T; Russo, A

    2014-01-01

    The onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients are conflicting. To date various new target drugs are under developed and other biological treatments normally indicated in other malignancies are under investigation also for HCC. These strategies aim to target the different biological pathways implicated in HCC development and progression. The target drugs studied in HCC include anti-VEGF and anti-EGFR monoclonal antibodies, tyrosine kinase inhibitors and mTOR inhibitors. The most important challenge is represented by the best integration of these drugs with standard treatments to achieve improvement in overall survival and quality of life.

  16. Challenges of advanced hepatocellular carcinoma

    PubMed Central

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  17. Analysis of subsets of B cells, Breg, CD4Treg and CD8Treg cells in adult patients with primary selective IgM deficiency

    PubMed Central

    Louis, Ankmalika Gupta; Agrawal, Sudhanshu; Gupta, Sudhir

    2016-01-01

    Primary selective IgM deficiency (SIGMD) is a rare and recently IUIS-recognized primary immunodeficiency disease with increased susceptibility to infections, allergy, and autoimmune diseases. The pathogenesis of selective IgM remains unclear. The objective of the study was to understand the pathogenesis of selective IgM deficiency via a comprehensive analysis of subsets of B cells, naïve and memory subsets of CD4+ and CD8+ T cells, and Breg, CD4Treg, and CD8Treg cells. Twenty adult patients with SIGMD (serum IgM 4 mg/dl-32 mg/dl) and age-and gender-matched healthy controls were studied. Naïve B cells, transitional B cells, marginal zone B cells, germinal center B cells, IgM memory B cells, switched memory B cells, plasmablasts, CD21low B cells, B1 cells, CXCR3+ naive and memory B cells; naïve, central memory, and effector memory subsets of CD4+ and CD8+ T cells, and CD4Treg, CD8Treg and Breg were phenotypically analyzed using multicolor flow cytometry. A significant increase in CD21low, IgM memory B cells, Breg and CD8Treg, and a significant decreased in germinal center B cells, and CXCR3+ naïve and memory B cells were observed in SIGMD. These alterations in subsets of B cells, and Breg and CD8Treg cells may play a role in the pathogenesis of SIGMD. PMID:27168952

  18. Localization of a locus (GLC1B) for adult-onset primary open angle glaucoma to the 2cen-q13 region

    SciTech Connect

    Stoilova, D.; Trifan, O.C.; Sarfarazi, M.

    1996-08-15

    Primary open angle glaucoma (GLC1) is a common ocular disorder with a characteristic degeneration of the optic nerve and visual field defects that is often associated with an elevated intraocular pressure. The severe but rare juvenile-onset type has previously been mapped to 1q21-q31, and its genetic heterogeneity has been established. Herein, we present a new locus (GLC1B) for one form of GLC1 on chromosome 2cen-q13 with a clinical presentation of low to moderate intraocular pressure, onset in late 40s, and a good response to medical treatment. Two-point and haplotype analyses of affected and unaffected meioses in six families provided maximum linkage information with D2S417, GATA112EO3, D2S113, D2S373, and D2S274 (lod scores ranging from 3.11 to 6.48) within a region of 8.5 cM that is flanked by D2S2161 and D2S2264. Analysis of affected meioses alone revealed no recombination with an additional two markers (D2S2264 and D2S135) in a region of 11.2 cM that is flanked by D2S2161 and D2S176. Analysis of unaffected meioses identified only one healthy 86-year-old male who has inherited the entire affected haplotype and, hence, is a gene carrier for this condition. Eight additional families with similar and/or different clinical presentation did not show any linkage to this region and, therefore, provided evidence for genetic heterogeneity of adult-onset primary open angle glaucoma. 63 refs., 2 figs., 2 tabs.

  19. Signal Transduction Mechanism for Serotonin 5-HT2B Receptor-Mediated DNA Synthesis and Proliferation in Primary Cultures of Adult Rat Hepatocytes.

    PubMed

    Naito, Kota; Tanaka, Chizuru; Mitsuhashi, Manami; Moteki, Hajime; Kimura, Mitsutoshi; Natsume, Hideshi; Ogihara, Masahiko

    2016-01-01

    The involvement of serotonin (5-hydroxytryptamine; 5-HT) and the 5-HT2 receptor subtypes in the induction of DNA synthesis and proliferation was investigated in primary cultures of adult rat hepatocytes to elucidate the intracellular signal transduction mechanisms. Hepatocyte parenchymal cells maintained in a serum-free, defined medium, synthesized DNA and proliferated in the presence of 5-HT or a selective 5-HT2B receptor agonist, BW723C86, but not in the presence of 5-HT2A, or 5-HT2C receptor agonists (TCB-2 and CP809101, respectively), in a time- and dose-dependent manner. A selective 5-HT2B receptor antagonist, LY272015 (10(-7) M), and a specific phospholipase C (PLC) inhibitor, U-73122 (10(-6) M), as well as specific inhibitors of growth-related signal transducers-including AG1478, LY294002, PD98059, and rapamycin-completely inhibited 5-HT (10(-6) M)- or BW723C86 (10(-6) M)-induced hepatocyte DNA synthesis and proliferation. Both 5-HT and BW723C86 were shown to significantly stimulate the phosphorylation of epidermal growth factor (EGF)/transforming growth factor (TGF)-α receptor tyrosine kinase (p175 kDa) and extracellular signal-regulated kinase (ERK) 2 on Western blot analysis. These results suggest that the proliferative mechanism of activating 5-HT is mediated mainly through 5-HT2B receptor-stimulated Gq/PLC and EGF/TGF-α-receptor/phosphatidylinositol 3-kinase (PI3K)/ERK2/mammalian target of rapamycin (mTOR) signaling pathways in primary cultured hepatocytes.

  20. Prevalence and factors associated with the presence of non alcoholic fatty liver disease in an apparently healthy adult population in primary care units

    PubMed Central

    Caballería, Llorenç; Auladell, Ma Antonia; Torán, Pere; Miranda, Dolores; Aznar, Jesús; Pera, Guillem; Gil, Dolors; Muñoz, Laura; Planas, Jaume; Canut, Santiago; Bernad, Jesús; Aubà, Josep; Pizarro, Gregorio; Aizpurua, Miren Maite; Altaba, Anna; Tibau, Albert

    2007-01-01

    Background Fatty liver disease is characterized by the accumulation of fat vacuoles inside of the hepatocytes. Non alcoholic fatty liver is associated with obesity, type 2 diabetes, dyslipemia, the intake of certain drugs and with the so-called metabolic syndrome. However, there is little information on the clinical relevance of this disorder as a healthcare problem in the general population, since the studies published generally include a limited number of patients and the diagnosis is established on the basis of clear biochemical alterations and liver biopsy. Methods/Design The aim of the study is the prevalence of non-alcoholic fatty liver disease in a general adult population by hepatic ultrasonography. A population-based, descriptive, transversal, multicentre study. Eighteen primary care centres of the north of Barcelona and the Maresme Areas of Healthcare Management attending an urban and semi-urban population of 360.000 inhabitants. A randomized sample of 786 subjects of 15 years or older were selected from the population and assigned to the participating centres according to the Primary Care Information System (SIAP): This population is practically the same as the general population of the area. The following determinations will be carried out in all the participants: hepatic ultrasonography to detect fatty liver, a questionnaire concerning liver diseases, alcohol intake, smoking and drug use, physical examination including abdominal perimeter and body mass index and biochemical analysis including liver function tests and parameters related to the metabolic syndrome and the HAIR score. Ultrasonographic diagnosis of fatty liver will be made according to established criteria (American Gastroenterology Association) and diagnosis of metabolic syndrome according to the criteria of the European Group for the Study of Insulin Resistance. Discussion This study will attempt to determine the prevalence of non alcoholic fatty liver disease, as well as, the factors

  1. Effects of butylated hydroxytoluene pretreatment on the metabolism and genotoxicity of aflatoxin B1 in primary cultures of adult rat hepatocytes: selective reduction of nucleic acid binding.

    PubMed

    Salocks, C B; Hsieh, D P; Byard, J L

    1984-12-01

    To elucidate biochemical mechanisms underlying the anticarcinogenic activity of butylated hydroxytoluene (BHT), studies were undertaken to characterize the influence of BHT pretreatment on the metabolism and genotoxicity of aflatoxin B1 (AFB1) in primary cultures of rat hepatocytes. During a 10-day pretreatment period, adult male rats were fed either a control diet or a diet supplemented with 0.5% BHT. Hepatocytes were subsequently isolated from each animal and cultured in chemically defined medium. Cultures prepared from rats which had been fed BHT metabolized AFB1 more rapidly than did controls. BHT pretreatment also enhanced oxidation of AFB1 to aflatoxin M1 (AFM1), and accelerated the rate of AFM1 conjugation. Covalent binding to DNA and RNA in BHT-pretreated cultures was reduced by 91 and 82%, respectively, while protein binding decreased by only 29%. AFB1 did not stimulate detectable DNA repair synthesis in BHT-pretreated cultures, although stimulation of DNA repair was clearly evident in control cultures. In a separate experiment, consistently higher baseline concentrations of reduced glutathione were observed in BHT-pretreated cells, indicating that BHT pretreatment may enhance formation of detoxified glutathione conjugates of AFB1. These findings suggest that the anticarcinogenic activity of BHT is due in part to preferential enhancement of hepatic detoxification mechanisms, with the result that intracellular concentrations of reactive metabolites are reduced and fewer covalently bound adducts are formed.

  2. Adult nutrition, but not inbreeding, affects male primary sexual traits in the leaf-footed cactus bug Narnia femorata (Hemiptera: Coreidae).

    PubMed

    Joseph, Paul N; Sasson, Daniel A; Allen, Pablo E; Somjee, Ummat; Miller, Christine W

    2016-07-01

    Adverse conditions may be the norm rather than the exception in natural populations. Many populations experience poor nutrition on a seasonal basis. Further, brief interludes of inbreeding can be common as population density fluctuates and because of habitat fragmentation. Here, we investigated the effects of poor nutrition and inbreeding on traits that can be very important to reproductive success and fitness in males: testes mass, sperm concentration, and sperm viability. Our study species was Narnia femorata, a species introduced to north-central Florida in the 1950s. This species encounters regular, seasonal changes in diet that can have profound phenotypic effects on morphology and behavior. We generated inbred and outbred individuals through a single generation of full-sibling mating or outcrossing, respectively. All juveniles were provided a natural, high-quality diet of Opuntia humifusa cactus cladode with fruit until they reached adulthood. New adult males were put on a high- or low-quality diet for at least 21 days before measurements were taken. As expected, the low-quality diet led to significantly decreased testes mass in both inbred and outbred males, although there were surprisingly no detectable effects on sperm traits. We did not find evidence that inbreeding affected testes mass, sperm concentration, and sperm viability. Our results highlight the immediate and overwhelming effects of nutrition on testes mass, while suggesting that a single generation of inbreeding might not be detrimental for primary sexual traits in this particular population. PMID:27547313

  3. A study on knowledge, attitude, and practice towards premarital carrier screening among adults attending primary healthcare centers in a region in Oman

    PubMed Central

    2014-01-01

    Background Despite that hereditary diseases are widespread among the Arab population due to high rates of consanguineous marriages, research regarding community awareness towards premarital carrier screening in some countries such as Oman, is extremely scarce. This study aimed to investigate knowledge and attitude towards premarital carrier screening (PMCS) in Oman. Methods A cross-sectional study was conducted using a self-administered questionnaire which was distributed to 400 Omani adults aged 20–35 who attended primary healthcare institutions at the South Batinah Governorate in Oman. Results The majority of the participants (84.5%) believed that PMCS was necessary, and about half of them (49.5%) supported the view of making PMCS compulsory. On the contrary, approximately one third (30.5%) of the participants reported that they were not in favor of taking the blood screening test. Overall, unwillingness to perform pre-marital testing was associated with female gender, younger age, being single, less education, and increased income. Conclusion Despite the relatively high level of knowledge, about one third of the participants were still reluctant to carry out premarital testing. Such attitude calls for immediate need for community-based campaigns to encourage the public to do premarital testing. PMID:24742222

  4. Adult nutrition, but not inbreeding, affects male primary sexual traits in the leaf-footed cactus bug Narnia femorata (Hemiptera: Coreidae).

    PubMed

    Joseph, Paul N; Sasson, Daniel A; Allen, Pablo E; Somjee, Ummat; Miller, Christine W

    2016-07-01

    Adverse conditions may be the norm rather than the exception in natural populations. Many populations experience poor nutrition on a seasonal basis. Further, brief interludes of inbreeding can be common as population density fluctuates and because of habitat fragmentation. Here, we investigated the effects of poor nutrition and inbreeding on traits that can be very important to reproductive success and fitness in males: testes mass, sperm concentration, and sperm viability. Our study species was Narnia femorata, a species introduced to north-central Florida in the 1950s. This species encounters regular, seasonal changes in diet that can have profound phenotypic effects on morphology and behavior. We generated inbred and outbred individuals through a single generation of full-sibling mating or outcrossing, respectively. All juveniles were provided a natural, high-quality diet of Opuntia humifusa cactus cladode with fruit until they reached adulthood. New adult males were put on a high- or low-quality diet for at least 21 days before measurements were taken. As expected, the low-quality diet led to significantly decreased testes mass in both inbred and outbred males, although there were surprisingly no detectable effects on sperm traits. We did not find evidence that inbreeding affected testes mass, sperm concentration, and sperm viability. Our results highlight the immediate and overwhelming effects of nutrition on testes mass, while suggesting that a single generation of inbreeding might not be detrimental for primary sexual traits in this particular population.

  5. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms

    PubMed Central

    Dondeti, Mahmoud Fathy; El-Maadawy, Eman Anwar; Talaat, Roba Mohamed

    2016-01-01

    Hepatocellular carcinoma (HCC) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of HCC; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of HCC development. Cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related HCC. PMID:27570418

  6. UHRF1 overexpression drives DNA hypomethylation and hepatocellular carcinoma

    PubMed Central

    Mudbhary, Raksha; Hoshida, Yujin; Chernyavskaya, Yelena; Jacob, Vinitha; Villanueva, Augusto; Fiel, M. Isabel; Chen, Xintong; Kojima, Kensuke; Thung, Swan; Bronson, Roderick T.; Lachenmayer, Anja; Revill, Kate; Alsinet, Clara; Sachidanandam, Ravi; Desai, Anal; SenBanerjee, Sucharita; Ukomadu, Chinweike; Llovet, Josep M.; Sadler, Kirsten C.

    2014-01-01

    SUMMARY UHRF1 is an essential regulator of DNA methylation that is highly expressed in many cancers. Here, we use transgenic zebrafish, cultured cells and human tumors to demonstrate that UHRF1 is an oncogene. UHRF1 overexpression in zebrafish hepatocytes destabilizes and delocalizes DNMT1, causes DNA hypomethylation and Tp53-mediated senescence. Hepatocellular carcinoma (HCC) emerges when senescence is bypassed. tp53 mutation both alleviates senescence and accelerates tumor onset. Human HCCs recapitulate this paradigm, as UHRF1 overexpression defines a subclass of aggressive HCCs characterized by genomic instability, TP53 mutation and abrogation of the TP53-mediated senescence program. We propose that UHRF1 overexpression is a mechanism underlying DNA hypomethylation in cancer cells and that senescence is a primary means of restricting tumorigenesis due to epigenetic disruption. PMID:24486181

  7. Progress in systemic therapy of advanced hepatocellular carcinoma

    PubMed Central

    Gong, Xin-Lei; Qin, Shu-Kui

    2016-01-01

    Primary liver cancer, mainly consisting of hepatocellular carcinoma (HCC), is one of common malignancies worldwide, and prevalent among the Chinese population. A diagnosis of early stage HCC has proven to be very difficult because of its insidious feature in onset and development. At the time of diagnosis, most HCC cases are locally advanced and/or distant metastatic, which results in difficulty to be treated and poor prognosis. For advanced HCC, systemic therapy is frequently adopted as an important palliative method. In recent years, clinical studies and observations have often reported about systemic anti-cancer therapy of advanced HCC, including molecular target therapy, systemic chemotherapy and immunotherapy. In this article, we review these treatment modalities to provide a reference for clinicians. PMID:27547002

  8. Magnetic Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy.

    PubMed

    Ungureanu, Bogdan Silviu; Teodorescu, Cristian-Mihail; Săftoiu, Adrian

    2016-09-01

    Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver, ranking as the second most common cause of death from cancer worldwide. Magnetic nanoparticles (MNPs) have been used so far in tumor diagnosis and treatment, demonstrating great potential and promising results. In principle, three different approaches can be used in the treatment of tumors with superparamagnetic iron oxide nanoparticles: magnetically induced hyperthermia, drug targeting and selective suppression of tumor growth. This review focuses on the use of iron oxide nanoparticles for the diagnosis and treatment of liver cancer and offers a walkthrough from the MNPs imaging applicability to further therapeutic options, including their potential flaws. The MNP unique physical and biochemical properties will be mentioned in close relationship to their subsequent effects on the human body, and, also, their toxic potential will be noted. A presentation of what barriers the MNPs should overcome to be more successful will conclude this review. PMID:27689203

  9. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms.

    PubMed

    Dondeti, Mahmoud Fathy; El-Maadawy, Eman Anwar; Talaat, Roba Mohamed

    2016-08-14

    Hepatocellular carcinoma (HCC) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of HCC; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of HCC development. Cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related HCC. PMID:27570418

  10. Hepatocellular adenomatosis is a rare entity that may mimic other hepatocellular lesions.

    PubMed

    Skarupa, David J; Ellison, E Christopher; Vitellas, Kenneth M; Frankel, Wendy L

    2004-02-01

    A 14-year-old girl presented to her pediatrician with right lower quadrant pain that progressed to right upper quadrant pain with radiation to her back. Her past medical history included mitral valve prolapse, and she had no history of oral contraceptive use. Abdominal computed tomography revealed a liver mass and multiple smaller areas of low attenuation, too small to characterize. The clinical and radiographic features were suggestive of hepatocellular adenoma, and she underwent a left hepatic lobectomy. The liver contained one 4.2 cm nodule and multiple (10 to 20) smaller nodules that were well-demarcated from the adjacent liver parenchyma. All lesions were histologically hepatocellular adenomas and, therefore, she was diagnosed with hepatocellular adenomatosis. This case is unique because of the small number of cases of hepatocellular adenomatosis diagnosed in teenagers, and little long-term follow-up.

  11. The Relationship of Diabetes and Smoking Status to Hepatocellular Carcinoma Mortality

    PubMed Central

    Chiang, Chien-Hsieh; Lu, Chia-Wen; Han, Hsieh-Cheng; Hung, Shou-Hung; Lee, Yi-Hsuan; Yang, Kuen-Cheh; Huang, Kuo-Chin

    2016-01-01

    Abstract The relationship of diabetes and smoking status to hepatocellular carcinoma (HCC) mortality is not clear. We aimed to investigate the association of smoking cessation relative to diabetes status with subsequent deaths from HCC. We followed up 51,164 participants (aged 44–94 years) without chronic hepatitis B or C from 1 January 1998 to 31 December 2008 enrolled from nationwide health screening units in a prospective cohort study. The primary outcomes were deaths from HCC. During the study period, there were 253 deaths from HCC. History of diabetes was associated with deaths from HCC for both total participants (adjusted hazard ratio [HR], 2.97; 95% confidence interval [CI], 2.08–4.23) and ever smokers with current or past smoking habits (HR, 1.92; 95% CI, 1.10–3.34). Both never smokers (HR, 0.46; 95% CI, 0.32–0.65) and quitters (HR, 0.62; 95% CI, 0.39–0.97) had a lower adjusted risk of HCC deaths compared with current smokers. Among all ever smokers with current or past smoking habits, as compared with diabetic smokers, only quitters without diabetes had a lower adjusted risk of HCC deaths (HR, 0.37; 95% CI, 0.18–0.78). However, quitters with diabetes were observed to have a similar risk of deaths from HCC when compared with smokers with diabetes. Regarding the interaction between diabetes and smoking status on adjusted HCC-related deaths, with the exception of quitters without history of diabetes, all groups had significantly higher HRs than nondiabetic never smokers. There was also a significant multiplicative interaction between diabetes and smoking status on risk of dying from HCC (P = 0.033). We suggest clinicians should promote diabetes prevention and never smoking to associate with reduced subsequent HCC mortality even in adults without chronic viral hepatitis. PMID:26871803

  12. Microwave ablation of hepatocellular carcinoma

    PubMed Central

    Poggi, Guido; Tosoratti, Nevio; Montagna, Benedetta; Picchi, Chiara

    2015-01-01

    Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma (HCC) in patients with well compensated cirrhosis, thermal ablation techniques provide a valid non-surgical treatment alternative, thanks to their minimal invasiveness, excellent tolerability and safety profile, proven efficacy in local disease control, virtually unlimited repeatability and cost-effectiveness. Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules. Among them, radiofrequency (RF) currents are the most used, while microwave ablations (MWA) are becoming increasingly popular. Starting from the 90s’, RF ablation (RFA) rapidly became the standard of care in ablation, especially in the treatment of small HCC nodules; however, RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks. MWA, first introduced in the Far Eastern clinical practice in the 80s’, showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors, resulting in a poor coagulative performance and a relatively high complication rate, nowadays shows better results both in terms of treatment controllability and of overall coagulative performance, thanks to the improvement of technology. In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems, and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications, both in absolute terms and in comparison with RFA. PMID:26557950

  13. New advances in hepatocellular carcinoma.

    PubMed

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-03-28

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  14. New advances in hepatocellular carcinoma

    PubMed Central

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  15. Microwave ablation of hepatocellular carcinoma.

    PubMed

    Poggi, Guido; Tosoratti, Nevio; Montagna, Benedetta; Picchi, Chiara

    2015-11-01

    Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma (HCC) in patients with well compensated cirrhosis, thermal ablation techniques provide a valid non-surgical treatment alternative, thanks to their minimal invasiveness, excellent tolerability and safety profile, proven efficacy in local disease control, virtually unlimited repeatability and cost-effectiveness. Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules. Among them, radiofrequency (RF) currents are the most used, while microwave ablations (MWA) are becoming increasingly popular. Starting from the 90s', RF ablation (RFA) rapidly became the standard of care in ablation, especially in the treatment of small HCC nodules; however, RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks. MWA, first introduced in the Far Eastern clinical practice in the 80s', showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors, resulting in a poor coagulative performance and a relatively high complication rate, nowadays shows better results both in terms of treatment controllability and of overall coagulative performance, thanks to the improvement of technology. In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems, and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications, both in absolute terms and in comparison with RFA. PMID:26557950

  16. Newer markers for hepatocellular carcinoma.

    PubMed

    Marrero, Jorge A; Lok, Anna S F

    2004-11-01

    The incidence of hepatocellular carcinoma (HCC) is increasing worldwide; the overall survival of patients with HCC is grim because most patients are diagnosed late, when curative treatment is not possible. Cirrhosis is the strongest risk factor for the development of HCC. HCC surveillance with alpha-fetoprotein (AFP) and ultrasonography has been recommended for persons with cirrhosis. However, AFP level is insensitive for the early detection of HCC, and ultrasonography is expensive and operator dependent. Clearly, there is a need for novel strategies for the early detection of HCC. The ideal biomarker assay for HCC would be sensitive, specific, noninvasive, reproducible, inexpensive, and acceptable to patients. The Early Detection Research Network of the National Cancer Institute has proposed 5 phases for biomarker validation: preclinical exploratory studies, clinical assay development for disease, retrospective longitudinal study to detect preclinical disease, prospective screening study, and cancer control studies. Several biomarkers, such as des-gamma carboxyprothrombin, lens culinaris agglutinin-reactive AFP, human hepatocyte growth factor, and insulin-like growth factor-1, are promising, but none of these markers has been validated for clinical use. Limitations of the current literature include inadequate sample size, heterogeneity in biomarker assay methods and result reporting, limited analysis of demographics and cause of liver disease as covariates in the expression of these markers, and a scarcity of longitudinal studies evaluating the ability of biomarkers to detect preclinical disease. There is an urgent need for novel biomarkers for the detection of early HCC; the National Cancer Institute proposal provides a framework for future validation studies. PMID:15508074

  17. Targeted Therapies for Hepatocellular Carcinoma

    PubMed Central

    Villanueva, Augusto; Llovet, Josep M.

    2013-01-01

    Unlike most solid tumors, incidence and mortality of hepatocellular carcinoma (HCC) have increased in the US and Europe in the last decade. Most patients are diagnosed at advanced stages, so there is an urgent need for new systemic therapies. Sorafenib, a tyrosine kinase inhibitor (TKI), has demonstrated clinical efficacy in patients with HCC. Studies in patients with lung, breast, or colorectal cancers indicated that the genetic heterogeneity of cancer cells within a tumor affect its response to therapeutics designed to target specific molecules. When tumor progression requires alterations in specific oncogenes (oncogene addiction), drugs that selectively block their products might slow tumor growth. However, no specific oncogene alterations are yet known to be implicated in HCC progression, so it is important to improve our understanding of its molecular pathogenesis. There are currently many clinical trials evaluating TKIs for HCC, including those tested in combination with (e.g., erlotinib) or compared to (e.g., linifanib) sorafenib as a first-line therapy. For patients that do not respond or are intolerant to sorafenib, TKIs such as brivanib, everolimus, and monoclonal antibodies (e.g. ramucirumab) are being tested as second-line therapies. There are early-stage trials investigating the efficacy for up to 60 reagents for HCC. Together, these studies might change the management strategy for HCC, and combination therapies might be developed for patients with advanced HCC. Identification of oncogenes that mediate progression of HCC, and trials that monitor their products as biomarkers, might lead to personalized therapy; reagents that interfere with signaling pathways required for HCC progression might be used to treat selected populations, and thereby maximize the efficacy and cost-benefit. PMID:21406195

  18. Hepatocellular carcinoma: Where are we?

    PubMed Central

    Mazzanti, Roberto; Arena, Umberto; Tassi, Renato

    2016-01-01

    Hepatocellular carcinoma (HCC) is the second cause of death due to malignancy in the world, following lung cancer. The geographic distribution of this disease accompanies its principal risk factors: Chronic hepatitis B virus and hepatitis C virus infection, alcoholism, aflatoxin B1 intoxication, liver cirrhosis, and some genetic attributes. Recently, type II diabetes has been shown to be a risk factor for HCC together with obesity and metabolic syndrome. Although the risk factors are quite well known and it is possible to diagnose HCC when the tumor is less than 1 cm diameter, it remains elusive at the beginning and treatment is often unsuccessful. Liver transplantation is thus far considered the best treatment for HCC as it cures HCC and the underlying liver disease. Using the Milan criteria, overall survival after liver transplantation for HCC is about 70% after 5 years. Many attempts have been made to go beyond the Milan Criteria and according to recent works reasonably good results have been achieved by using a histochemical marker such as cytokeratine 19 and the so-called “up to seven criteria” to divide patients into categories according to their risk of relapse. In addition to liver transplantation other therapies have been proposed such as resection, tumor ablation by different means, embolization and chemotherapy. An important step in the treatment of advanced HCC has been the introduction of sorafenib, the first oral, systemic drug that has provided significant improvement in survival. Treatment of HCC patients must be multidisciplinary and by using the different approaches discussed in this review it is possible to offer prolonged survival and quite good and sometimes even excellent quality of life to many patients. PMID:26929917

  19. Incidence, Characteristics, and Prognosis of Incidentally Discovered Hepatocellular Carcinoma after Liver Transplantation

    PubMed Central

    El Moghazy, Walid; Kashkoush, Samy; Meeberg, Glenda; Kneteman, Norman

    2016-01-01

    Background. We aimed to assess incidentally discovered hepatocellular carcinoma (iHCC) over time and to compare outcome to preoperatively diagnosed hepatocellular carcinoma (pdHCC) and nontumor liver transplants. Methods. We studied adults transplanted with a follow-up of at least one year. Patients were divided into 3 groups according to diagnosis of hepatocellular carcinoma. Results. Between 1990 and 2010, 887 adults were transplanted. Among them, 121 patients (13.6%) had pdHCC and 32 patients (3.6%) had iHCC; frequency of iHCC decreased markedly over years, in parallel with significant increase in pdHCC. Between 1990 and 1995, 120 patients had liver transplants, 4 (3.3%) of them had iHCC, and only 3 (2.5%) had pdHCC, while in the last 5 years, 263 patients were transplanted, 7 (0.03%) of them had iHCC, and 66 (25.1%) had pdHCC (P < 0.001). There was no significant difference between groups regarding patient survival; 5-year survival was 74%, 75.5%, and 77.3% in iHCC, pdHCC, and non-HCC groups, respectively (P = 0.702). Patients with iHCC had no recurrences after transplant, while pdHCC patients experienced 17 recurrences (15.3%) (P = 0.016). Conclusions. iHCC has significantly decreased despite steady increase in number of transplants for hepatocellular carcinoma. Patients with iHCC had excellent outcomes with no tumor recurrence and survival comparable to pdHCC. PMID:27403337

  20. Prognostic factors for hepatocellular carcinoma recurrence.

    PubMed

    Colecchia, Antonio; Schiumerini, Ramona; Cucchetti, Alessandro; Cescon, Matteo; Taddia, Martina; Marasco, Giovanni; Festi, Davide

    2014-05-28

    The recurrence of hepatocellular carcinoma, the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide, represents an important clinical problem, since it may occur after both surgical and medical treatment. The recurrence rate involves 2 phases: an early phase and a late phase. The early phase usually occurs within 2 years after resection; it is mainly related to local invasion and intrahepatic metastases and, therefore, to the intrinsic biology of the tumor. On the other hand, the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment. Since recent studies have reported that early and late recurrences may have different risk factors, it is clinically important to recognize these factors in the individual patient as soon as possible. The aim of this review was, therefore, to identify predicting factors for the recurrence of hepatocellular carcinoma, by means of invasive and non-invasive methods, according to the different therapeutic strategies available. In particular the role of emerging techniques (e.g., transient elastography) and biological features of hepatocellular carcinoma in predicting recurrence have been discussed. In particular, invasive methods were differentiated from non-invasive ones for research purposes, taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.

  1. Hepatocellular carcinoma and evidence-based surgery

    PubMed Central

    Braillon, Alain

    2009-01-01

    Transplantation cannot be considered the most important therapeutic procedure for hepatocellular carcinoma (HCC). In France, no more than 2% of patients with HCC undergo a transplantation. Randomized controlled trial must assess the benefit to risk ratio of various potentially “curative” treatment procedures (transplantation, resection, radio-frequency ablation). PMID:19908350

  2. [Comparative genomic classification of human hepatocellular carcinoma].

    PubMed

    Kaposi-Novák, Pál

    2009-03-01

    Global transcriptome analysis has been successfully applied to characterize various human tumors, including hepatocellular carcinomas. This novel technology can facilitate early diagnosis, as well as prognostic and therapeutic diversification of cancer patients. To enhance access to the genomic information buried in archived pathology samples, we assessed RT-PCR amplification rates in paraffin-embedded tissues preserved in three different fixatives. Reliable amplification could be achieved from all paraffin-embedded specimens, when the amplicon size did not exceed 225 bp. A longer amplicon size resulted in rapid decrease of yield and reproducibility. In addition, formalin provided superior morphology and better reactivity with claudin-4 and -7 immunohistochemistry. Amplification of the initial sample is often required before transcriptome analysis of clinical specimens could be performed. We introduced a random nonamer primed T3 polymerase reaction into the conventional linear RNA amplification protocol. The modified T3T7 method generated a sense strand product ideal for synthesizing indirectly labeled cDNA templates. Microarray analysis of amplified frozen and laser-microdissected Myc and Myc/TGFalpha mouse liver tumors confirmed good reproducibility (r=0.9) of the reaction and conservation of original transcriptional patterns (r=0.78). Finally, we tested the utility of expression profiling for the classification of human HCC samples. By comparing expression data from HGF-treated c-Met conditional knock-out and control primary mouse hepatocytes, we identified 690 HGF/c-Met target genes. Functional analysis of the significant gene set implicated c-Met as key regulator of hepatocyte motility and oxidative homeostasis. Cross comparison of the c-Met-induced transcription signature with human HCC expression profiles revealed a group of tumors (27%) with potentially activated c-Met signaling (MET+). These tumors were characterized by higher vascular invasion rate

  3. Localization of the fourth locus (GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region.

    PubMed

    Sarfarazi, M; Child, A; Stoilova, D; Brice, G; Desai, T; Trifan, O C; Poinoosawmy, D; Crick, R P

    1998-03-01

    One of the major causes of blindness is primary open-angle glaucoma, which affects millions of elderly people worldwide. Genetic studies have so far mapped three loci for the adult-onset form of this condition to the 2cen-q13, 3q21-q24, and 8q23 regions. Herein, we report the localization of a fourth locus, to the 10p15-p14 region, in one large British family with a classical form of normal-tension open-angle glaucoma. Of the 42 meioses genotyped in this pedigree, 39 subjects (16 affected) inherited a haplotype compatible with their prior clinical designation, whereas the remaining 3 were classified as unknown. Although a maximum LOD score of 10.00 at a recombination fraction of straight theta=.00 was obtained with D10S1216, 21 other markers provided significant values, varying between 3.77 and 9.70. When only the affected meioses of this kindred were analyzed, LOD scores remained statistically significant, ranging from 3.16 (D10S527) to 3.57 (D10S506). Two critical recombinational events in the affected subjects positioned this new locus to a region of approximately 21 cM, flanked by D10S1729 and D10S1664. However, an additional recombination in a 59-year-old unaffected female suggests that this locus resides between D10S585 (or D10S1172) and D10S1664, within a genetic distance of 5-11 cM. However, the latter minimum region must be taken cautiously, because the incomplete penetrance has previously been documented for this group of eye conditions. A partial list of genes that positionally are considered as candidates includes NET1, PRKCT, ITIH2, IL2RA, IL15RA, IT1H2, hGATA3, the mRNA for open reading frame KIAA0019, and the gene for D123 protein.

  4. Efficacy and Tolerability of ABT-869 Versus Sorafenib in Advanced Hepatocellular Carcinoma (HCC)

    ClinicalTrials.gov

    2012-09-07

    Hepatocellular Carcinoma Non-resectable; Hepatocellular Carcinoma Recurrent; Carcinoma, Hepatocellular; Liver Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Carcinoma; Liver Neoplasms; Neoplasms; Neoplasms by Site; Digestive System Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial

  5. Increased thyroxine turnover and thyroidal function after stimulation of hepatocellular binding of thyroxine by phenobarbital.

    PubMed

    Oppenheimer, J H; Bernstein, G; Surks, M I

    1968-06-01

    Administration of phenobarbital to rats in a dosage schedule previously demonstrated to increase hepatocellular binding of thyroxine results in increased hormonal turnover, due both to increased deiodination and to fecal disposition of thyroxine iodine. The rate of biliary excretion of thyroxine iodine is roughly proportional to the hepatic content of exchangeable thyroxine. The enhanced peripheral disposition of thyroxine appears to lead to increased thyroidal function, as measured by isotopic iodine studies, and the maintenance of a normal nonradioactive serum PBI. On the other hand, thyroidectomized animals maintained on a constant replacement dose of L-thyroxine and treated with phenobarbital exhibit a marked fall in serum PBI. These findings suggest that increased thyroxine flux in phenobarbital-treated animals is secondary to primary stimulation of hepatocellular binding. Exchangeable intracellular thyroxine may thus be an important determinant of hormone turnover and, possibly, of hormonal action.

  6. Lesion in Scalp and Skull as the First Manifestation of Hepatocellular Carcinoma.

    PubMed

    Ferraz, V R; Vitorino-Araújo, J L; Sementilli, L; Neto, J F; Veiga, J C E

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and the fifth most common cancer in the world. The lungs, bone, and lymph nodes are frequent sites of metastasis of HCC. The purpose of the present study is show that metastases, although rare, must be among the differential diagnosis of skin lesions and that a diagnostic research based on these findings can be conducted. The authors report a rare case of metastatic hepatocellular injury to the scalp and skull treated by a radical surgical approach. Excision of the lesion in the scalp was performed "en bloc." The tumor was supplied by the frontal branch of the superficial temporal artery. There are few case reports of metastatic HCC to scalp and skull; treatment of these lesions should be individualized in order to control symptoms, improve quality of life, and promote an increase in survival. PMID:27403358

  7. High-Dose Vitamin C Promotes Regression of Multiple Pulmonary Metastases Originating from Hepatocellular Carcinoma

    PubMed Central

    Seo, Min-Seok; Kim, Ja-Kyung

    2015-01-01

    We report a case of regression of multiple pulmonary metastases, which originated from hepatocellular carcinoma after treatment with intravenous administration of high-dose vitamin C. A 74-year-old woman presented to the clinic for her cancer-related symptoms such as general weakness and anorexia. After undergoing initial transarterial chemoembolization (TACE), local recurrence with multiple pulmonary metastases was found. She refused further conventional therapy, including sorafenib tosylate (Nexavar). She did receive high doses of vitamin C (70 g), which were administered into a peripheral vein twice a week for 10 months, and multiple pulmonary metastases were observed to have completely regressed. She then underwent subsequent TACE, resulting in remission of her primary hepatocellular carcinoma. PMID:26256994

  8. Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa.

    PubMed

    Bressac, B; Kew, M; Wands, J; Ozturk, M

    1991-04-01

    Hepatocellular carcinoma (HCC) is a prevalent cancer in sub-Saharan Africa and eastern Asia. Hepatitis B virus and aflatoxins are risk factors for HCC, but the molecular mechanism of human hepatocellular carcinogenesis is largely unknown. Abnormalities in the structure and expression of the tumour-suppressor gene p53 are frequent in HCC cell lines, and allelic losses from chromosome 17p have been found in HCCs from China and Japan. Here we report on allelic deletions from chromosome 17p and mutations of the p53 gene found in 50% of primary HCCs from southern Africa. Four of five mutations detected were G----T substitutions, with clustering at codon 249. This mutation specificity could reflect exposure to a specific carcinogen, one candidate being aflatoxin B1 (ref. 7), a food contaminant in Africa, which is both a mutagen that induces G to T substitution and a liver-specific carcinogen.

  9. Investigating the biochemical progression of liver disease through fibrosis, cirrhosis, dysplasia, and hepatocellular carcinoma using Fourier transform infrared spectroscopic imaging

    NASA Astrophysics Data System (ADS)

    Sreedhar, Hari; Pant, Mamta; Ronquillo, Nemencio R.; Davidson, Bennett; Nguyen, Peter; Chennuri, Rohini; Choi, Jacqueline; Herrera, Joaquin A.; Hinojosa, Ana C.; Jin, Ming; Kajdacsy-Balla, Andre; Guzman, Grace; Walsh, Michael J.

    2014-03-01

    Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma. HCC ranks the fourth most prevalent malignant tumor and the third leading cause of cancer related death in the world. Hepatocellular carcinoma develops in the context of chronic liver disease and its evolution is characterized by progression through intermediate stages to advanced disease and possibly even death. The primary sequence of hepatocarcinogenesis includes the development of cirrhosis, followed by dysplasia, and hepatocellular carcinoma.1 We addressed the utility of Fourier Transform Infrared (FT-IR) spectroscopic imaging, both as a diagnostic tool of the different stages of the disease and to gain insight into the biochemical process associated with disease progression. Tissue microarrays were obtained from the University of Illinois at Chicago tissue bank consisting of liver explants from 12 transplant patients. Tissue core biopsies were obtained from each explant targeting regions of normal, liver cell dysplasia including large cell change and small cell change, and hepatocellular carcinoma. We obtained FT-IR images of these tissues using a modified FT-IR system with high definition capabilities. Firstly, a supervised spectral classifier was built to discriminate between normal and cancerous hepatocytes. Secondly, an expanded classifier was built to discriminate small cell and large cell changes in liver disease. With the emerging advances in FT-IR instrumentation and computation there is a strong drive to develop this technology as a powerful adjunct to current histopathology approaches to improve disease diagnosis and prognosis.

  10. Lapatinib Ditosylate in Treating Patients With Unresectable Liver or Biliary Tract Cancer

    ClinicalTrials.gov

    2015-04-08

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  11. Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-12-18

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  12. Modelo Pedagogico de Educacion Primaria para Adultos: Manual para la Vinculacion y Funcionamiento de los Comites de Educacion para Adultos (A Teaching Model for Adult Primary Education: Manual for the Continuation and Operation of Adult Education Committees).

    ERIC Educational Resources Information Center

    Instituto Nacional para la Educacion de los Adultos, Mexico City (Mexico).

    This manual is part of a Mexican series of instructional materials designed for Spanish speaking adults who are in the process of becoming literate or have recently become literate in their native language. This document describes the concept of a model for community adult education for the purpose of supporting local educational committees…

  13. Multilayer-Coated Liquid Crystalline Nanoparticles for Effective Sorafenib Delivery to Hepatocellular Carcinoma.

    PubMed

    Thapa, Raj Kumar; Choi, Ju Yeon; Poudel, Bijay K; Hiep, Tran Tuan; Pathak, Shiva; Gupta, Biki; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2015-09-16

    Hepatocellular carcinoma is one of the most common cancers in adults and develops due to activation of oncogenes and inactivation of tumor suppressor genes. Sorafenib (SF) is a U.S. Food and Drug Administration (FDA) approved drug for the treatment of hepatocellular carcinoma. However, its clinical use is limited by its poor aqueous solubility and undesirable side effects. Monoolein-based liquid crystalline nanoparticles (LCN) are self-assembled structures that have been determined as promising drug-delivery vehicles. Therefore, the main aim of this study was to prepare layer-by-layer (LbL) polymer-assembled SF-loaded LCNs (LbL-LCN/SF) for effective delivery of SF to hepatocellular carcinoma. Results revealed that LbL-LCN/SF presented optimum particle size (∼165 nm) and polydispersity index (PDI, ∼0.14) with appropriate polymer layer assembly confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Furthermore, LbL-LCN/SF effectively controlled burst release and exhibited pH-sensitive release of SF, thereby increasing drug release in the acidic microenvironment of tumor cells. Compared to free SF and bare LCN, the hemolytic activity of LbL-LCN/SF was significantly reduced (p<0.01). Interestingly, LbL-LCN/SF was more cytotoxic to HepG2 cells than the free drug was. Additionally, high cellular uptake and greater apoptotic effects of LbL-LCN/SF in HepG2 cells indicates superior antitumor effects. Therefore, LbL-LCN/SF is a potentially effective formulation for hepatocellular carcinoma.

  14. Age-Related Prognostic Impact of Different Types of DNMT3A Mutations in Adults With Primary Cytogenetically Normal Acute Myeloid Leukemia

    PubMed Central

    Marcucci, Guido; Metzeler, Klaus H.; Schwind, Sebastian; Becker, Heiko; Maharry, Kati; Mrózek, Krzysztof; Radmacher, Michael D.; Kohlschmidt, Jessica; Nicolet, Deedra; Whitman, Susan P.; Wu, Yue-Zhong; Powell, Bayard L.; Carter, Thomas H.; Kolitz, Jonathan E.; Wetzler, Meir; Carroll, Andrew J.; Baer, Maria R.; Moore, Joseph O.; Caligiuri, Michael A.; Larson, Richard A.; Bloomfield, Clara D.

    2012-01-01

    Purpose To determine the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, and the associated gene- and microRNA-expression signatures in primary cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods Four hundred fifteen previously untreated adults were analyzed for DNMT3A mutations and established prognostic gene mutations and expression markers. Gene- and microRNA-expression profiles were derived using microarrays. Results Younger (< 60 years; n = 181) and older (≥ 60 years; n = 234) patients had similar frequencies of DNMT3A mutations (35.3% v 33.3%). Missense mutations affecting arginine codon 882 (R882-DNMT3A) were more common (n = 92; 62%) than those affecting other codons (non–R882-DNMT3A). DNMT3A-mutated patients did not differ regarding complete remission rate, but had shorter disease-free survival (DFS; P = .03) and, by trend, overall survival (OS; P = .07) than DNMT3A–wild-type patients. In multivariable analyses, DNMT3A mutations remained associated with shorter DFS (P = .01), but not with shorter OS. When analyzed separately, the two DNMT3A mutation types had different significance by age group. Younger patients with non–R882-DNMT3A mutations had shorter DFS (P = .002) and OS (P = .02), whereas older patients with R882-DNMT3A mutations had shorter DFS (P = .005) and OS (P = .002) after adjustment for other clinical and molecular prognosticators. Gene- and microRNA-expression signatures did not accurately predict DNMT3A mutational status. Conclusion DNMT3A mutations are frequent in CN-AML, and their clinical significance seems to be age dependent. DNMT3A-R882 mutations are associated with adverse prognosis in older patients, and non–R882-DNMT3A mutations are associated with adverse prognosis in younger patients. Low accuracy of gene- and microRNA-expression signatures in predicting DNMT3A mutation status suggested that the role of these mutations in AML remains to

  15. Relationship between obesity and antipsychotic drug use in the adult population: A longitudinal, retrospective claim database study in Primary Care settings

    PubMed Central

    Sicras-Mainar, Antoni; Navarro-Artieda, Ruth; Rejas-Gutiérrez, Javier; Blanca-Tamayo, Milagrosa

    2008-01-01

    Objective To describe the association between obesity and the use of antipsychotic drugs (APDs) in adult outpatients followed-up on in five Primary Care settings. Methods A longitudinal, retrospective design study carried out between July 2004 and June 2005, in patients who were included in a claim database and for whom an APD treatment had been registered. A body mass index (BMI) <30 kg/m2 was defined as obesity. The main measurements were: use of APDs, demographics, medical background and co-morbidities, and clinical parameters. Logistic regression analysis and ANCOVA with Bonferroni adjustment were applied to correct the model. Results A total of 42,437 subjects (mean age: 50.8 (18.4) years; women: 54.5%; obesity: 27.3% [95% confidence intervals (CI), 26.9%–27.7%]) were analyzed. A total of 1.3% of the patients were receiving APDs, without statistical differences in distribution by type of drug (typical: 48.8%; atypical: 51.2%). Obesity was associated with the use of APDs [OR = 1.5 (CI: 1.3–1.8)], hypertension [OR = 2.4 (CI: 2.2–2.5)], diabetes [OR = 1.4 (CI: 1.3–1.5)] and dyslipidemia [OR = 1.3 (CI: 1.2–1.4)], p < 0.0001 in all cases. BMI was significantly higher in subjects on APDs; 28.8 vs. 27.3 kg/m2, p = 0.002, and remained higher after adjusting by age and sex (mean difference 0.4 (CI: 0.1–0.7), p < 0.01). After adjusting by age, sex and the Charlson index, obese subjects generated higher average annual total costs than nonobese subjects; 811 (CI: 787–835) vs. 694 (CI: 679–709), respectively, p < 0.001. Conclusions Obesity was associated with the use of APDs, regardless of the type of drug, and with the presence of hypertension, diabetes and dyslipidemia. Obesity was also associated with substantially higher health care costs. PMID:18728769

  16. Transcriptomic characterization of fibrolamellar hepatocellular carcinoma.

    PubMed

    Simon, Elana P; Freije, Catherine A; Farber, Benjamin A; Lalazar, Gadi; Darcy, David G; Honeyman, Joshua N; Chiaroni-Clarke, Rachel; Dill, Brian D; Molina, Henrik; Bhanot, Umesh K; La Quaglia, Michael P; Rosenberg, Brad R; Simon, Sanford M

    2015-11-01

    Fibrolamellar hepatocellular carcinoma (FLHCC) tumors all carry a deletion of ∼ 400 kb in chromosome 19, resulting in a fusion of the genes for the heat shock protein, DNAJ (Hsp40) homolog, subfamily B, member 1, DNAJB1, and the catalytic subunit of protein kinase A, PRKACA. The resulting chimeric transcript produces a fusion protein that retains kinase activity. No other recurrent genomic alterations have been identified. Here we characterize the molecular pathogenesis of FLHCC with transcriptome sequencing (RNA sequencing). Differential expression (tumor vs. adjacent normal tissue) was detected for more than 3,500 genes (log2 fold change ≥ 1, false discovery rate ≤ 0.01), many of which were distinct from those found in hepatocellular carcinoma. Expression of several known oncogenes, such as ErbB2 and Aurora Kinase A, was increased in tumor samples. These and other dysregulated genes may serve as potential targets for therapeutic intervention. PMID:26489647

  17. Changing epidemiology of hepatocellular carcinoma in Asia.

    PubMed

    Goh, George Boon-Bee; Chang, Pik-Eu; Tan, Chee-Kiat

    2015-12-01

    Hepatocellular carcinoma is a major problem in Asia because of the presence of multiple risk factors in the region such as endemicity of hepatitis B and significant contamination of foodstuff by aflatoxin in some areas. Another risk factor for HCC, chronic hepatitis C infection, in Asia is most significant in Japan, the only Asian country with more HCV than HBV-related hepatocellular carcinoma. As these risk factors can and are being modified by measures such as universal hepatitis B immunisation, successful treatment of HCV infections, reduction and improved surveillance of aflatoxin contamination of foodstuff, it is not surprising that the epidemiology of HCC in Asia is changing. All these are offset by the rising importance of NAFLD and NASH as chronic liver diseases and risk factors for HCC which contributes to the changing epidemiology of HCC in Asia.

  18. Transcriptomic characterization of fibrolamellar hepatocellular carcinoma

    PubMed Central

    Simon, Elana P.; Freije, Catherine A.; Farber, Benjamin A.; Lalazar, Gadi; Darcy, David G.; Honeyman, Joshua N.; Chiaroni-Clarke, Rachel; Dill, Brian D.; Molina, Henrik; Bhanot, Umesh K.; La Quaglia, Michael P.; Rosenberg, Brad R.; Simon, Sanford M.

    2015-01-01

    Fibrolamellar hepatocellular carcinoma (FLHCC) tumors all carry a deletion of ∼400 kb in chromosome 19, resulting in a fusion of the genes for the heat shock protein, DNAJ (Hsp40) homolog, subfamily B, member 1, DNAJB1, and the catalytic subunit of protein kinase A, PRKACA. The resulting chimeric transcript produces a fusion protein that retains kinase activity. No other recurrent genomic alterations have been identified. Here we characterize the molecular pathogenesis of FLHCC with transcriptome sequencing (RNA sequencing). Differential expression (tumor vs. adjacent normal tissue) was detected for more than 3,500 genes (log2 fold change ≥1, false discovery rate ≤0.01), many of which were distinct from those found in hepatocellular carcinoma. Expression of several known oncogenes, such as ErbB2 and Aurora Kinase A, was increased in tumor samples. These and other dysregulated genes may serve as potential targets for therapeutic intervention. PMID:26489647

  19. Epidemiology of hepatocellular carcinoma (HCC) in hemophilia.

    PubMed

    Shetty, Shrimati; Sharma, Nitika; Ghosh, Kanjaksha

    2016-03-01

    Hepatocellular carcinoma (HCC) is an important cause of increasing mortality in elderly hemophilia population. Majority of the patients treated with virus non-inactivated factor concentrates prepared from large plasma pools prior to 1985 have been found to be infected with hepatitis C virus (HCV), a major risk factor for HCC. A PubMed search of articles published until February 2015 was performed utilizing the keywords hemophilia, malignancy, neoplasm, cancer, mortality, ageing hemophilia, epidemiology, hepatocellular carcinoma and liver cancer and the relevant articles were included. Contradictory reports are available in literature on the incidence of cancers in general in hemophilia population. Almost all the studies where the incidence of HCC or mortality due to HCC have been analyzed in hemophilia population show that a vast majority of these patients are HCV infected. The incidence of HCC though higher in hemophilic population is related to the higher incidence of HCV infection and not due to the hemophilia phenotype.

  20. Predictors of Microvascular Invasion in Hepatocellular Carcinoma.

    PubMed

    Yamashita, Yo-Ichi; Shirabe, Ken; Aishima, Shinichi; Maehara, Yoshihiko

    2015-09-01

    This chapter covers a range of important topics in the evaluation of the microvascular invasion (MVI) in hepatocellular carcinoma (HCC) before treatment. The malignant potential of HCC is reflected by the types of MVI such as portal venous (vp), hepatic vein (vv) or bile duct (b) infiltration. The identification of the type of MVI in HCC has a key role in decisions regarding the effective treatment of HCC. Here, we describe the possible and important predictors of MVI in HCC. PMID:26398341

  1. Human arylacetamide deacetylase hydrolyzes ketoconazole to trigger hepatocellular toxicity.

    PubMed

    Fukami, Tatsuki; Iida, Azumi; Konishi, Keigo; Nakajima, Miki

    2016-09-15

    Ketoconazole (KC), an antifungal agent, rarely causes severe liver injury when orally administered. It has been reported that KC is mainly hydrolyzed to N-deacetyl ketoconazole (DAK), followed by the N-hydroxylation of DAK by flavin-containing monooxygenase (FMO). Although the metabolism of KC has been considered to be associated with hepatotoxicity, the responsible enzyme(s) remain unknown. The purpose of this study was to identify the responsible enzyme(s) for KC hydrolysis in humans and to clarify their relevance to KC-induced toxicity. Kinetic analysis and inhibition studies using human liver microsomes (HLM) and recombinant enzymes revealed that human arylacetamide deacetylase (AADAC) is responsible for KC hydrolysis to form DAK, and confirmed that FMO3 is the enzyme responsible for DAK N-hydroxylation. In HLM, the clearance of KC hydrolysis occurred to the same extent as DAK N-hydroxylation, which indicates that both processes are not rate-limiting pathways. Cytotoxicity of KC and DAK was evaluated using HepaRG cells and human primary hepatocytes. Treatment of HepaRG cells with DAK for 24h showed cytotoxicity in a dose-dependent manner, whereas treatment with KC did not show due to the low expression of AADAC. Overexpression of AADAC in HepaRG cells with an adenovirus expression system elicited the cytotoxicity of KC. Cytotoxicity of KC in human primary hepatocytes was attenuated by diisopropylfluorophosphate, an AADAC inhibitor. In conclusion, the present study demonstrated that human AADAC hydrolyzes KC to trigger hepatocellular toxicity.

  2. Tumor Heterogeneity in Hepatocellular Carcinoma: Facing the Challenges.

    PubMed

    Lu, Li-Chun; Hsu, Chih-Hung; Hsu, Chiun; Cheng, Ann-Lii

    2016-04-01

    Tumor heterogeneity in hepatocellular carcinoma (HCC), such as that found in second primary tumors after curative treatment, synchronous multifocal tumors of different clonality, or intratumor heterogeneity, poses severe challenges for the development and administration of systemic molecular targeted therapies. Various methodologies, including historical DNA ploidy analysis, integrated hepatitis B virus DNA analysis, DNA fingerprinting, and next-generation sequencing technologies, are used to explore tumor heterogeneity in HCC. It is estimated that 30%-60% of recurrent or metastatic tumors harbor clones different from the primary tumor, 22%-79% of synchronous tumors vary clonally, and 12%-66% of single tumors contain intratumor heterogeneity. Substantial intertumor and intratumor heterogeneity renders biomarker identification, which is critical for the development and administration of molecular targeted therapy, challenging when applied to a single tumor biopsy specimen. The use of circulating tumor cells or circulating tumor DNA to evaluate overall tumor heterogeneity may help resolve this problem. This article reviews previous studies of tumor heterogeneity and discusses the implications and future opportunities regarding tumor heterogeneity in HCC. PMID:27386431

  3. Hepatocellular carcinoma in glycogen storage disease type IV

    PubMed Central

    de Moor, R A; Schweizer, J; van Hoek, B; Wasser, M; Vink, R; Maaswinkel-Mooy, P

    2000-01-01

    A 13 year old patient with juvenile type IV glycogen storage disease died of the complications of hepatocellular carcinoma. To our knowledge this is the first reported case of hepatocellular carcinoma in association with type IV glycogen storage disease.

 PMID:10833181

  4. Variceal bleeding caused by oesophageal varices: A manifestation of hepatocellular carcinoma in a 17-year-old girl

    PubMed Central

    Ali, Saadia Sasha; Sanmuganathan, Samuel N

    2015-01-01

    The authors present the rare case of a 17-year-old girl referred to the medical assessment unit following a large upper gastrointestinal haemorrhage. On further evaluation, she was found to have a primary hepatocellular carcinoma with extensive metastases. In our patient, the tumour was deemed incurable by resection, liver transplantation or percutaneous treatment. She underwent palliative chemotherapy and passed away 11 months following presentation. PMID:27489703

  5. IQuaD dental trial; improving the quality of dentistry: a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care

    PubMed Central

    2013-01-01

    Background Periodontal disease is the most common oral disease affecting adults, and although it is largely preventable it remains the major cause of poor oral health worldwide. Accumulation of microbial dental plaque is the primary aetiological factor for both periodontal disease and caries. Effective self-care (tooth brushing and interdental aids) for plaque control and removal of risk factors such as calculus, which can only be removed by periodontal instrumentation (PI), are considered necessary to prevent and treat periodontal disease thereby maintaining periodontal health. Despite evidence of an association between sustained, good oral hygiene and a low incidence of periodontal disease and caries in adults there is a lack of strong and reliable evidence to inform clinicians of the relative effectiveness (if any) of different types of Oral Hygiene Advice (OHA). The evidence to inform clinicians of the effectiveness and optimal frequency of PI is also mixed. There is therefore an urgent need to assess the relative effectiveness of OHA and PI in a robust, sufficiently powered randomised controlled trial (RCT) in primary dental care. Methods/Design This is a 5 year multi-centre, randomised, open trial with blinded outcome evaluation based in dental primary care in Scotland and the North East of England. Practitioners will recruit 1860 adult patients, with periodontal health, gingivitis or moderate periodontitis (Basic Periodontal Examination Score 0–3). Dental practices will be cluster randomised to provide routine OHA or Personalised OHA. To test the effects of PI each individual patient participant will be randomised to one of three groups: no PI, 6 monthly PI (current practice), or 12 monthly PI. Baseline measures and outcome data (during a three year follow-up) will be assessed through clinical examination, patient questionnaires and NHS databases. The primary outcome measures at 3 year follow up are gingival inflammation/bleeding on probing at the

  6. Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma

    PubMed Central

    Roncalli, Massimo; Sciarra, Amedeo; Tommaso, Luca Di

    2016-01-01

    Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed. PMID:27189732

  7. Elevated serum levels of Chromogranin A in hepatocellular carcinoma

    PubMed Central

    2012-01-01

    Background During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages. Methods The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed. Results The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001). Conclusions Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy. PMID:23173843

  8. Hepatocellular Carcinoma in Pakistan: National Trends and Global Perspective.

    PubMed

    Hafeez Bhatti, Abu Bakar; Dar, Faisal Saud; Waheed, Anum; Shafique, Kashif; Sultan, Faisal; Shah, Najmul Hassan

    2016-01-01

    Hepatocellular carcinoma (HCC) ranks second amongst all causes of cancer deaths globally. It is on a rise in Pakistan and might represent the most common cancer in adult males. Pakistan contributes significantly to global burden of hepatitis C, which is a known risk factor for HCC, and has one of the highest prevalence rates (>3%) in the world. In the absence of a national cancer registry and screening programs, prevalence of hepatitis and HCC only represents estimates of the real magnitude of this problem. In this review, we present various aspects of HCC in Pakistan, comparing and contrasting it with the global trends in cancer care. There is a general lack of awareness regarding risk factors of HCC in Pakistani population and prevalence of hepatitis C has increased. In addition, less common risk factors are also on a rise. Majority of patients present with advanced HCC and are not eligible for definitive treatment. We have attempted to highlight issues that have a significant bearing on HCC outcome in Pakistan. A set of strategies have been put forth that can potentially help reduce incidence and improve HCC outcome on national level. PMID:26955390

  9. Hepatocellular Carcinoma in Pakistan: National Trends and Global Perspective

    PubMed Central

    Hafeez Bhatti, Abu Bakar; Dar, Faisal Saud; Waheed, Anum; Shafique, Kashif; Sultan, Faisal; Shah, Najmul Hassan

    2016-01-01

    Hepatocellular carcinoma (HCC) ranks second amongst all causes of cancer deaths globally. It is on a rise in Pakistan and might represent the most common cancer in adult males. Pakistan contributes significantly to global burden of hepatitis C, which is a known risk factor for HCC, and has one of the highest prevalence rates (>3%) in the world. In the absence of a national cancer registry and screening programs, prevalence of hepatitis and HCC only represents estimates of the real magnitude of this problem. In this review, we present various aspects of HCC in Pakistan, comparing and contrasting it with the global trends in cancer care. There is a general lack of awareness regarding risk factors of HCC in Pakistani population and prevalence of hepatitis C has increased. In addition, less common risk factors are also on a rise. Majority of patients present with advanced HCC and are not eligible for definitive treatment. We have attempted to highlight issues that have a significant bearing on HCC outcome in Pakistan. A set of strategies have been put forth that can potentially help reduce incidence and improve HCC outcome on national level. PMID:26955390

  10. Hepatitis B vaccination and prevention of hepatocellular carcinoma.

    PubMed

    Kao, Jia-Horng

    2015-12-01

    Hepatitis B virus (HBV) infection is a global health threat; with 240 million people are chronic carriers of the virus. The infection can cause acute and chronic liver disease including liver cirrhosis and hepatocellular carcinoma (HCC). On the basis of disease burden and the availability of safe and effective vaccines, World Health Organization has recommended that hepatitis B vaccine be incorporated into routine infant and childhood immunization programs for all countries. The efficacy of universal immunization has been proven in many countries, with substantial reductions of the prevalence of HBV carriage in children, adolescents and young adults. Most important, hepatitis B vaccination can protect them from HCC, as has been demonstrated in Taiwan and other countries. Nevertheless, the implementation of worldwide vaccination against HBV indeed requires more effort to overcome the social and economic challenges. To have a global control of HBV infection, we have to continue the universal HBV vaccination, interrupt the possible transmission routes and treat eligible patients with antiviral agents. However, current treatments are still far from ideal as they cannot eradicate intrahepatic HBV cccDNA, and lifelong administration of these agents will pose a major economic burden, especially in the endemic Asia-Pacific region. Thus we need innovative treatment strategies and novel agents with difference modes of action to overcome the unmet medical need for an efficient HBV cure with subsequent global eradication of HBV infection, hopefully by the first half of 21st century.

  11. Hepatocellular carcinoma and food contamination: aflatoxins and ochratoxin A as a great prompter.

    PubMed

    Felizardo, Raphael J F; Câmara, Niels O S

    2013-06-28

    Prolonged exposure to mycotoxins in the diet is related to cancer, among other diseases. Hepatocellular carcinoma (HCC) accounts for 70%-90% of primary liver cancers and is the third leading cause of cancer-related deaths worldwide. Secondary metabolites, like aflatoxins and ochratoxin A (OTA), produced by some fungi species stocked in an inappropriate manner are considered an important way to increase HCC incidence. Future epidemiologic studies of HCC should focus on good practices in food preparation, food storage and the consumption of OTA-containing foods.

  12. Management of hepatocellular carcinoma: an overview of major findings from meta-analyses

    PubMed Central

    Guo, Xiaozhong; Han, Guohong

    2016-01-01

    This paper aims to systematically review the major findings from meta-analyses comparing different treatment options for hepatocellular carcinoma (HCC). A total of 153 relevant papers were searched via the PubMed, EMBASE, and Cochrane library databases. They were classified according to the mainstay treatment modalities (i.e., liver transplantation, surgical resection, radiofrequency ablation, transarterial embolization or chemoembolization, sorafenib, and others). The primary outcome data, such as overall survival, diseases-free survival or recurrence-free survival, progression-free survival, and safety, were summarized. The recommendations and uncertainties regarding the treatment of HCC were also proposed. PMID:27167195

  13. Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

    PubMed Central

    Bouattour, Mohamed; Payancé, Audrey; Wassermann, Johanna

    2015-01-01

    Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimizing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used. PMID:26380650

  14. Hepatocellular alterations and dysregulation of oncogenic pathways in the liver of transgenic mice overexpressing growth hormone.

    PubMed

    Miquet, Johanna G; Freund, Thomas; Martinez, Carolina S; González, Lorena; Díaz, María E; Micucci, Giannina P; Zotta, Elsa; Boparai, Ravneet K; Bartke, Andrzej; Turyn, Daniel; Sotelo, Ana I

    2013-04-01

    Growth hormone (GH) overexpression throughout life in transgenic mice is associated with the development of liver tumors at old ages. The preneoplastic pathology observed in the liver of young adult GH-overexpressing mice is similar to that present in humans at high risk of hepatic cancer. To elucidate the molecular pathogenesis underlying the pro-oncogenic liver pathology induced by prolonged exposure to elevated GH levels, the activation and expression of several components of signal transduction pathways that have been implicated in hepatocellular carcinogenesis were evaluated in the liver of young adult GH-transgenic mice. In addition, males and females were analyzed in parallel in order to evaluate sexual dimorphism. Transgenic mice from both sexes exhibited hepatocyte hypertrophy with enlarged nuclear size and exacerbated hepatocellular proliferation, which were higher in males. Dysregulation of several oncogenic pathways was observed in the liver of GH-overexpressing transgenic mice. Many signaling mediators and effectors were upregulated in transgenic mice compared with normal controls, including Akt2, NFκB, GSK3β, β-catenin, cyclin D1, cyclin E, c-myc, c-jun and c-fos. The molecular alterations described did not exhibit sexual dimorphism in transgenic mice except for higher gene expression and nuclear localization of cyclin D1 in males. We conclude that prolonged exposure to GH induces in the liver alterations in signaling pathways involved in cell growth, proliferation and survival that resemble those found in many human tumors.

  15. The long noncoding RNAs PVT1 and uc002mbe.2 in sera provide a new supplementary method for hepatocellular carcinoma diagnosis

    PubMed Central

    Yu, Jinyu; Han, Junqing; Zhang, Jian; Li, Guanzhen; Liu, Hui; Cui, Xianping; Xu, Yantian; Li, Tao; Liu, Juan; Wang, Chuanxi

    2016-01-01

    Abstract Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver in adults worldwide. Several studies have demonstrated that long noncoding RNAs (lncRNAs) are involved in the development of various types of cancer, including HCC. These findings prompted us to examine the detectability of lncRNAs in blood samples from patients with HCC. In this study, we explored the expression levels of 31 cancer-related lncRNAs in sera from 71 HCC patients and 64 healthy individuals by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). We found that 25 lncRNAs could be detected in the serum and that 7 had significantly different expression levels. A 2-lncRNA signature (PVT1 and uc002mbe.2) identified by stepwise regression showed potential as a diagnostic marker for HCC. The area under the receiver operating characteristic (ROC) curve was 0.764 (95% CI: 0.684–0.833). The sensitivity and specificity values of this serum 2-lncRNA signature for distinguishing HCC patients from the healthy group were 60.56% and 90.62%, respectively. The diagnostic ability of the combination of the serum 2-lncRNA signature with alpha-fetoprotein (AFP) was much greater than that of AFP alone. The expression levels of the 2 lncRNAs were associated with clinical parameters including tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, and serum bilirubin. PMID:27495068

  16. The long noncoding RNAs PVT1 and uc002mbe.2 in sera provide a new supplementary method for hepatocellular carcinoma diagnosis.

    PubMed

    Yu, Jinyu; Han, Junqing; Zhang, Jian; Li, Guanzhen; Liu, Hui; Cui, Xianping; Xu, Yantian; Li, Tao; Liu, Juan; Wang, Chuanxi

    2016-08-01

    Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver in adults worldwide. Several studies have demonstrated that long noncoding RNAs (lncRNAs) are involved in the development of various types of cancer, including HCC. These findings prompted us to examine the detectability of lncRNAs in blood samples from patients with HCC. In this study, we explored the expression levels of 31 cancer-related lncRNAs in sera from 71 HCC patients and 64 healthy individuals by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). We found that 25 lncRNAs could be detected in the serum and that 7 had significantly different expression levels. A 2-lncRNA signature (PVT1 and uc002mbe.2) identified by stepwise regression showed potential as a diagnostic marker for HCC. The area under the receiver operating characteristic (ROC) curve was 0.764 (95% CI: 0.684-0.833). The sensitivity and specificity values of this serum 2-lncRNA signature for distinguishing HCC patients from the healthy group were 60.56% and 90.62%, respectively. The diagnostic ability of the combination of the serum 2-lncRNA signature with alpha-fetoprotein (AFP) was much greater than that of AFP alone. The expression levels of the 2 lncRNAs were associated with clinical parameters including tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, and serum bilirubin. PMID:27495068

  17. Aflatoxins as a cause of hepatocellular carcinoma.

    PubMed

    Kew, Michael C

    2013-09-01

    Aflatoxins, metabolites of the fungi Aspergillus flavus and Aspergillus parasiticus, are frequent contaminants of a number of staple foods, particularly maize and ground nuts, in subsistence farming communities in tropical and sub-tropical climates in sub-Saharan Africa, Eastern Asia and parts of South America. Contamination of foods occurs during growth and as a result of storage in deficient or inappropriate facilities. These toxins pose serious public health hazards, including the causation of hepatocellular carcinoma by aflatoxin B1. Exposure begins in utero and is life-long. The innocuous parent molecule of the fungus is converted by members of the cytochrome p450 family into mutagenic and carcinogenic intermediates. Aflatoxin-B1 is converted into aflatoxin B1-8,9 exo-epoxide, which is in turn converted into 8,9-dihydroxy-8-(N7) guanyl-9-hydroxy aflatoxin B1 adduct. This adduct is metabolized into aflatoxin B1 formaminopyrimidine adduct. These adducts are mutagenic and carcinogenic. In addition, an arginine to serine mutation at codon 249 of the p53 tumor suppressor gene is produced, abrogating the function of the tumor suppressor gene, and contributing to hepatocarcinogenesis. Aflatoxin B1 acts synergistically with hepatitis B virus in causing hepatocellular carcinoma. A number of interactions between the two carcinogens may be responsible for this action, including integration of hepatitis B virus x gene and its consequences, as well as interference with nucleotide excision repair, activation of p21waf1/cip1, generation of DNA mutations, and altered methylation of genes. But much remains to be learnt about the precise pathogenetic mechanisms responsible for aflatoxin B1-induced hepatocellular carcinoma as well as the interaction between the toxin and hepatitis B virus in causing the tumor.

  18. Hepatocellular carcinoma and African iron overload.

    PubMed Central

    Gangaidzo, I T; Gordeuk, V R

    1995-01-01

    Both hepatocellular carcinoma (HCC) and iron overload are important health problems in Africa. Chronic hepatitis B virus (HBV) infection is recognised as a major risk factor for HCC, but iron overload in Africans has not been considered in pathogenesis. Up to half the patients with HCC in Africa do not have any recognised risk factors such as preceding chronic HBV infection, and other risk factors remain unidentified. HCC is an important complication of HLA-linked haemochromatosis, an iron loading disorder found in Europeans. It is proposed that African iron overload might also be a risk factor for HCC. PMID:8549953

  19. The Role of Autophagy in Hepatocellular Carcinoma

    PubMed Central

    Lee, Yoo Jin; Jang, Byoung Kuk

    2015-01-01

    Autophagy is a catabolic process involved in cellular homeostasis under basal and stressed conditions. Autophagy is crucial for normal liver physiology and the pathogenesis of liver diseases. During the last decade, the function of autophagy in hepatocellular carcinoma (HCC) has been evaluated extensively. Currently, autophagy is thought to play a dual role in HCC, i.e., autophagy is involved in tumorigenesis and tumor suppression. Recent investigations of autophagy have suggested that autophagy biomarkers can facilitate HCC prognosis and the establishment of therapeutic approaches. In this review, we briefly summarize the current understanding of autophagy and discuss recent evidence for its role in HCC. PMID:26561802

  20. Hepatitis C virus replication in hepatocellular carcinoma.

    PubMed Central

    Niu, J; Kumar, U; Monjardino, J; Goldin, R; Rosin, D; Thomas, H C

    1995-01-01

    Hepatitis C virus (HCV) replication is reported in both tumour and non-tumour tissue in a case of hepatocellular carcinoma. Viral replication was established by showing the presence of minus strand HCV RNA by PCR amplification, after excluding residual reverse transcriptase activity of Taq polymerase. No minus strand was found in serum derived virion RNA. PCR amplified products from both tumour and non-tumour parenchyma were sequenced in the 5' non-coding region and shown to be identical. The genotype of this Indonesian patient was found to be 1b (or II), the most prevalent type in the Far East. Images PMID:7490330

  1. Screening for Viral Hepatitis and Hepatocellular Cancer.

    PubMed

    Cameron, Andrew M

    2015-10-01

    Accurate tests for at-risk populations are available for hepatitis B virus, hepatitis C virus (HCV), and hepatocellular carcinoma (HCC). Effective treatments for all three diseases exist if diagnosed early. New antivirals are making a significant impact on HCV. Liver transplant is curative for early HCC and is prioritized by the United Network for Organ Sharing in the United States. Screening and surveillance for deadly disease only makes sense if there are identifiable populations at risk for the condition, there are sensitive and specific low-cost tests available for the condition, and there are effective treatments for the condition.

  2. Innovative surgical approaches for hepatocellular carcinoma

    PubMed Central

    Memeo, Riccardo; de’Angelis, Nicola; de Blasi, Vito; Cherkaoui, Zineb; Brunetti, Oronzo; Longo, Vito; Piardi, Tullio; Sommacale, Daniele; Marescaux, Jacques; Mutter, Didier; Pessaux, Patrick

    2016-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, with an increasing diffusion in Europe and the United States. The management of such a cancer is continuously progressing and the objective of this paper is to evaluate innovation in the surgical treatment of HCC. In this review, we will analyze the modern concept of preoperative management, the role of laparoscopic and robotic surgery, the intrao-perative use of three dimensional models and augme-nted reality, as well as the potential application of fluore-scence. PMID:27168871

  3. Transarterial radioembolization for hepatocellular carcinoma: a review

    PubMed Central

    Sacco, Rodolfo; Conte, Caterina; Tumino, Emanuele; Parisi, Giuseppe; Marceglia, Sara; Metrangolo, Salvatore; Eggenhoffner, Roberto; Bresci, Giampaolo; Cabibbo, Giuseppe; Giacomelli, Luca

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is the second cause of death due to malignancy in the world. The treatment of HCC is complex and includes potentially curative and palliative approaches. However, both curative and palliative treatments for HCC are often associated with a not-completely favorable safety/efficacy ratio. Therefore, other treatment options appear necessary in clinical practice. Transarterial radioembolization has shown a promising efficacy in terms of disease control and is associated with a good safety profile. This review discusses the use of transarterial radioembolization in HCC, with a focus on the clinical aspects of this therapeutic strategy. PMID:27574589

  4. The Role of Autophagy in Hepatocellular Carcinoma.

    PubMed

    Lee, Yoo Jin; Jang, Byoung Kuk

    2015-01-01

    Autophagy is a catabolic process involved in cellular homeostasis under basal and stressed conditions. Autophagy is crucial for normal liver physiology and the pathogenesis of liver diseases. During the last decade, the function of autophagy in hepatocellular carcinoma (HCC) has been evaluated extensively. Currently, autophagy is thought to play a dual role in HCC, i.e., autophagy is involved in tumorigenesis and tumor suppression. Recent investigations of autophagy have suggested that autophagy biomarkers can facilitate HCC prognosis and the establishment of therapeutic approaches. In this review, we briefly summarize the current understanding of autophagy and discuss recent evidence for its role in HCC. PMID:26561802

  5. Modelo Pedagogico de Educacion Primaria para Adultos: Guia General de Apoyo para el Estudiante de Primaria (Pedagogical Model for Adult Primary Education: General Guide for the Student).

    ERIC Educational Resources Information Center

    Instituto Nacional para la Educacion de los Adultos, Mexico City (Mexico).

    This book, part of a Mexican series of instructional materials, is directed toward people over the age of 15 who are interested in beginning, continuing or finishing their basic education. It explains the pedagogical model developed for adult education in Mexico based on the following features: (1) the content of the textbooks must be useful for…

  6. Significance of Rumex vesicarius as anticancer remedy against hepatocellular carcinoma: a proposal-based on experimental animal studies.

    PubMed

    Shahat, Abdelaaty A; Alsaid, Mansour S; Kotob, Soheir E; Ahmed, Hanaa H

    2015-01-01

    Rumex vesicarius is an edible herb distributed in Egypt and Saudi Arabia. The whole plant has significant value in folk medicine and it has been used to alleviate several diseases. Hepatocellular carcinoma (HCC), the major primary malignant tumor of the liver, is one of the most life-threatening human cancers. The goal of the current study was to explore the potent role of Rumex vesicarius extract against HCC induced in rats. Thirty adult male albino rats were divided into 3 groups: (I): Healthy animals received orally 0.9% normal saline and served as negative control group, (II): HCC group in which rats were orally administered N-nitrosodiethylamine NDEA, (III): HCC group treated orally with R. vesicarius extract in a dose of 400 mg/kg b.wt daily for two months. ALT and AST, ALP and γ-GT activities were estimated. CEA, AFP, AFU, GPC-3, Gp-73 and VEGF levels were quantified. Histopathological examination of liver tissue sections was also carried out. The results of the current study showed that the treatment of the HCC group with R. vesicarius extract reversed the significant increase in liver enzymes activity, CEA, AFP, AFU, glypican 3, golgi 73 and VEGF levels in serum as compared to HCC-untreated counterparts. In addition, the favorable impact of R. vesicarius treatment was evidenced by the marked improvement in the histopathological features of the liver of the treated group. In conclusion, the present experimental setting provided evidence for the significance of R. vesicarius as anticancer candidate with a promising anticancer potential against HCC. The powerful hepatoprotective properties, the potent antiangiogenic activity and the effective antiproliferative capacity are responsible for the anticancer effect of this plant. PMID:26028090

  7. In Vivo Magnetic Resonance Spectroscopic Imaging of Hyperpolarized [1-13C] Pyruvate Metabolism in Rat Hepatocellular Carcinoma

    PubMed Central

    Darpolor, Moses M.; Yen, Yi-Fen; Chua, Mei-Sze; Xing, Lei; Clarke-Katzenberg, Regina H.; Shi, Wenfang; Mayer, Dirk; Josan, Sonal; Hurd, Ralph E.; Pfefferbaum, Adolf; Senadheera, Lasitha; So, Samuel; Hofmann, Lawrence V.; Glazer, Gary M.; Spielman, Daniel M.

    2010-01-01

    Hepatocellular carcinoma (HCC), the primary form of human adult liver malignancy, is a highly aggressive tumor with average survival rates that are currently less than a year following diagnosis. Most patients with HCC are diagnosed at an advanced stage, and no efficient marker exists for predicting prognosis and/or response(s) to therapy. We previously reported a high level of [1-13C] alanine in an orthotopic HCC using single-voxel hyperpolarized [1-13C] pyruvate magnetic resonance spectroscopy (MRS). In the present study, we implemented a 3D-magnetic resonance spectroscopic imaging (MRSI) sequence to investigate this potential hallmark of cellular metabolism in rat livers bearing HCC (N=7 buffalo rats). In addition, quantitative real-time PCR was used to determine the mRNA levels of lactate dehydrogenase A, NAD(P)H dehydrogenase quinone 1, and alanine transaminase. The enzymes levels were significantly higher in the tumor than the normal liver tissues within each rat, which is associated with the in vivo MRSI signal of [1-13C]alanine and [1-13C]lactate after a bolus intravenous injection of [1-13C]pyruvate. Histopathological analysis of these tumors confirms successful growth of HCC as a nodule in buffalo rats’ livers revealing malignancy and hyper-vascular architecture. More importantly, the results demonstrate that the metabolic fate of [1-13C]pyruvate conversion to [1-13C]alanine significantly supersedes that of [1-13C]pyruvate conversion to [1-13C]lactate potentially serving as a marker of HCC tumors. PMID:21674652

  8. Significance of Rumex vesicarius as anticancer remedy against hepatocellular carcinoma: a proposal-based on experimental animal studies.

    PubMed

    Shahat, Abdelaaty A; Alsaid, Mansour S; Kotob, Soheir E; Ahmed, Hanaa H

    2015-01-01

    Rumex vesicarius is an edible herb distributed in Egypt and Saudi Arabia. The whole plant has significant value in folk medicine and it has been used to alleviate several diseases. Hepatocellular carcinoma (HCC), the major primary malignant tumor of the liver, is one of the most life-threatening human cancers. The goal of the current study was to explore the potent role of Rumex vesicarius extract against HCC induced in rats. Thirty adult male albino rats were divided into 3 groups: (I): Healthy animals received orally 0.9% normal saline and served as negative control group, (II): HCC group in which rats were orally administered N-nitrosodiethylamine NDEA, (III): HCC group treated orally with R. vesicarius extract in a dose of 400 mg/kg b.wt daily for two months. ALT and AST, ALP and γ-GT activities were estimated. CEA, AFP, AFU, GPC-3, Gp-73 and VEGF levels were quantified. Histopathological examination of liver tissue sections was also carried out. The results of the current study showed that the treatment of the HCC group with R. vesicarius extract reversed the significant increase in liver enzymes activity, CEA, AFP, AFU, glypican 3, golgi 73 and VEGF levels in serum as compared to HCC-untreated counterparts. In addition, the favorable impact of R. vesicarius treatment was evidenced by the marked improvement in the histopathological features of the liver of the treated group. In conclusion, the present experimental setting provided evidence for the significance of R. vesicarius as anticancer candidate with a promising anticancer potential against HCC. The powerful hepatoprotective properties, the potent antiangiogenic activity and the effective antiproliferative capacity are responsible for the anticancer effect of this plant.

  9. Galectin-1-Induced Autophagy Facilitates Cisplatin Resistance of Hepatocellular Carcinoma.

    PubMed

    Su, Yu-Chi; Davuluri, Goutham Venkata Naga; Chen, Cheng-Hao; Shiau, Dong-Che; Chen, Chien-Chin; Chen, Chia-Ling; Lin, Yee-Shin; Chang, Chih-Peng

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients. PMID:26859293

  10. Epigenetic inactivation of SLIT2 in human hepatocellular carcinomas.

    PubMed

    Jin, Jie; You, Haiyan; Yu, Bin; Deng, Yun; Tang, Ning; Yao, Genfu; Shu, Huiqun; Yang, Shengli; Qin, Wenxin

    2009-01-30

    Recent findings have shown that SLIT2 appears to function as a novel tumor suppressor gene. In addition, hypermethylation of its promoter region has been detected in various cancers, including breast and lung cancer, colorectal carcinoma, and gliomas. Here, we report for the first time that there is epigenetic silencing of SLIT2 in human hepatocellular carcinoma (HCC). Downregulation of SLIT2 was detected in 6 of 8 (75%) HCC cell lines by quantitative real-time RT-PCR (qRT-PCR), and the downregulation of SLIT2 was generally dependent on the degree of methylation at the promoter region. Furthermore, expression of SLIT2 was restored in relatively low-expressing cell lines after treatment with 5-aza-2-deoxycytidine (5-Aza-dC). Downregulation of SLIT2 expression was also detected in 45 of 54 primary HCC samples (83.3%), and the decrease in expression was significantly correlated with CpG island hypermethylation. This decrease of SLIT2 expression was also associated with lymph node metastasis in HCC. Moreover, overexpression of SLIT2 in SMMC-7721 cells induced by recombinant adenovirus suppressed cell growth, migration, and invasion, These results suggest that epigenetic inactivation of SLIT2 in HCC may be important in the development and progression of HCC. Thus, SLIT2 may be useful as a therapeutic target in the treatment of HCC.

  11. Causes of and prevention strategies for hepatocellular carcinoma.

    PubMed

    Cabibbo, Giuseppe; Maida, Marcello; Genco, Chiara; Antonucci, Michela; Cammà, Calogero

    2012-08-01

    Hepatocellular carcinoma (HCC) is a challenging malignancy of global importance. It is associated with a high rate of mortality and its prevalence in the United States and in Western Europe is increasing. Cirrhosis is the strongest and the most common known risk factor for HCC, usually due to hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. However, different lines of evidence identify in non-alcoholic fatty liver disease (NAFLD) a possible relevant risk factor for occurrence of HCC. Given the continuing increase in the prevalence of obesity and diabetes, the incidence of non-alcoholic steatohepatitis-related HCC may also be expected to increase, and a potential role of behavior treatment and/or insulin-sensitizing drugs can be envisaged. Vaccination against HBV is the most efficient primary prevention measure currently available to reduce the HCC incidence and mortality in high-incidence areas, while data on the role of interferon (IFN) and nucleos(t)ide analogues (NUC) are still controversial. The pooling of data from the literature suggests a slight preventive effect of antiviral therapy on HCC development in patients with HCV-related cirrhosis, but the preventive effect is limited to sustained virological responders. PMID:22846856

  12. Natural history of hepatocellular carcinoma and current treatment options.

    PubMed

    Raoul, Jean-Luc

    2008-03-01

    Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the most severe complication of chronic liver disease. The annual number of new cases worldwide is approximately 550,000, representing more than 5% of human cancers and is the third leading cause of cancer-related deaths. The stages of the malignancy as well as the severity of the underlying liver disease are essential factors in planning the therapeutic approach. Curative treatment options are represented mainly by surgery (ie, resection or transplantation), but most patients are not candidates for a curative option, and only palliative treatment could be given to these patients. Among palliative treatments, only chemoembolization has been proven to be effective, but other options are currently being investigated. Major risk factors for HCC are well known and are dependent on the geographic area. In Europe, the United States, and Japan, the main risk factors are liver cirrhosis, hepatitis B and C virus, alcohol, and tobacco; in contrast, in Africa and Asia, these factors are hepatitis B and C virus, tobacco use, and aflatoxin exposure. Cirrhosis from any cause is a predisposing factor for HCC and could be considered as a premalignant condition. The present concept of carcinogenesis in HCC is a multistage process. This article describes the natural history of HCC and discusses the various treatment options available at present. PMID:18243838

  13. Zebrafish as a disease model for studying human hepatocellular carcinoma

    PubMed Central

    Lu, Jeng-Wei; Ho, Yi-Jung; Yang, Yi-Ju; Liao, Heng-An; Ciou, Shih-Ci; Lin, Liang-In; Ou, Da-Liang

    2015-01-01

    Liver cancer is one of the world’s most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma (HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathogenesis of HCC consists of a stepwise process of liver damage that extends over decades, due to hepatitis, fatty liver, fibrosis, and cirrhosis before developing fully into HCC. Multiple risk factors are highly correlated with HCC, including infection with the hepatitis B or C viruses, alcohol abuse, aflatoxin exposure, and metabolic diseases. Over the last decade, genetic alterations, which include the regulation of multiple oncogenes or tumor suppressor genes and the activation of tumorigenesis-related pathways, have also been identified as important factors in HCC. Recently, zebrafish have become an important living vertebrate model organism, especially for translational medical research. In studies focusing on the biology of cancer, carcinogen induced tumors in zebrafish were found to have many similarities to human tumors. Several zebrafish models have therefore been developed to provide insight into the pathogenesis of liver cancer and the related drug discovery and toxicology, and to enable the evaluation of novel small-molecule inhibitors. This review will focus on illustrative examples involving the application of zebrafish models to the study of human liver disease and HCC, through transgenesis, genome editing technology, xenografts, drug discovery, and drug-induced toxic liver injury. PMID:26576090

  14. Promoter Methylation of SFRP3 Is Frequent in Hepatocellular Carcinoma

    PubMed Central

    Shih, Yu-Lueng; Lien, Gi-Shih; Suk, Fat-Moon; Hsieh, Chung-Bao; Yan, Ming-De

    2014-01-01

    Oncogenic activation of the Wnt/β-catenin signaling pathway is common in human cancers. The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications in carcinogenesis. Because there have been no reports about the role of SFRP3 in hepatocellular carcinoma (HCC), we investigated the level of methylation and transcription of SFRP3. Four HCC cell lines, 60 HCCs, 23 cirrhosis livers, 37 chronic hepatitis livers, and 30 control livers were prescreened for SFRP3 promoter methylation by methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing. SFRP3 promoter methylation was observed in 100%, 60%, 39.1%, 16.2%, and 0% in HCC cell lines, primary HCCs, cirrhosis livers, chronic hepatitis livers, and control livers, respectively. Demethylation treatment with 5-aza-2′-deoxycytidine in HCC cells restored or increased the SFRP3 mRNA expression. We next used quantitative MS-PCR (QMSP) to analyze the methylation level of SFRP3 in 60 HCCs and their corresponding nontumor tissues. Methylation of SFRP3 promoter region in HCCs increased significantly compared with control tissues. There is a positive correlation between promoter hypermethylation and SFRP3 mRNA downregulation. Our data suggest that promoter hypermethylation of SFRP3 is a common event in HCCs and plays an important role in regulation of SFRP3 mRNA expression. PMID:24591760

  15. Annexin A6 protein is downregulated in human hepatocellular carcinoma.

    PubMed

    Meier, Elisabeth M; Rein-Fischboeck, Lisa; Pohl, Rebekka; Wanninger, Josef; Hoy, Andrew J; Grewal, Thomas; Eisinger, Kristina; Krautbauer, Sabrina; Liebisch, Gerhard; Weiss, Thomas S; Buechler, Christa

    2016-07-01

    Annexin A6 (AnxA6) is a lipid-binding protein highly expressed in the liver, regulating cholesterol homeostasis and signaling pathways with a role in liver physiology. Here, we analyzed whether hepatic AnxA6 levels are affected by pathological conditions that are associated with liver dysfunction and liver injury. AnxA6 levels in the fatty liver of mice fed a high-fat diet, in ob/ob and db/db animals and in human fatty liver are comparable to controls. Similarly, AnxA6 levels appear unaffected in murine nonalcoholic steatohepatitis and human liver fibrosis. Accordingly, adiponectin, lysophosphatidylcholine, palmitate, and TGFbeta, all of which have a role in liver injury, do not affect AnxA6 expression in human hepatocytes. Likewise, adiponectin and IL8 do not alter AnxA6 levels in primary human hepatic stellate cells. However, in hepatic tumors of 18 patients, AnxA6 protein levels are substantially reduced compared to nontumorous tissues. AnxA6 mRNA is even increased in the tumors suggesting that posttranscriptional mechanisms are involved herein. Lipidomic analysis shows trends toward elevated cholesteryl ester and sphingomyelin in the tumor samples, yet the ratio of tumor to nontumorous AnxA6 does not correlate with these lipids. The current study shows that AnxA6 is specifically reduced in human hepatocellular carcinoma suggesting a role of this protein in hepatocarcinogenesis. PMID:27334756

  16. Lactate Dehydrogenase in Hepatocellular Carcinoma: Something Old, Something New

    PubMed Central

    Faloppi, Luca; Bianconi, Maristella; Memeo, Riccardo; Casadei Gardini, Andrea; Giampieri, Riccardo; Bittoni, Alessandro; Andrikou, Kalliopi; Del Prete, Michela; Cascinu, Stefano; Scartozzi, Mario

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver tumour (80–90%) and represents more than 5.7% of all cancers. Although in recent years the therapeutic options for these patients have increased, clinical results are yet unsatisfactory and the prognosis remains dismal. Clinical or molecular criteria allowing a more accurate selection of patients are in fact largely lacking. Lactic dehydrogenase (LDH) is a glycolytic key enzyme in the conversion of pyruvate to lactate under anaerobic conditions. In preclinical models, upregulation of LDH has been suggested to ensure both an efficient anaerobic/glycolytic metabolism and a reduced dependence on oxygen under hypoxic conditions in tumour cells. Data from several analyses on different tumour types seem to suggest that LDH levels may be a significant prognostic factor. The role of LDH in HCC has been investigated by different authors in heterogeneous populations of patients. It has been tested as a potential biomarker in retrospective, small, and nonfocused studies in patients undergoing surgery, transarterial chemoembolization (TACE), and systemic therapy. In the major part of these studies, high LDH serum levels seem to predict a poorer outcome. We have reviewed literature in this setting trying to resume basis for future studies validating the role of LDH in this disease. PMID:27314036

  17. Epidemiology and survival of hepatocellular carcinoma in north-east Peninsular Malaysia.

    PubMed

    Norsa'adah, Bachok; Nurhazalini-Zayani, Che Ghazali Che

    2013-01-01

    The incidence of hepatocellular carcinoma (HCC) is relatively high in Southeast Asia. Globally, HCC has a high fatality rate and short survival. The objectives of this retrospective cohort study were to review the epidemiology and survival of HCC patients at a tertiary centre in north-east of Peninsular Malaysia. Subjects were adult HCC patients diagnosed by histopathology or radio-imaging. Secondary liver carcinoma was excluded. Kaplan Meier and multiple Cox proportional hazard survival analyses were used. Only 210 HCC cases from years 1987-2008, were included in the final analysis. The number of cases was increasing annually. The mean age was 55.0 (SD 13.9) years with male:female ratio of 3.7:1. Approximately 57.6% had positive hepatitis B virus, 2.4% hepatitis C virus, 20% liver cirrhosis and 8.1% chronic liver disease. Only 2.9% had family history and 9.0% had frequently consumed alcohol. Most patients presented with abdominal pain or discomfort and had hepatomegaly, 47.9% had an elevated α-fetoprotein level of 800 IU/ml or more, 51.9% had multiple tumors and 44.8% involved multiple liver lobes. Approximately 63.3% were in stage 3 and 23.4% in stage 4, and 82.9% did not receive any treatment. The overall median survival time was 1.9 months (95% confidence interval (CI): 1.5, 2.3). The 1-month, 6-month, 1-year and 2-year survival rates were 71.8%, 23.3%, 13.0% and 7.3% respectively. Significant prognostic factors were Malay ethnicity [Adjusted hazard ratio (AHR) 1.6; 95%CI: 1.0, 2.5; p=0.030], no chemotherapy [AHR 1.7; 95%CI: 1.1, 2.5; p=0.017] and Child-Pugh class C [AHR 2.6; 95%CI: 1.4, 4.9; p=0.002]. HCC in our study affected a wide age range, mostly male, in advanced stage of disease, with no treatment and very low survival rates. Primary prevention should be advocated in view of late presentation and difficulty of treatment. Vaccination of hepatitis virus and avoidance of liver toxins are to be encouraged.

  18. Antineoplastic activity of monocrotaline against hepatocellular carcinoma.

    PubMed

    Kusuma, Sandeep Solmon; Tanneeru, Karunakar; Didla, Swroopa; Devendra, Bellary Nagaraju; Kiranmayi, Patnala

    2014-01-01

    Plants are fantastic sources for present day life saving drugs. Monocrotaline a natural ligand exhibits dose-dependent cytotoxicity with potent antineoplastic activity. This study was intended to disclose the therapeutic potential of monocrotaline against hepatocellular carcinoma. The in silico predictions have highlighted the antineoplastic potential, druglikeness and biodegradability of monocrotaline. The in silico docking study has provided an insight and evidence for the antineoplastic activity of monocrotaline against p53, HGF and TREM1 proteins which play a threatening role in causing hepatocellular carcinoma. The mode of action of monocrotaline was determined experimentally by in vitro techniques such as XTT assay, NRU assay and whole cell brine shrimp assay have further supported our in silico studies. The in vitro cytotoxicity of monocrotaline was proved at IC50 24.966 µg/mL and genotoxicity at 2 X IC50 against HepG2 cells. Further, the credible druglike properties with non-mutagenicity, non-toxic on mammalian fibroblast and the potential antineoplastic activity through in vitro experimental validations established monocrotaline as a novel scaffold for liver cancer with superior efficacy and lesser side effects. PMID:25028149

  19. Epidemiology and carcinogenesis of hepatocellular carcinoma

    PubMed Central

    Leong, Trishe Y.-M.

    2005-01-01

    The incidence of hepatocellular carcinoma (HCC) shows marked variation worldwide but the magnitude of this tumor is reflected by the occurrence of at least 1 million new cases annually and the uniformly dismal outlook with median survivals of <25 months after resection and <6 months with symptomatic treatment. The strikingly uneven distribution of this tumor parallels the prevalence of hepatitis B infection with rising incidence in western countries attributed to hepatitis C infection. Chronic hepatitis and cirrhosis constitute the major preneoplastic conditions in the majority of HCCs and may be related to other etiologic agents such as environmental chemical carcinogens including nitrites, hydrocarbons, solvents, organochlorine pesticides, and the chemicals in processed foods, cleaning agents, cosmetics and pharmaceuticals, as well as plant toxins such as anatoxins produced by fungi that cause spoilage of grain and food in the tropics. Genetic diseases such as genetic hematochromatosis, Wilson's disease, α-1-antitrypsin deficiency, and the inborn errors of metabolism including hereditary tyrosinemia and hepatic porphyria, are known to be associated with HCC. Numerous genetic alterations and the modulation of DNA methylation are recognized in HCC and it is likely that these genetic and epigenetic changes combine with factors involved in chronic hepatocyte destruction and regeneration to result in neoplastic growth and multiple molecular pathways may be involved in the production of subsets of hepatocellular tumors. PMID:18333156

  20. Malignant transformation of hepatocellular adenoma over a decade

    PubMed Central

    Tokoro, Takamasa; Kato, Yutaro; Sugioka, Atsushi; Mizoguchi, Yoshikazu

    2014-01-01

    A 72-year-old man diagnosed with a benign hepatocellular lesion 11 years prior was referred to our hospital for an outgrowth of the tumour in liver segment 7. Extended segmentectomy was performed and the patient's postoperative course was uneventful with no recurrence for 2 years. Histopathological examination confirmed a highly differentiated hepatocellular carcinoma (HCC) coexisting with the hepatocellular adenoma (HCA), and it was suspected to have originated from the HCA. The findings from this case demonstrate that CT can be useful for detecting the transformation of HCA into HCC. PMID:25246462

  1. Markedly Elevated Liver Enzymes in Choledocholithiasis in the absence of Hepatocellular Disease: Case Series and Literature Review.

    PubMed

    Tetangco, Eula Plana; Shah, Natasha; Arshad, Hafiz Muhammad Sharjeel; Raddawi, Hareth

    2016-01-01

    Liver enzyme levels are commonly obtained in the evaluation of many conditions. Elevated alanine transaminase and aspartate transaminase have traditionally been considered a "hepatocellular" pattern concerning for ischemic, viral, or toxic hepatitis. Elevations in these levels pose a diagnostic dilemma in patients without a clinical picture consistent with liver disease. On the other hand, elevated alkaline phosphatase historically represents a "cholestatic" pattern concerning for gallbladder and biliary tract disease. Often, patients present with a "mixed" picture of elevation in all 3 liver enzymes, further confounding the clinical scenario. We present 4 cases of women with severe upper abdominal pain and markedly elevated transaminases. Three of the patients had accompanying jaundice. A higher rise in enzyme levels was seen in those who had greater bile duct dilation. All patients saw a rapid decrease in transaminases after biliary decompression, along with a fall in alkaline phosphatase and total bilirubin levels. No evidence of liver disease was found, nor were there any signs of hepatocellular disease on imaging. The patients were ultimately found to have choledocholithiasis on endoscopic retrograde cholangiopancreatography with no hepatocellular disease. Furthermore, our cases show that severe abdominal pain in the setting of elevated liver enzymes is likely associated with biliary disease rather than a primary hepatic process. Recognition of this rare pattern of markedly elevated transaminases in isolated biliary disease can aid in avoiding unnecessary evaluation of primary hepatic disease and invasive surgical interventions such as liver biopsy. PMID:27408902

  2. Adult lupus-prone MRL/MpJ2+ mice express a primary antibody repertoire that differs in CDR-H3 length distribution and hydrophobicity from that expressed in the C3H parental strain.

    PubMed

    Zemlin, Michael; Ippolito, Gregory C; Zemlin, Cosima; Link, Jason; Monestier, Marc; Schroeder, Harry W

    2005-05-01

    Anti-dsDNA antibodies tend to be enriched for heavy chain complementarity determining region 3 (CDR-H3) intervals of above average length that contain an increased frequency of charged amino acids. It is unclear whether these types of CDR-H3s are more common in the primary B-cell repertoire of auto-immune prone strains or whether their increased prevalence in affected individuals reflects positive selection and expansion of atypical CDR-H3s in the pathogenic response to self-antigen. Here, we present evidence that when compared to C3H, a MRL/MpJ(2+) parental strain, CDR-H3 intervals from pre-B cells of adult lupus-prone MRL/MpJ(2+) mice are longer on average and are enriched for charged amino acids. The predicted prevalence of deformed loops per Shirai H3 criteria is also higher. In contrast, the frequency of charge, the distribution of length, and the pattern of predicted deformed loop structures did not differ in sequences obtained from neonates of the same two strains. These observations suggest that the mechanisms that serve to shape the initial CDR-H3 repertoire in adults, but not neonates, are being regulated differently in C3H versus MRL/MpJ(2+). Dysregulation of the adult pre-B CDR-H3 antibody repertoire could be a contributing factor for the development of florid auto-immune disease in MRL/MpJ(2+) mice.

  3. Effectiveness of regular reporting of spirometric results combined with a smoking cessation advice by a primary care physician on smoking quit rate in adult smokers: a randomized controlled trial. ESPIROTAB study

    PubMed Central

    2011-01-01

    Background Undiagnosed airflow limitation is common in the general population and is associated with impaired health and functional status. Smoking is the most important risk factor for this condition. Although primary care practitioners see most adult smokers, few currently have spirometers or regularly order spirometry tests in these patients. Brief medical advice has shown to be effective in modifying smoking habits in a large number of smokers but only a small proportion remain abstinent after one year. The aim of this study is to evaluate the effectiveness of regular reporting of spirometric results combined with a smoking cessation advice by a primary care physician on smoking quit rate in adult smokers. Methods/design Intervention study with a randomized two arms in 5 primary care centres. A total of 485 smokers over the age of 18 years consulting their primary care physician will be recruited. On the selection visit all participants will undergo a spirometry, peak expiratory flow rate, test of smoking dependence, test of motivation for giving up smoking and a questionnaire on socio-demographic data. Thereafter an appointment will be made to give the participants brief structured advice to give up smoking combined with a detailed discussion on the results of the spirometry. After this, the patients will be randomised and given appointment for follow up visits at 3, 6, 12 and 24 months. Both arms will receive brief structured advice and a detailed discussion of the spirometry results at visit 0. The control group will only be given brief structured advice about giving up smoking on the follow up. Cessation of smoking will be tested with the carbon monoxide test. Discussion Early identification of functional pulmonary abnormalities in asymptomatic patients or in those with little respiratory symptomatology may provide "ideal educational opportunities". These opportunities may increase the success of efforts to give up smoking and may improve the opportunities

  4. Sunitinib (SUTENT, SU11248) suppresses tumor growth and induces apoptosis in xenograft models of human hepatocellular carcinoma.

    PubMed

    Huynh, H; Ngo, V C; Choo, S P; Poon, D; Koong, H N; Thng, C H; Toh, H C; Zheng, L; Ong, L C; Jin, Y; Song, I C; Chang, A P C; Ong, H S; Chung, A Y F; Chow, P K H; Soo, K C

    2009-09-01

    Hepatocellular carcinoma (HCC) is the fifth most common and third deadliest primary neoplasm. Since HCC is a particularly vascular solid tumor, we determined the antitumor and antiangiogenic activities of sunitinib malate, a potent inhibitor of two receptors involved in angiogenesis - vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). In the present study, we reported that treatment of HepG2 and SK-Hep-1 cells with sunitinib led to growth inhibition and apoptosis in a dose-dependent fashion. Sunitinib inhibited phosphorylation of VEGFR-2 at Tyr951 and PDGFR-beta at Tyr1021 both in vitro and in vivo. Sunitinib also suppressed tumor growth of five patient-derived xenografts. Sunitinib-induced tumor growth inhibition was associated with increased apoptosis, reduced microvessel density and inhibition of cell proliferation. This study provides a strong rationale for further clinical investigation of sunitinib in patients with hepatocellular carcinoma.

  5. Non-viral factors contributing to hepatocellular carcinoma

    PubMed Central

    Hamed, Manal A; Ali, Sanaa A

    2013-01-01

    Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide, accounting for over half a million deaths per year. The geographic pattern of HCC incidence is parallel to exposure to viral etiologic factors. Its incidence is increasing, ranging between 3% and 9% annually depending on the geographical location, and variability in the incidence rates correspond closely to the prevalence and pattern of the primary etiologic factors. Chronic infections with hepatitis B viruses or hepatitis C viruses have both been recognized as human liver carcinogens with a combined attributable fraction of at least 75% of all HCC cases. Multiple non-viral factors have been implicated in the development of HCC. Increased body mass index and diabetes with subsequent development of non-alcoholic steatohepatitis represent significant risk factors for HCC. Other non-viral causes of HCC include iron overload syndromes, alcohol use, tobacco, oral contraceptive, aflatoxin, pesticides exposure and betel quid chewing, a prevalent habit in the developing world. Wilson disease, α-1 antitrypsin deficiency, Porphyrias, autoimmune hepatitis, Schistosoma japonicum associated with positive hepatitis B surface antigen, and thorotrast-ray are also contributing hepatocellualar carcinoma. In addition, primary biliary cirrhosis, congestive liver disease and family history of liver cancer increase the risk of HCC incident. In conclusion, clarification of relevant non-viral causes of HCC will help to focus clinicians on those risk factors that are modifiable. The multilevel preventative approach will hopefully lead to a reduction in incidence of non-viral HCC, and a decrease in the patient morbidity and mortality as well as the societal economic burden associated with HCC. PMID:23805355

  6. Liver transplantation for non-hepatocellular carcinoma malignancy.

    PubMed

    Castaldo, Eric T; Pinson, C Wright

    2007-01-01

    Liver transplantation (LT) for hepatocellular carcinoma is effective for selected patients. LT for other malignancies like cholangiocarcinoma (CCA), hepatoblastoma (HB), hepatic epithelioid hemangioepithelioma (HEHE), angiosarcoma (AS), and neuroendocrine tumors (NET) is being defined. For CCA, series that did not emphasize highly selected early stage disease and neoadjuvant or adjuvant chemoradiation had an average 5-year survival of 10%. However, emphasizing neoadjuvant radiation and chemosensitization in operatively confirmed stage I or II hilar CCA has led to improved 5-year survival, up to 82%. LT is indicated under strict research protocols at selected centers, for patients with early stage CCA and anatomically unresectable (Bismuth type IV) lesions. HB is typically sensitive to cisplatin-based chemotherapy. LT plays a role as primary surgical therapy for those individuals in whom tumors remain unresectable after chemotherapy or as rescue therapy for those who are incompletely resected, recur after resection, or develop hepatic insufficiency after chemotherapy and/or resection. Long-term survival is reported at 58-88%. HEHE is a multifocal tumor that lies somewhere between benign hemangiomas and malignant AS. The extensive multifocal nature makes resection difficult and LT an attractive option. Series on LT for HEHE report overall survival of 71-78% at 5 years. However, AS is an aggressive tumor and LT is contraindicated. For NET, resection of the primary tumor and all gross metastatic disease is reported to provide 5-year survival of 70-85%. LT has been employed for some patients for unresectable tumors or for palliation of medically uncontrollable symptoms with 5-year survival reported between 36% and 80%. PMID:18333123

  7. Liver transplantation for non-hepatocellular carcinoma malignancy1

    PubMed Central

    Castaldo, Eric T.

    2007-01-01

    Liver transplantation (LT) for hepatocellular carcinoma is effective for selected patients. LT for other malignancies like cholangiocarcinoma (CCA), hepatoblastoma (HB), hepatic epithelioid hemangioepithelioma (HEHE), angiosarcoma (AS), and neuroendocrine tumors (NET) is being defined. For CCA, series that did not emphasize highly selected early stage disease and neoadjuvant or adjuvant chemoradiation had an average 5-year survival of 10%. However, emphasizing neoadjuvant radiation and chemosensitization in operatively confirmed stage I or II hilar CCA has led to improved 5-year survival, up to 82%. LT is indicated under strict research protocols at selected centers, for patients with early stage CCA and anatomically unresectable (Bismuth type IV) lesions. HB is typically sensitive to cisplatin-based chemotherapy. LT plays a role as primary surgical therapy for those individuals in whom tumors remain unresectable after chemotherapy or as rescue therapy for those who are incompletely resected, recur after resection, or develop hepatic insufficiency after chemotherapy and/or resection. Long-term survival is reported at 58–88%. HEHE is a multifocal tumor that lies somewhere between benign hemangiomas and malignant AS. The extensive multifocal nature makes resection difficult and LT an attractive option. Series on LT for HEHE report overall survival of 71–78% at 5 years. However, AS is an aggressive tumor and LT is contraindicated. For NET, resection of the primary tumor and all gross metastatic disease is reported to provide 5-year survival of 70–85%. LT has been employed for some patients for unresectable tumors or for palliation of medically uncontrollable symptoms with 5-year survival reported between 36% and 80%. PMID:18333123

  8. MR Imaging Evaluation of Intracerebral Hemorrhages and T2 Hyperintense White Matter Lesions Appearing after Radiation Therapy in Adult Patients with Primary Brain Tumors

    PubMed Central

    Yun, Tae Jin; Kim, Tae Min; Lee, Se-Hoon; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sung-Hye; Park, Chul-Kee; Kim, Il Han; Choi, Seung Hong

    2015-01-01

    The purpose of our study was to determine the frequency and severity of intracerebral hemorrhages and T2 hyperintense white matter lesions (WMLs) following radiation therapy for brain tumors in adult patients. Of 648 adult brain tumor patients who received radiation therapy at our institute, magnetic resonance (MR) image data consisting of a gradient echo (GRE) and FLAIR T2-weighted image were available three and five years after radiation therapy in 81 patients. Intracerebral hemorrhage was defined as a hypointense dot lesion appearing on GRE images after radiation therapy. The number and size of the lesions were evaluated. The T2 hyperintense WMLs observed on the FLAIR sequences were graded according to the extent of the lesion. Intracerebral hemorrhage was detected in 21 (25.9%) and 35 (43.2) patients in the three- and five-year follow-up images, respectively. The number of intracerebral hemorrhages per patient tended to increase as the follow-up period increased, whereas the size of the intracerebral hemorrhages exhibited little variation over the course of follow-up. T2 hyperintense WMLs were observed in 27 (33.3%) and 32 (39.5) patients in the three and five year follow-up images, respectively. The age at the time of radiation therapy was significantly higher (p < 0.001) in the patients with T2 hyperintense WMLs than in those without lesions. Intracerebral hemorrhages are not uncommon in adult brain tumor patients undergoing radiation therapy. The incidence and number of intracerebral hemorrhages increased over the course of follow-up. T2 hyperintense WMLs were observed in more than one-third of the study population. PMID:26322780

  9. Paraneoplastic alopecia associated with hepatocellular carcinoma in a cat.

    PubMed

    Marconato, Laura; Albanese, Francesco; Viacava, Paolo; Marchetti, Veronica; Abramo, Francesca

    2007-08-01

    A 15-year-old spayed female domestic shorthair cat presented with alopecia associated with hepatocellular carcinoma. Clinical signs, which had commenced 6 months previously, included loss of appetite, loss of weight, and depression. As reported by the owner, the cat developed alopecia a week before referral. The hair loss was localized to the ventral aspect of the thorax and abdomen, medial aspect of front and hind limbs, and ventral aspect of the tail, and was associated with histological features consistent with paraneoplastic alopecia. At necropsy, multiple hepatic nodules were observed, and subsequent histopathological investigation showed cords and sheets of hepatocyte-like neoplastic cells positive for the hepatocyte marker (Hep Par 1), thereby demonstrating the hepatocellular origin of the tumour, which was diagnosed as a hepatocellular carcinoma. This is the first report of feline paraneoplastic alopecia associated with hepatocellular carcinoma confirmed by the Hep Par 1 marker.

  10. Latest developments in targeted therapy for hepatocellular carcinoma.

    PubMed

    Montella, Liliana; Addeo, Raffaele; Caraglia, Michele; Del Prete, Salvatore

    2010-10-01

    The advent of sorafenib can be considered as a turning point in the history of advanced hepatocellular carcinoma. After unfortunate attempts at using chemotherapy, drugs targeting key pathways have generated new perspectives in this field. This means not only killing both tumor cells and cirrhotic fragile tissue, but killing them selectively; more than was previously possible. This seems like the Copernican Revolution. However, hepatocellular carcinoma is pathogenetically complicated, resulting from the number of mutations. Until now, there has not been a single drug able to block and reverse abnormally activated signaling in hepatocellular carcinoma cells. In this article, we describe the most promising targeted drugs being studied in hepatocellular carcinoma and depict the possible future scenarios. PMID:20942634

  11. Primary Nephrotic Syndrome in Adults as a Risk Factor for Pulmonary Embolism: An Up-to-Date Review of the Literature

    PubMed Central

    Mirrakhimov, Aibek E.; Ali, Alaa M.; Barbaryan, Aram; Prueksaritanond, Suartcha; Hussain, Nasir

    2014-01-01

    Patients with nephrotic syndrome are at an increased risk for thrombotic events; deep venous thrombosis, renal vein thrombosis, and pulmonary embolism are quite common in patients with nephrotic syndrome. It is important to note that nephrotic syndrome secondary to membranous nephropathy may impose a greater thrombotic risk for unclear reasons. Increased platelet activation, enhanced red blood cell aggregation, and an imbalance between procoagulant and anticoagulant factors are thought to underlie the excessive thrombotic risk in patients with nephrotic syndrome. The current scientific literature suggests that patients with low serum albumin levels and membranous nephropathy may benefit from primary prophylactic anticoagulation. A thorough approach which includes accounting for all additional thrombotic risk factors is, therefore, essential. Patient counseling regarding the pros and cons of anticoagulation is of paramount importance. Future prospective randomized studies should address the question regarding the utility of primary thromboprophylaxis in patients with nephrotic syndrome. PMID:24829800

  12. Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells.

    PubMed

    Wang, X; Al-Dhalimy, M; Lagasse, E; Finegold, M; Grompe, M

    2001-02-01

    The emergence of cells with hepatocellular properties in the adult pancreas has been described in several experimental models. To determine whether adult pancreas contains cells that can give rise to therapeutically useful and biochemically normal hepatocytes, we transplanted suspensions of wild-type mouse pancreatic cells into syngeneic recipients deficient in fumarylacetoacetate hydrolase and manifesting tyrosinemia. Four of 34 (12%) mutant mice analyzed were fully rescued by donor-derived cells and had normal liver function. Ten additional mice (29%) showed histological evidence of donor-derived hepatocytes in the liver. Previous work has suggested that pancreatic liver precursors reside within or close to pancreatic ducts. We therefore performed additional transplantations using either primary cell suspensions enriched for ducts or cultured ducts. Forty-four mutant mice were transplanted with cells enriched for pancreatic duct cells, but only three of the 34 (9%) recipients analyzed displayed donor-derived hepatocytes. In addition, 28 of the fumarylacetoacetate hydrolase-deficient mice were transplanted with cultured pancreatic duct cells, but no donor-derived hepatocytes were observed. Our results demonstrate for the first time that adult mouse pancreas contains hepatocyte progenitor cells capable of significant therapeutic liver reconstitution. However, contrary to previous reports, we were unable to detect these cells within the duct compartment. PMID:11159194

  13. Hepatocellular Carcinoma—Etiologic Considerations: A Review of the Literature

    PubMed Central

    Worrell, Roger G.; Moazami, Mohamad; Worrell, Louise A.

    1981-01-01

    There are an estimated 120 million hepatitis B virus carriers worldwide. More than 200,000 of these are in the United States. A higher incidence of active hepatitis B virus infection has been observed in patients with hepatocellular carcinoma than in controls, in all geographical regions. This paper reviews the world literature on the relationship of hepatitis B virus to the pathogenesis of hepatocellular carcinoma. PMID:6267318

  14. Transport and Metabolism of Radiolabeled Choline in Hepatocellular Carcinoma

    PubMed Central

    Kuang, Yu; Salem, Nicolas; Corn, David J.; Erowku, Bernadette; Tian, Haibin; Wang, Fangjing; Lee, Zhenghong

    2010-01-01

    Objectives Altered choline (Cho) metabolism in cancerous cells can be used as a basis for molecular imaging with PET using radiolabeled Cho. In this study, the metabolism of tracer Cho was investigated in a woodchuck hepatocellular carcinoma (HCC) cell line (WCH17) and in freshly-derived rat hepatocytes. The transporter responsible for [11C]-Cho uptake in HCC was also characterized in WCH17 cells. The study helped to define the specific mechanisms responsible for radio-Cho uptake seen on the PET images of primary liver cancer such as HCC. Methods Cells were pulsed with [14C]-Cho for 5 min and chased for varying durations in cold media to simulate the rapid circulation and clearance of [11C]-Cho. Radioactive metabolites were extracted and analyzed by radio-HPLC and radio-TLC. The Cho transporter (ChoT) was characterized in WCH17 cells. Results WCH17 cells showed higher 14C uptake than rat primary hepatocytes. [14C]-Phosphocholine (PC) was the major metabolite in WCH17. In contrast, the intracellular Cho in primary hepatocytes was found to be oxidized to betaine (partially released into media) and to a less degree, phosphorylated to PC. [14C]-Cho uptake by WCH17 cells was found to have both facilitative transport and non-facilitative diffusion components. The facilitative transport was characterized by Na+ dependence and low affinity (Km = 28.59 ± 6.75 μM) with partial energy dependence. In contrast, ChoT in primary hepatocytes is Na+ independent and low affinity. Conclusions Our data suggest that transport and phosphorylation of Cho are responsible for the tracer accumulation during [11C]-Cho PET imaging of HCC. WCH17 cells incorporate [14C]-Cho preferentially into PC. Conversion of [14C]-PC into phosphatidylcholine occurred slowly in vitro. Basal oxidation and phosphorylation activities in surrounding hepatic tissue contribute to the background seen in [11C]-Cho PET images. PMID:20698576

  15. Hepatocellular carcinoma metastatic to the mandible.

    PubMed

    Miller, Mia E; McCall, Andrew A; Juillard, Guy F; Nadelman, Celina M; Wang, Marilene B; Nabili, Vishad

    2013-02-01

    We describe the case of a 55-year-old man with known multifocal hepatocellular carcinoma (HCC) who presented with a painful mandibular mass. Fine-needle aspiration cytology of the mass revealed the presence of bile canaliculi and bile formation, an extremely rare finding. Findings on immunoperoxidase staining of the aspirate were consistent with an HCC. Since the patient was known to have multiorgan metastatic disease, he was administered palliative radiation therapy to the mandibular metastasis for pain control, which was achieved. One year after presentation, the patient died as a result of disease progression. HCC rarely metastasizes to the mandible, as only about 70 such cases have been reported in the literature. We discuss the histopathologic appearance of HCC metastatic to the mandible, the radiologic findings, and the established treatment modalities.

  16. Charged Particle Therapy for Hepatocellular Carcinoma

    PubMed Central

    Skinner, Heath D.; Hong, Theodore S.; Krishnan, Sunil

    2011-01-01

    Historically, the use of external beam radiotherapy for hepatocellular carcinoma (HCC) has been limited by toxicity to the uninvolved liver and surrounding structures. Advances in photon radiotherapy have improved dose conformality to the tumor and facilitated dose escalation, a key contributor to improved HCC radiation treatment outcomes. However, despite these advances in photon radiotherapy, significant volumes of liver still receive low doses of radiation that can preclude dose escalation, particularly in patients with limited functional liver reserves. By capitalizing on the lack of exit dose along the beam path beyond the tumor and higher biological effectiveness, charged particle therapy offers the promise of maximizing tumor control via dose escalation without excessive liver toxicity. In this review we discuss the distinctive biophysical attributes of both proton and carbon ion radiotherapy, particularly as they pertain to treatment of HCC. We also review the available literature regarding clinical outcomes and toxicity of using charged particles for the treatment of HCC. PMID:21939857

  17. Fibrolamellar hepatocellular carcinoma: current clinical perspectives

    PubMed Central

    Lafaro, Kelly J; Pawlik, Timothy M

    2015-01-01

    Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC), which comprises ∼1%–9% of all HCCs. Although FLC is a variant of HCC, it is distinct from HCC in that it most often affects younger patients (10–35 years of age) with no underlying liver disease. FLC often presents with vague abdominal pain, nausea, abdominal fullness, malaise, and weight loss. Surgery is the current mainstay of treatment for FLC and remains the only potentially curative option. While FLCs are considered less responsive to chemotherapy than their classic HCC counterparts, there have been suggestions that multimodality treatments may be effective, especially in advanced cases. Further research is necessary to determine effective systemic therapies as an adjunct to surgery for FLC. PMID:27508204

  18. Metastatic Hepatocellular Carcinoma Responsive to Pembrolizumab.

    PubMed

    Truong, Phu; Rahal, Ahmad; Kallail, K James

    2016-06-04

    Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs with chronic liver disease. Surgical resection is the mainstay of therapy for localized disease whereas therapeutic options for advanced disease are limited. The innovative blockade of immune checkpoints with targeted immunotherapies, such as monoclonal antibodies against programmed death receptor 1 (PD-1), have shown promise in the treatment of solid malignancies. The PD-1 inhibiting antibodies, nivolumab and pembrolizumab prolonged overall survival in randomized trials in metastatic melanoma and advanced non-small cell lung cancer. This is a report of a 75-year-old male patient with metastatic HCC who was initially treated with the standard of therapy sorafenib. After failure of sorafenib therapy, pembrolizumab was started. There was a dramatic response to pembrolizumab with decrease in tumor size and drop in alfa fetoprotein. To the best of our knowledge, this is the first case report of metastatic HCC responsive to pembrolizumab after failure of sorafenib.

  19. Hepatocellular carcinoma from an immunological perspective

    PubMed Central

    Greten, Tim F.; Duffy, Austin G.; Korangy, Firouzeh

    2013-01-01

    Hepatocellular carcinoma is the 3rd most common cancer worldwide. It is an inflammation-associated cancer. Multiple investigators have demonstrated that analysis of the tumor microenvironment may be used to predict patient outcome indicating the importance of local immune responses in this disease. In contrast to other types of cancer, in which surgery, radiation and systemic cytotoxic chemotherapies dominate the treatment options, in HCC loco-regional treatments are widely applied. Such treatments induce rapid tumor cell death and anti-tumor immune responses, which may favor or impair patients’ outcome. Recent immunotherapy studies demonstrating promising results include trials evaluating intra-tumoral injection of an oncolytic virus expressing GM-CSF, glypican-3 targeting treatments and anti-CTLA4 treatment. While some of these novel approaches may provide benefit as single agents, there is a clear opportunity in HCC to evaluate these in combination with the standard modalities to more effectively harness the immune response. PMID:24030702

  20. Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism

    NASA Astrophysics Data System (ADS)

    Zhang, Qingyu; Liu, Jie; Liu, Bin; Xia, Juan; Chen, Nianping; Chen, Xiaofeng; Cao, Yi; Zhang, Chen; Lu, Caijie; Li, Mingyi; Zhu, Runzhi

    2014-04-01

    The development of antitumor chemotherapy drugs remains a key goal for oncologists, and natural products provide a vast resource for anti-cancer drug discovery. In the current study, we found that the flavonoid dihydromyricetin (DHM) exhibited antitumor activity against liver cancer cells, including primary cells obtained from hepatocellular carcinoma (HCC) patients. In contrast, DHM was not cytotoxic to immortalized normal liver cells. Furthermore, DHM treatment resulted in the growth inhibition and remission of xenotransplanted tumors in nude mice. Our results further demonstrated that this antitumor activity was caused by the activation of the p53-dependent apoptosis pathway via p53 phosphorylation at serine (15Ser). Moreover, our results showed that DHM plays a dual role in the induction of cell death when administered in combination with cisplatin, a common clinical drug that kills primary hepatoma cells but not normal liver cells.

  1. Hepatocellular Carcinoma-Cause, Treatment and Metastasis

    PubMed Central

    Tang, Zhao-You

    2001-01-01

    In the recent decades, the incidence of hepatocellular carcinoma (HCC) has been found to be increasing in males in some countries. In China, HCC ranked second of cancer mortality since 1990s. Hepatitis B and C viruses (HBV and HCV) and dietary aflatoxin intake remain the major causative factors of HCC. Surgery plays a major role in the treatment of HCC, particularly for small HCC. Down-staging unresectable huge HCC to smaller HCC and followed by resection will probably be a new approach for further study. Liver transplantation is indicated for small HCC, however, some issues remain to be solved. Different modes of “regional cancer therapy for HCC” have been tried. Systemic chemotherapy has been disappointing in the past but the future can be promising. Biotherapy, such as cytokines, differentiation inducers, anti-angiogenic agents, gene therapy and tumor vaccine will probably play a role, particularly in the prevention of tumor recurrence. HCC invasiveness is currently the major target of study. Tremendous works have been done at the molecular level, which will provide clues for biomarker of HCC progression as well as targets for intervention. Abbreviation: HCC-hepatocellular carcinoma, HBV-hepatitis B virus, HCV-hepatitis C virus, HGV-hepatitis G virus, TTV-transfusion transmitted virus, AFB1-aflatoxin B1, IFN-interferon, OLT-orthotopic liver transplantation, PH-partial hepatectomy, RCT-randomized controlled trial, TACE-transcatheter arterial chemoembolization, PEI-percutaneous ethanol injection, PMCT-percutaneous microwave coagulation therapy, RF-radiofrequency, AFP-alpha fetoprotein, VEGF-vascular endothelial growth factor. PMID:11819809

  2. Fine mapping of juvenile primary open angle glaucoma (POAG) on 1q21-q31 and exculsion of adult-POAG from the respective region

    SciTech Connect

    Child, A.; Sarfarazi, M.; Crick, R.P.

    1994-09-01

    Juvenile POAG is an autosomal dominant eye disorder which has recently been mapped to 1q21-q24, in a region of 14-23 cM. We report here linkage analysis of 9 microsatellite repeat markers spanning this region in families from England, Scotland and Sardinia. We have observed no recombinants with D1S433 (Z=2.86) and obtained looser linkage with D1S196 ({theta}=0.03; Z=6.38), D1S431 ({theta}=0.14; Z=2.74), D1S210 ({theta}=0.06; Z=1.32), D1S452 ({theta}=0.18; Z=0.729) and D1S242 ({theta}=0.08; Z=2.29). In one family, a critical recombinant in an affected individual localizes the J-POAG locus between D1S452 and D1S242 in a 3 cM region. However, other recombinants in two normal individuals from different families suggests that J-POAG may be localized in a 1 cM distance between D1S433 and D1S431. These unaffected individuals have well passed the age-of-onset in their respective pedigrees. This result suggests that either these two recombinant individuals are gene carriers (i.e., non-penetrants) or there are more than one gene in this region causing the same disease. The possibility of the latter is less likely, since in addition to a total of 4 non-penetrant individuals in our panel, other such cases have also been reported previously. This in turn suggests that the precentage of non-penetrant cases in J-POAG may be considerably higher than it was previously appreciated. Study of 14 families with adult-onset POAG revealed no segregation with the above-mentioned linked microsatellite markers. Our findings confirm, for the first time, that adult-POAG is genetically distinct from the J-POAG. Genetic linkage study of adult families with additional STRPs is currently in progress.

  3. Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei.

    PubMed Central

    Van Rensburg, S. J.; Cook-Mozaffari, P.; Van Schalkwyk, D. J.; Van der Watt, J. J.; Vincent, T. J.; Purchase, I. F.

    1985-01-01

    Estimations of the incidence of hepatocellular carcinoma (HCC) for the period 1968-74 in the Province of Inhambane, Mozambique, have been calculated and together with rates observed in South Africa among mineworkers from the same Province indicate very high levels of incidence in certain districts of Inhambane. Exceptionally high incidence levels in adolescents and young adults are not sustained at older ages and suggest the existence of a subgroup of highly susceptible individuals. A sharp decline in incidence occurred during the period of study. Concurrently with the studies of incidence, 2183 samples of prepared food were randomly collected from 6 districts of Inhambane as well as from Manhica-Magude, a region of lower HCC incidence to the south. A further 623 samples were taken during 1976-77 in Transkei, much further south, where an even lower incidence had been recorded. The mean aflatoxin dietary intake values for the regions studied were significantly related to HCC rates. Furthermore, data on aflatoxin B1 contamination of prepared food from 5 different countries showed overall a highly significant relationship with crude HCC rates. In view of the evidence that chronic hepatitis B virus (HBV) infection may be a prerequisite for the development of virtually all cases of HCC and given the merely moderate prevalence of carrier status that has been observed in some high incidence regions, it is likely that an interaction between HBV and aflatoxin is responsible for the exceptionally high rates evident in parts of Africa and Asia. Various indications from Mozambique suggest that aflatoxin may have a late stage effect on the development of HCC. This points to avenues for intervention that could be more rapidly implemented than with vaccination alone. PMID:2986667

  4. Evaluation of a multidisciplinary Tier 3 weight management service for adults with morbid obesity, or obesity and comorbidities, based in primary care

    PubMed Central

    Jennings, A; Hughes, C A; Kumaravel, B; Bachmann, M O; Steel, N; Capehorn, M; Cheema, K

    2014-01-01

    A multidisciplinary Tier 3 weight management service in primary care recruited patients with a body mass index ≥40 kg·m−2, or 30 kg·m−2 with obesity-related co-morbidity to a 1-year programme. A cohort of 230 participants was recruited and evaluated using the National Obesity Observatory Standard Evaluation Framework. The primary outcome was weight loss of at least 5% of baseline weight at 12 months. Diet was assessed using the two-item food frequency questionnaire, activity using the General Practice Physical Activity questionnaire and quality of life using the EuroQol-5D-5L questionnaire. A focus group explored the participants' experiences. Baseline mean weight was 124.4 kg and mean body mass index was 44.1 kg·m−2. A total of 102 participants achieved 5% weight loss at 12 months. The mean weight loss was 10.2 kg among the 117 participants who completed the 12-month programme. Baseline observation carried forward analysis gave a mean weight loss of 5.9 kg at 12 months. Fruit and vegetable intake, activity level and quality of life all improved. The dropout rate was 14.3% at 6 months and 45.1% at 1 year. Focus group participants described high levels of satisfaction. It was possible to deliver a Tier 3 weight management service for obese patients with complex co-morbidity in a primary care setting with a full multidisciplinary team, which obtained good health outcomes compared with existing services. PMID:25825858

  5. Primary Prevention of Sudden Cardiac Death in Adults with Transposition of the Great Arteries: A Review of Implantable Cardioverter-Defibrillator Placement

    PubMed Central

    Cedars, Ari M.

    2015-01-01

    Transposition of the great arteries encompasses a set of structural congenital cardiac lesions that has in common ventriculoarterial discordance. Primarily because of advances in medical and surgical care, an increasing number of children born with this anomaly are surviving into adulthood. Depending upon the subtype of lesion or the particular corrective surgery that the patient might have undergone, this group of adult congenital heart disease patients constitutes a relatively new population with unique medical sequelae. Among the more common and difficult to manage are cardiac arrhythmias and other sequelae that can lead to sudden cardiac death. To date, the question of whether implantable cardioverter-defibrillators should be placed in this cohort as a preventive measure to abort sudden death has largely gone unanswered. Therefore, we review the available literature surrounding this issue. PMID:26413012

  6. Primary Prevention of Sudden Cardiac Death in Adults with Transposition of the Great Arteries: A Review of Implantable Cardioverter-Defibrillator Placement.

    PubMed

    Sodhi, Sandeep S; Cedars, Ari M

    2015-08-01

    Transposition of the great arteries encompasses a set of structural congenital cardiac lesions that has in common ventriculoarterial discordance. Primarily because of advances in medical and surgical care, an increasing number of children born with this anomaly are surviving into adulthood. Depending upon the subtype of lesion or the particular corrective surgery that the patient might have undergone, this group of adult congenital heart disease patients constitutes a relatively new population with unique medical sequelae. Among the more common and difficult to manage are cardiac arrhythmias and other sequelae that can lead to sudden cardiac death. To date, the question of whether implantable cardioverter-defibrillators should be placed in this cohort as a preventive measure to abort sudden death has largely gone unanswered. Therefore, we review the available literature surrounding this issue. PMID:26413012

  7. What do we need for airway management of adult casualties on the Primary Casualty Receiving Facility? A review of airway management on Role 3 Afloat.

    PubMed

    Mercer, S; Read, J; Sudheer, S; Risdall, J E; Connor, D

    2015-01-01

    The Primary Casualty Receiving Facility (PCRF) of the Royal Navy (RN) is currently based on Royal Fleet Auxiliary (RFA) ARGUS and provides a functioning hospital with surgical teams and a CT scanner (Role 3) within the maritime environment. The case mix could include complex trauma, critically ill patients returning to theatre several times, as well as non-battle injury procedures. This paper describes how we have used national guidelines, evidence from recent military experience, and the Clinical Guidelines for Operations (CGOs) to review and rationalise the airway equipment that is available and that would be required for the PCRF in its current configuration, whilst maintaining capability in a deployed setting. PMID:26867417

  8. A Study of the Infant Nasal Microbiome Development over the First Year of Life and in Relation to Their Primary Adult Caregivers Using cpn60 Universal Target (UT) as a Phylogenetic Marker.

    PubMed

    Peterson, Shelley W; Knox, Natalie C; Golding, George R; Tyler, Shaun D; Tyler, Andrea D; Mabon, Philip; Embree, Joanne E; Fleming, Fiona; Fanella, Sergio; Van Domselaar, Gary; Mulvey, Michael R; Graham, Morag R

    2016-01-01

    Whereas the infant gut microbiome is the subject of intense study, relatively little is known regarding the nares microbiome in newborns and during early life. This study aimed to survey the typical composition and diversity of human anterior nare microflora for developing infants over time, and to explore how these correlate to their primary caregivers. Single nare swabs were collected at five time points over a one-year period for each subject from infant-caregiver pairs. Our study comprised of 50 infants (recruited at 2 weeks, post delivery) and their 50 primary caregivers. Applying the chaperonin-60 (cpn60) universal target (UT) amplicon as our molecular barcoding marker to census survey the microbial communities, we longitudinally surveyed infant nares microbiota at 5 time points over the course of the first year of life. The inter- and intra-subject diversity was catalogued and compared, both longitudinally and relative to their adult primary caregivers. Although within-subject variability over time and inter-subject variability were both observed, the assessment detected only one or two predominant genera for individual infant samples, belonging mainly to phyla Actinobacteria, Firmicutes, and Proteobacteria. Consistent with previously observed microbial population dynamics in other body sites, the diversity of nares microflora increased over the first year of life and infants showed differential operational taxonomic units (OTUs) relative to their matched primary caregiver. The collected evidence also support that both temporal and seasonal changes occur with respect to carriage of potentially pathogenic bacteria (PPBs), which may influence host predisposition to infection. This pilot study surveying paired infant/caregiver nare microbiomes provides novel longitudinal diversity information that is pertinent to better understanding nare microbiome development in infants.

  9. A Study of the Infant Nasal Microbiome Development over the First Year of Life and in Relation to Their Primary Adult Caregivers Using cpn60 Universal Target (UT) as a Phylogenetic Marker

    PubMed Central

    Peterson, Shelley W.; Knox, Natalie C.; Golding, George R.; Tyler, Shaun D.; Tyler, Andrea D.; Mabon, Philip; Embree, Joanne E.; Fleming, Fiona; Fanella, Sergio; Van Domselaar, Gary; Mulvey, Michael R.; Graham, Morag R.

    2016-01-01

    Whereas the infant gut microbiome is the subject of intense study, relatively little is known regarding the nares microbiome in newborns and during early life. This study aimed to survey the typical composition and diversity of human anterior nare microflora for developing infants over time, and to explore how these correlate to their primary caregivers. Single nare swabs were collected at five time points over a one-year period for each subject from infant-caregiver pairs. Our study comprised of 50 infants (recruited at 2 weeks, post delivery) and their 50 primary caregivers. Applying the chaperonin-60 (cpn60) universal target (UT) amplicon as our molecular barcoding marker to census survey the microbial communities, we longitudinally surveyed infant nares microbiota at 5 time points over the course of the first year of life. The inter- and intra-subject diversity was catalogued and compared, both longitudinally and relative to their adult primary caregivers. Although within-subject variability over time and inter-subject variability were both observed, the assessment detected only one or two predominant genera for individual infant samples, belonging mainly to phyla Actinobacteria, Firmicutes, and Proteobacteria. Consistent with previously observed microbial population dynamics in other body sites, the diversity of nares microflora increased over the first year of life and infants showed differential operational taxonomic units (OTUs) relative to their matched primary caregiver. The collected evidence also support that both temporal and seasonal changes occur with respect to carriage of potentially pathogenic bacteria (PPBs), which may influence host predisposition to infection. This pilot study surveying paired infant/caregiver nare microbiomes provides novel longitudinal diversity information that is pertinent to better understanding nare microbiome development in infants. PMID:27019455

  10. Risk and Surveillance of Cancers in Primary Biliary Tract Disease

    PubMed Central

    Hrad, Valery; Abebe, Yoftahe; Ali, Syed Haris; Velgersdyk, Jared

    2016-01-01

    Primary biliary diseases have been associated in several studies with various malignancies. Understanding the risk and optimizing surveillance strategy of these malignancies in this specific subset of patients are an important facet of clinical care. For instance, primary sclerosing cholangitis is associated with an increased risk for cholangiocarcinoma (which is very challenging to diagnose) and when IBD is present for colorectal cancer. On the other hand, primary biliary cirrhosis patients with cirrhosis or not responding to 12 months of ursodeoxycholic acid therapy are at increased risk of hepatocellular carcinoma. In this review we will discuss in detail the risks and optimal surveillance strategies for patients with primary biliary diseases. PMID:27413366

  11. Tissue-Specific Expression of Herpes Simplex Virus Thymidine Kinase Gene Delivered by Adeno-Associated Virus Inhibits the Growth of Human Hepatocellular Carcinoma in Athymic Mice

    NASA Astrophysics Data System (ADS)

    Su, Hua; Lu, Ronghua; Chang, Judy C.; Kan, Yuet Wai

    1997-12-01

    About 70% of hepatocellular carcinomas are known to express α -fetoprotein, which is normally expressed in fetal but not in adult livers. To induce herpes simplex virus-thymidine kinase expression in these cancer cells, we constructed an adeno-associated viral vector containing the HSV-TK gene under the control of the α -fetoprotein enhancer and albumin promoter. We previously demonstrated in vitro that although this vector can transduce a variety of human cells, only transduced AFP and albumin-expressing hepatocellular carcinoma cell lines were sensitive to killing by ganciclovir (GCV). In the present study, we explored the effect of this vector on hepatocellular carcinoma cells in vivo. Subcutaneous tumors generated in nude mice by implanting hepatocellular carcinoma cells previously transduced with this vector shrank dramatically after treatment with GCV. Bystander effect was also observed on the tumors generated by mixing transduced and untransduced cells. To test whether the tumor cells can be transduced by the virus in vivo, we injected the recombinant adeno-associated virus into tumors generated by untransduced hepatocarcinoma cell line. Tumor growth were retarded after treatment with GCV. These experiments demonstrate the feasibility of in vivo transduction of tumor cell with rAAV.

  12. Management of the clinical issue of constipation with abdominal complaints in adults. A national survey of Primary Care physicians and gastroenterologists.

    PubMed

    Rey Díaz-Rubio, Enrique; Mascort Roca, Juan José; Peña Forcada, Enrique; Cañones Garzón, Pedro; Tenias Burillo, Jose María; Júdez Gutiérrez, Francisco Javier

    2016-06-01

    Irritable bowel syndrome and functional constipation represent a relevant and common health issue. However, real-world clinical practice includes patients with constipation who may or may not have other abdominal complaints (pain, bloating, abdominal discomfort) with variable frequency. The goal of the present study was to obtain information on the workload entailed by patients with constipation and associated abdominal complaints, predominant clinical behaviors, education needs, and potential daily practice aids both in Primary Care and gastroenterology settings. The clinical behavior of doctors is generally similar at both levels, despite differences in healthcare approach: use of empiric therapies and clinically guided diagnostic tests, with some differences in colonoscopy use (not always directly accessible from Primary Care). Regarding perceptions, general support and osmotic laxatives are most valued by PC doctors, whereas osmotic laxatives, combined laxatives, and linaclotide are most valued by GE specialists. Furthermore, over half of respondents considered differentiating both diagnoses as challenging. Finally, considerable education needs are self-acknowledged at both levels, as is a demand for guidelines and protocols to help in managing this issue in clinical practice. A strength of this study is its providing a joint photograph of the medical approach and the perceptions of constipation with abdominal discomfort from a medical standpoint. Weaknesses include self-declaration (no formal validation) and a response rate potentially biased by professional motivation. PMID:27165279

  13. Management of the clinical issue of constipation with abdominal complaints in adults. A national survey of Primary Care physicians and gastroenterologists.

    PubMed

    Rey Díaz-Rubio, Enrique; Mascort Roca, Juan José; Peña Forcada, Enrique; Cañones Garzón, Pedro; Tenias Burillo, Jose María; Júdez Gutiérrez, Francisco Javier

    2016-06-01

    Irritable bowel syndrome and functional constipation represent a relevant and common health issue. However, real-world clinical practice includes patients with constipation who may or may not have other abdominal complaints (pain, bloating, abdominal discomfort) with variable frequency. The goal of the present study was to obtain information on the workload entailed by patients with constipation and associated abdominal complaints, predominant clinical behaviors, education needs, and potential daily practice aids both in Primary Care and gastroenterology settings. The clinical behavior of doctors is generally similar at both levels, despite differences in healthcare approach: use of empiric therapies and clinically guided diagnostic tests, with some differences in colonoscopy use (not always directly accessible from Primary Care). Regarding perceptions, general support and osmotic laxatives are most valued by PC doctors, whereas osmotic laxatives, combined laxatives, and linaclotide are most valued by GE specialists. Furthermore, over half of respondents considered differentiating both diagnoses as challenging. Finally, considerable education needs are self-acknowledged at both levels, as is a demand for guidelines and protocols to help in managing this issue in clinical practice. A strength of this study is its providing a joint photograph of the medical approach and the perceptions of constipation with abdominal discomfort from a medical standpoint. Weaknesses include self-declaration (no formal validation) and a response rate potentially biased by professional motivation.

  14. Epidemiology, risk factors, and natural history of hepatocellular carcinoma.

    PubMed

    Montalto, Giuseppe; Cervello, Melchiorre; Giannitrapani, Lydia; Dantona, Fabio; Terranova, Angela; Castagnetta, Luigi A M

    2002-06-01

    The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio. The heterogeneous geographic distribution reflects the epidemiologic impact of the main etiologic factors and environmental risk, which are the hepatitis B (HBV) and hepatitis C (HCV) viruses. The percentage of cases of hepatocellular carcinoma attributable to HBV worldwide is 52.3% and is higher in Asia where the seroprevalence of HBsAg in the population is high. However, the vaccination campaign against this virus in some eastern countries has tended to lower the incidence of new cases of hepatocellular carcinoma. The percentage of cases of hepatocellular carcinoma attributable to HCV is 25%, and it is more prevalent in Japan, Spain, and Italy where the association between hepatocellular carcinoma and antibodies to HCV ranges between 50 and 70%. In most cases hepatocellular carcinoma develops in cirrhotic livers, where the persistent proliferation of liver cells represents the key factor of progression to hepatocellular carcinoma independent of the etiology. Another minor risk factor is aflatoxin B1 consumption, which is responsible for most cases of hepatocellular carcinoma in Africa, where the consumption of contaminated foods is common. Other known risk factors are some hereditary diseases, such as hemochromatosis, porphyria cutanea tarda, hereditary tyrosinemia, and alpha1 anti-trypsin deficiency. The natural history of hepatocellular carcinoma is heterogeneous and is influenced by nodule dimension, the mono- or plurifocality of lesions at diagnosis, the growth rate of the tumor, and the stage of the underlying cirrhosis. Available data to date suggest that tumor growth in a cirrhotic

  15. A Primary Care Nurse-Delivered Walking Intervention in Older Adults: PACE (Pedometer Accelerometer Consultation Evaluation)-Lift Cluster Randomised Controlled Trial

    PubMed Central

    Harris, Tess; Kerry, Sally M.; Victor, Christina R.; Ekelund, Ulf; Woodcock, Alison; Iliffe, Steve; Whincup, Peter H.; Beighton, Carole; Ussher, Michael; Limb, Elizabeth S.; David, Lee; Brewin, Debbie; Adams, Fredrika; Rogers, Annabelle; Cook, Derek G.

    2015-01-01

    Background Brisk walking in older people can increase step-counts and moderate to vigorous intensity physical activity (MVPA) in ≥10-minute bouts, as advised in World Health Organization guidelines. Previous interventions have reported step-count increases, but not change in objectively measured MVPA in older people. We assessed whether a primary care nurse-delivered complex intervention increased objectively measured step-counts and MVPA. Methods and Findings A total of 988 60–75 year olds, able to increase walking and randomly selected from three UK family practices, were invited to participate in a parallel two-arm cluster randomised trial; randomisation was by household. Two-hundred-ninety-eight people from 250 households were randomised between 2011 and 2012; 150 individuals to the intervention group, 148 to the usual care control group. Intervention participants received four primary care nurse physical activity (PA) consultations over 3 months, incorporating behaviour change techniques, pedometer step-count and accelerometer PA intensity feedback, and an individual PA diary and plan. Assessors were not blinded to group status, but statistical analyses were conducted blind. The primary outcome was change in accelerometry assessed average daily step-counts between baseline and 3 months, with change at 12 months a secondary outcome. Other secondary outcomes were change from baseline in time in MVPA weekly in ≥10-minute bouts, accelerometer counts, and counts/minute at 3 months and 12 months. Other outcomes were adverse events, anthropometric measures, mood, and pain. Qualitative evaluations of intervention participants and practice nurses assessed the intervention’s acceptability. At 3 months, eight participants had withdrawn or were lost to follow-up, 280 (94%) individuals provided primary outcome data. At 3 months changes in both average daily step-counts and weekly MVPA in ≥10-minute bouts were significantly higher in the intervention than control

  16. Expression of Yes-associated protein modulates Survivin expression in primary liver malignancies.

    PubMed

    Bai, Haibo; Gayyed, Mariana F; Lam-Himlin, Dora M; Klein, Alison P; Nayar, Suresh K; Xu, Yang; Khan, Mehtab; Argani, Pedram; Pan, Duojia; Anders, Robert A

    2012-09-01

    Hepatocellular carcinoma and intrahepatic cholangiocarcinoma account for 95% of primary liver cancer. For each of these malignancies, the outcome is dismal; incidence is rapidly increasing, and mechanistic understanding is limited. We observed abnormal proliferation of both biliary epithelium and hepatocytes in mice after genetic manipulation of Yes-associated protein, a transcription coactivator. Here, we comprehensively documented Yes-associated protein expression in the human liver and primary liver cancers. We showed that nuclear Yes-associated protein expression is significantly increased in human intrahepatic cholangiocarcinoma and hepatocellular carcinoma. We found that increased Yes-associated protein levels in hepatocellular carcinoma are due to multiple mechanisms including gene amplification and transcriptional and posttranscriptional regulation. Survivin, a member of the inhibitors-of-apoptosis protein family, has been reported as an independent prognostic factor for poor survival in both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. We found that nuclear Yes-associated protein expression correlates significantly with nuclear Survivin expression for both intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Furthermore, using mice engineered to conditionally overexpress Yes-associated protein in the liver, we found that Survivin messenger RNA expression depends upon Yes-associated protein levels. Our findings suggested that Yes-associated protein contributes to primary liver tumorigenesis and likely mediates its oncogenic effects through modulating Survivin expression.

  17. Long term survival of mice with hepatocellular carcinoma after pulse power ablation with nanosecond pulsed electric fields.

    PubMed

    Chen, X; Zhuang, J; Kolb, J F; Schoenbach, K H; Beebe, S J

    2012-02-01

    Novel therapies are needed for treating hepatocellular carcinoma (HCC) without recurrence in a single procedure. In this work we evaluated anti-neoplastic effects of a pulse power ablation (PPA) with nanosecond pulsed electric fields (nsPEFs), a non-thermal, non-drug, local, regional method and investigated its molecular mechanisms for hepatocellular carcinoma tumor ablation in vivo. An ectopic tumor model was established using C57BL/6 mice with Hepa1-6 hepatocellular carcinoma cells. Pulses with durations of 30 or 100 ns and fast rise times were delivered by a needle or ring electrode with different electric field strengths (33, 50 and 68 kV/cm), and 900 pulses in three treatment sessions (300 pulses each session) or a single 900 pulse treatment. Treated and control tumor volumes were monitored by ultrasound and apoptosis and angiogenesis markers were evaluated by immunohistochemistry. Seventy five percent of primary hepatocellular carcinoma tumors were eradicated with 900 hundred pulses at 100 ns pulses at 68 kV/cm in a single treatment or in three treatment sessions without recurrence within 9 months. Using quantitative analysis, tumors in treated animals showed nsPEF-mediated nuclear condensation (3 h post-pulse), cell shrinkage (1 h), increases in active executioner caspases (caspase-3 > -7 > -6) and terminal deoxynucleotidyl transferase dUTP nick-end-labeling (1 h) with decreases in vascular endothelial growth factor expression (7d) and micro-vessel density (14d). NsPEF ablation eliminated hepatocellular carcinoma tumors by targeting two therapeutic sites, apoptosis induction and inhibition of angiogenesis, both important cancer hallmarks. These data indicate that PPA with nsPEFs is not limited to treating skin cancers and provide a rationale for continuing to investigate pulse power ablation for hepatocellular carcinoma using other models in pre-clinical applications and ultimately in clinical trials. Based on present treatments for specific HCC stages, it

  18. Functional and Topological Properties in Hepatocellular Carcinoma Transcriptome

    PubMed Central

    Wex, Thomas; Valeyev, Najl V.; Tsoka, Sophia; Malfertheiner, Peter

    2012-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of global cancer mortality. However, little is known about the precise molecular mechanisms involved in tumor formation and pathogenesis. The primary goal of this study was to elucidate genome-wide molecular networks involved in development of HCC with multiple etiologies by exploring high quality microarray data. We undertook a comparative network analysis across 264 human microarray profiles monitoring transcript changes in healthy liver, liver cirrhosis, and HCC with viral and alcoholic etiologies. Gene co-expression profiling was used to derive a consensus gene relevance network of HCC progression that consisted of 798 genes and 2,012 links. The HCC interactome was further confirmed to be phenotype-specific and non-random. Additionally, we confirmed that co-expressed genes are more likely to share biological function, but not sub-cellular localization. Analysis of individual HCC genes revealed that they are topologically central in a human protein-protein interaction network. We used quantitative RT-PCR in a cohort of normal liver tissue (n = 8), hepatitis C virus (HCV)-induced chronic liver disease (n = 9), and HCC (n = 7) to validate co-expressions of several well-connected genes, namely ASPM, CDKN3, NEK2, RACGAP1, and TOP2A. We show that HCC is a heterogeneous disorder, underpinned by complex cross talk between immune response, cell cycle, and mRNA translation pathways. Our work provides a systems-wide resource for deeper understanding of molecular mechanisms in HCC progression and may be used further to define novel targets for efficient treatment or diagnosis of this disease. PMID:22539975

  19. Recent advances in the surgical treatment of hepatocellular carcinoma.

    PubMed

    Morise, Zenichi; Kawabe, Norihiko; Tomishige, Hirokazu; Nagata, Hidetoshi; Kawase, Jin; Arakawa, Satoshi; Yoshida, Rie; Isetani, Masashi

    2014-10-21

    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation (LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed. PMID:25339825

  20. Gelatin sponge microparticles for the treatment of the spontaneous rupture of hepatocellular carcinoma hemorrhage

    PubMed Central

    Wu, Pu Zhao; Zhou, Jun; Zhang, Yue Wei

    2016-01-01

    Spontaneous rupture of hepatocellular carcinoma hemorrhage is life-threatening. The aim of the present study was to retrospectively analyze the effect of gelatin sponge microparticles (GSMs) of various diameters on the treatment of spontaneous rupture of hepatocellular carcinoma hemorrhage. GSMs serve as embolization agents by transcatheter arterial chemoembolization (TACE), and the current study analyzed their safety and efficacy. Data from a total of 13 cases of spontaneous rupture of hepatocellular carcinoma hemorrhage, who were treated with GSM-TACE at the Affiliated Zhongshan Hospital of Dalian University (Dalian, China) between August 2010 and June 2014, were collected. Post-operative complications were classified according to the National Cancer Institute Common Terminology Criteria. Review computed tomography was conducted 1, 3 and 6 months after GSM-TACE treatment in order to determine the occurrence of re-bleeding; the tumor response was evaluated based on the Modified Response Evaluation Criteria In Solid Tumors and the expression levels of α-feroprotein. The patients were followed-up for 1–6 months (average, 5.15±1.67 months). Following GSM-TACE treatment, 13 cases reached successful hemostasis without technical complications. The survival rates 1, 3 and 6 months after treatment were 76.9 (10/13), 61.5 (8/13) and 53.8% (7/13), respectively; the objective response rates were 61.6, 53.9 and 38.5%, respectively. The primary post-operative complications were pain (100%), nausea and vomiting (69.2%), and fever (53.8%). Among the 13 patients, 2 cases underwent surgical excision 10 and 30 days after GSM-TACE, and 1 case experienced re-bleeding 3 months after treatment, after which the patient received a second treatment with TACE and successful achieved hemostasis. In conclusion, GSM-TACE of various diameters is a safe and effective method in the treatment of spontaneous rupture of hepatocellular carcinoma hemorrhage. GSM-TACE is able to achieve immediate

  1. Gelatin sponge microparticles for the treatment of the spontaneous rupture of hepatocellular carcinoma hemorrhage

    PubMed Central

    Wu, Pu Zhao; Zhou, Jun; Zhang, Yue Wei

    2016-01-01

    Spontaneous rupture of hepatocellular carcinoma hemorrhage is life-threatening. The aim of the present study was to retrospectively analyze the effect of gelatin sponge microparticles (GSMs) of various diameters on the treatment of spontaneous rupture of hepatocellular carcinoma hemorrhage. GSMs serve as embolization agents by transcatheter arterial chemoembolization (TACE), and the current study analyzed their safety and efficacy. Data from a total of 13 cases of spontaneous rupture of hepatocellular carcinoma hemorrhage, who were treated with GSM-TACE at the Affiliated Zhongshan Hospital of Dalian University (Dalian, China) between August 2010 and June 2014, were collected. Post-operative complications were classified according to the National Cancer Institute Common Terminology Criteria. Review computed tomography was conducted 1, 3 and 6 months after GSM-TACE treatment in order to determine the occurrence of re-bleeding; the tumor response was evaluated based on the Modified Response Evaluation Criteria In Solid Tumors and the expression levels of α-feroprotein. The patients were followed-up for 1–6 months (average, 5.15±1.67 months). Following GSM-TACE treatment, 13 cases reached successful hemostasis without technical complications. The survival rates 1, 3 and 6 months after treatment were 76.9 (10/13), 61.5 (8/13) and 53.8% (7/13), respectively; the objective response rates were 61.6, 53.9 and 38.5%, respectively. The primary post-operative complications were pain (100%), nausea and vomiting (69.2%), and fever (53.8%). Among the 13 patients, 2 cases underwent surgical excision 10 and 30 days after GSM-TACE, and 1 case experienced re-bleeding 3 months after treatment, after which the patient received a second treatment with TACE and successful achieved hemostasis. In conclusion, GSM-TACE of various diameters is a safe and effective method in the treatment of spontaneous rupture of hepatocellular carcinoma hemorrhage. GSM-TACE is able to achieve immediate

  2. Hepatocellular Carcinoma with Prominent Intracytoplasmic Inclusions: A Report of Two Cases

    PubMed Central

    Chelliah, Adeline R.

    2016-01-01

    Hepatocellular carcinoma (HCC) is the commonest primary malignant neoplasm of the liver in most countries with a notoriously poor prognosis. Variation in global incidence is well-recognized and the occurrence of HCC is linked to several established environmental, dietary, and lifestyle factors. HCC demonstrates morphological heterogeneity both within the same tumor and from patient to patient. Differing architectural patterns and cytological variants may be seen. Inclusion bodies are believed to represent organized structures of proteins which contribute to their pathogenesis and share several constituents like chaperones, p62, ubiquitin, and Valosin containing protein. The various hepatocyte cytoplasmic inclusions described in HCC include Mallory-Denk bodies (MDBs), hyaline bodies (HBs), glycogen, fat, fibrinogen, alpha 1 antitrypsin (AAT), and ground glass. MDBs are the most common inclusions seen in hepatocellular carcinomas. The two cases shared intracytoplasmic inclusions which are characterized by larger sizes and present in every section examined. These exhibited features of MDBs and HBs present in most tumor cells, further supporting close relationship.

  3. A feasibility study of a telephone-supported self-care intervention for depression among adults with a comorbid chronic physical illness in primary care

    PubMed Central

    2012-01-01

    Objective We assessed the feasibility and acceptability to patients of a telephone-supported self-care intervention for depression among adults aged 40 years or over with one of six targeted chronic physical illnesses and comorbid depressive symptoms in family practice settings. Methods An open, uncontrolled trial (feasibility study) was conducted among patients treated in Montreal family practices. Eligible patients were aged 40 years or over, had one or more of the targeted chronic physical illnesses for at least 6 months (arthritis, hypertension, diabetes, heart disease, asthma and chronic obstructive pulmonary disease) and were evaluated as having at least mild depressive symptoms (a score of ≥ 5 on the 9-item Patient Health Questionnaire, PHQ-9). Participants received a package of six self-care tools (information booklet, video, Internet programme, action plan, workbook and mood-monitoring tool) with telephone support by a lay coach for up to 6 months. Results In total, 63 eligible patients provided written consent and completed the baseline interview; 57 (90%) and 55 (87%) patients completed 2-month and 6-month follow-up interviews, respectively. The mean number of telephone calls made by coaches to participants was 10.5 (SD 4.0), and the average length of these calls was 10.6 minutes. At the 6-month follow-up, 83.6% of the participants reported that one or more of the tools were helpful. Clinically significant improvements were seen in depressive symptoms (as assessed by the PHQ-9) at 6 months, with an effect size of 0.88 (95% CI, 0.55, 1.14). Conclusion A telephone-supported self-care intervention for depression was feasible, was acceptable to patients, and was associated with a significant 6-month improvement in depressive symptoms. A randomised trial of this intervention is justified. PMID:24294301

  4. Adult Books for Young Adults.

    ERIC Educational Resources Information Center

    Carter, Betty

    1997-01-01

    Considers the differences between young adult and adult books and maintains that teachers must be familiar with young adults' tastes for both. Suggests that traffic between these publishing divisions is a two-way street, with young adults reading adult books and adults reading young adult books. (TB)

  5. Overexpression of WWP1 Promotes tumorigenesis and predicts unfavorable prognosis in patients with hepatocellular carcinoma

    PubMed Central

    Pan, Qiu-Zhong; Pan, Ke; Weng, De-Sheng; Wang, Qi-Jing; Zhao, Jing-Jing; He, Jia; Liu, Qing; Jiang, Shan-Shan; Chen, Chang-Long; Zhang, Hong-Xia; Xia, Jian-Chuan

    2015-01-01

    WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) has been speculated to play important roles in the development of several kinds of cancers. However, the role of WWP1 in hepatocellular carcinoma(HCC) is not clear. In the present study, we investigated the expression and prognostic role of WWP1 in primary hepatocellular carcinoma (HCC) using cell lines and 149 archived HCC samples. Correlation between the functions of WWP1 in HCC was also explored. We used human HCC cell lines (BEL-7402, SMMC-7721, Hep-G2, Hep-3B, SK-hep1 and Huh7) and a normal hepatocyte cell line (LO2) along with HCC samples from patients who had undergone resection for HCC previously at our hospital. A battery of methods (real-time quantitative polymerase chain reaction; western blotting; immunohistochemical analyses; cell proliferation and colony formation assays; cell migration and cell invasion assays) were employed to assess various aspects of WWP1. We found that WWP1 expression was upregulated aberrantly at mRNA and protein levels in human primary HCC tissues. Amplified expression of WWP1 was highly correlated with poor outcome. Silencing of WWP1 expression by siRNA inhibited the proliferation, colony formation, migration and invasion of HCC cells in vitro, and resulted in significant apoptosis and cycle arrest in HCC cells. Our findings suggest that WWP1 might have an oncogenic role in human primary HCC, and that it could be used as a prognostic marker as well as a potential molecular target for the treatment of HCC. PMID:26506518

  6. Development and evaluation of information resources for patients, families, and healthcare providers addressing behavioral and cognitive sequelae among adults with a primary brain tumor.

    PubMed

    Wright, Kylie M; Simpson, Grahame K; Koh, Eng-Siew; Whiting, Diane L; Gillett, Lauren; Simpson, Teresa; Firth, Rochelle

    2015-06-01

    Behavioral and cognitive changes in patients with primary brain tumor (PBT) are common and may be distressing to patients and their family members. Healthcare professionals report a strong need for information, practical strategies, and training to assist consumers and better address management issues. A literature review by the current project found that 53% of the information resources currently available to consumers and health professionals contained minimal or no information about cognitive/behavioral changes after PBT, and 71% of the resources contained minimal or no information on associated strategies to manage these changes. This project aimed to develop an information resource for patients, carers, and health professionals addressing the behavioral and cognitive sequelae of PBT, including strategies to minimize the disabling impact of such behaviors. In consultation with staff and patient groups, 16 key information topics were identified covering cognitive and communication changes and challenging behaviors including executive impairment, behavioral disturbance, and social/emotional dysfunction. Sixteen fact sheets and 11 additional resource sheets were developed and evaluated according to established consumer communication guidelines. Preliminary data show that these resources have been positively received and well utilized. These sheets are the first of their kind addressing challenging behaviors in the neuro-oncology patient group and are a practical and useful information resource for health professionals working with these patients and their families. The new resource assists in reinforcing interventions provided to individual patients and their relatives who are experiencing difficulties in managing challenging behaviors after PBT. PMID:25827649

  7. Culturally Sensitive Approaches to Identification and Treatment of Depression among HIV Infected African American Adults: A Qualitative Study of Primary Care Providers’ Perspectives

    PubMed Central

    Le, Huynh-Nhu; Hipolito, Maria Mananita S; Lambert, Sharon; Terrell-Hamilton, Flora; Rai, Narayan; McLean, Charlee; Kapetanovic, Suad; Nwulia, Evaristus

    2016-01-01

    Background Major depressive disorder (MDD) is highly prevalent among HIV-infected (HIV+) individuals, and is associated with non-adherence to antiretroviral therapy (ART), and accelerated disease progression. MDD is underdiagnosed and undertreated among low-income African Americans, who are disproportionately impacted by the HIV epidemic. To improve detection and treatment of depression among African Americans living with HIV/AIDS, it is important to understand culturally and contextually relevant aspects of MDD and attitudes about mental health treatment. Methods A focus group session was conducted with seven providers and staff at a primary care center that serves a largely African-American community heavily impacted by the HIV epidemic in Washington, DC. Data were analyzed using an inductive approach to distill prominent themes, perspectives, and experiences among participating providers. Results Five themes emerged to characterize the lived experiences of HIV+ African-American patients: (a) Changes in perceptions of HIV over time; (b) HIV is comorbid with mental illness, particularly depression and substance abuse; (c) Stigma is associated with both HIV and depression; (d) Existing mental health services vary and are insufficient and (e) Suggestions for optimal treatment for comorbid HIV and depression. Limitation This study reflects the views of providers from one clinic in this community. Conclusion Substantial economic disadvantage, pervasive childhood adversity, limited education and limited resources jointly put members of this community at risk for acquisition of HIV and for development of depression and addictions. These contextual factors provide an important reminder that any patient-level depression identification or intervention in this community will have to be mindful of such circumstances. PMID:27347445

  8. Acute myeloid leukemia masquerading as hepatocellular carcinoma

    PubMed Central

    Abu-Zeinah, Ghaith F.; Weisman, Paul; Ganesh, Karuna; Katz, Seth S.; Dogan, Ahmet; Abou-Alfa, Ghassan K.; Stein, Eytan M.; Jarnagin, William; Mauro, Michael J.

    2016-01-01

    Hepatocellular carcinoma (HCC) is often diagnosed on the basis of high quality imaging without a biopsy in the cirrhotic liver. This is a case of a 64-year-old Caucasian man with no history of liver disease or cirrhosis that presented with fatigue, weight loss, and abdominal distension and was found to have a large, isolated liver mass with arterial enhancement and portal venous washout on triple-phase computed tomography (CT) suspicious for HCC. The patient was initially referred for a surgical evaluation. Meanwhile, he developed fevers, pancytopenia, and worsening back pain, and a subsequent spinal MRI revealed a heterogeneous bone marrow signal suspicious for metastatic disease. A bone marrow biopsy that followed was diffusely necrotic. A core biopsy of the patient’s liver mass was then performed and was diagnostic of acute monocytic-monoblastic leukemia. Findings from peripheral flow cytometry and a repeat bone marrow biopsy were also consistent with this diagnosis, and induction chemotherapy with cytarabine and idarubicin was initiated. This case describes a rare presentation of myeloid sarcoma (MS) as an isolated, hypervascular liver mass that mimics HCC in its radiographic appearance. Due to the broad differential for a liver mass, a confirmatory biopsy should routinely be considered prior to surgical intervention. PMID:27284485

  9. Diagnostic and therapeutic management of hepatocellular carcinoma

    PubMed Central

    Bellissimo, Francesco; Pinzone, Marilia Rita; Cacopardo, Bruno; Nunnari, Giuseppe

    2015-01-01

    Hepatocellular carcinoma (HCC) is an increasing health problem, representing the second cause of cancer-related mortality worldwide. The major risk factor for HCC is cirrhosis. In developing countries, viral hepatitis represent the major risk factor, whereas in developed countries, the epidemic of obesity, diabetes and nonalcoholic steatohepatitis contribute to the observed increase in HCC incidence. Cirrhotic patients are recommended to undergo HCC surveillance by abdominal ultrasounds at 6-mo intervals. The current diagnostic algorithms for HCC rely on typical radiological hallmarks in dynamic contrast-enhanced imaging, while the use of α-fetoprotein as an independent tool for HCC surveillance is not recommended by current guidelines due to its low sensitivity and specificity. Early diagnosis is crucial for curative treatments. Surgical resection, radiofrequency ablation and liver transplantation are considered the cornerstones of curative therapy, while for patients with more advanced HCC recommended options include sorafenib and trans-arterial chemo-embolization. A multidisciplinary team, consisting of hepatologists, surgeons, radiologists, oncologists and pathologists, is fundamental for a correct management. In this paper, we review the diagnostic and therapeutic management of HCC, with a focus on the most recent evidences and recommendations from guidelines. PMID:26576088

  10. Problem of hepatocellular carcinoma in West Africa

    PubMed Central

    Ladep, Nimzing G; Lesi, Olufunmilayo A; Mark, Pantong; Lemoine, Maud; Onyekwere, Charles; Afihene, Mary; Crossey, Mary ME; Taylor-Robinson, Simon D

    2014-01-01

    The incidence of hepatocellular carcinoma (HCC) is known to be high in West Africa with an approximate yearly mortality rate of 200000. Several factors are responsible for this. Early acquisition of risk factors; with vertical or horizontal transmission of hepatitis B (HBV), environmental food contaminants (aflatoxins), poor management of predisposing risk factors and poorly-managed strategies for health delivery. There has been a low uptake of childhood immunisation for hepatitis B in many West African countries. Owing to late presentations, most sufferers of HCC die within weeks of their diagnosis. Highlighted reasons for the specific disease pattern of HCC in West Africa include: (1) high rate of risk factors; (2) failure to identify at risk populations; (3) lack of effective treatment; and (4) scarce resources for timely diagnosis. This is contrasted to the developed world, which generally has sufficient resources to detect cases early for curative treatment. Provision of palliative care for HCC patients is limited by availability and affordability of potent analgesics. Regional efforts, as well as collaborative networking activities hold promise that could change the epidemiology of HCC in West Africa. PMID:25429316

  11. Hepatitis C virus-induced hepatocellular carcinoma

    PubMed Central

    Goossens, Nicolas

    2015-01-01

    Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host's genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs. PMID:26157746

  12. Activins and activin antagonists in hepatocellular carcinoma

    PubMed Central

    Deli, Alev; Kreidl, Emanuel; Santifaller, Stefan; Trotter, Barbara; Seir, Katja; Berger, Walter; Schulte-Hermann, Rolf; Rodgarkia-Dara, Chantal; Grusch, Michael

    2008-01-01

    In many parts of the world hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood. There is increasing evidence that activins, which are members of the transforming growth factor β (TGFβ) superfamily of growth and differentiation factors, could play important roles in liver carcinogenesis. Activins are disulphide-linked homo- or heterodimers formed from four different β subunits termed βA, βB, βC, and βE, respectively. Activin A, the dimer of two βA subunits, is critically involved in the regulation of cell growth, apoptosis, and tissue architecture in the liver, while the hepatic function of other activins is largely unexplored so far. Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG, and at the cell membrane antagonistic co-receptors like Cripto or BAMBI. Additionally, in the intracellular space inhibitory Smads can modulate and control activin activity. Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation, fibrosis and development of cancer. The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis. PMID:18350601

  13. Aflatoxins, hepatocellular carcinoma and public health.

    PubMed

    Magnussen, Arvin; Parsi, Mansour A

    2013-03-14

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide, primarily affecting populations in the developing countries. Aflatoxin, a food contaminant produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is a known human carcinogen that has been shown to be a causative agent in the pathogenesis of HCC. Aflatoxin can affect a wide range of food commodities including corns, oilseeds, spices, and tree nuts as well as milk, meat, and dried fruit. Many factors affect the growth of Aspergillus fungi and the level of aflatoxin contamination in food. Drought stress is one of the factors that increase susceptibility of plants to Aspergillus and thus aflatoxin contamination. A recent drought is thought to be responsible for finding of trace amounts of aflatoxin in some of the corn harvested in the United States. Although it's too soon to know whether aflatoxin will be a significant problem, since United States is the world's largest corn producer and exporter, this has raised alarm bells. Strict regulations and testing of finished foods and feeds in the United States should prevent a major health scare, and prevent human exposure to deleterious levels of aflatoxin. Unfortunately, such regulations and testing are not in place in many countries. The purpose of this editorial is to summarize the current knowledge on association of aflatoxin and HCC, encourage future research and draw attention to this global public health issue. PMID:23539499

  14. Hepatocellular carcinoma: clinical frontiers and perspectives

    PubMed Central

    Bruix, Jordi; Gores, Gregory J; Mazzaferro, Vincenzo

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death and is currently the main event leading to death in patients with cirrhosis. Evolving information suggests that the metabolic syndrome with non-alcoholic liver disease may be an important cause of HCC in addition to viral hepatitis and alcohol-induced liver disease. The molecular pathogenesis is extremely complex and heterogeneous. To date the molecular information has not impacted on treatment decisions. Periodic surveillance imaging of patients with cirrhosis is widely practiced, especially because diagnostic, radiographic criteria for early-stage HCC have been defined (including nodules between 1 and 2 cm) and effective treatment is available for tumours detected at an early stage. Worldwide the approach to resection versus transplantation varies depending upon local resources, expertise and donor availability. The criteria for transplantation are discussed, and the controversial areas highlighted with evidence-based recommendations provided. Several approaches are available for intermediate stage disease, including radiofrequency ablation, transarterial chemoembolisation and radioembolisation; the rationale for these therapies is buttressed by appropriate outcome-based studies. For advanced disease, systemic therapy with sorafenib remains the option best supported by current data. Thus, while several trials have failed to improve the benefits of established therapies, studies assessing the sequential or combined application of those already known to be beneficial are needed. Also, new concepts are provided in regards to selecting and stratifying patients for second-line studies, which may help explain the failure of prior studies. PMID:24531850

  15. Management of hepatocellular carcinoma in the elderly

    PubMed Central

    Borzio, Mauro; Dionigi, Elena; Parisi, Giancarlo; Raguzzi, Ivana; Sacco, Rodolfo

    2015-01-01

    Mean age of hepatocellular carcinoma (HCC) patients has been progressively increasing over the last decades and ageing of these patients is becoming a real challenge in every day clinical practice. Unfortunately, international guidelines on HCC management do not address this problem exhaustively and do not provide any specific recommendation. We carried out a literature search in MEDLINE database for studies reporting on epidemiology, clinical characteristics and treatment outcome of HCC in elderly patients. Available data seem to indicate that in elderly patients the outcome of HCC is mostly influenced by liver function and tumor stage rather than by age and the latter should not influence treatment allocation. Age is not a risk for resection and older patients with resectable HCC and good liver function could gain benefit from surgery. Mild comorbidities do not seem a contraindication for surgery in aged patients. Conversely, major resection in elderly, even when performed in experienced high-volume centres, should be avoided. Both percutaneous ablation and transarterial chemoembolization are not contraindicated in aged patients and safety profile of these procedures is acceptable. Sorafenib is a viable option for advanced HCC in elderly provided that a careful evaluation of concomitant comorbidities, particularly cardiovascular ones, is taken into account. Available data seem to suggest that in either elderly and younger, treatment is a main predictor of outcome. Consequently, a nihilistic attitude of physicians towards under- or no-treatment of aged patients should not be longer justified. PMID:26085911

  16. Diabetes mellitus and metformin in hepatocellular carcinoma

    PubMed Central

    Fujita, Koji; Iwama, Hisakazu; Miyoshi, Hisaaki; Tani, Joji; Oura, Kyoko; Tadokoro, Tomoko; Sakamoto, Teppei; Nomura, Takako; Morishita, Asahiro; Yoneyama, Hirohito; Masaki, Tsutomu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Diabetes mellitus, a risk factor for cancer, is also globally endemic. The clinical link between these two diseases has been the subject of investigation for a century, and diabetes mellitus has been established as a risk factor for HCC. Accordingly, metformin, a first-line oral anti-diabetic, was first proposed as a candidate anti-cancer agent in 2005 in a cohort study in Scotland. Several subsequent large cohort studies and randomized controlled trials have not demonstrated significant efficacy for metformin in suppressing HCC incidence and mortality in diabetic patients; however, two recent randomized controlled trials have reported positive data for the tumor-preventive potential of metformin in non-diabetic subjects. The search for biological links between cancer and diabetes has revealed intracellular pathways that are shared by cancer and diabetes. The signal transduction mechanisms by which metformin suppresses carcinogenesis in cell lines or xenograft tissues and improves chemoresistance in cancer stem cells have also been elucidated. This review addresses the clinical and biological links between HCC and diabetes mellitus and the anti-cancer activity of metformin in clinical studies and basic experiments. PMID:27468203

  17. Cancer-associated fibroblasts in hepatocellular carcinoma.

    PubMed

    Kubo, Norio; Araki, Kenichiro; Kuwano, Hiroyuki; Shirabe, Ken

    2016-08-14

    The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts (CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines. CAFs crosstalk with cancer cells stimulates tumor progression by creating a favorable microenvironment for progression, invasion, and metastasis through the epithelial-mesenchymal transition. Basic studies on CAFs have advanced, and the role of CAFs in tumors has been elucidated. In particular, for hepatocellular carcinoma, carcinogenesis from cirrhosis is a known fact, and participation of CAFs in carcinogenesis is supported. In this review, we discuss the current literature on the role of CAFs and CAF-related signaling in carcinogenesis, crosstalk with cancer cells, immunosuppressive effects, angiogenesis, therapeutic targets, and resistance to chemotherapy. The role of CAFs is important in cancer initiation and progression. CAFtargeted therapy may be effective for suppression not only of fibrosis but also cancer progression. PMID:27570421

  18. Biological features and biomarkers in hepatocellular carcinoma

    PubMed Central

    Chiba, Tetsuhiro; Suzuki, Eiichiro; Saito, Tomoko; Ogasawara, Sadahisa; Ooka, Yoshihiko; Tawada, Akinobu; Iwama, Atsushi; Yokosuka, Osamu

    2015-01-01

    Similar to other cancers, a multistep process of carcinogenesis is observed in hepatocellular carcinoma (HCC). Although the mechanisms underlying the development of HCC have been investigated in terms of oncology, virology, and stem cell biology, the whole picture of hepatocarcinogenesis remains to be elucidated. Recent progress in molecular biology has provided clues to the underlying cause of various diseases. In particular, sequencing technologies, such as whole genome and exome sequencing analyses, have made an impact on genomic research on a variety of cancers including HCC. Comprehensive genomic analyses have detected numerous abnormal genetic alterations, such as mutations and copy number alterations. Based on these findings, signaling pathways and cancer-related genes involved in hepatocarcinogenesis could be analyzed in detail. Simultaneously, a number of novel biomarkers, both from tissue and blood samples, have been recently reported. These biomarkers have been successfully applied to early diagnosis and prognostic prediction of patients with HCC. In this review, we focus on the recent developments in molecular cancer research on HCC and explain the biological features and novel biomarkers. PMID:26261691

  19. Treatment of hepatocellular carcinoma: beyond international guidelines.

    PubMed

    Sangiovanni, Angelo; Colombo, Massimo

    2016-01-01

    Treatment of hepatocellular carcinoma (HCC) is guided by the tumour stage. The Barcelona clinical liver cancer (BCLC) score endorsed by the European Society of the Liver EASL divides patients into five prognostic categories, each with a distinct treatment indication. Hepatic resection, orthotopic liver transplantation and percutaneous local ablation are strongly indicated in accurately selected patients with very early (BCLC 0) and early stage (BCLC A) tumours providing a survival rate of between 50 and 75% at year five. In patients with a large tumour burden such as those with intermediate stage BCLC B, repeated treatments with transarterial chemoembolization (TACE) are advocated with clinical benefits (from 16 to 22 months). Survival may also improve in patients who are in poor condition or who do not respond to TACE and those with an advanced HCC (BCLC C), following oral therapy with the multikinase inhibitor, sorafenib. However, most recommendations are based on uncontrolled studies and expert opinions rather than well-designed controlled trials, and up to one-third of patients do not fit recommendations because of advanced age, the presence of significant comorbidities or a strategic location of the nodule. For these patients, treatment of HCC beyond guidelines is often advocated.

  20. Synchronous Hepatic Epithelioid Hemangioendothelioma and Hepatocellular Carcinoma

    PubMed Central

    Athanasopoulos, Panagiotis G.; Hadjittofi, Christopher; Luong, Tu Vinh; O’Beirne, James; Sharma, Dinesh

    2015-01-01

    Abstract We would like to report the first case in English literature, to the best of our knowledge, of a synchronous hepatic epithelioid hemangioendothelioma (HEHE) and hepatocellular carcinoma (HCC), as well as to address the current trends and challenges in the management of HEHE. An otherwise well 58-year-old man was referred to his local hepatology service with elevated serum γ-GT levels. Imaging revealed bilobar liver lesions consistent with HEHE, a discrete left lobe lesion suspected as HCC, and multiple pulmonary nodules. Biopsies confirmed HEHE with pulmonary metastases. After multidisciplinary team discussions, the patient was admitted under our team and underwent an uneventful laparoscopic left lateral hepatectomy for suspected HCC, which was confirmed histologically. As part of a watch-and-wait approach to metastatic HEHE, in the first follow-up (3 months postoperatively) the patient was clinically fine and the surveillance CT scan did not show recurrent disease. By presenting this case, we aim to raise awareness that this rare entity can coexist with others, potentially complicating their management. PMID:26313777

  1. Occult hepatitis B virus and hepatocellular carcinoma.

    PubMed

    Pollicino, Teresa; Saitta, Carlo

    2014-05-28

    Occult hepatitis B virus (HBV) infection (OBI) is a challenging pathobiological and clinical issue that has been widely debated for several decades. By definition, OBI is characterized by the persistence of HBV DNA in the liver tissue (and in some cases also in the serum) in the absence of circulating HBV surface antigen (HBsAg). Many epidemiological and molecular studies have indicated that OBI is an important risk factor for hepatocellular carcinoma (HCC) development. OBI may exert direct pro-oncogenic effects through the activation of the same oncogenic mechanisms that are activated in the course of an HBsAg-positive infection. Indeed, in OBI as in HBV-positive infection, HBV DNA can persist in the hepatocytes both integrated into the host genome as well as free episome, and may maintain the capacity to produce proteins-mainly X protein and truncated preS-S protein - provided with potential transforming properties. Furthermore, OBI may indirectly favor HCC development. It has been shown that the persistence of very low viral replicative activity during OBI may induce mild liver necro-inflammation continuing for life, and substantial clinical evidence indicates that OBI can accelerate the progression of liver disease towards cirrhosis that is considered the most important risk factor for HCC development.

  2. Cellular reprogramming and hepatocellular carcinoma development.

    PubMed

    Zheng, Yun-Wen; Nie, Yun-Zhong; Taniguchi, Hideki

    2013-12-21

    Hepatocellular carcinoma (HCC) is one of the most common cancers, and is also the leading cause of death worldwide. Studies have shown that cellular reprogramming contributes to chemotherapy and/or radiotherapy resistance and the recurrence of cancers. In this article, we summarize and discuss the latest findings in the area of cellular reprogramming in HCC. The aberrant expression of transcription factors OCT4, KLF4, SOX2, c-MYC, NANOG, and LIN28 have been also observed, and the expression of these transcription factors is associated with unfavorable clinical outcomes in HCC. Studies indicate that cellular reprogramming may play a critical role in the occurrence and recurrence of HCC. Recent reports have shown that DNA methylation, miRNAs, tumor microenvironment, and signaling pathways can induce the expression of stemness transcription factors, which leads to cellular reprogramming in HCC. Furthermore, studies indicate that therapies based on cellular reprogramming could revolutionize HCC treatment. Finally, a novel therapeutic concept is discussed: reprogramming control therapy. A potential reprogramming control therapy method could be developed based on the reprogramming demonstrated in HCC studies and applied at two opposing levels: differentiation and reprogramming. Our increasing understanding and control of cellular programming should facilitate the exploitation of this novel therapeutic concept and its application in clinical HCC treatment, which may represent a promising strategy in the future that is not restricted to liver cancer. PMID:24379607

  3. Laser Ablation for Small Hepatocellular Carcinoma

    PubMed Central

    Pacella, Claudio Maurizio; Francica, Giampiero; Di Costanzo, Giovanni Giuseppe

    2011-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is increasingly detected at small size (<5 cm) owing to surveillance programmes in high-risk patients. For these cases, curative therapies such as resection, liver transplantation, or percutaneous ablation have been proposed. When surgical options are precluded, image-guided tumor ablation is recommended as the most appropriate therapeutic choice in terms of tumor local control, safety, and improvement in survival. Laser ablation (LA) represents one of currently available loco-ablative techniques: light is delivered via flexible quartz fibers of diameter from 300 to 600 μm inserted into tumor lesion through either fine needles (21g Chiba needles) or large-bore catheters. The thermal destruction of tissue is achieved through conversion of absorbed light (usually infrared) into heat. A range of different imaging modalities have been used to guide percutaneous laser ablation, but ultrasound and magnetic resonance imaging are most widely employed, according to local experience and resource availability. Available clinical data suggest that LA is highly effective in terms of tumoricidal capability with an excellent safety profile; the best results in terms of long-term survival are obtained in early HCC so that LA can be proposed not only in unresectable cases but, not differently from radiofrequency ablation, also as the first-line treatment. PMID:22191028

  4. Cancer-associated fibroblasts in hepatocellular carcinoma

    PubMed Central

    Kubo, Norio; Araki, Kenichiro; Kuwano, Hiroyuki; Shirabe, Ken

    2016-01-01

    The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts (CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines. CAFs crosstalk with cancer cells stimulates tumor progression by creating a favorable microenvironment for progression, invasion, and metastasis through the epithelial-mesenchymal transition. Basic studies on CAFs have advanced, and the role of CAFs in tumors has been elucidated. In particular, for hepatocellular carcinoma, carcinogenesis from cirrhosis is a known fact, and participation of CAFs in carcinogenesis is supported. In this review, we discuss the current literature on the role of CAFs and CAF-related signaling in carcinogenesis, crosstalk with cancer cells, immunosuppressive effects, angiogenesis, therapeutic targets, and resistance to chemotherapy. The role of CAFs is important in cancer initiation and progression. CAFtargeted therapy may be effective for suppression not only of fibrosis but also cancer progression. PMID:27570421

  5. Aflatoxins, hepatocellular carcinoma and public health.

    PubMed

    Magnussen, Arvin; Parsi, Mansour A

    2013-03-14

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide, primarily affecting populations in the developing countries. Aflatoxin, a food contaminant produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is a known human carcinogen that has been shown to be a causative agent in the pathogenesis of HCC. Aflatoxin can affect a wide range of food commodities including corns, oilseeds, spices, and tree nuts as well as milk, meat, and dried fruit. Many factors affect the growth of Aspergillus fungi and the level of aflatoxin contamination in food. Drought stress is one of the factors that increase susceptibility of plants to Aspergillus and thus aflatoxin contamination. A recent drought is thought to be responsible for finding of trace amounts of aflatoxin in some of the corn harvested in the United States. Although it's too soon to know whether aflatoxin will be a significant problem, since United States is the world's largest corn producer and exporter, this has raised alarm bells. Strict regulations and testing of finished foods and feeds in the United States should prevent a major health scare, and prevent human exposure to deleterious levels of aflatoxin. Unfortunately, such regulations and testing are not in place in many countries. The purpose of this editorial is to summarize the current knowledge on association of aflatoxin and HCC, encourage future research and draw attention to this global public health issue.

  6. Transplant benefit for patients with hepatocellular carcinoma.

    PubMed

    Vitale, Alessandro; Volk, Michael; Cillo, Umberto

    2013-12-28

    Although liver transplantation is theoretically the best treatment for hepatocellular carcinoma (HCC), it is limited by the realities of perioperative complications, and the shortage of donor organs. Furthermore, in many cases there are available alternative treatments such as resection or locoregional therapy. Deciding upon the best option for a patient with HCC is complicated, involving numerous ethical principles including: urgency, utility, intention-to-treat survival, transplant benefit, harm to candidates on waiting list, and harm to living donors. The potential contrast between different principles is particularly relevant for patients with HCC for several reasons: (1) HCC candidates to liver transplantation are increasing; (2) the great prognostic heterogeneity within the HCC population; (3) in HCC patients tumor progression before liver transplantation may significantly impair post transplant outcome; and (4) effective alternative therapies are often available for HCC candidates to liver transplantation. In this paper we suggest that allocating organs by transplant benefit could help balance these competing principles, and also introduce equity between patients with HCC and nonmalignant liver disease. We also propose a triangular equipoise model to help decide between deceased donor liver transplantation, living donor liver transplantation, or alternative therapies. PMID:24409046

  7. Hepatocellular carcinoma and hepatitis B surface protein

    PubMed Central

    Li, Yong-Wei; Yang, Feng-Cai; Lu, Hui-Qiong; Zhang, Jiong-Shan

    2016-01-01

    The tumorigenesis of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) has been widely studied. HBV envelope proteins are important for the structure and life cycle of HBV, and these proteins are useful for judging the natural disease course and guiding treatment. Truncated and mutated preS/S are produced by integrated viral sequences that are defective for replication. The preS/S mutants are considered “precursor lesions” of HCC. Different preS/S mutants induce various mechanisms of tumorigenesis, such as transactivation of transcription factors and an immune inflammatory response, thereby contributing to HCC. The preS2 mutants and type II “Ground Glass” hepatocytes represent novel biomarkers of HBV-associated HCC. The preS mutants may induce the unfolded protein response and endoplasmic reticulum stress-dependent and stress-independent pathways. Treatments to inhibit hepatitis B surface antigen (HBsAg) and damage secondary to HBsAg or the preS/S mutants include antivirals and antioxidants, such as silymarin, resveratrol, and glycyrrhizin acid. Methods for the prevention and treatment of HCC should be comprehensive. PMID:26877602

  8. Management of Hepatocellular Adenoma: Recent Advances.

    PubMed

    Agrawal, Shefali; Agarwal, Sheela; Arnason, Thomas; Saini, Sanjay; Belghiti, Jacques

    2015-07-01

    Hepatocellular adenoma (HCA) is a rare benign liver cell neoplasm that occurs more frequently in young women with a history of prolonged use of oral contraceptives. Surgical resection is considered because of the risk of hemorrhage in 25% and of malignant transformation in 5% of patients with HCA. HCA is a heterogeneous disease comprising 3 subtypes with distinct molecular and complication profiles. The inflammatory or telangiectatic subtype is at increased risk for hemorrhage, the β-catenin-activated subtype is at increased risk for malignant transformation, and the hepatocyte nuclear factor-1α-inactivated or steatotic subtype is at the least risk for complications. One-third of the patients with HCA have multiple tumors on imaging with no increased risk of complications. Magnetic resonance imaging is the modality of choice for the diagnosis and subtype characterization of HCA. Systematic resection of HCA is recommended in male patients owing to the higher incidence of malignant transformation, and surgical excision in women should be reserved for tumors 5 cm or larger associated with an increased risk of complications. Cessation of hormonal therapy and radiologic surveillance in women with HCA tumors smaller than 5 cm shows that the vast majority of HCA remain stable or undergo spontaneous regression. Percutaneous core needle biopsy is of limited value because the therapeutic strategy is based primarily on patient sex and tumor size. Transarterial embolization is the initial treatment for HCA complicated by hemorrhage. Pregnancy should not be discouraged in the presence of HCA, however, frequent sonographic surveillance is recommended.

  9. Advances in Management of Hepatocellular Carcinoma.

    PubMed

    Intaraprasong, Pongphob; Siramolpiwat, Sith; Vilaichone, Ratha-Korn

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor and a high impact health problem worldwide. The prevalence of HCC is particularly high in many Asian and African countries. Some HCC patients have no symptoms prior to diagnosis and many of them therefore present at late stage and have a grave prognosis. The well-established causes of HCC are chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or alcoholic cirrhosis and nonalcoholic steatohepatitis. The Barcelona Clinic Liver Cancer (BCLC) Staging System remains the most widely used for HCC management guidelines. To date, the treatments for HCC are still very challenging for physicians due to limited resources in many parts of the world, but many options of management have been proposed, including hepatic resection, liver transplantation, ablative therapy, chemoembolization, sora nib and best supportive care. This review article describes the current evidence-based management of HCC with focus on early to advance stages that impact on patient overall survival. PMID:27644603

  10. Mechanisms of HBV-induced hepatocellular carcinoma.

    PubMed

    Levrero, Massimo; Zucman-Rossi, Jessica

    2016-04-01

    Hepatitis B virus (HBV) contributes to hepatocellular carcinoma (HCC) development through direct and indirect mechanisms. HBV DNA integration into the host genome occurs at early steps of clonal tumor expansion and induces both genomic instability and direct insertional mutagenesis of diverse cancer-related genes. Prolonged expression of the viral regulatory protein HBx and/or altered versions of the preS/S envelope proteins dysregulates cell transcription and proliferation control and sensitizes liver cells to carcinogenic factors. Accumulation of preS1 large envelope proteins and/or preS2/S mutant proteins activates the unfold proteins response, that can contribute to hepatocyte transformation. Epigenetic changes targeting the expression of tumor suppressor genes occur early in the development of HCC. A major role is played by the HBV protein, HBx, which is recruited on cellular chromatin and modulates chromatin dynamics at specific gene loci. Compared with tumors associated with other risk factors, HBV-related tumors have a higher rate of chromosomal alterations, p53 inactivation by mutations and overexpression of fetal liver/hepatic progenitor cells genes. The WNT/β-catenin pathway is also often activated but HBV-related tumors display a low rate of activating β-catenin mutations. HBV-related HCCs may arise on non-cirrhotic livers, further supporting the notion that HBV plays a direct role in liver transformation by triggering both common and etiology specific oncogenic pathways in addition to stimulating the host immune response and driving liver chronic necro-inflammation.

  11. Screening process failures for hepatocellular carcinoma.

    PubMed

    Singal, Amit G; Marrero, Jorge A; Yopp, Adam

    2014-03-01

    More than 60% of patients with hepatocellular carcinoma (HCC) are diagnosed at a late stage, suggesting potential breakdowns in the HCC screening process. Understanding which steps in the screening process are not being performed is essential for designing effective interventions. To characterize HCC screening process failures, a retrospective cohort study of patients with cirrhosis diagnosed with HCC at a large urban safety-net hospital was conducted between 2005 and 2012. Screening process failures during the year before HCC diagnosis were characterized into 3 categories: absence of surveillance, failure of detection, and delayed follow-up. Univariate and multivariate analyses were performed to identify predictors of screening process failures. A total of 185 patients with cirrhosis and HCC were identified, of whom 91 (49%) were diagnosed at an early stage (Barcelona Clinic Liver Cancer system stage A). Only 16 (8.6%) patients successfully completed the screening process. Absence of surveillance was the most common screening process failure, found in 75.7% of all patients, and was associated with trends toward lower rates of early tumor detection (odds ratio, 0.51; 95% CI, 0.23-1.09) and worse overall survival (hazard ratio, 0.79; 95% CI, 0.49-1.25). Failure of detection and delayed follow-up were found in 11.4% and 2.7% of patients, respectively.

  12. Cellular reprogramming and hepatocellular carcinoma development

    PubMed Central

    Zheng, Yun-Wen; Nie, Yun-Zhong; Taniguchi, Hideki

    2013-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers, and is also the leading cause of death worldwide. Studies have shown that cellular reprogramming contributes to chemotherapy and/or radiotherapy resistance and the recurrence of cancers. In this article, we summarize and discuss the latest findings in the area of cellular reprogramming in HCC. The aberrant expression of transcription factors OCT4, KLF4, SOX2, c-MYC, NANOG, and LIN28 have been also observed, and the expression of these transcription factors is associated with unfavorable clinical outcomes in HCC. Studies indicate that cellular reprogramming may play a critical role in the occurrence and recurrence of HCC. Recent reports have shown that DNA methylation, miRNAs, tumor microenvironment, and signaling pathways can induce the expression of stemness transcription factors, which leads to cellular reprogramming in HCC. Furthermore, studies indicate that therapies based on cellular reprogramming could revolutionize HCC treatment. Finally, a novel therapeutic concept is discussed: reprogramming control therapy. A potential reprogramming control therapy method could be developed based on the reprogramming demonstrated in HCC studies and applied at two opposing levels: differentiation and reprogramming. Our increasing understanding and control of cellular programming should facilitate the exploitation of this novel therapeutic concept and its application in clinical HCC treatment, which may represent a promising strategy in the future that is not restricted to liver cancer. PMID:24379607

  13. Recent advances in immunotherapy for hepatocellular cancer.

    PubMed

    Butterfield, Lisa H

    2007-02-10

    There is a continuing need for innovative, alternative therapies for hepatocellular carcinoma (HCC). Immunotherapy of cancer is attractive because of the exquisite specificity of the immune response. Activation of an HCC-specific response can be accomplished by strategies targeting tumour-associated antigens (for example: alpha fetoprotein (AFP)) or viral antigens in those patients infected with hepatitis B or C. Uncharacterised and mutated antigens can also be targeted with whole tumour cell or tumour lysate-based immunisation strategies. Viral vectors coding for genes which make the patient's tumour immunogenic can allow the immune system to naturally evolve specificity against immunogenic target antigens. Strategies which have been tested in human clinical trials include adoptive transfer of lymphocytes, cytokine injections, autologous tumour-pulsed dendritic cells (DC) as well as AFP-derived peptides in adjuvant and pulsed onto autologous DC. These trials, testing novel immune-based interventions in HCC subjects, have resulted in immunological responses and some have impacted recurrence and survival of HCC subjects.

  14. BMS-247550 in Treating Patients With Liver or Gallbladder Cancer

    ClinicalTrials.gov

    2014-05-13

    Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  15. Beneath the Copper-Pediatric Wilson's Disease Cirrhosis and Hepatocellular Carcinoma: A Case Report with Literature Review.

    PubMed

    Rosencrantz, Richard A; LeCompte, Lesli; Yusuf, Yasmin

    2015-11-01

    Primary hepatic malignancies are uncommon in pediatrics. Tumors such as hepatocellular carcinoma (HCC) develop typically in the setting of chronic liver disease. The incidence of HCC in Wilson's disease-related cirrhosis is disproportionately lower than in many other forms of end-stage liver disease. A preadolescent girl presented with Wilson's disease cirrhosis and a HCC requiring orthotopic liver transplantation. This case highlights the need to consider hepatic malignancies even in young Wilson's disease patients. Pediatric Wilson's disease and the hepatic tumor literature are reviewed.

  16. Beneath the Copper-Pediatric Wilson's Disease Cirrhosis and Hepatocellular Carcinoma: A Case Report with Literature Review.

    PubMed

    Rosencrantz, Richard A; LeCompte, Lesli; Yusuf, Yasmin

    2015-11-01

    Primary hepatic malignancies are uncommon in pediatrics. Tumors such as hepatocellular carcinoma (HCC) develop typically in the setting of chronic liver disease. The incidence of HCC in Wilson's disease-related cirrhosis is disproportionately lower than in many other forms of end-stage liver disease. A preadolescent girl presented with Wilson's disease cirrhosis and a HCC requiring orthotopic liver transplantation. This case highlights the need to consider hepatic malignancies even in young Wilson's disease patients. Pediatric Wilson's disease and the hepatic tumor literature are reviewed. PMID:26676818

  17. HGF, MET, and matrix-related proteases in hepatocellular carcinoma, fibrolamellar variant, cirrhotic and normal liver.

    PubMed

    Schoedel, Karen E; Tyner, Valerie Zajac; Kim, Tae-Hyoung; Michalopoulos, George K; Mars, Wendy M

    2003-01-01

    Fibrolamellar variant is an uncommon subcategory of he