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Sample records for adult primary hepatocellular

  1. Fibrolamellar Hepatocellular Carcinoma: Mechanistic Distinction From Adult Hepatocellular Carcinoma

    PubMed Central

    Riggle, Kevin M.; Turnham, Rigney; Scott, John D.; Yeung, Raymond S.

    2016-01-01

    Fibrolamellar hepatocellular carcinoma (FL‐HCC) has historically been classified as a rare subtype of HCC. However, unlike “classic” HCC, it occurs in children and young adults without underlying liver disease. The recent discovery of a deletion mutation in all FL‐HCCs represented a major advancement in understanding the pathogenesis of this disease. This deletion results in the fusion of the genes encoding a heat shock protein (DNAJB1) and the catalytic subunit of protein kinase A (PKA, PRKACA), and overexpression of PRKACA and enhanced cAMP‐dependent PKA activity. This review summarizes recent advancements in FL‐HCC pathogenesis and characteristics of the HSP40‐PKA C protein. PMID:26990031

  2. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  3. Gingival metastasis from primary hepatocellular carcinoma. Report of a case.

    PubMed

    Wedgwood, D; Rusen, D; Balk, S

    1979-03-01

    A case of primary hepatocellular carcinoma metastatic to the gingiva is described. Hepatocellular carcinoma is an uncommon malignancy, generally occurring in a cirrhotic liver, which rarely metastasizes to the maxillofacial area. Of eight such cases in the English-language literature, the present case is the fourth involving metastasis to the gingiva. Hepatocellular carcinoma would seem to metastasize with equal frequency to the gingiva and to the mandibular bone. In the case described, histologic examination of the gingival lesion definitively established the diagnosis following somewhat equivocal results of needle biopsy of the liver.

  4. 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.

  5. 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

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

    ClinicalTrials.gov

    2017-01-24

    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

  7. The Correlation between NK Cell and Liver Function in Patients with Primary Hepatocellular Carcinoma

    PubMed Central

    Zeng, Xiao-Hui; Min, Lu

    2014-01-01

    Background/Aims This study aimed to detect the expression of natural killer (NK) cell receptor natural killer group 2D (NKG2D) in the peripheral blood of patients with primary hepatocellular carcinoma and to discuss the correlation between NK cell cytotoxicity and liver function. Methods The number of NK cells and the expression of NK cell receptor NKG2D in peripheral blood were determined by flow cytometry in patients with primary hepatocellular carcinoma, hepatitis B cirrhosis, chronic hepatitis B, and healthy controls. Results When compared with patients in the healthy and the chronic hepatitis B groups, the primary hepatocellular carcinoma group showed significant decreases in all parameters, including the cytotoxicity of NK cells on K562 cells, expression rate of NKG2D in NK cells, number of NKG2D+ NK cells, expression level of NKG2D, and number of NK cells (p<0.05). The activity of NK cells showed a positive correlation, whereas the Child-Pugh scores in the primary hepatocellular carcinoma and the hepatitis B cirrhosis groups showed a negative correlation with all parameters detected above. Conclusions The decrease of NK cell activity in patients with primary hepatocellular carcinoma is closely related to their lower expression of NKG2D. Liver function affects the expression of NKG2D and the activity of NK cells. PMID:24827627

  8. Treatment Options for Adult Primary Liver Cancer

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  9. Treatment Option Overview (Adult Primary Liver Cancer)

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  10. Stages of Adult Primary Liver Cancer

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  11. General Information about Adult Primary Liver Cancer

    MedlinePlus

    ... Cancer Prevention Liver Cancer Screening Research Adult Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health Professional Version Key Points ...

  12. Complete remission of diffuse hepatocellular carcinoma in a young adult after GSP-TACE: a case report.

    PubMed

    Liu, Song; Zhang, Yuewei; Zhao, Guangsheng; Liu, Ying

    2014-09-25

    Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver. It mostly occurs in older age groups (usually those 50 to 60 years old), and rarely in young adults. The survival rate of these young HCC patients is usually very low. The authors report a case of a 22-year old man with diffuse-type HCC who successfully achieved complete remission for 46 months after second transcatheter arterial chemoembolization using gelatin sponge particles (Eric Kang Pharmaceutical Technology Co., Ltd. Hangzhou, China) combined with pirarubicin.

  13. Primary brain tumours in adults.

    PubMed

    Ricard, Damien; Idbaih, Ahmed; Ducray, François; Lahutte, Marion; Hoang-Xuan, Khê; Delattre, Jean-Yves

    2012-05-26

    Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas--the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the knowledge of tumour biology, which should lead to a better classification of gliomas and pave the way for so-called targeted therapy trials. Primary CNS lymphomas are a group of rare non-Hodgkin lymphomas. High-dose methotrexate-based regimens increase survival, but the standards of care and the place of whole-brain radiotherapy remain unclear, and are likely to depend on the age of the patient. The focus now is on the development of new polychemotherapy regimens to reduce or defer whole-brain radiotherapy and its delayed complications.

  14. Different anticancer effects of fluvastatin on primary hepatocellular tumors and metastases in rats.

    PubMed

    Paragh, György; Fóris, Gabriella; Paragh, György; Seres, Ildikó; Karányi, Zsolt; Fülöp, Péter; Balogh, Zoltán; Kosztáczky, Béla; Teichmann, Farkas; Kertai, Pál

    2005-05-10

    Rats (FLF1) were pretreated with 2 and 20 mg/kg/day fluvastatin (Flu), and after 6 weeks, hepatocellular tumor cells were inoculated under the left renal capsule. At different times, growth and pyruvate kinase (PK) activity of the primary tumors and lymph node metastases were determined. Flu had a dose-dependent inhibitory effect on primary and metastatic tumors, and the inhibitory effect on growth and PK activity in metastases were higher than in primary tumors. Finally, Flu had an earlier inhibitory effect on the early appeared PK activity in metastases than in primary tumors.

  15. 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.

  16. Syndrome of Inappropriate Anti-Diuretic Hormone Secondary to Non-Cirrhotic Primary Hepatocellular Carcinoma

    PubMed Central

    Eltawansy, Sherif; Gomez, Johnson; Liss, Kenneth; Nivera, Noel; Babyatsky, Mark

    2015-01-01

    Patient: Male, 71 Final Diagnosis: SIADH Symptoms: Cachexia • confusion Medication: — Clinical Procedure: Percutaneous liver biopsy Specialty: Oncology Objective: Rare disease Background: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is usually seen in pulmonary malignancies, central nervous system disorders, and secondary to medications. SIADH has very rarely been encountered in primary hepatocellular carcinoma. Two cases were reported in Japan and 1 case in Spain after extensive investigation of the medical records. Case Report: We report a case of a 71-year-old man who presented with confusion, cachexia, and abdominal symptoms in the form of vomiting and abdominal discomfort. On the initial work-up, SIADH diagnosis was made. After an extensive work-up, the reason for SIADH turned out to be a newly diagnosed hepatocellular carcinoma. The precipitating factor for the cancer was not identified by history or by work-up. No metastasis was identified. Liver functions were preserved but patient was severely malnourished. Conclusions: SIADH can occur as a para-malignant feature of the malignancy. In our case, it was related to the hepatocellular carcinoma, which is a malignancy very rare to cause SIADH. PMID:25612883

  17. 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

  18. Salvage Liver Transplantation Leads to Poorer Outcome in Hepatocellular Carcinoma Compared with Primary Liver Transplantation

    PubMed Central

    Shan, Yuhua; Huang, Lifeng; Xia, Qiang

    2017-01-01

    Hepatocellular carcinoma is the most common liver malignancy. Salvage liver transplantation (SLT) is viewed as a feasible cure for recurrence of HCC after resectomy, but the effect is under dispute. A retrospective study examined data at Renji Hospital for 239 transplants from January 2006 to December 2015, including 211 who received primary liver transplantation (PLT) and 28 who underwent SLT. A multivariable cox regression model was employed to pick out relative factors to overall survival (OS) and recurrence free survival (RFS). Propensity score matching (PSM) was used to balance the bias. Both OS and RFS were worse in SLT group than in PLT group, especially for those patients within Milan criteria. Our study demonstrates that SLT bears higher risk of recurrence and death than PLT, indicating that SLT should be given a more careful thought at performance. PMID:28294176

  19. Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis

    PubMed Central

    Watanabe, Takuya; Soga, Kenji; Hirono, Haruka; Hasegawa, Katsuhiko; Shibasaki, Koichi; Kawai, Hirokazu; Aoyagi, Yutaka

    2009-01-01

    AIM: To characterize the clinical features of hepatocellular carcinoma (HCC) associated with autoimmune liver disease, we critically evaluated the literature on HCC associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). METHODS: A systematic review of the literature was conducted using the Japana Centra Revuo Medicina database which produced 38 cases of HCC with AIH (AIH-series) and 50 cases of HCC with PBC (PBC-series). We compared the clinical features of these two sets of patients with the general Japanese HCC population. RESULTS: On average, HCC was more common in men than in women with AIH or PBC. While many patients underwent chemolipiodolization (CL) or transcatheter arterial embolization (TAE) (AIH-series: P = 0.048 (vs operation), P = 0.018 (vs RFA, PEIT); PBC-series: P = 0.027 (vs RFA, PEIT), others refused therapeutic interventions [AIH-series: P = 0.038 (vs RFA, PEIT); PBC-series: P = 0.003 (vs RFA, PEIT)]. Liver failure was the primary cause of death among patients in this study, followed by tumor rupture. The survival interval between diagnosis and death was fairly short, averaging 14 ± 12 mo in AIH patients and 8.4 ± 14 mo in PBC patients. CONCLUSION: We demonstrated common clinical features among Japanese cases of HCC arising from AIH and PBC. PMID:19132775

  20. Primary carnitine deficiency in a male adult.

    PubMed

    Karmaniolas, Konstantinos; Ioannidis, Panagiotis; Liatis, Stavros; Dalamanga, Maria; Papalambros, Theoharis; Migdalis, Ilias

    2002-01-01

    The case is described of a 36 year-old man who presented with progressive proximal muscle weakness and weight loss. His serum creatine phosphokinase (CPK) levels were markedly elevated. The muscle biopsy showed lipid storage myopathy. The muscle carnitine concentration was extremely low (5.6% of normal levels), establishing the diagnosis of myopathic carnitine deficiency. The disorder was considered as primary because there were no indications of any other identifiable condition which could result in a secondary carnitine deficiency. The patient was treated with oral L-carnitine (2 g per day) and showed rapid improvement. Primary myopathic carnitine deficiency is a curable disorder and therefore it should always be considered as a potential diagnosis in cases of myopathy in young adults.

  1. 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

  2. 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

  3. Preoperative lymphocyte-to-monocyte ratio predicts survival in primary hepatitis B virus-positive hepatocellular carcinoma after curative resection

    PubMed Central

    Li, Guang-Jun; Ji, Juan-Juan; Yang, Fang; Xu, Hong-Wei; Bai, Yu

    2017-01-01

    Background Both inflammation and immunity are associated with the development of malignancy. The lymphocyte-to-monocyte ratio (LMR) has been confirmed as a prognostic factor for several malignant diseases. The purpose of our study was to analyze prognostic significance of preoperative LMR in hepatitis B virus (HBV)-related hepatocellular carcinoma after curative resection. Patients and methods A total of 253 patients with primary HBV-positive hepatocellular carcinoma who underwent a curative operation were enrolled in this retrospective study. The relationship between preoperative LMR and survival outcomes was analyzed through Kaplan–Meier curves and multivariate Cox regression analyses. Results Patients with a high LMR had a significantly higher mean overall survival than those with a low LMR (67 months vs 55 months, P=0.023), and high LMR remained significant for longer survival in the multivariate analysis (hazard ratio, 0.147; 95% confidence interval [CI]: 0.085–0.253; P=0.021). Furthermore, patients with a high LMR also had a higher median recurrence-free survival than those with a low LMR in univariate analyses (60 months vs 48 months, P=0.026) and multivariate analyses (hazard ratio, 0.317; 95% CI: 0.042–1.023; P=0.032). However, the survival benefit was limited to patients with advanced cancer. Conclusion LMR was confirmed as an independent prognostic biomarker for primary HBV-positive hepatocellular carcinoma after curative resection. PMID:28260933

  4. 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

  5. Natural history of untreated primary hepatocellular carcinoma: a retrospective study of 157 patients.

    PubMed

    Pawarode, A; Voravud, N; Sriuranpong, V; Kullavanijaya, P; Patt, Y Z

    1998-08-01

    Primary hepatocellular carcinoma (HCC) is a common malignancy with a dismal prognosis; new modalities of treatment as alternatives to surgery have been developed for unresectable patients. The authors obtain baseline data for the natural history of HCC so that the efficacy of new treatments may be evaluated. A retrospective study of 157 untreated patients with tissue-proven or serodiagnosed HCC was conducted. Clinical characteristics including laboratory investigation, treatment received, survival from the time of diagnosis, and prognostic factors were evaluated. There were 129 men and 28 women (ratio, 4.6:1). Median age was 50.9 years (range, 14.1-85.3 years). The most common symptoms and signs were weight loss (68.2%), abdominal fullness (62.5%), abdominal pain (51.6%), hepatomegaly (73.7%), ascites (45.2%), and jaundice (40.6%). Eighteen percent had extrahepatic metastases of which the lungs were the most common site. Seventy percent were hepatitis B virus related. Overall median survival was 8.7 weeks after the time of diagnosis. Survivals by stages were: TNM II, 16.6 weeks; TNM III, 7.3 weeks; TNM IVA, 9.7 weeks; TNM IVB, 7.6 weeks; Okuda II, 10.7 weeks; and Okuda III, 7.3 weeks. Multivariate analysis revealed serum total bilirubin and albumin as independent prognostic factors of survival. Common causes of death were upper gastrointestinal hemorrhage (34.1%), cancer-related causes (cachexia, HCC rupture, metastatic disease, 31.8%), and hepatic failure (25.0%). Patients with HCC were diagnosed at late stages of their disease and the advanced nature of the tumor precluded effective therapy. Earlier tumor detection at a time when patients are better candidates for treatment may be aided by an active surveillance program of high risk groups.

  6. 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

  7. Pulmonary Metastasis of Combined Hepatocellular and Cholangiocarcinoma: A Unique Radiographic Presentation with Air-space Consolidation Masquerading as Pneumonia and Primary Pulmonary Adenocarcinoma.

    PubMed

    Ishii, Takashi; Goto, Yasushi; Matsuzaki, Hirotaka; Ohishi, Nobuya; Sakamoto, Yoshihiro; Saito, Ruri; Matsusaka, Keisuke; Shibahara, Junji; Nagase, Takahide

    2015-01-01

    Lung metastasis showing radiographic findings of air-space consolidation is considered to be rare. This report describes the case of a man with progressive left lower lobe air-space consolidation with a history of hepatocellular carcinoma. The pulmonary lesion was initially suspected to be infection and later clinically diagnosed as primary adenocarcinoma of the lung. Although the patient was treated with systemic chemotherapy, the disease progressed very rapidly. A postmortem examination revealed that the alveolar spaces were filled with neoplastic cells subsequently proven to be metastases of combined hepatocellular and cholangiocarcinoma.

  8. Solitary Metastasis to a Distant Lymph Node in the Descending Mesocolon After Primary Resection for Hepatocellular Carcinoma: Is Surgical Resection Valid?

    PubMed Central

    Aisu, Yuki; Furuyama, Hiroaki; Hori, Tomohide; Machimoto, Takafumi; Hata, Toshiyuki; Kadokawa, Yoshio; Kato, Shigeru; Ando, Yasuhisa; Uchida, Yuichiro; Yasukawa, Daiki; Kimura, Yusuke; Sasaki, Maho; Takamatsu, Yuichiro; Yoshimura, Tunehiro

    2016-01-01

    Patient: Female, 65 Final Diagnosis: Mesocolic lymph node metastasis of Hetpatocellular carcinoma Symptoms: None Medication: — Clinical Procedure: Partial resection of descending colon including metastatic lymph node Specialty: Surgery Objective: Rare disease Background: Lymph node metastasis of hepatocellular carcinoma is rare, and lymph nodes located on hepatic hilar and hepatoduodenal ligaments are primary targets. Metastasis to a mesocolic lymph node has not been reported previously. Case Report: A 65-year-old woman with liver cirrhosis underwent primary resection of hepatocellular carcinoma. Two and a half years later, tumor marker levels increased remarkably and imaging revealed a mesocolic mass. The tumor measured 27 mm in diameter and showed characteristic findings consistent with hepatocellular carcinoma in dynamic computed tomographic images, although the tumor was negative in fluorine-18-fluorodeoxyglucose positron emission tomographic images. A preoperative diagnosis of solitary metastasis to a mesocolic lymph node was made, and we elected to perform surgical resection, although therapeutic strategies for rare solitary extrahepatic metastasis are controversial. The tumor was located in the mesocolon nearly at the wall of the descending colon. Curative resection was performed and histopathological analysis confirmed metastatic hepatocellular carcinoma to a mesocolic lymph node. Tumor marker levels normalized immediately postoperatively. To date, the patient remains free from recurrence without adjuvant therapy. Conclusions: This is the first known case of solitary hepatocellular carcinoma metastasis to a distant mesocolic lymph node, successfully treated. Diagnosing solitary hepatocellular carcinoma metastases to distant lymph nodes can be difficult. Although the ideal therapeutic approach has not be defined, surgical resection of solitary metastatic lymph nodes may be beneficial in carefully selected cases. PMID:27904130

  9. Synchronous primary breast cancer and hepatocellular carcinoma in a male patient: a case report

    PubMed Central

    Tian, Fei; Cui, Xiuzheng; Li, Lin; Lu, Haizhen; Rong, Weiqi; Bi, Chao; Wu, Jianxiong

    2015-01-01

    Male breast cancer is a rare malignant disease characterized by hormonal imbalance. Hepatocellular carcinoma (HCC) is the most common neoplasm of the liver, and is generally correlated with hepatitis B or C virus-related cirrhosis. While to our knowledge a case with these two malignant diseases in a same male patient in the concomitant period is an exceptional event, rarely reported in literature. In this report, we present a case in which a Chinese patient with hepatitis B developed a tumor mass that originated from segment V of the liver and presented with right breast nodules at the same time. Synchronous mastectomy and hepatectomy were performed, and standard endocrine therapy and chemotherapy as adjuvant treatment were therefore followed. The diverse histogenesis of the two kinds of cancers highlights the need for us to investigate any common physiopathogenetic elements. PMID:26617917

  10. Primary Care Providers' HIV Prevention Practices Among Older Adults

    PubMed Central

    Davis, Tracy; Teaster, Pamela B.; Thornton, Alice; Watkins, John F.; Alexander, Linda; Zanjani, Faika

    2016-01-01

    Purpose To explore primary care providers' HIV prevention practices for older adults. Primary care providers' perceptions and awareness were explored to understand factors that affect their provision of HIV prevention materials and HIV screening for older adults. Design and Method Data were collected through 24 semistructured interviews with primary care providers (i.e., physicians, physician assistants, and nurse practitioners) who see patients older than 50 years. Results Results reveal facilitators and barriers of HIV prevention for older adults among primary care providers and understanding of providers' HIV prevention practices and behaviors. Individual, patient, institutional, and societal factors influenced HIV prevention practices among participants, for example, provider training and work experience, lack of time, discomfort in discussing HIV/AIDS with older adults, stigma, and ageism were contributing factors. Furthermore, factors specific to primary and secondary HIV prevention were identified, for instance, the presence of sexually transmitted infections influenced providers' secondary prevention practices. Implications HIV disease, while preventable, is increasing among older adults. These findings inform future research and interventions aimed at increasing HIV prevention practices in primary care settings for patients older than 50. PMID:25736425

  11. 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 ...

  12. Current update on combined hepatocellular-cholangiocarcinoma

    PubMed Central

    Maximin, Suresh; Ganeshan, Dhakshina Moorthy; Shanbhogue, Alampady K.; Dighe, Manjiri K.; Yeh, Matthew M.; Kolokythas, Orpheus; Bhargava, Puneet; Lalwani, Neeraj

    2014-01-01

    Combined hepatocellular-cholangiocarcinoma is a rare but unique primary hepatic tumor with characteristic histology and tumor biology. Recent development in genetics and molecular biology support the fact that combined hepatocellular-cholangiocarcinoma is closely linked with cholangiocarcinoma, rather than hepatocellular carcinoma. Combined hepatocellular cholangiocarcinoma tends to present with an more aggressive behavior and a poorer prognosis than either hepatocellular carcinoma or cholangiocarcinoma. An accurate preoperative diagnosis and aggressive treatment planning can play crucial roles in appropriate patient management. PMID:26937426

  13. Paraneoplastic pemphigus mimicking erosive mucosal lichen planus associated with primary hepatocellular carcinoma.

    PubMed

    Yokokura, Hideto; Demitsu, Toshio; Kakurai, Maki; Umemoto, Naoka; Azuma, Ryuichi; Yamada, Tomoko; Suzuki, Masayuki; Jimbu, Yoshinori; Yoneda, Kozo; Ishii, Norito; Hashimoto, Takashi

    2006-12-01

    A 58-year-old Japanese male visited us with painful lesions on the lower lip, oral mucosa and genital region of an 8-month duration. Histological features of the genital lesion were almost consistent with lichenoid tissue reaction. A few intraepidermal acantholytic keratinocytes were also seen in the suprabasal clefts. Direct immunofluorescence exhibited cell surface immunoglobulin (Ig)G deposition and linear deposition of fibrinogen at the dermoepidermal junction. IgG anti-desmoglein (Dsg)3 antibody, but not anti-Dsg1 antibody, was detected in the patient's serum by enzyme-linked immunosorbent assay. Immunoblotting using normal human epidermal extract detected the 210-kD envoplakin, 190-kD periplakin and 130-kD Dsg3. The diagnosis of paraneoplastic pemphigus (PNP) was made. Subsequent investigation revealed a large space-occupying lesion in the liver. Histological findings from liver biopsy specimen were consistent with hepatocellular carcinoma. The patient has been alive 38 months after the diagnosis of PNP was made, although the liver mass has slowly enlarged. Our case is clinically and histologically similar to erosive mucosal lichen planus. Immunological studies confirmed the diagnosis of PNP. The results of negative Dsg1 and positive Dsg3 were consistent with clinical features showing severe mucosal involvement without cutaneous erosion. In PNP, the association with non-hematological solid tumor is extremely rare.

  14. Treatment of Adult Primary Alveolar Proteinosis.

    PubMed

    Rodríguez Portal, José Antonio

    2015-07-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant-like lipoproteinaceous material in the distal air spaces and terminal bronchi, which may lead to impaired gas exchange. This accumulation of surfactant is due to decreased clearance by the alveolar macrophages. Its primary, most common form, is currently considered an autoimmune disease. Better knowledge of the causes of PAP have led to the emergence of alternatives to whole lung lavage, although this is still considered the treatment of choice. Most studies are case series, often with limited patient numbers, so the level of evidence is low. Since the severity of presentation and clinical course are variable, not all patients will require treatment. Due to the low level of evidence, some objective criteria based on expert opinion have been arbitrarily proposed in an attempt to define in which patients it is best to initiate treatment.

  15. Refractory Adult Primary Autoimmune Neutropenia that Responded to Alemtuzumab.

    PubMed

    Neerukonda, Anu R; Lan, Fengshuo; Gabig, Theodore; Saraya, Takeshi

    2016-01-01

    Primary autoimmune neutropenia (P-AIN) is an extremely rare disease. The most effective treatment for primary P-AIN is a granulocyte colony-stimulating factor; however, no curative treatment has been reported. We herein report a case of an adult P-AIN patient with a relatively mild medical history (irrespective of the severe neutropenia) who showed a sustained hematological response over seventeen months after the initiation of treatment with subcutaneous Alemtuzumab.

  16. 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

  17. 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.

  18. 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

  19. Cross-modal synaptic plasticity in adult primary sensory cortices.

    PubMed

    Lee, Hey-Kyoung; Whitt, Jessica L

    2015-12-01

    Sensory loss leads to widespread adaptation of brain circuits to allow an organism to navigate its environment with its remaining senses, which is broadly referred to as cross-modal plasticity. Such adaptation can be observed even in the primary sensory cortices, and falls into two distinct categories: recruitment of the deprived sensory cortex for processing the remaining senses, which we term 'cross-modal recruitment', and experience-dependent refinement of the spared sensory cortices referred to as 'compensatory plasticity.' Here we will review recent studies demonstrating that cortical adaptation to sensory loss involves LTP/LTD and homeostatic synaptic plasticity. Cross-modal synaptic plasticity is observed in adults, hence cross-modal sensory deprivation may be an effective way to promote plasticity in adult primary sensory cortices.

  20. Stereotactic Body Radiotherapy for Patients With Unresectable Primary Hepatocellular Carcinoma: Dose-Volumetric Parameters Predicting the Hepatic Complication

    SciTech Connect

    Son, Seok Hyun; Choi, Byung Ock; Ryu, Mi Ryeong; Kang, Young Nam; Jang, Ji Sun; Bae, Si Hyun; Yoon, Seung Kew; Choi, Ihl Bohng; Kang, Ki Mun; Jang, Hong Seok

    2010-11-15

    Purpose: To identify the parameters that predict hepatic toxicity and deterioration of hepatic function. Materials and Methods: A total of 47 patients with small unresectable primary hepatocellular carcinoma received hypofractionated stereotactic body radiotherapy (SBRT) using the CyberKnife. Of those, 36 patients received no other local treatments that could influence hepatic toxicity at least for 3 months after the completion of SBRT. The gross tumor volume (GTV) was 18.3 {+-} 15.9 cm{sup 3} (range, 3.0-81.3 cm{sup 3}), and the total dose administered was 30-39 Gy (median, 36 Gy). To assess the deterioration of hepatic function, we evaluated the presence or absence of the progression of Child-Pugh class (CP class). To identify the parameters of predicting the radiation-induced hepatic toxicity and deterioration of the hepatic function, several clinical and dose-volumetric parameters were evaluated. Results: Of 36 patients, 12 (33%) developed Grade 2 or higher hepatic toxicity and 4 (11%) developed progression of CP class. The multivariate analysis showed that the only significant parameter associated with the progression of CP class was the total liver volume receiving a dose less than 18 Gy (<18 Gy). Conclusions: The progression of CP class after SBRT limits other additional local treatments and also reflects the deterioration of hepatic function. Therefore, it would be important to note that the presence or absence of the progression of CP class is a dose-limiting factor. The total liver volume receiving <18 Gy should be greater than 800 cm{sup 3} to reduce the risk of the deterioration of hepatic function.

  1. Elevated Pretherapy Serum IL17 in Primary Hepatocellular Carcinoma Patients Correlate to Increased Risk of Early Recurrence after Curative Hepatectomy

    PubMed Central

    Li, Qian; Rong, Weiqi; Wang, Liming; Wang, Ying; Zang, Mengya; Wu, Zhiyuan; Zhang, Yawei; Qu, Chunfeng

    2012-01-01

    Background and Aims Primary hepatocellular carcinoma (HCC) is usually presented in inflamed fibrotic/cirrhotic liver with extensive lymphocyte infiltration. We examined the associations between the HCC early recurrence and alterations in serum levels of inflammatory cytokines. Methods A cohort of 105 HCC patients with chronic hepatitis B virus infection were included. Pre-therapy, we quantified their serum concentrations of Th1-, Th2-, Th17-, Treg-related, and other cytokines that have been reported to be associated with poor prognosis in human cancers. IL17-producing T-cells were generated in vitro from HCC patients and co-cultured with HCC cell lines separated by a 0.4 µM transwell. Results All the 105 cases of HCC patients had liver cirrhosis. The patients who suffered from HCC early recurrence had higher pre-therapy serum levels of IL17 and lower levels of IL10 than those who did not suffer from recurrence after curative hepatectomy. After adjustment for general tumor clinicopathological factors, elevated serum levels of IL17 (≥0.9 pg/ml) was found to be an independent risk factor for HCC early recurrence with a hazard ratio of 2.46 (95%CI 1.34–4.51). Patients with bigger tumors (>5 cm in diameter) and elevated serum levels of IL17 had the highest risk of early recurrence as compared to those with only one of these factors (P = 0.009) or without any (P<0.001). These factors showed similar effects on the HCC patient overall survival. Intrahepatic infiltrated T-cells in HCC patients were identified as the major IL17-producing cells. Proliferation of HCC cells, QGY-7703, was augmented QGY-7703, was augmented in the presence of IL17-producing T-cells. This effect diminished after neutralizing antibody against human IL17A or TNFα was included. Conclusion Both tumors and IL17 from liver infiltrated T-cells contributed to HCC early recurrence and progression after curative resection. Pre-therapy serum IL17 levels may serve as an additional indicator for

  2. Primary Colonic Eosinophilia and Eosinophilic Colitis in Adults.

    PubMed

    Turner, Kevin O; Sinkre, Richa A; Neumann, William L; Genta, Robert M

    2017-02-01

    The normal content of eosinophils in the adult colon and the criteria for the histopathologic diagnosis of eosinophilic colitis remain undefined. This study aimed at: (1) establishing the numbers of eosinophils in the normal adult colon; and (2) proposing a clinicopathologic framework for the diagnosis of primary colonic eosinophilia and eosinophilic colitis. To accomplish these goals, we counted the eosinophils in the right, transverse, and left colon of 159 adults with normal colonic histology. Using a database of 1.2 million patients with colonic biopsies, we extracted all adults with a diagnosis of colonic eosinophilia. We reviewed the slides from all cases and captured demographic, clinical, and pathologic data, including information about eosinophilia in other organs. We then compared the clinical manifestations of the study patients (those with no identifiable cause of eosinophilia) to those of patients with other types of colitis. The normal eosinophil counts (per mm) were 55.7±23.4 in the right, 41.0±18.6 in the transverse, and 28.6±17.2 in the left colon. Of the 194 study patients (eosinophil counts 166-5050/mm), 63 were asymptomatic and had a normal colonoscopy. Diarrhea and abdominal pain were the commonest indications for colonoscopy (38% and 27%, respectively) among the 131 patients who had symptoms, endoscopic abnormalities, or both. Neither clinical manifestations nor endoscopic appearance were sufficiently characteristic to elicit the suspicion of colonic eosinophilia. In conclusion, primary colonic eosinophilia was extremely rare in this series (<1 in 6000 patients); one third of these patients were asymptomatic. Their clinical manifestations were not distinctive and could not have led clinicians to suspect this condition; one third of the patients were asymptomatic. We suggest that regularly reporting high colonic eosinophilia may result in increased opportunities for clinicopathologic studies that might lead to a better definition of this

  3. Laparoscopic Nephroureterectomy for Adult Patient with Primary Obstructive Megaureter

    PubMed Central

    Makiyama, Kazuhide; Ohtake, Shinji; Yamanaka, Hiroyuki; Sano, Futoshi; Nakaigawa, Noboru; Kubota, Yoshinobu

    2013-01-01

    A 29-year-old female with a complaint of abdominal distension was referred to our hospital. She had a history of being treated for pyelonephritis three times. By computed tomography and retrograde pyelography, she was diagnosed with adult left primary megaureter. Her left renal function was severely deteriorated. She hoped for surgical intervention before becoming pregnant. Laparoscopic nephroureterectomy for megaureters seems to be difficult due to the large size. By sucking urine from an inserted ureteral catheter and setting trocar positions, we successfully performed laparoscopic nephroureterectomy for megaureter. PMID:24455395

  4. A Genetic Variant in Primary miR-378 Is Associated with Risk and Prognosis of Hepatocellular Carcinoma in a Chinese Population

    PubMed Central

    An, Jiaze; Liu, Jibin; Liu, Li; Liu, Yao; Pan, Yun; Huang, Mingde; Qi, Fuzhen; Wen, Juan; Xie, Kaipeng; Ma, Hongxia; Shen, Hongbing; Hu, Zhibin

    2014-01-01

    Background MiR-378 has been reported to be related to cell survival, tumor growth and angiogenesis and may participate in hepatocellular carcinoma (HCC) development and prognosis. Genetic variants in primary miR-378 (pri-miR-378) may impact miR-378 expression and contribute to HCC risk and survival. This study aimed to assess the associations between a genetic variant in primary miR-378 and HCC susceptibility and prognosis. Methods We conducted a case-control study to analyze the association of rs1076064 in pri-miR-378 with hepatocellular carcinoma risk in 1300 HCC patients with positive hepatitis B virus (HBV) and 1344 HBV carriers. Then, we evaluated the correlation between the polymorphism and hepatocellular carcinoma prognosis in 331 HCC patients at either intermediate or advanced stage without surgical treatment. Results The variant genotypes of rs1076064 were associated with a decreased HCC risk in HBV carriers [Adjusted odds ratio (OR) = 0.90, 95% confidence intervals (CI) = 0.81–1.00, P = 0.047]. Moreover, HCC patients with the variant genotypes were associated with a better survival [Adjusted hazard ratio (HR) = 0.70, 95% CIs = 0.59–0.83, P<0.0001 in an additive genetic model]. The reporter gene assay showed that the variant G allele of rs1076064 exerted higher promoter activity than the A allele. Conclusions These findings indicate that rs1076064 may be a biomarker for HCC susceptibility and prognosis through altering pri-miR-378 transcription. PMID:24751683

  5. Hepatocellular carcinoma.

    PubMed

    Macdonald, G A

    1999-05-01

    Hepatitis C infection is associated with the development of hepatocellular carcinoma, and progress has been made in a number of areas. Transgenic mice lines expressing the hepatitis C core protein develop hepatic steatosis, adenomas, and hepatocellular carcinomas, with no significant hepatitis or fibrosis. This implies that hepatitis C can lead directly to malignant transformation. A new lesion, irregular regeneration, has been described in chronic hepatitis C infection and is associated with a 15-fold increase in the relative risk of developing hepatocellular carcinoma. A minority of patients with hepatitis C-related hepatocellular carcinoma have intense lymphocytic infiltration of the cancer, a feature associated with a better prognosis. Several studies have confirmed the association between large cell dysplasia and hepatocellular carcinoma. However, large cell dysplasia may not be a premalignant lesion and instead may be a marker for premalignant alterations elsewhere in the liver. Oral contraceptives previously have been linked to an increased risk of hepatocellular carcinoma. A large multicenter European case-control study has shown minimal increased risk of hepatocellular carcinoma with use of steroidal contraception. Tamoxifen had shown promise in the management of advanced hepatocellular carcinoma. However, a randomized placebo-controlled study of 477 patients with hepatocellular carcinoma found no benefit from tamoxifen. In a preliminary study, however, octreotide has shown improved survival and quality of life in patients with advanced hepatocellular carcinoma. Finally, interferon treatment continues to be linked to a reduced risk of hepatocellular carcinoma in patients with hepatitis C. These studies generally are not randomized, and a randomized prospective study is required to address this issue.

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

    ClinicalTrials.gov

    2017-03-08

    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

  7. The evaluation of saphenofemoral insufficiency in primary adult varicocele.

    PubMed

    Koyuncu, Hakan; Ergenoglu, Mehmet; Yencilek, Faruk; Gulcan, Nilay; Tasdelen, Neslihan; Yencilek, Esin; Sarica, Kemal

    2011-01-01

    The aim of this study was to evaluate the possible relationship between varicocele and saphenofemoral insufficiency in patients diagnosed with primary varicocele. A total of 70 patients with the primary diagnosis of varicocele were included into the study. A total of 30 age-matched healthy adults were also included in the study as a control group. Varicocele was diagnosed by palpation and observation of each spermatic cord in standing position before and during a valsalva maneuver. Additionally, scrotal Doppler and lower extremity venous Doppler ultrasonography were performed. Patients who were with spermatic varicose vein larger than 3.0 mm were included in the study group as a varicocele patient. At the lower extremity venous Doppler ultrasonography, a retrograde flow lasting longer than 0.5 seconds during normal breathing or at the valsalva maneuver was considered to be meaningful for saphenofemoral junction insufficiency. Thirty-six (51.35%) patients had insufficiency in saphenofemoral junction in the study group (6 [8.5%] bilateral, 30 [42.85%] unilateral) whereas 8 (26.6%) had insufficiency in the control group (2 [6.6%] bilateral, 6 [20%] unilateral insufficiency). The patients with primary varicocele had a statistically significant (P = .02) higher rate of venous insufficiency in their saphenofemoral junctions when compared with the control group. In the present study, the rate of saphenofemoral insufficiency has been found to be statistically higher in patients with primary varicocele compared with healthy men. Depending on the common presence of valvular insufficiency, we believe that the presence of varicocele should be investigated in the young population suffering from saphenofemoral junction insufficiency.

  8. Hepatocellular carcinoma

    SciTech Connect

    Nakashima, T.; Kojiro, M.

    1986-01-01

    With the remarkable recent diagnostic and therapeutic advances and the discovery of a possible pathogenetic role of hepatitis B virus, the study and treatment of hepatocellular carcinoma are entering a new era. Parallel developments in the pathological study of this malignancy are also to be expected. To coincide with this new era, this book presents the authors' accumulated pathomorphological knowledge of hepatocellular carcinoma. The detailed coverage is based on the examination findings of 439 cases of hepatocellular carcinoma autopsied at the authors' department in the last twenty years.

  9. Prevalence and predictors of change in adult-child primary caregivers.

    PubMed

    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 waves of the Health and Retirement Study (HRS) represent 1,068 parent-level care occasions and 3,616 child-level occasions. There is considerable 2-year stability in primary adult-child caregivers. Parents are more prone to experience a change in adult-child primary caregivers if they live by themselves and if they have more sons and daughters. As far as the adult children are concerned, daughters and children living closer to parents are more likely to remain primary caregivers. Results suggest that change in primary caregivers is more strongly associated with available alternatives and gender norms than burden and competing obligations.

  10. 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

  11. 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

  12. Priorities for young adults when accessing UK primary care: literature review.

    PubMed

    Davey, Antoinette; Carter, Mary; Campbell, John L

    2013-10-01

    This literature review focuses on what matters to young adults when they access primary care services in the United Kingdom. Patients' access to and experience of primary care services differs across age groups. Existing research has largely focused on the needs and experiences of children, adolescents, and adults. There is some evidence to suggest the views of young adults (aged 18-25 years) that may differ from the views of other age groups, and research has not previously reported specifically on the views of this group of the population. The literature was reviewed to identify the views and priorities of young UK adults regarding primary healthcare provision, and furthermore, to identify those related topics that would benefit from further research. Relevant academic publications and grey literature published from 2000 onwards was reviewed and synthesised. We identified and reported emerging themes that were of importance to young adults in respect of the UK primary care provision. A total of 19 papers met our inclusion criteria. Young adults access primary care services less frequently than other age groups; this may be because of their experience of primary care throughout childhood and adolescence. Five aspects of primary care provision emerged as being of importance to young adults--the accessibility and availability of services, the confidentiality of health-related information, issues relating to communication with healthcare professionals, continuity of care, and behaviours and attitudes expressed towards young adults by healthcare professionals. There is a lack of focus of current research on the expectations, needs, and primary healthcare experiences of young adults. Young adults may hold views that are distinct from other age groups. Further research is needed to better understand the needs of a young adult population as their needs may impact the future use of services.

  13. 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…

  14. Enhancing Primary Health Care Services for Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Melville, C. A.; Finlayson, J.; Cooper, S.-A.; Allan, L.; Robinson, N.; Burns, E.; Martin, G.; Morrison, J.

    2005-01-01

    Primary health care teams have an important part to play in addressing the health inequalities and high levels of unmet health needs experienced by people with intellectual disabilities (ID). Practice nurses have an expanding role within primary health care teams. However, no previous studies have measured their attitudes, knowledge, training…

  15. Application of hepatitis B core particles produced by human primary hepatocellular carcinoma (PLC/342) propagated in nude mice to the determination of anti-HBc by passive hemagglutination.

    PubMed

    Miyamoto, K; Itoh, Y; Tsuda, F; Matsui, T; Tanaka, T; Miyamoto, H; Naitoh, S; Imai, M; Usuda, S; Nakamura, T

    1986-05-22

    Human primary hepatocellular carcinoma (PLC/342), carried by nude mice, produces hepatitis B core particles as well as hepatitis B surface antigen particles. Core particles purified form PLC/342 tumors displayed epitopes of hepatitis B core antigen (HBcAg) but not epitopes of hepatitis B e antigen (HBeAg) on their surface, unlike core particles prepared from Dane particles, derived from plasma of asymptomatic carriers, that expressed epitopes of both HBcAg and HBeAg. Core particles obtained from PLC/342 tumors were applied to the determination of antibody to HBcAg (anti-HBc) by passive hemagglutination. The assay detected anti-HBc not only in individuals with persistent infection with hepatitis B virus and in those who had recovered from transient infection, but also in patients with acute type B hepatitis, indicating that it can detect anti-HBc of either IgG or IgM class. A liberal availability of core particles from tumors carried by nude mice, taken together with an easy applicability of the method, would make the passive hemagglutination for anti-HBc a valuable tool in clinical and epidemiological studies, especially in places where sophisticated methods are not feasible.

  16. Risk and prognosis of adult primary immune thrombocytopenia.

    PubMed

    Frederiksen, Henrik; Christiansen, Christian Fynbo; Nørgaard, Mette

    2012-04-01

    Adult immune thrombocytopenia was previously considered a benign disease affecting young people and with a low risk of severe bleeding. This view was challenged by studies published during the past decade, as the median age of adult immune thrombocytopenia patients has been found to be 55-60 years and the incidence increases with age. Recent studies reported that mortality and morbidity are increased compared with the general population. In this review, we describe patient-specific factors associated with the outcome of disease, the clinical course of immune thrombocytopenia including the potential adverse impact of some treatments and finally the overall prognosis.

  17. 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…

  18. 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

  19. 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

  20. Primary afferent synapses on developing and adult Renshaw cells.

    PubMed

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

    2006-12-20

    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.

  1. Improving nutritional support for adults in primary and secondary care.

    PubMed

    Cartwright, Andrea

    There has been serious concern about the nutritional care provided in some secondary and primary care settings. As a result, best practice, benchmarking initiatives and nutritional guidance have been issued by government and non-government agencies. This article helps nurses to synthesise these initiatives and improve their knowledge of nutritional care.

  2. Primary primitive neuroectodermal tumour of the kidney in adults.

    PubMed

    Verma, Ritu; Singhal, Mitali; Pandey, Rakesh

    2013-03-04

    Primitive neuroectodermal tumour (PNET) is a neural crest tumour derived from neuroectoderm. Renal PNET is a very rare tumour occurring during childhood or adolescence. We report two cases of PNET involving kidney in adults. Presenting signs and symptoms include abdominal/flank pain and/or haematuria. Microscopy reveals the tumour consisted of small round cells with round nuclei and scant cytoplasm. Diagnosis was confirmed by immunohistochemistry with diffuse membranous positivity of tumour cells with CD99. As these tumours have an aggressive clinical course with rapid death in many reported cases, it is important to differentiate them from other small round-cell tumours.

  3. Environmental factors associated with primary care access among urban older adults.

    PubMed

    Ryvicker, Miriam; Gallo, William T; Fahs, Marianne C

    2012-09-01

    Disparities in primary care access and quality impede optimal chronic illness prevention and management for older adults. Although research has shown associations between neighborhood attributes and health, little is known about how these factors - in particular, the primary care infrastructure - inform older adults' primary care use. Using geographic data on primary care physician supply and surveys from 1260 senior center attendees in New York City, we examined factors that facilitate and hinder primary care use for individuals living in service areas with different supply levels. Supply quartiles varied in primary care use (visit within the past 12 months), racial and socio-economic composition, and perceived neighborhood safety and social cohesion. Primary care use did not differ significantly after controlling for compositional factors. Individuals who used a community clinic or hospital outpatient department for most of their care were less likely to have had a primary care visit than those who used a private doctor's office. Stratified multivariate models showed that within the lowest-supply quartile, public transit users had a higher odds of primary care use than non-transit users. Moreover, a higher score on the perceived neighborhood social cohesion scale was associated with a higher odds of primary care use. Within the second-lowest quartile, nonwhites had a lower odds of primary care use compared to whites. Different patterns of disadvantage in primary care access exist that may be associated with - but not fully explained by - local primary care supply. In lower-supply areas, racial disparities and inadequate primary care infrastructure hinder access to care. However, accessibility and elder-friendliness of public transit, as well as efforts to improve social cohesion and support, may facilitate primary care access for individuals living in low-supply areas.

  4. Highly efficient transduction of primary adult CNS and PNS neurons

    PubMed Central

    Levin, Evgeny; Diekmann, Heike; Fischer, Dietmar

    2016-01-01

    Delivery and expression of recombinant genes, a key methodology for many applications in biological research, remains a challenge especially for mature neurons. Here, we report easy, highly efficient and well tolerated transduction of adult peripheral and central neuronal populations of diverse species in culture using VSV-G pseudo-typed, recombinant baculovirus (BacMam). Transduction rates of up to 80% were reliably achieved at high multiplicity of infection without apparent neuro-cytopathic effects. Neurons could be transduced either shortly after plating or after several days in culture. Co-incubation with two different baculoviruses attained near complete co-localization of fluorescent protein expression, indicating multigene delivery. Finally, evidence for functional protein expression is provided by means of cre-mediated genetic recombination and neurite outgrowth assays. Recombinant protein was already detected within hours after transduction, thereby enabling functional readouts even in relatively short-lived neuronal cultures. Altogether, these results substantiate the usefulness of baculovirus-mediated transduction of mature neurons for future research in neuroscience. PMID:27958330

  5. Transformation of adult rat cardiac myocytes in primary culture.

    PubMed

    Banyasz, Tamas; Lozinskiy, Ilya; Payne, Charles E; Edelmann, Stephanie; Norton, Byron; Chen, Biyi; Chen-Izu, Ye; Izu, Leighton T; Balke, C William

    2008-03-01

    We characterized the morphological, electrical and mechanical alterations of cardiomyocytes in long-term cell culture. Morphometric parameters, sarcomere length, T-tubule density, cell capacitance, L-type calcium current (I(Ca,L)), inward rectifier potassium current (I(K1)), cytosolic calcium transients, action potential and contractile parameters of adult rat ventricular myocytes were determined on each day of 5 days in culture. We also analysed the health of the myocytes using an apoptotic/necrotic viability assay. The data show that myocytes undergo profound morphological and functional changes during culture. We observed a progressive reduction in the cell area (from 2502 +/- 70 microm(2) on day 0 to 1432 +/- 50 microm(2) on day 5), T-tubule density, systolic shortening (from 0.11 +/- 0.02 to 0.05 +/- 0.01 microm) and amplitude of calcium transients (from 1.54 +/- 0.19 to 0.67 +/- 0.19) over 5 days of culture. The negative force-frequency relationship, characteristic of rat myocardium, was maintained during the first 2 days but diminished thereafter. Cell capacitance (from 156 +/- 8 to 105 +/- 11 pF) and membrane currents were also reduced (I(Ca,L), from 3.98 +/- 0.39 to 2.12 +/- 0.37 pA pF; and I(K1), from 34.34p +/- 2.31 to 18.00 +/- 5.97 pA pF(-1)). We observed progressive depolarization of the resting membrane potential during culture (from 77.3 +/- 2.5 to 34.2 +/- 5.9 mV) and, consequently, action potential morphology was profoundly altered as well. The results of the viability assays indicate that these alterations could not be attributed to either apoptosis or necrosis but are rather an adaptation to the culture conditions over time.

  6. Primary cutaneous smoldering adult T-cell leukemia/ lymphoma.

    PubMed

    Gittler, Julia; Martires, Kathryn; Terushkin, Vitaly; Brinster, Nooshin; Ramsay, David

    2016-12-15

    HTLV-1 is a virus that is endemic in southwesternJapan and the Caribbean and has been implicatedin the development of ATLL. ATLL, which is anuncommon malignant condition of peripheralT-lymphocytes, is characterized by four clinicalsubtypes, which include acute, lymphomatous,chronic, and smoldering types, that are based onLDH levels, calcium levels, and extent of organinvolvement. We present a 52-year- old woman withpruritic patches with scale on the buttocks and withtender, hyperpigmented macules and papules oftwo-years duration. Histopathologic examinationwas suggestive of mycosis fungoides, laboratoryresults showed HTLV-I and II, and the patient wasdiagnosed with primary cutaneous ATLL. We reviewthe literature on HTLV-1 and ATLL and specifically theprognosis of cutaneous ATLL. The literature suggeststhat a diagnosis of ATLL should be considered amongpatients of Caribbean origin or other endemicareas with skin lesions that suggest a cutaneousT-cell lymphoma, with clinicopathologic features ofmycosis fungoides. Differentiation between ATLLand cutaneous T-cell lymphoma is imperative as theyhave different prognoses and treatment approaches.

  7. A Comparison of Intralesional Triamcinolone Acetonide Injection for Primary Chalazion in Children and Adults

    PubMed Central

    Lee, Jacky W. Y.; Yau, Gordon S. K.; Wong, Michelle Y. Y.; Yuen, Can Y. F.

    2014-01-01

    Purpose. To investigate outcome differences of intralesional triamcinolone acetonide (TA) injection for primary chalazia in children versus adults. Methods. A retrospective review of consecutive subjects with primary chalazion who received intralesional TA injection was conducted. A single investigator injected 0.05–0.15 mL of TA (40 mg/mL) intralesionally. Patients were stratified into the pediatric (<18 years old) and adult (≥18 years old) group. In both groups, the correlation of resolution time with chalazion size and TA dose was performed. Results. 17 children and 24 adults were enrolled, with a mean age of 7.4 ± 5.5 and 39.3 ± 16.7 years, respectively. Both groups had statistically similar baseline characteristics. There was no significant difference between the resolution time in the pediatric (18.2 ± 11.4 days) and adult (16.5 ± 11.0 days) group (P = 0.7). There were no significant complications from the TA injection. There was no significant correlation of resolution time to chalazion size (P = 0.7) nor TA dose (P = 0.3) in both groups. Conclusion. TA for the treatment of primary chalazion was equally effective in children and adults, without any significant complications, and the rate of clinical response did not appear to be dose-dependent. PMID:25386597

  8. 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.

  9. 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;…

  10. 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…

  11. 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…

  12. 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…

  13. 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

  14. Liver (Hepatocellular) Cancer Prevention

    MedlinePlus

    ... Treatment Liver Cancer Prevention Liver Cancer Screening Research Liver (Hepatocellular) Cancer Prevention (PDQ®)–Patient Version What is ... to keep cancer from starting. General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer is a ...

  15. Liver (Hepatocellular) Cancer Screening

    MedlinePlus

    ... Treatment Liver Cancer Prevention Liver Cancer Screening Research Liver (Hepatocellular) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer is a ...

  16. Urolithiasis in an Adult with Primary Obstructive Megaureter: A Case Report

    PubMed Central

    Al-Marhoon, Mohammed S.; Venkiteswaran, Khrishna P.; Shareef, Omar W.

    2013-01-01

    This is a rare case of adult primary obstructive megaureter complicated by combined uric acid-oxalate lithiasis of the ureter and renal stones. A 24-year-old male patient presented with frank hematuria on exercise of 4 years duration. The patient had an open surgery in the form of excision of stenotic segment of ureter and left ureteric re-implantation with removal of ureteric and renal stones. Congenital megaureter is a diagnosis that urologists and radiologists need to consider in the setting of isolated distal ureteral dilation, as the diagnosis of adult megaureter may require more involved surgical measures to prevent recurrence of adverse symptoms. PMID:24044065

  17. Hepatocellular carcinoma.

    PubMed

    Tang, Z Y

    2000-10-01

    Hepatocellular carcinoma (HCC) has ranked second in cancer mortality in China since the 1990s and is increasing in frequency among males in many countries. Hepatitis B and C viruses, aflatoxin and algal toxin in the contaminated drinking water remain major aetiological factors and hepatitis G virus and transfusion-transmitted virus can not be excluded. A prospective randomized control trial screening for HCC in a high-risk population using alpha fetoprotein (AFP) and ultrasonography has demonstrated a decrease in HCC mortality. Rapidly progressing medical imaging has continuously contributed to the improving treatment results. Surgical resection still plays a major role in influencing prognosis of HCC. Studies on recurrence and metastasis after curative resection have become a key issue for further improvement of the surgical outcome. Regional cancer therapies are progressing rapidly, based on the advances in early diagnosis. The advantages and disadvantages of these are noted. Multimodality combination and sequential treatment has been accepted as an important approach for unresectable HCC and cytoreduction and sequential resection have attracted attention. Conformal radiotherapy has shown important potential for HCC treatment. Intra-arterial chemotherapy has been repeatedly proved effective; however, systemic chemotherapy for HCC remains disappointing. The effects of tamoxifen are questionable, whereas alpha-interferon has been shown to have significant potential, particularly in prevention of recurrence. All of these treatments have resulted in continuing improvement of HCC prognosis in some centres.

  18. [Autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in adults: report of three cases].

    PubMed

    Santos, Oscar Mauricio; Muñoz Ortiz, Edison; Pérez, Camilo; Restrepo, Juan Carlos

    2012-04-01

    Overlap syndromes are cases of liver diseases that share clinical, serological, histological and radiological criteria of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). No definitions have been fully established and therefore there is no solid evidence on the diagnosis and treatment. This article presents the cases of three adult patients with overlapping features of AIH and PSC. Orthotopic liver transplantation was considered the best therapeutic alternative due to advanced disease progression in one patient, while medical treatment was provided in the remaining two patients.

  19. A Rare Case of Primary Anterior Mediastinal Yolk Sac Tumor in an Elderly Adult Male

    PubMed Central

    Nakhla, Sammy G.; Sundararajan, Srinath

    2016-01-01

    Mediastinal germ cell tumors are extragonadal germ cell tumors (EGGCTs) commonly seen in children and young adults. They are more common in men. Clinically they are classified as teratomas, seminomas, and nonseminomatous germ cell tumors. Primary mediastinal yolk sac neoplasm is an extremely rare tumor. We present here a very rare case of primary yolk sac tumor of the anterior mediastinum in a 73-year-old male. Mediastinal germ cell tumors have a worse prognosis than gonadal germ cell tumors. Chemotherapy followed by adjuvant surgery improves overall response in EGGCTs. However, comorbidities can render treatment with chemotherapy and surgery challenging in elderly patients. PMID:27144043

  20. 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

  1. 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.

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

    PubMed Central

    Wirtz, M K; Samples, J R; Kramer, P L; Rust, K; Topinka, J R; Yount, J; Koler, R D; Acott, T S

    1997-01-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-onset 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. PMID:9012402

  3. [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.

  4. Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis--an entity different from adults.

    PubMed

    DeLario, Melissa R; Sheehan, Andrea M; Ataya, Ramona; Bertuch, Alison A; Vega, Carlos; Webb, C Renee; Lopez-Terrada, Dolores; Venkateswaran, Lakshmi

    2012-05-01

    Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients.

  5. 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.

  6. 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.

  7. 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

  8. Adult depression screening in Saudi primary care: prevalence, instrument and cost

    PubMed Central

    2014-01-01

    Background By the year 2020 depression would be the second major cause of disability adjusted life years lost, as reported by the World Health Organization. Depression is a mental illness which causes persistent low mood, a sense of despair, and has multiple risk factors. Its prevalence in primary care varies between 15.3-22%, with global prevalence up to 13% and between 17-46% in Saudi Arabia. Despite several studies that have shown benefit of early diagnosis and cost-savings of up to 80%, physicians in primary care setting continue to miss out on 30-50% of depressed patients in their practices. Methods A cross sectional study was conducted at three large primary care centers in Riyadh, Saudi Arabia aiming at estimating point prevalence of depression and screening cost among primary care adult patients, and comparing Patient Health Questionnaires PHQ-2 with PHQ-9. Adult individuals were screened using Arabic version of PHQ-2 and PHQ-9. PHQ-2 scores were correlated with PHQ-9 scores using linear regression. A limited cost-analysis and cost saving estimates of depression screening was done using the Human Capital approach. Results Patients included in the survey analysis were 477, of whom 66.2% were females, 77.4% were married, and nearly 20% were illiterate. Patients exhibiting depressive symptoms on the basis of PHQ9 were 49.9%, of which 31% were mild, 13.4% moderate, 4.4% moderate-severe and 1.0% severe cases. Depression scores were significantly associated with female gender (p-value 0.049), and higher educational level (p-value 0.002). Regression analysis showed that PHQ-2 & PHQ-9 were strongly correlated R = 0.79, and R2 = 0.62. The cost-analysis showed savings of up to 500 SAR ($133) per adult patient screened once a year. Conclusion The point prevalence of screened depression is high in primary care visitors in Saudi Arabia. Gender and higher level of education were found to be significantly associated with screened depression. Majority of cases were mild to

  9. 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.

  10. Adult onset primary focal dystonia of the foot: an orthopaedic intervention.

    PubMed

    Logan, Loretta; Resseque, Barbara; Dontamsetti, Monica Sakshi

    2016-03-30

    A 54-year-old woman presented to a foot centre with a chief symptom of cramping in her toes, which, she believed, was of a secondary cause originating from a bunion. She was treated conservatively; however, she returned a month later as the symptoms had progressed to painful cramping of toes, toe-curling and instability while walking, due to involuntary movement of her toes. It was believed that the patient presented with a rare case of primary adult onset focal foot dystonia. This case report explains dystonia further in detail and delves into the different treatment and management options available today, including the unique orthopaedic intervention provided for this patient.

  11. 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.

  12. Splenomegaly as a Primary Manifestation of Gaucher Disease in a Young Adult Woman

    PubMed Central

    Merra, Giuseppe; Lago, Antonio Dal; Ricci, Roberta; Antuzzi, Daniela; Gasbarrini, Giovanni; Gasbarrini, Antonio; Ghirlanda, Giovanni

    2008-01-01

    Gaucher disease is the most common lysosomal storage disease. It is caused by the defective activity of acid β-glucosidase, which results in the accumulation of lipid glucocerebroside in macrophages throughout the body. In this case report we describe the case of a young adult woman with splenomegaly as the primary manifestation of this pathology. This is a case of type 1 Gaucher disease because there is a lack of primary neurological involvement but we have, instead, an age-independent involvement of the visceral organs. It is very important to classify or characterize these patients in a precise manner and to make a complete diagnosis with the help of the many diagnostic resources now at our disposal, especially with genetics, radiology and new techniques of advanced microscopy, also because Gaucher disease requires a long and complex management from early life to adulthood. PMID:21897802

  13. 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

  14. Raising awareness of bronchiectasis in primary care: overview of diagnosis and management strategies in adults.

    PubMed

    Chalmers, James D; Sethi, Sanjay

    2017-12-01

    Bronchiectasis is a chronic lung disease characterised by recurrent infection, inflammation, persistent cough and sputum production. The disease is increasing in prevalence, requiring a greater awareness of the disease across primary and secondary care. Mild and moderate cases of bronchiectasis in adults can often be managed by primary care clinicians. Initial assessments and long-term treatment plans that include both pharmacological and non-pharmacological treatments, however, should be undertaken in collaboration with a secondary care team that includes physiotherapists and specialists in respiratory medicine. Bronchiectasis is often identified in patients with other lung diseases, such as chronic obstructive pulmonary disease, asthma, and in a lesser but not insignificant number of patients with other inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. Overall goals of therapy are to prevent exacerbations, improve symptoms, improve quality of life and preserve lung function. Prompt treatment of exacerbations with antibiotic therapy is important to limit the impact of exacerbations on quality of life and lung function decline. Patient education and cooperation with health-care providers to implement treatment plans are key to successful disease management. It is important for the primary care provider to work with secondary care providers to develop an individualised treatment plan to optimise care with the goal to delay disease progression. Here, we review the diagnosis and treatment of bronchiectasis with a focus on practical considerations that will be useful to primary care.

  15. 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.

  16. 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.…

  17. 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.…

  18. Primary afferent plasticity following deafferentation of the trigeminal brainstem nuclei in the adult rat.

    PubMed

    De Riu, Pier Luigi; Russo, Antonella; Pellitteri, Rosalia; Stanzani, Stefania; Tringali, Giovanni; Roccazzello, Anna Maria; De Riu, Giacomo; Marongiu, Patrizia; Mameli, Ombretta

    2008-09-01

    Alpha-tyrosinated tubulin is a cytoskeletal protein that is involved in axonal growth and is considered a marker of neuronal plasticity in adult mammals. In adult rats, unilateral ablation of the left facial sensorimotor cortical areas induces degeneration of corticotrigeminal projections and marked denervation of the contralateral sensory trigeminal nuclei. Western blotting and real-time-PCR of homogenates of the contralateral trigeminal ganglion (TG) revealed consistent overexpression of growth proteins 15 days after left decortication in comparison with the ipsilateral side. Immunohistochemical analyses indicated marked overexpression of alpha-tyrosinated tubulin in the cells of the ganglion on the right side. Cytoskeletal changes were primarily observed in the small ganglionic neurons. Application of HRP-CT, WGA-HRP, and HRP to infraorbital nerves on both sides 15 days after left decortication showed a significant degree of terminal sprouting and neosynaptogenesis from right primary afferents at the level of the right caudalis and interpolaris trigeminal subnuclei. These observations suggest that the adaptive response of TG neurons to central deafferentation, leading to overcrowding and rearrangement of the trigeminal primary afferent terminals on V spinal subnuclei neurons, could represent the anatomical basis for distortion of facial modalities, perceived as allodynia and hyperalgesia, despite nerve integrity.

  19. Isolation and cultivation of adult primary bovine hepatocytes from abattoir derived liver

    PubMed Central

    Ehrhardt, Sonja; Schmicke, Marion

    2016-01-01

    The aim was to establish a cell culture of adult primary bovine hepatocytes obtained from liver following slaughter and to cultivate the cells in a sandwich culture. Cells and medium samples were taken after separation of cells (day 0), during monolayer (days 1, 2 and 3) and during sandwich culture (days 1, 2, 3, 4, 7, 10 and 14). The mRNA expression of BAX, BCL2L, FAS, IGF-1 and GHR1A was measured as well as urea and LDH. Hepatocytes were obtained by using a two-step collagenase perfusion and were purified thereafter by density gradient centrifugation. The viability was 68.2 ± 9.5 %. In sandwich culture, cells have a typical polygonal hepatocyte-like shape, build cell-cell contacts, and show irregularity of cell borders suggesting bile canaliculi generation. The BAX mRNA expression increased on day 1 as well but decreased steadily until day 3 and remained constant for 14 days. Urea- and LDH-concentrations increased from day 4 to day 7. In conclusion, we found that it is possible to gather viable primary hepatocytes from adult bovine liver after slaughter, and that cells gathered this way show typical morphologies, urea-production and low LDH-leakage especially at day 4 in a sandwich system. PMID:28275320

  20. 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.

  1. 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

  2. Yttrium-90 Radioembolization for Hepatocellular Carcinoma.

    PubMed

    Hickey, Ryan M; Lewandowski, Robert J; Salem, Riad

    2016-03-01

    (90)Y radioembolization refers to the selective, transcatheter, and intra-arterial injection of micrometer-sized particles loaded with the radioisotope yttrium-90 for the treatment of primary and metastatic hepatic malignancies. In the treatment of intermediate- and advanced-stage hepatocellular carcinoma, (90)Y radioembolization provides favorable outcomes with minimal side effects, offering an alternative treatment option to other transarterial therapies, such as bland embolization and chemoembolization. This review provides an overview of the use of (90)Y radioembolization in the treatment of hepatocellular carcinoma, including patient selection criteria, dosimetry, and clinical outcomes.

  3. Frequent somatic TERT promoter mutations and CTNNB1 mutations in hepatocellular carcinoma

    PubMed Central

    Lee, Seung Eun; Chang, Seong-Hwan; Kim, Wook Youn; Lim, So Dug; Kim, Wan Seop; Hwang, Tea Sook; Han, Hye Seung

    2016-01-01

    Genetic alterations of TERT and CTNNB1 have been documented in hepatocellular carcinoma. TERT promoter mutations are the earliest genetic events in the multistep process of hepatocarcinogenesis related to cirrhosis. However, analyses of TERT promoter and CTNNB1 mutations in hepatocellular carcinoma tumor samples have not been performed in the Korean population, where hepatitis B virus-related hepatocellular carcinoma is prevalent. In order to identify the role of TERT promoter and CTNNB1 mutations in the hepatocarcinogenesis and pathogenesis of recurrent hepatocellular carcinoma, we performed the sequence analyses in 140 hepatocellular nodules (including 107 hepatocellular carcinomas), and 8 pairs of matched primary and relapsed hepatocellular carcinomas. TERT promoter and CTNNB1 mutations were only observed in hepatocellular carcinomas but not in precursor lesions. Of 109 patients with hepatocellular carcinoma, 41 (39.0%) and 15 (14.6%) harbored TERT and CTNNB1 mutations, respectively. TERT promotermutations were significantly more frequent in hepatocellular carcinomas related to hepatitis C virus infection (5/6; 83.3%) compared to tumors of other etiologies (P = 0.001). In two cases, discordance in TERT promoter mutation status was observed between the primary and the corresponding recurrent hepatocellular carcinoma. The two patients with discordant cases had early relapses. In conclusion, we identified TERT promoter and CTNNB1 mutations as the most frequent somatic genetic alterations observed in hepatocellular carcinoma, indicating its pivotal role in hepatocarcinogenesis. Furthermore, we suggest the possibility of intratumoral genetic heterogeneity of TERT promoter mutations in hepatocellular carcinoma as indicated by the discordance in TERT promoter mutations between primary and corresponding recurrent hepatocellular carcinoma. PMID:27661004

  4. Coping, quality of life, and hope in adults with primary antibody deficiencies

    PubMed Central

    Sigstad, Hanne Marie Høybråten; Stray-Pedersen, Asbjørg; Frøland, Stig S

    2005-01-01

    Background Living with a chronic disease, such as primary antibody deficiency, will often have consequences for quality of life. Previous quality-of-life studies in primary antibody deficiency patients have been limited to different treatment methods. We wanted to study how adults with primary antibody deficiencies manage their conditions and to identify factors that are conducive to coping, good quality of life and hope. Methods Questionnaires were sent to all patients ≥20 years of age with primary antibody deficiencies who were served by Rikshospitalet University Hospital. The questionnaires consisted of several standardized scales: Ferrans and Powers Quality of Life Index (QLI), Short Form-36 (SF-36), Jalowiec Coping Scale (JCS), Nowotny Hope Scale (NHS), and one scale we devised with questions about resources and pressures in the past. Of a total of 91, 55 patients (aged 23–76 years) answered the questionnaires. The questionnaire study were supplemented with selected interviews of ten extreme cases, five with low and five with high quality of life scores. Results Among the 55 patients, low quality of life scores were related to unemployment, infections in more than four organs, more than two additional diseases, or more than two specific occurrences of stress in the last 2–3 months. Persons with selective IgA deficiency had significantly higher QLI scores than those with other antibody deficiencies. An optimistic coping style was most frequent used, and hope values were moderately high. Based on the interviews, the patients could be divided into three groups: 1) low QLI scores, low hope values, and reduced coping, 2) low QLI scores, moderate hope values, and good coping, and 3) high QLI scores, moderate to strong hope values, and good coping. Coping was related to the patients' sense of closeness and competence. Conclusion Low quality of life scores in adults with primary antibody deficiencies were linked to unemployment and disease-related strains

  5. Incidence of diabetes mellitus type 2 complications among Saudi adult patients at primary health care center

    PubMed Central

    Alsenany, Samira; Al Saif, Amer

    2015-01-01

    [Purpose] This study analyzed type 2 diabetes and its role in complications among adult Saudi patients. [Subjects] Patients attending four primary health care centers in Jeddah were enrolled. [Methods] A cross-sectional design study among Saudi patients attending Ministry of Health primary health care centers in Jeddah was selected for use by the Primary Health Care administration. Patients were interviewed with structured questionnaires to determine the presence of diabetes and risk factors using questions about the history of any disease. [Results] Diabetes mellitus was present in 234 subjects during the data collection period (March–June 2014). Mean patient age was 58 years; diabetes prevalence was 42% in males and 58% in females. The mean age for diabetes onset in males and females was 34 and 39 years, respectively. There was a higher incidence of obesity (75%) associated with a sedentary lifestyle (body mass index ≥25) in females (N= 96; 40%) compared with males (N= 87; 36%). In this study, >44% of individuals aged 55 or older had severe to uncontrolled diabetes with long-term complications. The age-adjusted incidence of hypertension and coronary heart disease was 38% and 24%, respectively, showing a clear incidence of diabetes associated with cardiovascular disease in Saudi Arabia. [Conclusion] This study found that a multifactorial approach to managing diabetes complication risks is needed. PMID:26180307

  6. Protein-engineered scaffolds for in vitro 3D culture of primary adult intestinal organoids.

    PubMed

    DiMarco, Rebecca L; Dewi, Ruby E; Bernal, Gabriela; Kuo, Calvin; Heilshorn, Sarah C

    2015-10-15

    Though in vitro culture of primary intestinal organoids has gained significant momentum in recent years, little has been done to investigate the impact of microenvironmental cues provided by the encapsulating matrix on the growth and development of these fragile cultures. In this work, the impact of various in vitro culture parameters on primary adult murine organoid formation and growth are analyzed with a focus on matrix properties and geometric culture configuration. The air-liquid interface culture configuration was found to result in enhanced organoid formation relative to a traditional submerged configuration. Additionally, through use of a recombinantly engineered extracellular matrix (eECM), the effects of biochemical and biomechanical cues were independently studied. Decreasing mechanical stiffness and increasing cell adhesivity were found to increase organoid yield. Tuning of eECM properties was used to obtain organoid formation efficiency values identical to those observed in naturally harvested collagen I matrices but within a stiffer construct with improved ease of physical manipulation. Increased ability to remodel the surrounding matrix through mechanical or enzymatic means was also shown to enhance organoid formation. As the engineering and tunability of recombinant matrices is essentially limitless, continued property optimization may result in further improved matrix performance and may help to identify additional microenvironmental cues that directly impact organoid formation, development, differentiation, and functional behavior. Continued culture of primary organoids in recombinant matrices could therefore prove to be largely advantageous in the field of intestinal tissue engineering for applications in regenerative medicine and in vitro tissue mimics.

  7. 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

  8. Impact of Patient Portal Secure Messages and Electronic Visits on Adult Primary Care Office Visits

    PubMed Central

    Crane, Sarah J.; Chaudhry, Rajeev; Ebbert, Jon O.; Ytterberg, Karen; Tulledge-Scheitel, Sidna M.; Stroebel, Robert J.

    2014-01-01

    Abstract Introduction: Secure messages and electronic visits (“e-visits”) through patient portals provide patients with alternatives to face-to-face appointments, telephone contact, letters, and e-mails. Limited information exists on how portal messaging impacts face-to-face visits in primary care. Materials and Methods: We conducted a retrospective cohort study of 2,357 primary care patients who used electronic messaging (both secure messages and e-visits) on a patient portal. Face-to-face appointment frequencies (visits/year) of each patient were calculated before and after the first message in a matched-pairs analysis. We analyzed visit frequencies with and without adjustments for a first message surge in visits, and we examined subgroups of high message utilizers and long-term users. Results: Primary care patients who sent at least one message (secure message or e-visit) had a mean of 2.43 (standard deviation [SD] 2.3) annual face-to-face visits before the first message and 2.47 (SD 2.8) after, a nonsignificant difference (p=0.45). After adjustment for a first message surge in visits, no significant visit frequency differences were observed (mean, 2.35 annual visits per patient both before and after first message; p=0.93). Subgroup analysis also showed no significant change in visit frequency for patients with higher message utilization or for those who had used the messaging feature longer. Conclusions: No significant change in face-to-face visit frequency was observed following implementation of portal messaging. Secure messaging and e-visits through a patient portal may not result in a change of adult primary care face-to-face visits. PMID:24350803

  9. In-hospital Mobility Variations across Primary Diagnoses among Older Adults

    PubMed Central

    Valiani, Vincenzo; Gao, Shiyao; Chen, Zhiguo; Swami, Sunil; Harle, Christopher A.; Lipori, Gigi; Sourdet, Sandrine; Wu, Samuel; Nayfield, Susan G.; Sabbá, Carlo; Pahor, Marco; Manini, Todd M.

    2016-01-01

    Objectives To examine the relationship between primary diagnoses and mobility impairment and recovery among hospitalized older adults. Design Prospective cohort study. Setting UF Health Shands Hospital, an 852-bed level I trauma center located in Gainesville, Florida. Participants 18,551 older adults (≥65 years) with 29,148 hospitalizations between 1/2009 and 4/2014. Measurements Incident and discharge mobility impairment and recovery were assessed using the Braden activity subscale score that was recorded by the nursing staff at every shift change–approximately three times per day. Primary diagnosis ICD-9 codes were used as predictors and re-categorized by using the Agency for Health Care Research and Quality Clinical Classification Software. Results Out of the 15,498 hospital records where the patient was initially observed to “walk frequently”, 3,186 (20.6%) developed incident mobility impairment (chair-fast or bedfast). Primary diagnoses with a surgical or invasive procedure were the most prevalent (77.2 %) among the hospital observations with incident mobility impairment; otherwise primary diagnoses without surgery were much more associated with discharge mobility impairment (59%). The highest incidence of mobility impairment occurred in patients with heart valve disorders and aortic and peripheral/visceral artery aneurysms (6.24 and 6.05 events per 30 person-days, respectively); septicemia showed the highest incidence rate for mobility limitation at discharge (0.94 events per 30 person-days). Mobility impairment was observed in 13,650 (46.8% of total) records at admission and 5,930 (43.44%) were observed to recover to a state of walking occasionally or frequently. Osteoarthritis and cancer of gastrointestinal organs/peritoneum had the highest incidence rate for mobility recovery (7.68 and 5.63 events per 30 person-days respectively). Conclusions Approximately 1 out of 5 patients who were mobile at admission became significantly impaired during

  10. Assessing the Quality of a Nonrandomized Pragmatic Trial for Primary Prevention of Falls among Older Adults

    PubMed Central

    Albert, Steven M.; Edelstein, Offer; King, Jennifer; Flatt, Jason; Lin, Chyongchiou J.; Boudreau, Robert; Newman, Anne B.

    2014-01-01

    Background Current approaches to falls prevention mostly rely on secondary and tertiary prevention and target individuals at high risk of falls. An alternative is primary prevention, in which all seniors are screened, referred as appropriate, and educated regarding falls risk. Little information is available on research designs that allow investigation of this approach in the setting of aging services delivery, where randomization may not be possible. Methods Healthy Steps for Older Adults, a statewide program of the Pennsylvania (PA) Department of Aging, involves a combination of education about falls and screening for balance problems, with referral to personal physicians and home safety assessments. We developed a nonrandomized statewide trial, Falls Free PA, to assess its effectiveness in reducing falls incidence over 12 months. We recruited 814 seniors who completed the program (503 first time participants, 311 people repeating the program) and 1020 who did not participate in the program, from the same sites. We assessed the quality of this nonrandomized design by examining recruitment, follow-up across study groups, and comparability at baseline. Results Of older adults approached in senior centers, 90.5% (n=2219) signed informed consent, and 1834 (82.4%) completed baseline assessments and were eligible for follow-up. Attrition in the three groups over 12 months was low and non-differential (<10% for withdrawal and <2% for other loss to follow-up). Median follow-up, which involved standardized monthly assessment of falls, was 10 months in all study groups. At baseline the groups did not differ in measures of health or falls risk factors. Conclusions Comparable status at baseline, recruitment from common sites, and similar experience with retention suggest that the nonrandomized design will be effective for assessment of this approach to primary prevention of falls. PMID:24488533

  11. Activity, Inhibition, and Induction of Cytochrome P450 2J2 in Adult Human Primary Cardiomyocytes

    PubMed Central

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

    2013-01-01

    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 Km value of 1.5 μM. The Vmax 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

  12. 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.

  13. 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

  14. 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

  15. Voluntary physical exercise promotes ocular dominance plasticity in adult mouse primary visual cortex.

    PubMed

    Kalogeraki, Evgenia; Greifzu, Franziska; Haack, Franziska; Löwel, Siegrid

    2014-11-12

    Ocular dominance (OD) plasticity in the mouse primary visual cortex (V1) declines during aging and is absent beyond postnatal day (P) 110 when mice are raised in standard cages (SCs; Lehmann and Löwel, 2008). In contrast, raising mice in an enriched environment (EE) preserved a juvenile-like OD plasticity into late adulthood (Greifzu et al., 2014). EE raising provides the mice with more social interactions, voluntary physical exercise, and cognitive stimulation compared with SC, raising the question whether all components are needed or whether one of them is already sufficient to prolong plasticity. To test whether voluntary physical exercise alone already prolongs the sensitive phase for OD plasticity, we raised mice from 7 d before birth to adulthood in slightly larger than normal SCs with or without a running wheel (RW). When the mice were older than P135, we visualized V1 activity before and after monocular deprivation (MD) using intrinsic signal optical imaging. Adult RW-raised mice continued to show an OD shift toward the open eye after 7 d of MD, while age-matched SC mice without a RW did not show OD plasticity. Notably, running just during the 7 d MD period restored OD plasticity in adult SC-raised mice. In addition, the OD shift of the RW mice was mediated by a decrease of deprived-eye responses in V1, a signature of "juvenile-like" plasticity. We conclude that voluntary physical exercise alone is sufficient to promote plasticity in adult mouse V1.

  16. Most Uninsured Adults Could Schedule Primary Care Appointments Before The ACA, But Average Price Was $160.

    PubMed

    Saloner, Brendan; Polsky, Daniel; Kenney, Genevieve M; Hempstead, Katherine; Rhodes, Karin V

    2015-05-01

    Provisions of the Affordable Care Act (ACA) allow millions more Americans to obtain health insurance. However, a sizable number of people remain uninsured because they live in states that have not expanded Medicaid coverage or because they feel that Marketplace coverage is not affordable. Using data from a ten-state telephone survey in which callers posed as patients, we examined prices for primary care visits offered by physician offices to new uninsured patients in 2012-13, prior to ACA insurance expansions. Patients were quoted a mean price of $160. Significantly lower prices for the uninsured were offered by family practice offices compared to general internists, in offices participating in Medicaid managed care plans, and in federally qualified health centers. Prices were also lower for offices in ZIP codes with higher poverty rates. Only 18 percent of uninsured callers were told that they could bring less than the full amount to the visit and arrange to pay the rest later. ACA insurance expansions could greatly decrease out-of-pocket spending for low-income adults seeking primary care. However, benefits of health reform are likely to be greater in states expanding Medicaid eligibility.

  17. [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.

  18. 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

  19. Adult T-cell leukemia/lymphoma: a case report of primary cutaneous tumoral type

    PubMed Central

    Lyra-da-Silva, Julia Ocampo; de Mello Gonzaga, Yung Bruno; de Melo Espíndola, Otávio; de Andrada-Serpa, Maria José; Dib, Cassio; Jeunon, Thiago

    2012-01-01

    Background: Adult T-cell leukemia/lymphoma (ATLL) is a distinctive peripheral T- lymphocytic malignancy associated with human T-cell lymphotropic virus type 1 (HTLV-1). It may closely resemble other skin lymphomas, particularly mycosis fungoides (MF). Case report: A 38-year-old woman presented some ellipsoid scaling patches lasting 18 months and developed a large tumoral lesion in the abdomen, which were previously diagnosed as MF. Although histopathologic and immunohistochemistry findings were in consonance with this diagnosis, the fast progression of the disease raised the suspicion that it could represent another type of T-cell lymphoma. The work-up revealed a positive anti-HTLV-1 serology and molecular studies confirmed the monoclonal integration of HTLV-1 provirus into neoplastic cells of the skin, but not into circulating lymphocytes. Extensive investigations were unable to demonstrate any systemic involvement. The final diagnosis was of primary cutaneous type of ATLL. The patient was submitted to a chemotherapy regimen with cyclophosphamide, doxorubicin, vincristine and prednisone, later to conjugated dexamethasone and surgical cytoreduction and then to a second line treatment with gemcitabine, resulting in partial response. A bone marrow heterologous transplantation was performed, but failed to achieve a sustained remission. Discussion: ATLL is a rare lymphoid malignancy in non-endemic HTLV-1 areas, the diagnosis of which could be missed if not highly suspected. In addition to the four subtypes of Shimoyama classification (acute, lymphomatous, chronic and smoldering), a fifth one denominated primary cutaneous and characterized by presence of lesions only in the skin had been proposed and is herein exemplified. PMID:23785591

  20. 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.

  1. 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

  2. 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

  3. Mental ability performance among adults with type 2 diabetes in primary care.

    PubMed

    Mount, David L; Lambert, Michael C

    2009-06-01

    Aim and method The present university-based outpatient clinic, cross-sectional study assessed cognitive performance in a sample of 137 adults, with the primary objective of determining differences in cognitive performance as a function of gender and hypertension status in a type 2 diabetes cohort.Results Approximately 64% of the sample was 65 years old and younger, and 50 subjects had > 13 years of education. Global mental ability scores were relatively similar by age grouping, and higher-ordered cognitive functioning and reading literacy were strongly correlated, r (98) = 0.62, P < 0.01. Approximately 30% of the sample posted global mental ability scores in the slow learner range on tasks measuring attention, immediate memory and verbal reasoning. Males achieved higher cognitive functioning scores compared to females on multiple mental ability tasks. The presence of hypertension was associated with significantly worse cognitive performance compared to those subjects without hypertension, t = 2.11, P = 0.03. Approximately 57% of the hypertension group was classified as mild cognitive impaired.Conclusion While approximately half of the general population can be expected to demonstrate an average range of performance on cognitive ability measures, such an expectation could be inappropriately generalised to persons diagnosed with type 2 diabetes, even among those who were high school educated.

  4. Mental ability performance among adults with type 2 diabetes in primary care

    PubMed Central

    2009-01-01

    Aim and method The present university-based outpatient clinic, cross-sectional study assessed cognitive performance in a sample of 137 adults, with the primary objective of determining differences in cognitive performance as a function of gender and hypertension status in a type 2 diabetes cohort. Results Approximately 64% of the sample was 65 years old and younger, and 50 subjects had > 13 years of education. Global mental ability scores were relatively similar by age grouping, and higher-ordered cognitive functioning and reading literacy were strongly correlated, r (98) = 0.62, P < 0.01. Approximately 30% of the sample posted global mental ability scores in the slow learner range on tasks measuring attention, immediate memory and verbal reasoning. Males achieved higher cognitive functioning scores compared to females on multiple mental ability tasks. The presence of hypertension was associated with significantly worse cognitive performance compared to those subjects without hypertension, t = 2.11, P = 0.03. Approximately 57% of the hypertension group was classified as mild cognitive impaired. Conclusion While approximately half of the general population can be expected to demonstrate an average range of performance on cognitive ability measures, such an expectation could be inappropriately generalised to persons diagnosed with type 2 diabetes, even among those who were high school educated. PMID:22477898

  5. 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

  6. 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.

  7. 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.

  8. [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.

  9. A Nation-Wide Epidemiological Study of Newly Diagnosed Primary Spine Tumor in the Adult Korean Population, 2009–2011

    PubMed Central

    Sohn, Seil; Kim, Jinhee; Chung, Chun Kee; Lee, Na Rae; Sohn, Moon Jun; Kim, Sung Hwan

    2017-01-01

    Objective This 2009–2011 nation-wide study of adult Koreans was aimed to provide characteristics, medical utilization states, and survival rates for newly diagnosed patients with primary nonmalignant and malignant spine tumors. Methods Data for patients with primary spine tumors were selected from the Korean Health Insurance Review and Assessment Service database. The data included their age, sex, health insurance type, co-morbidities, medical cost, and hospital stay duration. Hospital stay duration and medical costs per person occurring in one calendar year were used. In addition, survival rates of patients with primary malignant spine tumors were evaluated. Results The incidence rate of a primary spine tumor increased with age, and the year of diagnosis (p≤0.0001). Average annual medical costs ranged from 1627 USD (pelvis & sacrum & coccyx tumors) to 6601 USD (spinal cord tumor) for primary nonmalignant spine tumor and from 12137 USD (spinal meningomas) to 20825 USD (pelvis & sacrum & coccyx tumors) for a primary malignant spine tumor. Overall survival rates for those with a primary malignant spine tumor were 87.0%, 75.3%, and 70.6% at 3, 12, and 24 months, respectively. The Cox regression model results showed that male sex, medicare insurance were significantly positive factors affecting survival after a diagnosis of primary malignant spine tumor. Conclusion Our study provides a detailed view of the characteristics, medical utilization states, and survival rates of patients newly diagnosed with primary spine tumors in Korea. PMID:28264240

  10. Adults with ADHD: use and misuse of stimulant medication as reported by patients and their primary care physicians.

    PubMed

    Lensing, Michael B; Zeiner, Pål; Sandvik, Leiv; Opjordsmoen, Stein

    2013-12-01

    This study investigated the agreement on treatment for attention-deficit/hyperactivity disorder (ADHD) between adults with ADHD and the primary care physicians responsible for their treatment. Adults with ADHD and the primary care physicians responsible for their ADHD treatment completed a survey. The κ-statistic assessed physician-patient agreement on ADHD treatment variables. The eligible sample consisted of 274 patients with confirmed current or previous psychopharmacological treatment for ADHD and the physicians responsible for their treatment. We received 159 questionnaires (58.0 %) with sufficient information from both sources. There were no significant differences between participants and nonparticipants (N = 115) on ADHD sample characteristics. Participants' mean age was 37.6 years, and 75 (47.2 %) were females. There was high agreement for current pharmacological treatment for ADHD, current and last ADHD drug prescription, treatment for substance use, and misuse of stimulant medication. Agreement for nonpharmacological treatment for ADHD and treatment termination because of the side effects was low. A minority of participants from both sources reported misuse of stimulant medication. There was a moderate correlation between the physicians' clinical judgment and patients' self-report on current functioning. The study showed that primary care physicians and their patients agreed on the pharmacological but not the nonpharmacological, treatments given. They also agreed on patients' current functioning. Physicians and patients reported low levels of misuse of stimulant medication. The results show that pharmacological treatment for adults with ADHD can be safely undertaken by primary care physicians.

  11. Hepatocellular adenoma: An update.

    PubMed

    Vijay, Adarsh; Elaffandi, Ahmed; Khalaf, Hatem

    2015-11-08

    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.

  12. Fibrolamellar hepatocellular carcinoma mimicking ornithine transcarbamylase deficiency.

    PubMed

    Sulaiman, Raashda A; Geberhiwot, Tarekegn

    2014-01-01

    We report an unusual case of recurrent non-hepatic hyperammonaemic encephalopathy in an adult patient. She had a previous history of treated fibrolamellar hepatocellular carcinoma (FLC). This posed a diagnostic challenge, as she had normal liver function tests and normal looking liver on imaging but with extra hepatic metastases. This case highlights the importance of measuring plasma ammonia levels in all patients presenting with unexplained acute confusion. Clinical awareness of non-hepatic hyperammonaemic encephalopathy can contribute to early diagnosis and timely initiation of life-saving treatment. Delay in treatment results in irreversible brain damage, deep coma and death. Treatment of hyperammonaemia must begin prior to confirmation of aetiology, for a favourable outcome. This case also highlights the need for further research to understand the exact mechanism of hyperammonaemia in hepatocellular carcinoma.

  13. Identifying adults at risk of COPD who need confirmatory spirometry in primary care

    PubMed Central

    Hill, Kylie; Hodder, Richard; Blouin, Maria; Heels-Ansdell, Diane; Guyatt, Gordon; Goldstein, Roger

    2011-01-01

    Abstract Objective To examine the usefulness of a symptom-based case-finding questionnaire (CFQ) and the Medical Research Council (MRC) dyspnea scale in identifying which individuals with known risk factors for chronic obstructive pulmonary disease (COPD) require targeted spirometry in primary care. Design Cross-sectional study. Setting Three community primary care practices in Ontario. Participants Men and women 40 years of age and older with a smoking history of 20 pack-years or more. Main outcome measures We administered a CFQ for the presence of cough, sputum, wheeze, dyspnea, and recurrent respiratory infections (possible range of scores from 0 to 5) and applied the MRC dyspnea scale to assess the severity of COPD (possible range of scores from 1 to 5). Spirometric measures of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were collected, with COPD defined as a postbronchodilator FEV1/FVC of less than 0.7 and FEV1 of less than 80% of the predicted value. Using spirometric data to confirm the diagnosis of COPD, likelihood ratios, pretest and posttest probabilities, and area under a receiver operating characteristic curve were calculated for the total CFQ and MRC scores. Results Scores for the CFQ and MRC dyspnea scale were available for 996 and 829 participants, respectively. The likelihood ratios for a total CFQ score of 3 or higher and an MRC dyspnea score of 4 or 5 were 1.82 (95% confidence interval [CI] 1.48 to 2.22) and 4.22 (95% CI 2.08 to 8.56), respectively. The likelihood ratios for a total CFQ score of 2 or less and an MRC dyspnea score of 1 were 0.75 (95% CI 0.66 to 0.85) and 0.50 (95% CI 0.39 to 0.65), respectively. Area under the receiver operating characteristic curve was 0.62 (95% CI 0.58 to 0.67; P < .001) for the total CFQ scores and 0.64 (95% CI 0.60 to 068; P < .001) for the MRC dyspnea scores. Conclusion In adults with known risk factors, the likelihood of having moderate to severe COPD is increased in those who

  14. 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

  15. Exploring knowledge, attitudes, and practices toward older adults with hypertension in primary care

    PubMed Central

    Chotisiri, Luckwirun; Yamarat, Khemika; Taneepanichskul, Surasak

    2016-01-01

    Purpose High blood pressure increases the risk of cardiovascular and kidney diseases. The purpose of this study was to explore a baseline of hypertension knowledge, attitudes, and practices among older adults with hypertension at a sub-district Health Promoting Hospital in the Pathum Thani province of Thailand. Patients and methods A cross-sectional study was conducted at the outpatient clinic of the sub-district Health Promoting Hospital, one of the primary care sectors, between January and March 2015, and a total of 144 cases were recruited. All clinical parameters were collected and a structured questionnaire was used. Data were analyzed by means of descriptive statistics and chi-square tests. Results Most of the participants (74.3%) were females, and their mean age was 66.1 years. Two-thirds (66.7%) were married, unemployed/retired (67.4%), and had completed elementary education (79.2%). The screenings showed that their mean blood pressure was 136.4 (±14.4)/79.2 (±10.1) mmHg, the group’s mean body mass index was 24.9 kg/m2 (± 3.6 kg/m2), and their mean waist circumference was 88.6 cm (±7.1 cm) for males and 85.7 cm (±6.8 cm) for females. In addition, their mean score of hypertension knowledge was high, and most of the participants had a neutral attitude toward hypertension; their practices in terms of dietary and exercise habits for controlling blood pressure were low in nature. Conclusion This study indicated that increasing patients’ practices would be useful for promoting their healthy behaviors to achieve blood pressure control. PMID:27822057

  16. Primary mature cystıc teratoma mimickıng an adrenal mass in an adult male patient.

    PubMed

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

    2014-02-01

    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.

  17. Research in the Integration of Behavioral Health for Adolescents and Young Adults in Primary Care Settings: A Systematic Review.

    PubMed

    Richardson, Laura P; McCarty, Carolyn A; Radovic, Ana; Suleiman, Ahna Ballonoff

    2017-03-01

    Despite the recognition that behavioral and medical health conditions are frequently intertwined, the existing health care system divides management for these issues into separate settings. This separation results in increased barriers to receipt of care and contributes to problems of underdetection, inappropriate diagnosis, and lack of treatment engagement. Adolescents and young adults with mental health conditions have some of the lowest rates of treatment for their conditions of all age groups. Integration of behavioral health into primary care settings has the potential to address these barriers and improve outcomes for adolescents and young adults. In this paper, we review the current research literature for behavioral health integration in the adolescent and young adult population and make recommendations for needed research to move the field forward.

  18. Primary tumors of the liver.

    PubMed Central

    Anderson, B. B.; Ukah, F.; Tette, A.; Villaflor, S. G.; Koh, D.; Seton, P.

    1992-01-01

    Primary tumors of the liver that are of clinical significance are rare. Ninety-five percent of such lesions when encountered will be malignant and only 5% will be benign. Malignant primary hepatic lesions represent 2% to 3% of primary cancers encountered in the United States. Hepatocellular carcinoma constitutes 90% of malignant liver primaries in the adult. Seventy-five percent of cases are associated with cirrhosis of the liver and patients with hepatitis B infection have a 33- to 200-fold excess risk for this malignancy. Cholangiocarcinoma represents 5% to 10% of hepatic primary malignancies while hepatoblastoma is distinctly uncommon in adults. Treatment is primarily surgical, and resectability is limited by the presence of cirrhosis and spread of the tumor within and outside of the liver. Of the benign liver tumors, the liver cell adenoma seem to be associated with oral contraception and have a proclivity for intraperitoneal hemorrhage, especially during pregnancy. Focal nodular hyperplasia is a tumor-like condition that also may be associated with oral contraception. This article describes five cases, two of which had quite unique presentations. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:1602511

  19. 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

  20. 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…

  1. 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

  2. Anti-Neurotrophic Effects from Autoantibodies in Adult Diabetes Having Primary Open Angle Glaucoma or Dementia

    PubMed Central

    Zimering, Mark B.; Moritz, Thomas E.; Donnelly, Robert J.

    2013-01-01

    Aim: To test for anti-endothelial and anti-neurotrophic effects from autoantibodies in subsets of diabetes having open-angle glaucoma, dementia, or control subjects. Methods: Protein-A eluates from plasma of 20 diabetic subjects having glaucoma or suspects and 34 age-matched controls were tested for effects on neurite outgrowth in rat pheochromocytoma PC12 cells or endothelial cell survival. The mechanism of the diabetic glaucoma autoantibodies’ neurite-inhibitory effect was investigated in co-incubations with the selective Rho kinase inhibitor Y27632 or the sulfated proteoglycan synthesis inhibitor sodium chlorate. Stored protein-A eluates from certain diabetic glaucoma or dementia subjects which contained long-lasting, highly stable cell inhibitory substances were characterized using mass spectrometry and amino acid sequencing. Results: Diabetic primary open angle glaucoma (POAG) or suspects (n = 20) or diabetic dementia (n = 3) autoantibodies caused significantly greater mean inhibition of neurite outgrowth in PC12 cells (p < 0.0001) compared to autoantibodies in control diabetic (n = 24) or non-diabetic (n = 10) subjects without glaucoma (p < 0.01). Neurite inhibition by the diabetic glaucoma autoantibodies was completely abolished by 10 μM concentrations of Y27632 (n = 4). It was substantially reduced by 30 mM concentrations of sodium chlorate (n = 4). Peak, long-lasting activity survived storage ×5 years at 0–4°C and was associated with a restricted subtype of Ig kappa light chain. Diabetic glaucoma or dementia autoantibodies (n = 5) caused contraction and process retraction in quiescent cerebral cortical astrocytes effects which were blocked by 5 μM concentrations of Y27632. Conclusion: These data suggest that autoantibodies in subsets of adult diabetes having POAG (glaucoma suspects) and/or dementia inhibit neurite outgrowth and promote a reactive astrocyte morphology by a mechanism which may involve

  3. Molecular and immunocytochemical characterization of primary neuronal cultures from adult rat brain: Differential expression of neuronal and glial protein markers.

    PubMed

    Ray, Balmiki; Bailey, Jason A; Sarkar, Sumit; Lahiri, Debomoy K

    2009-11-15

    Neurobiological studies using primary neuronal cultures commonly employ fetal-derived neurons, but much less often adult brain-derived neurons. Our goal is to perform morphological and molecular characterization of primary neuronal cultures from adult rat brain, including the relative expression of neuronal and glial cell markers at different time points. We tested the hypothesis that long-term neuronal viability is compatible with glial proliferation in adult neuron culture. We examined neuron culture from adult rat brain, which was maintained at steady state up to 24 days, and characterized them on the basis of cellular, molecular and biochemical properties at different time points of the culture. We identified neuronal and glial cells by both immunocytochemical and western immunoblotting techniques using NSE and Tau as neuronal markers and GFAP as glial protein marker, which revealed the presence of predominantly neuronal cells in the initial phase of the culture and a rise in glial cells from day 12 onwards. Notably, neuronal cells were preserved in the culture along with the glial cells even at day 24. Transfection of the cultured cells with a GFP expression vector and plasmids containing a luciferase reporter gene under the control of two different gene promoters demonstrated DNA transfectability. Taken together, these results suggest a differential expression of neuronal and glial cells at different time points and long-term neuronal viability in the presence of glial proliferation. Such adult neurons serve as a suitable system for the application of neurodegeneration models and for drug target discovery in various brain disorders including Alzheimer's disease.

  4. Comorbidity and its impact in adult patients with attention-deficit/hyperactivity disorder: a primary care perspective.

    PubMed

    Babcock, Thomas; Ornstein, Craig S

    2009-05-01

    The objective of this manuscript was to review the literature relevant to the primary care practitioner concerning comorbidity and its impact on diagnosis and treatment efficacy in adults with attention-deficit/hyperactivity disorder (ADHD). A MEDLINE literature review was performed using the keywords: attention-deficit/hyperactivity disorder; psychiatric comorbidity; bipolar disorder; major depressive disorder; oppositional defiant disorder; conduct disorder; and substance use disorder. The authors assessed and summarized literature identified as relevant to primary care practitioners. Results demonstrated high rates of psychiatric comorbidity in patients with ADHD. These comorbid disorders, coupled with the differing characteristics of ADHD symptoms in adults versus children, may complicate accurate diagnosis and treatment of ADHD. Controlled clinical trials indicate that the presence of comorbidity does not substantially alter the safety and efficacy of ADHD pharmacotherapy and that treatment of ADHD can sometimes improve symptoms of the comorbid disorder. Although rates of psychiatric comorbidity are high in adults with ADHD, available data suggest that the benefits of pharmacotherapy for ADHD are not compromised by the presence of psychiatric comorbidity.

  5. Sleep paralysis and trauma, psychiatric symptoms and disorders in an adult African American population attending primary medical care.

    PubMed

    Mellman, Thomas A; Aigbogun, Notalelomwan; Graves, Ruth Elaine; Lawson, William B; Alim, Tanya N

    2008-01-01

    The occurrence of sleep paralysis (SP) absent narcolepsy appears to not be uncommon in African Americans and probably other non-European groups. Prior research has linked SP to trauma and psychiatric disorders and suggested a specific relationship to panic disorder in African Americans. The objective of our study was to evaluate relationships of SP with trauma, concurrent psychiatric symptoms and lifetime psychiatric diagnoses in an adult African American population recruited from primary care. Cross sectional study with surveys and diagnostic interviews; Patients attending primary care clinics filled out a survey that determined the 6 month prevalence and associated features of SP, a panic disorder screen, the self-rated Hamilton Depression Scale, and an inventory of trauma exposure. A subset of trauma-exposed participants (N = 142) received comprehensive diagnostic interviews that incorporated the Structured Clinical Interview for DSM-IV and the Clinician Assessed PTSD Scale. Four hundred and forty-one adults participated (mean age-40.0 SD = 13.3, 68% female, 95% African American). Fourteen percent endorsed recent SP. In approximately 1/3 of those with SP, episodes also featured panic symptoms. SP was strongly associated with trauma history, and concurrent anxiety and mood symptoms. SP was not associated with specific psychiatric disorders other than lifetime (but not current) alcohol or substance use disorders. Our findings suggest that SP is not uncommon in adult African Americans and is associated with trauma and concurrent distress but not with a specific psychiatric diagnosis.

  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.; ...

    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. Study origin of germ cells and formation of new primary follicles in adult human and rat ovaries.

    PubMed

    Bukovsky, Antonin; Gupta, Satish K; Virant-Klun, Irma; Upadhyaya, Nirmala B; Copas, Pleas; Van Meter, Stuart E; Svetlikova, Marta; Ayala, Maria E; Dominguez, Roberto

    2008-01-01

    The central thesis regarding the human ovaries is that, although primordial germ cells in embryonal ovaries are of extraovarian origin, those generated during the fetal period and in postnatal life are derived from the ovarian surface epithelium (OSE) bipotent cells. With the assistance of immune system-related cells, secondary germ cells and primitive granulosa cells originate from OSE stem cells in the fetal and adult human gonads. Fetal primary follicles are formed during the second trimester of intrauterine life, prior to the end of immune adaptation, possibly to be recognized as self-structures and renewed later. With the onset of menarche, a periodical oocyte and follicular renewal emerges to replace aging primary follicles and ensure that fresh eggs for healthy babies are always available during the prime reproductive period. The periodical follicular renewal ceases between 35 and 40 yr of age, and the remaining primary follicles are utilized during the premenopausal period until exhausted. However, the persisting oocytes accumulate genetic alterations and may become unsuitable for ovulation and fertilization. The human OSE stem cells preserve the character of embryonic stem cells, and they may produce distinct cell types, including new eggs in vitro, particularly when derived from patients with premature ovarian failure or aging and postmenopausal ovaries. Our observations also indicate that there are substantial differences in follicular renewal between adult human and rat ovaries. As part of this chapter, we present in detail protocols utilized to analyze oogenesis in humans and to study interspecies differences when compared to the ovaries of rat females.

  8. [Metastasis of hepatocellular carcinoma to the urinary bladder].

    PubMed

    Kurimoto, S; Komatsu, H; Doi, N; Wakumoto, Y; Tominaga, T; Nishimura, Y

    1993-01-01

    We report a case of metastasis of a hepatocellular carcinoma to the bladder. Clinically the tumor was suspected to be a primary bladder tumor with subsequent metastasis to the liver. However, the pathological diagnosis yielded different results. The tumor cells resembled liver cells and sometimes bile production was even observed. No therapy was available and the patient died of cachexia 6 months later.

  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. Frequency-change in DPOAE evoked by 1 s/octave sweeping primaries in newborns and adults.

    PubMed

    AlMakadma, Hammam A; Henin, Simon; Prieve, Beth A; Dyab, Walid M; Long, Glenis R

    2015-10-01

    Distortion product otoacoustic emissions (DPOAE) in newborns and adults were evoked by sweeping primaries up and down in frequency at 1 s/octave. Sweeping up and down in frequency resulted in changes in the amplitude vs. frequency functions of the composite DPOAE and its two major components. In addition, DPOAE component phases differed slightly between the up- and down-swept conditions. The changes in amplitude vs. frequency functions were quantified using a covariate correlation technique, yielding single-valued estimates of the magnitude of the frequency changes. Separate analyses were performed for the entire DPOAE frequency range and split into low and high frequency ranges. There were consistent changes in newborn and adult composite DPOAEs and reflection components, but not generator components. Adults had significant frequency changes in the composite DPOAE for all frequency ranges and in the reflection component for the entire frequency range. Newborns had significant frequency change in the reflection component for all frequency ranges. Differences in frequency change between adults and newborns may stem from developmental changes in cochlear processing. Alignment of the component phase differences between the up- and down-swept conditions resulted in elimination of frequency-change in reconstructed composite DPOAEs.

  11. Combined hepatocellular-cholangiocarcinoma in a lesser flamingo (Phoenicopterus minor).

    PubMed

    Van Wettere, A J; Degernes, L A; Barnes, H John

    2010-08-01

    A case of combined hepatocellular-cholangiocarcinoma (CHCC) in an adult male lesser flamingo (Phoenicopterus minor) that was part of a breeding programme at a private facility is reported. Grossly, the liver was markedly enlarged with multifocal, well-circumscribed, pinpoint to 2 cm diameter pale tan nodular masses. Histologically, the hepatic parenchyma was replaced by neoplastic cells that demonstrated hepatocellular and, less frequently, biliary epithelial cell differentiation. Positive pan-cytokeratin (AE1/AE3/PCK26) immunolabelling of the neoplastic cells forming bile ducts with the scattered immunoreactivity of cells forming glandular structures within the areas of hepatocellular differentiation supported the diagnosis. No metastases were detected. CHCC is a rare neoplasm in mammals and birds. This is the first report where gross, histological, and immunohistochemical characteristics of CHCC in a bird are described, and the first report of CHCC in a lesser flamingo.

  12. 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

  13. 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,…

  14. Microscopy, culture, and sensitive management of uncomplicated urinary tract infections in adults in the primary care setting.

    PubMed

    Sivathasan, Niroshan; Rakowski, Krzysztof R

    2011-06-01

    The high prevalence of urinary tract infections (UTIs) places a significant burden on healthcare systems. Clinicians may over-manage the issue, and there is great variability in practice, with economic- and resource- implications. Up to 40% of patients with a suspected UTI do not have an infection. Using PubMed (Medline) to shortlist relevant papers in English from the last 30 years, and further sub-selection to include only uncomplicated UTIs in adults in primary care, we reviewed the literature pertaining to uncomplicated UTIs, and how it should be managed efficiently in the primary care setting. In general practice, there is no advantage to routinely request microscopy and culture of urine samples in the presence of an appropriate history and urinalysis reagent-strip testing. If antibiotics are required, then a 3-day course shall suffice. Larger epidemiological studies focusing on more susceptible sub-populations may provide better guidance for discriminatory factors to produce an algorithm for treatment.

  15. Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans.

    PubMed

    Soriano-Arroquia, Ana; Clegg, Peter D; Molloy, Andrew P; Goljanek-Whysall, Katarzyna

    2017-02-16

    Skeletal muscle homeostasis depends on muscle growth (hypertrophy), atrophy and regeneration. During ageing and in several diseases, muscle wasting occurs. Loss of muscle mass and function is associated with muscle fiber type atrophy, fiber type switching, defective muscle regeneration associated with dysfunction of satellite cells, muscle stem cells, and other pathophysiological processes. These changes are associated with changes in intracellular as well as local and systemic niches. In addition to most commonly used rodent models of muscle ageing, there is a need to study muscle homeostasis and wasting using human models, which due to ethical implications, consist predominantly of in vitro cultures. Despite the wide use of human Myogenic Progenitor Cells (MPCs) and primary myoblasts in myogenesis, there is limited data on using human primary myoblast and myotube cultures to study molecular mechanisms regulating different aspects of age-associated muscle wasting, aiding in the validation of mechanisms of ageing proposed in rodent muscle. The use of human MPCs, primary myoblasts and myotubes isolated from adult and aged people, provides a physiologically relevant model of molecular mechanisms of processes associated with muscle growth, atrophy and regeneration. Here we describe in detail a robust, inexpensive, reproducible and efficient protocol for the isolation and maintenance of human MPCs and their progeny - myoblasts and myotubes from human muscle samples using enzymatic digestion. Furthermore, we have determined the passage number at which primary myoblasts from adult and aged people undergo senescence in an in vitro culture. Finally, we show the ability to transfect these myoblasts and the ability to characterize their proliferative and differentiation capacity and propose their suitability for performing functional studies of molecular mechanisms of myogenesis and muscle wasting in vitro.

  16. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

    PubMed

    Slike, Bonnie M; Creegan, Matthew; Marovich, Mary; Ngauy, Viseth

    2017-01-01

    Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10-20 years post vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112-3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

  17. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations

    PubMed Central

    Slike, Bonnie M.; Creegan, Matthew

    2017-01-01

    Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5–10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10–20 years post vaccination. This contrasted with a comparator group of adults, ages 35–49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112–3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program. PMID:28046039

  18. 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

  19. Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis

    PubMed Central

    Gomaa, Asmaa Ibrahim; Khan, Shahid A; Toledano, Mireille B; Waked, Imam; Taylor-Robinson, Simon D

    2008-01-01

    Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance. PMID:18666317

  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. Is laparoscopic hepatectomy superior to open hepatectomy for hepatocellular carcinoma?

    PubMed Central

    Zhong, Jian-Hong; Peng, Ning-Fu; Gu, Jian-Hong; Zheng, Ming-Hua; Li, Le-Qun

    2017-01-01

    The low perioperative morbidity and shorter hospital stay associated with laparoscopic hepatectomy have made it an often-used option at many liver centers, despite the fact that many patients with hepatocellular carcinoma have cirrhosis, which makes the procedure more difficult and dangerous. Type of surgical procedure proves not to be a primary risk factor for poor outcomes after hepatic resection for hepatocellular carcinoma, the available evidence clearly shows that laparoscopic hepatectomy is an effective alternative to the open procedure for patients with early-stage hepatocellular carcinoma, even in the presence of cirrhosis. Whether the same is true for patients with intermediate or advanced disease is less clear, since laparoscopic major hepatectomy remains a technically demanding procedure. PMID:28217254

  2. Reduced expression of TANGO in colon and hepatocellular carcinomas.

    PubMed

    Arndt, Stephanie; Bosserhoff, Anja K

    2007-10-01

    The TANGO gene was originally identified as a new family member of the MIA gene family. The gene codes for a 14-kDa protein of so far unknown function. Recently, we identified TANGO as a tumor suppressor in malignant melanoma. In this study we evaluated TANGO transcription in different colon and hepatocellular carcinoma cell lines and tissue samples, to analyze whether loss of TANGO expression is a more general process in tumor development. TANGO was down-regulated or lost in all hepatocellular and colon cell lines compared to primary human hepatocytes or normal colon epithelial cells, respectively, and in most of the tumor samples compared to non-tumorous tissue. These results were confirmed in situ by immunohistochemistry on paraffin-embedded sections of colon and hepatocellular tumors. Functional assays with exogenous TANGO treatment of colon and hepatoma cell lines revealed reduced motility and invasion capacity. Our studies present for the first time the down-regulation of TANGO in colon and hepatocellular carcinoma and provide the first indications for a tumor suppressor role of the TANGO gene in human colon and hepatocellular carcinoma. Thus, functional relevant loss of TANGO expression may contribute to general tumor development and progression, and may provide a new target for therapeutic strategies.

  3. 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

  4. Comparison of primary repair and patch plasty procedure on the P wave in adult atrial septal defect closure

    PubMed Central

    Ucak, Alper; Temizkan, Veysel; Ugur, Murat; Selcuk, Arif; Yilmaz, Ahmet Turan; Yedekci, Ahmet Erturk; Uz, Omer

    2016-01-01

    Summary Introduction: In this study we compared the effects of two different surgical procedures for closure of adult atrial septal defect (ASD) on postoperative P-wave changes. Methods: Patients who underwent cardiac surgery for secundum type ASD closure were evaluated retrospectively. Seventy-two patients with primary repair of ASD and 29 patients with pericardial patch plasty repair were compared according to Pmax, Pmin and P-wave dispersions (Pd). Results: In each group, the increases in postoperative maximum P-wave duration (Pmax) and minimum P-wave duration (Pmin) were statistically significant. There was no statistically significant difference between post- and pre-operative Pd values. In the comparison between group 1 and group 2 in terms of postoperative P-wave changes (Pmax, Pmin, Pd) there was no statistically significant difference. Conclusion: Comparing patch plasty and primary repair for the surgical closure of ASD in the early to mid-postoperative period, no difference was found and both surgical procedures can be performed in adult ASDs. PMID:27149297

  5. 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.

  6. Care of Older Adults: Role of Primary Care Physicians in the Treatment of Cataracts and Macular Degeneration.

    PubMed

    Marra, Kyle V; Wagley, Sushant; Kuperwaser, Mark C; Campo, Rafael; Arroyo, Jorge G

    2016-02-01

    This article aims to facilitate optimal management of cataracts and age-related macular degeneration (AMD) by providing information on indications, risk factors, referral guidelines, and treatments and to describe techniques to maximize quality of life (QOL) for people with irreversible vision loss. A review of PubMed and other online databases was performed for peer-reviewed English-language articles from 1980 through August 2012 on visual impairment in elderly adults. Search terms included vision loss, visual impairment, blind, low vision, QOL combined with age-related, elderly, and aging. Articles were selected that discussed vision loss in elderly adults, effects of vision impairment on QOL, and care strategies to manage vision loss in older adults. The ability of primary care physicians (PCPs) to identify early signs of cataracts and AMD in individuals at risk of vision loss is critical to early diagnosis and management of these common age-related eye diseases. PCPs can help preserve vision by issuing aptly timed referrals and encouraging behavioral modifications that reduce risk factors. With knowledge of referral guidelines for soliciting low-vision rehabilitation services, visual aids, and community support resources, PCPs can considerably increase the QOL of individuals with uncorrectable vision loss. By offering appropriately timed referrals, promoting behavioral modifications, and allocating low-vision care resources, PCPs may play a critical role in preserving visual health and enhancing the QOL for the elderly population.

  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.

  9. Effect of culture conditions on microRNA expression in primary adult control and COPD lung fibroblasts in vitro.

    PubMed

    Ikari, Jun; Smith, Lynette M; Nelson, Amy J; Iwasawa, Shunichiro; Gunji, Yoko; Farid, Maha; Wang, Xingqi; Basma, Hesham; Feghali-Bostwick, Carol; Liu, Xiangde; DeMeo, Dawn L; Rennard, Stephen I

    2015-04-01

    In vitro cell cultures, including lung fibroblasts, have been used to identify microRNAs (miRNAs) associated with chronic obstructive pulmonary disease (COPD) pathogenesis. However, culture conditions may affect miRNA expression. We examined whether miRNA expression in primary adult lung fibroblasts varies with cell density or passage in vitro and whether culture conditions confound the identification of altered miRNA expression in COPD lung fibroblasts. Primary adult control and COPD lung fibroblasts were cultured until passage 3 or 8, after which cells were further cultured for 3 or 7 d (low vs. high density). Then, cells at low density were cultured with serum-free media, and those at high density were cultured with serum-free media in the absence or presence of interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) for 24 h. RNA was extracted to perform miRNA microarray from which 1.25-fold differential expression and 10% false discovery rate were applied to identify "invariant" and "variant" miRNA for the various culture conditions. Of the 2226 miRNAs evaluated, 39.0% for cell density, 40.7% for cell passage, and 29.4% for both conditions were identified as "invariant" miRNAs. Furthermore, 38.1% of the evaluated miRNAs were "invariant" for cell passage with IL-1β and TNF-α. Differentially expressed miRNAs between control and COPD lung fibroblasts were identified with and without IL-1β and TNF-α, and of these, 32 out of the 34 top-ranked miRNAs exceeded the differences due to culture conditions. Thus, culture conditions may affect miRNA expression of adult human lung fibroblasts. Nevertheless, in vitro cultures can be used to assess differential miRNA expression in COPD lung fibroblasts.

  10. 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.

  11. Hepatocellular carcinoma: a global view

    PubMed Central

    Yang, Ju Dong; Roberts, Lewis R.

    2014-01-01

    Hepatocellular carcinoma (HCC) is a global health problem, although developing countries are disproportionally affected: over 80% of HCCs occur in such regions. About three-quarters of HCCs are attributed to chronic HBV and HCV infections. In areas endemic for HCV and HBV, viral transmission occurs at an early age, and infected individuals develop HCC in mid-adulthood. As these are their most productive years of life, HCC accounts for a substantial burden on the health-care system and drain of productive capacity in the low-income and middle-income countries most affected by HCV and HBV infections. Environments with disparate resource levels require different strategies for the optimal management of HCC. In high-resource environments, guidelines from the American Association for the Study of Liver Diseases or European Association for the Study of the Liver should be applied. In intermediate-resource or low-resource environments, the fundamental focus should be on primary prevention of HCC, through universal HBV vaccination, taking appropriate precautions and antiviral treatments. In intermediate-resource and low-resource environments, the infrastructure and capacity for abdominal ultrasonography, percutaneous ethanol injection, radiofrequency ablation and surgical resection should be established. Programs to provide targeted therapy at low cost, similar to the approach used for HIV therapy in the developing world, should be pursued. PMID:20628345

  12. 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

  13. Histopathology of hepatocellular carcinoma

    PubMed Central

    Schlageter, Manuel; Terracciano, Luigi Maria; D’Angelo, Salvatore; Sorrentino, Paolo

    2014-01-01

    Hepatocellular carcinoma (HCC) is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence worldwide. Its etiology is usually linked to environmental, dietary or life-style factors. HCC most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be observed. Although this process is yet to be completely understood, this changing scenario also has impact on the material seen by pathologists, presenting them with new diagnostic dilemmas. Histopathologic criteria for diagnosing classical, progressed HCC are well established and known, but with an increase in detection of small and early HCCs due to routine screening programs, the diagnosis of these small lesions in core needle biopsies poses a difficult challenge. These lesions can be far more difficult to distinguish from one another than progressed HCC, which is usually a clear cut hematoxylin and eosin diagnosis. Furthermore lesions thought to derive from progenitor cells have recently been reclassified in the WHO. This review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs reclassification. Furthermore it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas. PMID:25473149

  14. 'SIMPLES': a structured primary care approach to adults with difficult asthma.

    PubMed

    Ryan, Dermot; Murphy, Anna; Ställberg, Björn; Baxter, Noel; Heaney, Liam G

    2013-09-01

    The substantial majority of patients with asthma can expect minimal breakthrough symptoms on standard doses of inhaled corticosteroids with or without additional add-on therapies. SIMPLES is a structured primary care approach to the review of a person with uncontrolled asthma which encompasses patient education monitoring, lifestyle and pharmacological management and addressing support needs which will achieve control in most patients. The small group of patients presenting with persistent asthma symptoms despite being prescribed high levels of treatment are often referred to as having 'difficult asthma'. Some will have difficult, 'therapy resistant' asthma, some will have psychosocial problems which make it difficult for them to achieve asthma control and some may prove to have an alternative diagnosis driving their symptoms. A few patients will benefit from referral to a 'difficult asthma' clinic. The SIMPLES approach, aligned with close co-operation between primary and specialist care, can identify this patient group, avoid inappropriate escalation of treatment, and streamline clinical assessment and management.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. Lipid-mediated transfection of normal adult human hepatocytes in primary culture.

    PubMed

    Ourlin, J C; Vilarem, M J; Daujat, M; Harricane, M C; Domergue, J; Joyeux, H; Baulieux, J; Maurel, P

    1997-04-05

    The aim of this work was to develop a procedure for the lipid-mediated transfection of DNA into normal adult human hepatocytes in culture. Cells were plated in a serum-free culture medium at various cell densities, on plastic or collagen-coated dishes, both in the absence and in the presence of epidermal growth factor (EGF). The cells were incubated for various periods of time with mixtures of DNA-lipofectin or DNA-3 beta[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-chol) liposomes, and the efficiency of transfection was assessed by measuring the activity of reporter genes, beta-galactosidase or chloramphenicol acetyl-transferase (CAT). For comparison, similar experiments were carried out with human cell lines including HepG2, Caco-2, and WRL68. The efficiency of transfection (in percentage of cells) was not significantly different after transfection with lipofectin or DC-chol and comprised between 0.04 and 1.7% (extreme values) for different cultures. The efficiency of transfection decreased as the age or density of the culture increased and increased in cultures treated with EGF. Direct measurement of the rate of DNA synthesis suggested that the efficiency of transfection was related to the number of cells entering the S phase. Under the same conditions, the efficiency of transfection was one to two orders of magnitude greater in the three cell lines. A plasmid harboring 660 bp of the 5'-flanking region of CYP1A1 (containing two xenobiotic enhancer elements) fused upstream of the promoter of thymidine kinase and the CAT reporter gene was constructed. When this plasmid was transfected in human hepatocytes, CAT activity was induced as expected. We conclude that normal adult human hepatocytes can be transfected with exogenous DNA and that the transfected construct is regulated in the manner expected from in vivo studies.

  2. Primary and rescue immune tolerance induction in children and adults: a multicentre international study with a VWF-containing plasma-derived FVIII concentrate.

    PubMed

    Oldenburg, J; Jiménez-Yuste, V; Peiró-Jordán, R; Aledort, L M; Santagostino, E

    2014-01-01

    Most studies on immune tolerance induction (ITI) therapy in haemophilia A patients are focused on primary ITI in children. Here we report on the ITI outcome in a large retrospective cohort, including adults and patients with rescue ITI, treated with a pdFVIII/VWF concentrate. Retrospective data from haemophilic patients (FVIII< 2%) with inhibitors from 22 centres in Spain, Italy and Germany, who underwent primary or rescue ITI with pdFVIII/VWF concentrate, were collected. Complete success (CS), partial success (PS) and failure were defined based on the criteria of the consensus recommendations of the 2006 International ITI Workshop. A total of 41 cases of primary ITI (32 children and 9 adults) and 19 cases of rescue ITI (17 children and 2 adults) were evaluated. Success (CS+PS) rate of 87% was achieved in primary ITI and 74% in the higher risk profile of rescue ITI. Eight of nine (85%) patients with poorest prognosis (three or more of the known risk factors of poor response to ITI) achieved success (CS+PS). CS of 100% was observed in eight primary ITI patients with titre at start of ITI ≤2.5 BU and inhibitor peak ≤25 BU. The favourable response rates in primary and rescue ITI in children and in adult patients, even in the presence of poor prognostic factors, should be encouraged for broadening the indication of immune tolerance therapy in haemophilia A patients with inhibitors.

  3. Global cardiovascular risk assessment in the primary prevention of cardiovascular disease in adults: systematic review of systematic reviews

    PubMed Central

    Tompson, Alice C; Onakpoya, Igho J; Roberts, Nia; Ward, Alison M; Heneghan, Carl J

    2017-01-01

    Objective To identify, critically appraise and summarise existing systematic reviews on the impact of global cardiovascular risk assessment in the primary prevention of cardiovascular disease (CVD) in adults. Design Systematic review of systematic reviews published between January 2005 and October 2016 in The Cochrane Library, EMBASE, MEDLINE or CINAHL databases, and post hoc analysis of primary trials. Participants, interventions, outcomes Systematic reviews of interventions involving global cardiovascular risk assessment relative to no formal risk assessment in adults with no history of CVD. The primary outcomes of interest were CVD-related morbidity and mortality and all-cause mortality; secondary outcomes were systolic blood pressure (SBP), cholesterol and smoking. Results We identified six systematic reviews of variable but generally of low quality (mean Assessing the Methodological Quality of Systematic Reviews 4.2/11, range 0/11 to 7/11). No studies identified by the systematic reviews reported CVD-related morbidity or mortality or all-cause mortality. Meta-analysis of reported randomised controlled trials (RCTs) showed small reductions in SBP (mean difference (MD) −2.22 mm Hg (95% CI −3.49 to −0.95); I2=66%; n=9; GRADE: very low), total cholesterol (MD −0.11 mmol/L (95% CI −0.20 to −0.02); I2=72%; n=5; GRADE: very low), low-density lipoprotein cholesterol (MD −0.15 mmol/L (95% CI −0.26 to −0.05), I2=47%; n=4; GRADE: very low) and smoking cessation (RR 1.62 (95% CI 1.08 to 2.43); I2=17%; n=7; GRADE: low). The median follow-up time of reported RCTs was 12 months (range 2–36 months). Conclusions The quality of existing systematic reviews was generally poor and there is currently no evidence reported in these reviews that the prospective use of global cardiovascular risk assessment translates to reductions in CVD morbidity or mortality. There are reductions in SBP, cholesterol and smoking but they may not be clinically

  4. 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

  5. General Practitioners’ Decision Making about Primary Prevention of Cardiovascular Disease in Older Adults: A Qualitative Study

    PubMed Central

    Jansen, Jesse; Bonner, Carissa; Irwig, Les; Doust, Jenny; Glasziou, Paul; Bell, Katy; Naganathan, Vasi; McCaffery, Kirsten

    2017-01-01

    Background Primary cardiovascular disease (CVD) prevention in older people is challenging as they are a diverse group with varying needs, frequent presence of comorbidities, and are more susceptible to treatment harms. Moreover the potential benefits and harms of preventive medication for older people are uncertain. We explored GPs’ decision making about primary CVD prevention in patients aged 75 years and older. Method 25 GPs participated in semi-structured interviews in New South Wales, Australia. Transcribed audio-recordings were thematically coded and Framework Analysis was used. Results Analysis identified factors that are likely to contribute to variation in the management of CVD risk in older people. Some GPs based CVD prevention on guidelines regardless of patient age. Others tailored management based on factors such as perceptions of prevention in older age, knowledge of limited evidence, comorbidities, polypharmacy, frailty, and life expectancy. GPs were more confident about: 1) medication and lifestyle change for fit/healthy older patients, and 2) stopping or avoiding medication for frail/nursing home patients. Decision making for older patients outside of these categories was less clear. Conclusion Older patients receive different care depending on their GP’s perceptions of ageing and CVD prevention, and their knowledge of available evidence. GPs consider CVD prevention for older patients challenging and would welcome more guidance in this area. PMID:28085944

  6. Cognitive behavioral treatment for older adults with generalized anxiety disorder. A therapist manual for primary care settings.

    PubMed

    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 suggested the potential benefits of a new version of CBT for GAD among older patients in primary care. The manual developed and tested in this pilot project is presented here. Treatment components include motivation and education, relaxation skills, cognitive therapy, problem-solving-skills training, exposure exercises, and sleep-management-skills training. Procedures are designed to be administered flexibly to maximize attention to individual patient needs. Examples of session summaries, patient handouts, and homework forms are provided.

  7. 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).

  8. 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

  9. Surgery and Hepatocellular Carcinoma

    PubMed Central

    Akamatsu, Nobuhisa; Cillo, Umberto; Cucchetti, Alessandro; Donadon, Matteo; Pinna, Antonio Daniele; Torzilli, Guido; Kokudo, Norihiro

    2016-01-01

    The optimal surgical strategy for hepatocellular carcinoma (HCC) is under active debate. Bio-markers of the liver functional reserve as well as volumetric analysis of the future liver remnant are essential for safe liver resection of HCC. The present algorithms applied to surgical strategies for HCC are not ideal because many patients who could potentially undergo safe resection are deemed liver transplant candidates in Western countries, whereas the opposite is the case in Eastern countries. In addition, there is too much focus on expanded criteria for patients with HCC to undergo liver transplantation. The transplantation benefit for patients with HCC should be considered based not only on the individual's benefit, but also on the effect of other patients waiting for LT for other indications. PMID:27995087

  10. Immunotherapy of hepatocellular carcinoma

    PubMed Central

    Pardee, Angela D.; Butterfield, Lisa H.

    2012-01-01

    Current therapies for advanced hepatocellular carcinoma (HCC) are marginally effective and exacerbate underlying liver disease. The ability of immunotherapy to elicit nontoxic, systemic, long-lived anti-tumor activity makes it particularly well-suited for use in the setting of HCC. While therapeutic benefit has been achieved in early clinical trials, the efficacy of immune-based therapies is limited by several unique properties of HCC, most notably the inherently tolerogenic character of the liver in both healthy and diseased (chronically-infected or tumor-bearing) states. Therapeutic regimens that both counteract these immunosuppressive mechanisms and amplify tumor-specific immunity are expected to profoundly improve clinical outcomes for HCC patients. PMID:22720211

  11. Primary sleep disorders and paroxysmal nocturnal nonepileptic events in adults with epilepsy from the perspective of sleep specialists.

    PubMed

    Grigg-Damberger, Madeleine; Ralls, Frank

    2011-04-01

    Sleep specialists are frequently referred adults with epilepsy to evaluate their sleep/wake complaints, sometimes to determine whether their paroxysmal nocturnal behaviors are epileptic or not. Many patients with epilepsy have at least one parasomnia (some more than one), and the sleep specialists are often asked to differentiate and treat these. Sleep specialists review which primary sleep disorders are more common in adults with epilepsy and how to evaluate and best treat these. The authors summarize (1) how to evaluate and differentiate parasomnias using video-polysomnography; (2) the value of sleep deprivation and loud auditory stimuli to increase the likelihood of provoking a non-rapid eye movement arousal parasomnia with a single night of video-polysomnography; and (3) how to score excessive muscle activity during rapid eye movement sleep to confirm a diagnosis of rapid eye movement sleep behavior disorder. The clinical semiology and video-polysomnography features of simple and complex sleep-related movement disorders and parasomnias are reviewed.

  12. 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.

  13. Adult primary pulmonary primitive neuroectodermal tumor: molecular features and translational opportunities.

    PubMed

    Andrei, Mirela; Cramer, Stewart F; Kramer, Zachary B; Zeidan, Amer; Faltas, Bishoy

    2013-02-01

    Primitive neuroectodermal tumors (PNET) arising directly from the lung are very rare but particularly aggressive neoplasms. We report a case of a 31-y-old man with primary pulmonary neuroectodermal tumor. We review the clinical as well as pathological features. As typical for these tumors, the diagnosis was initially delayed in our patient and prognosis was poor despite aggressive surgical resection, postoperative chemotherapy and local irradiation. Recent biological insights have revealed unique chromosomal translocations crucial to the pathogenesis of these tumors, most notably the EWS-FLI-1 translocation. We provide an overview of the molecular features of the Ewing Sarcoma Family of Tumors (ESFT) including PNET and their potential implications for therapeutic targeting.

  14. 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

  15. Primary-to-secondary care referral experience of suspected colorectal malignancy in young adults

    PubMed Central

    Patel, K; Doulias, T; Hoad, T; Lee, C; Alberts, JC

    2016-01-01

    Introduction Colorectal cancer in patients younger than 50 years of age is increasing steadily in the UK with limited guidelines available indicating need for secondary care referral. The aims of this study were to report the cancer incidence in those aged under 50 years referred to secondary care with suspected colorectal malignancy and also to analyse the quality of those referrals. Methods A total of 197 primary care referrals made between 2008 and 2014 to a UK district general hospital for suspected colorectal malignancy were analysed. All confirmed cancers were further evaluated regarding presenting symptoms, tumour characteristics and clinical outcomes. Each referral was given a referral performance score (out of 9) dependant on relevant information documented. Results The overall malignancy rate was 9.1% (11 male and 7 female patients). The median age in this cohort was 41.5 years (interquartile range [IQR]: 37–49 years). Abdominal pain was the only presenting symptom to differ significantly when comparing malignant with non-malignant patients (44.4% vs 21.8% respectively, p=0.042). The median time period between referral date and colorectal specialist consultation was 11 days (IQR: 7–13 days) and the median referral performance score was 5 (range: 3–9). Conclusions Malignancy is prevalent in patients under 50 years of age who are referred to secondary care for suspected colorectal cancer. Those referred with abdominal pain in the presence of other high risk lower gastrointestinal symptoms are at significant risk of having a malignancy. Major deficiencies are apparent in urgent primary care referrals, highlighting the need for further national guidance to aid early diagnosis of colorectal cancer in the young. PMID:27023637

  16. Medication regimen complexity in adults and the elderly in a primary healthcare setting: determination of high and low complexities

    PubMed Central

    Ferreira, Juliana M.; Galato, Dayani; Melo, Angelita C.

    2015-01-01

    Background: The complexity of a medication regimen is related to the multiple characteristics of the prescribed regimen and can negatively influence the health outcomes of patients. Objective: To propose cut-off points in the complexity of pharmacotherapy to distinguish between patients with low and high complexities seen in a primary health care (PHC) setting to enable prioritization of patient management. Methods: This is a cross-sectional study, which included 517 adult and elderly patients, analyzing different cut-off points to define the strata of low and high pharmacotherapy complexities based on percentiles of the population evaluated. Data collection began with the solicitation of prescriptions, followed by a questionnaire that was administered by an interviewer. The complexity of a medication regimen was estimated from the Medication Regimen Complexity Index (MRCI). High complexity pharmacotherapy scores were analyzed from patient profiles, the use of health services, and pharmacotherapy. The criteria for subject inclusion in the sample population were as follows: inhabitant of the area covered by the municipality, 18 years or older, and being prescribed at least one drug during the collection period. Exclusion criteria at the time of collection were the use of any medication whose prescription was not available. All medications were accessed through the Primary Healthcare Service (PHS). Results: The median total pharmacotherapy complexity score was 8.5. High MRCI scores were correlated with age, medications taken with in the Brazilian PHS, having at least one potential drug-related problem, receiving up to eight years of schooling, number of medications and polypharmacy (five or more medicines), number of medical conditions, number of medical appointments, and number of cardiovascular diseases and endocrine metabolic diseases. We suggest different complexity tracks according to age (e.g., adult or elderly) that consider the pharmacotherapy and population

  17. 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

  18. 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.

  19. Primary central nervous system ALK-positive anaplastic large cell lymphoma in an adult

    PubMed Central

    Dong, Xiaoqin; Li, Jun; Huo, Na; Wang, Yan; Wu, Zhao; Lin, Xiaohong; Zhao, Hong

    2016-01-01

    Abstract Rationale: Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin lymphoma. It mostly invades lymph nodes with extranodal involvement observed in the soft tissue, bone, and skin. Patient concerns: We report a 34-year-old Chinese male patient who presented with headache, diplopia, and vomit. Cerebrospinal fluid (CSF) analysis via lumbar puncture showed elevated CSF pressure, elevated CSF protein concentrations, decreased CSF glucose and chloride concentration significantly, and pleocytosis of 68 to 350 × 106/L, in which lymphocytes and monocytes were predominant. These changes could be suggestive of tuberculous (TB) meningitis. Enhanced magnetic resonance imaging of spinal cord delineated multiple enhancing nodules in spinal cord, cauda equina, and cristae membrane, and multiple abnormal enhancing lesions in bilateral lumbar intervertebral foramen. Diagnoses: Spinal dura mater biopsy and paraffin pathology examination revealed anaplastic lymphoma kinase positive ALCL. Interventions: High-dose methotrexate, cytosine arabinoside craniospinal, and radiotherapy. Outcomes: Last follow-up on September 22, 2015 showed no evidence of tumor recurrence and the lower extremity muscle strength recovered to 4/5. Lessons: ALCL of primary central nervous system is an exceedingly rare tumor, which is usually misdiagnosed as meningitis (especially TB meningitis) according to clinical manifestation and laboratory examination. Thus closely monitoring patient's conditions and timely adjusting therapeutic regimen during treatment are necessary. PMID:27930548

  20. Echocardiographic dimensions and function in adults with primary growth hormone resistance (Laron syndrome).

    PubMed

    Feinberg, M S; Scheinowitz, M; Laron, Z

    2000-01-15

    Patients with primary growth hormone (GH) resistance-Laron Syndrome (LS)-have no GH signal transmission, and thus, no generation of circulating insulin-like growth factor-I (IGF-I), and should serve as a unique model to explore the controversies concerning the longterm effect of GH/IGF-I deficiency on cardiac dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a mean (+/- SD) age of 38+/-7 years (range 22 to 45), and 8 aged-matched controls (4 men, 4 women) with a mean age of 38+/-9 years (range 18 to 47) by echocardiography at rest, following exercise, and during dobutamine administration. Left ventricular (LV) septum, posterior wall, and end-diastolic diameter were significantly reduced in untreated patients with LS compared with the control group (p<0.05 for all). Systolic Doppler-derived parameters, including LV stroke volume, stroke index, cardiac output, and cardiac index, were significantly lower (p<0.05 for all) than in the control subjects, whereas LV diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E deceleration time, were similar in both groups. LV ejection fraction at rest as well as the stress-induced increment of the LV ejection fraction were similar in both groups. Our results show that untreated patients with long-term IGF-I deficiency have reduced cardiac dimensions and output but normal LV ejection fraction at rest and LV contractile reserve following stress.

  1. Acute primary canine herpesvirus-1 dendritic ulcerative keratitis in an adult dog.

    PubMed

    Gervais, Kristen J; Pirie, Christopher G; Ledbetter, Eric C; Pizzirani, Stefano

    2012-03-01

    We present a report of dendritic ulcerative keratitis in a 4-year old locally immunosuppressed dog suspected to result from acute primary canine herpesvirus-1 (CHV-1) infection. The dog was presented for evaluation of mild blepharospasm and conjunctival hyperemia in the right eye (OD) shortly after attending a public boarding facility. For approximately 3 months, the dog had been receiving topical prednisolone acetate 1.0% and tacrolimus 0.02% in both eyes (OU) q12h for treatment of follicular conjunctivitis. Ophthalmic examination revealed three regions of corneal fluorescein retention OD. The lesions had a dendritic pattern, were approximately 2-3 mm in length, and were located at the dorsomedial, lateral, and ventromedial aspects of the cornea. No additional abnormalities were noted on complete ophthalmic and physical examinations. CHV-1 was identified in conjunctival samples OD by polymerase chain reaction, and paired CHV-1 serum virus neutralization antibody titers were positive and consistent with acute infection. Topical prednisolone acetate and tacrolimus were discontinued. The dog was treated with cidofovir 0.5% OU q12h for a period of 4 weeks, with resolution of corneal disease noted within 1 week of treatment. In conjunction with previous studies, this case report supports a central role for alterations in host immune status in the pathogenesis and clinical manifestations of CHV-1 ocular disease in dogs.

  2. Primary Gliosarcoma of the Optic Nerve: A Unique Adult Optic Pathway Glioma.

    PubMed

    Cimino, Patrick J; Sychev, Yevgeniy V; Gonzalez-Cuyar, Luis F; Mudumbai, Raghu C; Keene, C Dirk

    2016-10-11

    A 90-year-old woman presented with 1-year history of right-sided progressive proptosis, neovascular glaucoma, blindness, and worsening ocular pain. No funduscopic examination was possible because of a corneal opacity. Head CT scan without contrast demonstrated a heterogeneous 4.1 cm (anterior-posterior) by 1.7 cm (transverse) cylindrical mass arising in the right optic nerve and extending from the retrobulbar globe to the optic canal. She underwent palliative enucleation with subtotal resection of the orbital optic nerve and tumor. Pathological examination showed effacement of the optic nerve by an infiltrative high-grade glial neoplasm with biphasic sarcomeric differentiation. Invasion into the uvea and retina was present. The neoplasm was negative for melan-A, HMB45, tyrosinase, synaptophysin, smooth muscle actin, and epithelial membrane antigen. The glioma had strongly intense, but patchy immunopositivity for glial fibrillary acidic protein. Multiple foci of neoplastic cells had pericellular reticulin staining. The overall features were diagnostic of a gliosarcoma (World Health Organization grade IV) of the optic nerve. Postoperative MRI demonstrated postsurgical changes and residual gliosarcoma with extension into the optic chiasm. The patient died 2 and a half months after her enucleation surgery at her nursing home. Autopsy was unavailable due to the caregiver wishes, making a definitive cause of death unknown. Gliosarcoma is a rare variant of glioblastoma, and this is the first documented case presenting as a primary neoplasm of the optic nerve.

  3. General Information about Liver (Hepatocellular) Cancer

    MedlinePlus

    ... Treatment Liver Cancer Prevention Liver Cancer Screening Research Liver (Hepatocellular) Cancer Prevention (PDQ®)–Patient Version What is ... to keep cancer from starting. General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer is a ...

  4. Risks of Liver (Hepatocellular) Cancer Screening

    MedlinePlus

    ... Treatment Liver Cancer Prevention Liver Cancer Screening Research Liver (Hepatocellular) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer is a ...

  5. 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 Central

    Engstrom, Anna; Wang, Hao; Xia, Zhengui

    2015-01-01

    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. PMID:25967738

  6. Neurotrophic Factors NGF, GDNF and NTN Selectively Modulate HSV1 and HSV2 Lytic Infection and Reactivation in Primary Adult Sensory and Autonomic Neurons.

    PubMed

    Yanez, Andy A; Harrell, Telvin; Sriranganathan, Heather J; Ives, Angela M; Bertke, Andrea S

    2017-02-07

    Herpes simplex viruses (HSV1 and HSV2) establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF) maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs). Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 and HSV2 latency in adult neurons, we investigated acute and latently-infected primary adult sensory trigeminal (TG) and sympathetic superior cervical ganglia (SCG) after NTF removal. NGF and glial cell line-derived neurotrophic factor (GDNF) deprivation induced HSV1 reactivation in adult sympathetic neurons. In adult sensory neurons, however, neurturin (NTN) and GDNF deprivation induced HSV1 and HSV2 reactivation, respectively, while NGF deprivation had no effects. Furthermore, HSV1 and HSV2 preferentially reactivated from neurons expressing GFRα2 and GFRα1, the high affinity receptors for NTN and GDNF, respectively. Thus, NTN and GDNF play a critical role in selective maintenance of HSV1 and HSV2 latency in primary adult sensory neurons.

  7. Neurotrophic Factors NGF, GDNF and NTN Selectively Modulate HSV1 and HSV2 Lytic Infection and Reactivation in Primary Adult Sensory and Autonomic Neurons

    PubMed Central

    Yanez, Andy A.; Harrell, Telvin; Sriranganathan, Heather J.; Ives, Angela M.; Bertke, Andrea S.

    2017-01-01

    Herpes simplex viruses (HSV1 and HSV2) establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF) maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs). Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 and HSV2 latency in adult neurons, we investigated acute and latently-infected primary adult sensory trigeminal (TG) and sympathetic superior cervical ganglia (SCG) after NTF removal. NGF and glial cell line-derived neurotrophic factor (GDNF) deprivation induced HSV1 reactivation in adult sympathetic neurons. In adult sensory neurons, however, neurturin (NTN) and GDNF deprivation induced HSV1 and HSV2 reactivation, respectively, while NGF deprivation had no effects. Furthermore, HSV1 and HSV2 preferentially reactivated from neurons expressing GFRα2 and GFRα1, the high affinity receptors for NTN and GDNF, respectively. Thus, NTN and GDNF play a critical role in selective maintenance of HSV1 and HSV2 latency in primary adult sensory neurons. PMID:28178213

  8. 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

  9. Hepatocellular carcinoma: Therapy and prevention

    PubMed Central

    Blum, Hubert E

    2005-01-01

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

  10. Living Donor Liver Transplantation for Combined Hepatocellular Carcinoma and Cholangiocarcinoma: Experience of a Single Center.

    PubMed

    Chang, Cheng-Chih; Chen, Ying-Ju; Huang, Tzu-Hao; Chen, Chun-Han; Kuo, Fang-Ying; Eng, Hock-Liew; Yong, Chee-Chien; Liu, Yueh-Wei; Lin, Ting-Lung; Li, Wei-Feng; Lin, Yu-Hung; Lin, Chih-Che; Wang, Chih-Chi; Chen, Chao-Long

    2017-02-28

    BACKGROUND Because the outcome of liver transplantation for cholangiocarcinoma is often poor, cholangiocarcinoma is a contraindication for liver transplantation in most centers. Combined hepatocellular carcinoma and cholangiocarcinoma is a rare type of primary hepatic malignancy containing features of hepatocellular carcinoma and cholangiocarcinoma. Diagnosing combined hepatocellular carcinoma and cholangiocarcinoma pre-operatively is difficult. Because of sparse research presentations worldwide, we report our experience with living donor liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma. MATERIAL AND METHODS A total of 710 patients underwent living donor liver transplantation at our institution from April 2006 to June 2014; 377 of them received transplantation because of hepatocellular carcinoma with University of California San Francisco (UCSF) staging criteria fulfilled pre-operatively. Eleven patients (2.92%) were diagnosed with combined hepatocellular carcinoma and cholangiocarcinoma confirmed pathologically from explant livers; we reviewed these cases retrospectively. Long-term survival was compared between patients diagnosed with combined hepatocellular carcinoma and cholangiocarcinoma and patients diagnosed with hepatocellular carcinoma. RESULTS The mean age of the patients in our series was 60.2 years, and the median follow-up period was 23.9 months. Four patients were diagnosed with a recurrence during the follow-up period, including one intra-hepatic and three extra-hepatic recurrences. Four patients died due to tumor recurrence. Except for patients with advanced-stage cancer, disease-free survival of patients with combined hepatocellular carcinoma and cholangiocarcinoma compared with that of patients with hepatocellular carcinoma was 80% versus 97.2% in 1 year, and 46.7% versus 92.5% in 3 years (p<0.001), and overall survival was 90% versus 97.2% in 1 year, and 61.7% versus 95.1% in 3 years (p<0.001). CONCLUSIONS

  11. 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

  12. 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

  13. 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.

  14. Cardiovascular exercise intervention improves the primary antibody response to keyhole limpet hemocyanin (KLH) in previously sedentary older adults.

    PubMed

    Grant, R W; Mariani, R A; Vieira, V J; Fleshner, M; Smith, T P; Keylock, K T; Lowder, T W; McAuley, E; Hu, L; Chapman-Novakofski, K; Woods, J A

    2008-08-01

    Based upon a prior cross-sectional study, we hypothesized that an aerobic exercise intervention in sedentary older adults would improve a primary T cell-dependent immune response. Participants were a subset of older subjects from a large, ongoing exercise intervention study who were randomly assigned to either an aerobic exercise (Cardio, n=30, 68.9+0.8 years) or flexibility/balance (Flex, n=20, 69.9+1.2 years) intervention. The intervention consisted of either three aerobic sessions for 30-60 min at 55-70% VO(2 max) or two 60 min flexibility/balance sessions weekly for 10 months. Eight months into the intervention, samples were collected before intramuscular administration of KLH (125 microg), followed by sampling at 2, 3, and 6 weeks post-KLH. Serum anti-KLH IgM, IgG1, and IgG2 was measured by ELISA. Physiological and psychosocial measures were also assessed pre- and post-intervention. While there was no difference in the anti-KLH IgG2 response between groups, Cardio displayed significantly (p<0.05) higher anti-KLH IgG1 (at weeks 2, 3, and 6 post) and IgM responses when compared to Flex. Despite cardiovascular intervention-induced improvement in physical fitness (approximately 11% vs. 1% change in VO(2 peak) in Cardio vs. Flex, respectively), we found no relationship between improved fitness and enhanced anti-KLH antibody responses. Optimism, perceived stress, and affect were all associated with enhanced immune response. We have shown for the first time that cardiovascular training in previously sedentary elderly results in significantly higher primary IgG1 and IgM antibody responses, while having no effect on IgG2 production.

  15. 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.

  16. 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.

  17. RNA interference as therapeutics for hepatocellular carcinoma.

    PubMed

    Xu, Chuanrui; Lee, Susie A; Chen, Xin

    2011-01-01

    Hepatocellular carcinoma (HCC), a major form of primary liver cancer, is one of the leading causes of cancer related deaths worldwide. Hepatitis B and C infections are major risk factors for the development of HCC. Currently, the treatment options are rather limited, and the prognosis for this malignancy is poor for most of these patients. RNA interference has emerged as an innovative technology for gene silencing and as a potential therapeutic for various diseases, including cancer. HCC has been widely chosen as a model system for the development of RNAi therapy due to the convenience and availability of effective delivery of RNA molecules into liver tissues. Targets for HCC treatment include HBV and HCV viruses, oncogenes, as well as cellular genes mediating angiogenesis, tumor growth and metastasis. Here, we summarized the progress of RNAi therapeutics in HCC treatment, relevant patents, potential challenges and prospects in the future.

  18. [Physical inactivity among adults and elderly living in areas covered by primary healthcare units with and without the Family Health Program in Pernambuco State, Brazil].

    PubMed

    Alves, João Guilherme Bezerra; Siqueira, Fernando Vinholes; Figueiroa, José Natal; Facchini, Luiz Augusto; Silveira, Denise Silva da; Piccini, Roberto Xavier; Tomasi, Elaine; Thumé, Elaine; Hallal, Pedro C

    2010-03-01

    The epidemiological transition in Brazil has been explained partially by the low levels of physical activity. However, few studies have explored physical inactivity in low-income population groups. Within this context, primary healthcare units gain strategic importance. This article describes the prevalence of sedentary lifestyle and associated factors in a cross-sectional study, including 1,018 adults and 1,010 elderly adults in 10 cities in Pernambuco State. Prevalence of sedentary lifestyle was 37.8% (95%CI: 34.0-40.2) in adults and 68.3% (95%CI: 65.3-71.3) in the elderly. Identification of physical activity as the most important factor for good health was associated with sedentary lifestyle in elderly adults. A lower proportion of sedentary lifestyle among non-elderly adults was associated with good self-reported health status. We concluded that sedentary lifestyle prevalence is high in elderly and non-elderly people covered by primary healthcare units in Pernambuco State as compared to the South of Brazil.

  19. Meeting the needs? Perceived support of a nurse-led lifestyle programme for young adults with mental illness in a primary health-care setting.

    PubMed

    Rönngren, Ylva; Björk, Annette; Kristiansen, Lisbeth; Haage, David; Enmarker, Ingela; Audulv, Åsa

    2017-04-04

    Being a young adult with mental illness challenges all aspects of health, including an increased risk for developing lifestyle-related diseases. There is a lack of lifestyle programmes in primary health care that target physical, mental, and social needs for young adults with mental illness. The aim of the present study was to describe the experiences of young adults with mental illness receiving support from a nurse-led lifestyle programme, and how this support was related to their life context, including challenges and coping strategies. Two focus groups and six individual interviews were performed with 13 young adults (16-25 years), and analysed using a qualitative content analysis. The findings showed that the young adults experienced challenges in their daily lives, including psychiatric symptoms, lack of social understanding, and loneliness. The study indicated that the programme could support lifestyle habits with its components of supportive interpersonal relationships, awareness of coping strategies, understanding of health and illness, and cognitive support (e.g. schedules and reminders). However, the programme could not meet everyone's needs for new social relationships or more comprehensive support. Even so, this nurse-led programme provides health information-management strategies that could easily be integrated in a primary health-care setting.

  20. 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

  1. Primary intracranial soft tissue sarcomas in children, adolescents, and young adults: single institution experience and review of the literature.

    PubMed

    Maher, Ossama M; Khatua, Soumen; Mukherjee, Devashis; Olar, Adriana; Lazar, Alexander; Luthra, Raja; Liu, Diane; Wu, Jimin; Ketonen, Leena; Zaky, Wafik

    2016-03-01

    There is a paucity of literature reporting the outcome of intracranial sarcomas (IS) in children, adolescents, and young adults (CAYA). A multimodal therapeutic approach is commonly used, with no well-established treatment consensus. We conducted a retrospective review of CAYA with IS, treated at our institution, to determine their clinical findings, treatments, and outcomes. Immunohistochemistry (PDGFRA and EGFR) and DNA sequencing were performed on 5 tumor samples. A literature review of IS was also conducted. We reviewed 13 patients (median age, 7 years) with a primary diagnosis of IS between 1990 and 2015. Diagnoses included unclassified sarcoma (n = 9), chondrosarcoma (n = 2), and rhabdomyosarcoma (n = 2). Five patients underwent upfront gross total resection (GTR) of the tumor. The 5-drug regimen (vincristine, doxorubicin, cyclophosphamide, etoposide, and ifosfamide) was the most common treatment used. Nine patients died due to progression or recurrence (n = 8) or secondary malignancy (n = 1). The median follow-up period of the 4 surviving patients was 1.69 years (range 1.44-5.17 years). The 5-year progression-free survival and overall survival rates were 21 and 44 %, respectively. BRAF, TP53, KRAS, KIT, ERBB2, MET, RET, ATM, and EGFR mutations were detected in 4 of the 5 tissue samples. All 5 samples were immunopositive for PDGFRA, and only 2 were positive for EGFR. IS remain a therapeutic challenge due to high progression and recurrence rates. Collaborative multi-institutional studies are warranted to delineate a treatment consensus and investigate tumor biology to improve the disease outcome.

  2. 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.

  3. 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

  4. SPECT/CT imaging in 99mTc-PMT hepatobiliary scintigraphy to detect bone metastases from hepatocellular carcinoma.

    PubMed

    Ono, Yuko; Yamamoto, Yuka; Itoh, Senri; Arai, Hanae; Aga, Fumitoshi; Nishiyama, Yoshihiro

    2012-10-01

    We report a 62-year-old man who presented with pain on the right side of his hip. CT revealed destructive masses in the right femur and left ilium. Histological examination indicated metastases from hepatocellular carcinoma, and further investigations revealed the primary tumor in the liver. Hepatobiliary scintigraphy using 99mTc N-pyrydoxyl-5-methyltryptophan and fused SPECT/CT clearly showed abnormal accumulation in these bone metastases from hepatocellular carcinoma.

  5. 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

  6. [Hepatocellular nodular hyperplasias, adenomas and carcinomas].

    PubMed

    Altmann, H W

    1995-01-01

    Nodular hyperplasias ("hyperplasiomas") are new formations whose development as a required and regulated response can be traced either to compensatory reactions to the loss of cells (regeneration in a narrow sense) and to decreased cellular performance, or to primary growth impulses. Included in this group are: the "macroregenerative nodules" after extensive cell losses; solitary nodules of uncertain etiology; and the minute foci of "micronodular transformation" whose origin can be traced to a particular disturbance of the hepatic blood supply. The so-called "adenomatous hyperplasias" of the cirrhotic liver that have a tendency towards carcinomatous change are not included in this group and are perhaps better considered as "hyperplasiogenic adenomas". The so-called "focal nodular hyperplasia" too, it must be stressed, should be separated from the simple hyperplasias, for it is more closely related to the adenomas, but represents a new formation of limited growth potential. Morphologically it is conspicuously subdivided by multiple connective tissue bands and scars, but it is above all characterized by metaplastically derived neoductuli, and hence it is appropriately designated as a "combined nodule". Among the true uninodular adenomas there are several variants differing in their morphology,--the so-called "atypical" or "intermediate" forms, that can give rise to carcinomas. The hepatocellular carcinoma, that may arise in a variety of ways, presents multiple cytological and histological variants, but only the so-called "fibrolamellar carcinoma" presents also a clinical peculiarity. "Hepatoblastomas" differ from the common hepatocellular carcinomas by their origin in early childhood from immature early precursor cells and, in the later phases of life, from redifferentiated cells that can even give rise to mesenchymal elements. There is no evidence of the existence of particular pluripotential stem cells.

  7. Giant ectopic liver, hepatocellular carcinoma and pachydermia-a rare genetic syndrome?

    PubMed

    Dettmer, Matthias; Itin, Peter; Miny, Peter; Gandhi, Manoj; Cathomas, Gieri; Willi, Niels

    2011-08-10

    Ectopic liver is a very uncommon developmental anomaly that predisposes to the development of hepatocellular carcinoma. We describe the second documented case of a hepatocellular carcinoma developing in the primary liver of a patient with a rare and uncharacterized genetic symptom complex. Also present was the largest ectopic liver ever reported, measuring 12 cm in diameter which contained a solitary focus of metastatic hepatocellular carcinoma. The primary hepatocellular carcinoma is believed to have arisen in the native liver from a hepatic adenoma that was diagnosed 15 years earlier. The patient's uncharacterised condition featured prominent thick, yellow skin over the dorsum of the fingers, and was associated with follicular hyperkeratosis, abnormal plantar creases, digital clubbing, misshaped ears, a lingua plicata and an angioleiomyolipoma of the right kidney. This unique case of hepatocellular carcinoma arising from liver cell adenoma in a patient with an uncharacterised condition featuring a large ectopic liver invites discussion of the role of local factors in carcinogenesis in the parent liver but not the ectopic liver. It also underlines the imperative ongoing need for clinical autopsies.

  8. Tactile impoverishment and sensorimotor restriction deteriorate the forepaw cutaneous map in the primary somatosensory cortex of adult rats.

    PubMed

    Coq, J O; Xerri, C

    1999-12-01

    We investigated the effects of sensory deprivation on the forepaw representation in the primary somatosensory cortex (SI) in the adult rat. Cortical maps were constructed from high-resolution multiunit recordings of the response of layer IV neurons to somatosensory stimuli. The main features of the forepaw representation were described in terms of areal extent and topography of the cortical map, and sensory submodality, size, and location of the receptive field (RF) of small clusters of the cortical neurons. After being weaned, two groups of Long-Evans rats were housed in a standard (SE) or impoverished (IE) environment for 65-115 days. A third group of SE rats was subjected to severe sensorimotor restriction (SR) of one forepaw for 7 days or 14 days, by using a one-sleeved cast. A concomitant effect of unilateral forelimb immobilization was a forced use of the nonrestricted forelimb in postural balance. The maps of both forepaws were derived 24 h after the cast was removed and the animal was allowed normal limb use. In a fourth group, SE rats experienced a 7-day immobilization followed by symmetrical limb use for 7 days before we mapped the hemisphere contralateral to the casted limb. For the SE and IE rats, the total areal extent of the cutaneous forepaw representation was similar, but IE rats exhibited a significant expansion of cortical islets serving high-threshold, presumably noncutaneous inputs, which were included in the cutaneous maps. In addition, SI neurons of IE rats had greatly enlarged glabrous, but not hairy, skin RFs. For the SR rats, the areal extent of the cutaneous map of the casted forepaw decreased by about 50%, after both 7- and 14-day forelimb immobilization. Large cortical sectors presumed to be formerly activated by cutaneous inputs were driven by high-threshold inputs that disrupted the somatotopic representation of the forepaw skin surfaces. These "emergent" representational sectors were topographically organized. By contrast, the areal

  9. 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)

  10. Functional Roles and Therapeutic Applications of Exosomes in Hepatocellular Carcinoma.

    PubMed

    Santangelo, Laura; Battistelli, Cecilia; Montaldo, Claudia; Citarella, Franca; Strippoli, Raffaele; Cicchini, Carla

    2017-01-01

    Exosomes are important in intercellular communication. They assure the horizontal transfer of specific functional contents (i.e., proteins, lipids, RNA molecules, and circulating DNA) from donor to recipient cells. Notably, tumor-derived exosomes (TDEs) appear to be an important vehicle of specific signals in cancer, impacting on tumor growth and metastasis. Recent researches point to the characterization of exosomes in Hepatocellular Carcinoma (HCC), the major adult liver malignancy. In this review, we summarize current findings on HCC exosomes, focusing on the identification of noncoding RNAs as exosome-enriched functional regulators and new potential biomarkers. The great potential of exosomes in future HCC diagnostic and therapeutic approaches is underlined.

  11. Functional Roles and Therapeutic Applications of Exosomes in Hepatocellular Carcinoma

    PubMed Central

    Montaldo, Claudia; Strippoli, Raffaele

    2017-01-01

    Exosomes are important in intercellular communication. They assure the horizontal transfer of specific functional contents (i.e., proteins, lipids, RNA molecules, and circulating DNA) from donor to recipient cells. Notably, tumor-derived exosomes (TDEs) appear to be an important vehicle of specific signals in cancer, impacting on tumor growth and metastasis. Recent researches point to the characterization of exosomes in Hepatocellular Carcinoma (HCC), the major adult liver malignancy. In this review, we summarize current findings on HCC exosomes, focusing on the identification of noncoding RNAs as exosome-enriched functional regulators and new potential biomarkers. The great potential of exosomes in future HCC diagnostic and therapeutic approaches is underlined. PMID:28265569

  12. Current Status of Therapy for Hepatocellular Carcinoma

    PubMed Central

    Corey, Kathleen E.

    2009-01-01

    The incidence of hepatocellular carcinoma (HCC) is increasing worldwide. A multi-disciplinary approach is required for its management. Screening high-risk patients allows for earlier diagnosis and the use of potentially curative therapies. Current recommendations for HCC screening for patients with cirrhosis are an abdominal ultrasound and serum alpha fetoprotein level every 6 to 12 months. Treatment choice depends on tumor stage, liver function and the patient's overall functional status. Curative therapies include surgical resection, liver transplantation (LT), transarterial chemoembolization, and radiofrequency ablation (RFA). Surgical resection, either primary resection or LT, is the treatment most likely to result in cure of HCC. Which option to pursue is based on multiple factors. LT has the potential benefit of treating both HCC and the underlying cirrhosis; however, long wait times incur the risk of tumor progression. Firm recommendations regarding the role of living donor LT for HCC are not yet possible because of conflicting data. HCC recurrence after LT is 8–11% and several adjuvant therapies have been investigated to reduce this. Bridging therapy and tumor downsizing are techniques that also may be considered to deal with long waiting periods and qualification for LT, respectively. If neither LT nor primary resection is possible, loco-regional therapies such as RFA and TACE should be considered. Systemic chemotherapies have proved disappointing for the treatment of HCC; however, newer targeted therapies such as sorafenib and cetuximab have provided new hope for the future. PMID:21180533

  13. Solitary sternal metastasis from hepatocellular carcinoma detected by F-18 FDG PET/CT.

    PubMed

    Kamaleshwaran, Koramadai Karuppusamy; Kashyap, Raghava; Bhattacharya, Anish; Mittal, Bhagwant Rai

    2013-01-01

    Fluorine-18 fluoro-deoxy-glucose positron emission tomography (F-18 FDG PET) is not sensitive modality for the diagnosis of primary hepatocellular carcinoma (HCC). However, FDG-PET imaging may be useful in the identification of extrahepatic metastases. We report an interesting image of HCC with solitary metastasis to sternum detected by F-18 FDG PET/CT.

  14. [Hepatocellular carcinoma. Part 2. Treatment].

    PubMed

    Conte, V P

    2000-01-01

    Recent improvements on the therapeutical management of hepatocellular carcinoma are revised with special attention to evaluate the role of surgery for the disease. Considering that definitive surgical intervention is not feasible in most cases because of extreme tumor extension, multiplicity of tumor foci, and associated advanced liver cirrhosis at the time of diagnosis, others forms of treatment are listed, such as transcatheterarterial chemoembolization, percutaneous ethanol and acetic acid injections, and chemotherapy only to a small portion of patients with no indication for standard treatments. The emerging role of retinoic acid metabolism blocking agents, was examined and may offer a significant new potential treatment for cancer, inclusive the possibility of combining other anticancer drugs with exogenous retinoids or modulation of endogenous retinoids as a real opportunity to advance our ability to treat or prevent human cancer effectively Octreotide, nitrosamine and other drugs are analyzed and is concluded that improves survival and is a valuable alternative in the treatment of inoperable hepatocellular carcinoma. The potential role of intersticial laser coagulation for patients with irresectable hepatic tumors was investigated, and in terms of experience, it has now been developed sufficiently to study its effect on these patients survival. The homeostatic control of angiogenesis and its influences on the tumor growth and for migration of metastatic cells, was focused in this concise review, given that hepatocytes are the source of much of the precursor pool, regulation of angiogenesis may be regarded as a new liver function with important consequences for tissue repair and cancer. Early hepatocellular carcinoma and its recognition in routine clinical practice contributes to improved patients survival. Recombinant-Interferon-alpha therapy surely prevents, the development of cirrhosis or hepatocellular carcinoma in about one-third of patients, with

  15. 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.

  16. 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

  17. Kinetics of antibody responses after primary immunization with meningococcal serogroup C conjugate vaccine or secondary immunization with either conjugate or polysaccharide vaccine in adults.

    PubMed

    de Voer, Richarda M; van der Klis, Fiona R M; Engels, Carla W A M; Schepp, Rutger M; van de Kassteele, Jan; Sanders, Elisabeth A M; Rijkers, Ger T; Berbers, Guy A M

    2009-11-23

    In the Netherlands the meningococcal serogroup C conjugate (MenCC) vaccine is administered as a single dose at 14 months. We evaluated the kinetics of isotype-specific antibodies in adults (n=21) after primary immunization with MenCC or secondary immunization with MenCC or plain MenC polysaccharide vaccine. Blood samples were collected prior to immunization and at 6 additional time points, from 3 to 25 days post-immunization. Secondary immunization resulted in 5-10-fold higher IgG titers compared to the primary immunization group, 25 days post-immunization. Prior to the secondary immunization, but 5 years after the first immunization, protective bactericidal antibodies and levels of MenC-specific IgG and IgM were still present. Furthermore, IgG antibodies present before secondary immunization were of higher avidity compared to antibodies produced one month after primary immunization. In addition, secondary immunization with nonconjugated MenC polysaccharide seemed to induce a higher IgG2 response compared to MenCC immunization. The kinetics of the observed secondary immune responses were not really faster than the observed primary responses. However, the rate of increase in antibodies seemed faster than the primary responses, representing a booster response. As the course of infection by Neisseria meningitidis can be very rapid, these data support the idea that sustainment of high antibody levels induced by MenCC are important for immediate protection.

  18. Environmental enrichment alters organizational features of the forepaw representation in the primary somatosensory cortex of adult rats.

    PubMed

    Coq, J O; Xerri, C

    1998-07-01

    The cortical forepaw area of young adult rats was mapped by recording the response properties of small clusters of neurons in layer IV of the primary somatosensory (SI) cortex. First we quantitatively analyzed the somatotopic organizational features of the cortical forepaw representation in terms of areal extent and topography, receptive field (RF) sensory modality, size, and location. We also assessed the influence of environmental enrichment, known to induce structural alterations in cortical connectivity, on the representational characteristics of the forepaw maps. Long-Evans rats were housed in environments (standard, SE; enriched, EE) promoting differential tactile experience for 71-113 days from weaning. Within the SI, we found a single and complete topographic map of the cutaneous surfaces of the forepaw consisting of a rostrolateral-caudomedial sequence of digit and pad representational zones. Small islets of noncutaneous responses (NCR; high-threshold, deep-receptor input) within the boundaries of the cutaneous maps were a conspicuous feature of the forepaw map for SE rats. These islets created discontinuities in the representation of contiguous skin territories. In the SE rats, about 79% of the cortical sites activated by light tactile stimulation had a single cutaneous RF, whereas about 21% exhibited multiple RFs. Most single-digit RFs we delineated in the SE rats extended across two or three phalanges. As a result, the representations of the phalangeal skin surfaces were not segregated but formed an overlapping continuum. Moreover, within these regions, as the electrode was displaced in regular steps across the mediolateral axis, RFs did not shift across the digit skin surface in an orderly manner, suggesting a lack of internal topography in the finger representation zones. Tactile experience promoted by environmental enrichment induced alterations in the representational features of the SI cutaneous map of the forepaw. In EE rats, the areal extent of

  19. Cervical Spinal Cord Compression: A Rare Presentation of Hepatocellular Carcinoma

    PubMed Central

    Chime, Chukwunonso; Arjun, Shiva; Reddy, Pavithra; Niazi, Masooma

    2017-01-01

    Hepatocellular carcinoma (HCC) is the most common primary malignancy of liver. Distant metastasis to various organs is well known. Skeletal metastasis is also reported to various locations. Vertebral metastasis has been reported mostly to thoracic spine. However, cervical spinal cord involvement leading to cord compression has been reported very rarely in literature. We present a case of 58-year-old male with liver cirrhosis presenting as neck pain. Further work-up revealed metastatic HCC to cervical spinal cord resulting in acute cord compression. Patient has been treated with neurosurgical intervention. PMID:28299213

  20. Esthetic restoration of infra-occluded retained primary mandibular incisors with all-ceramic crowns in adult dentition.

    PubMed

    Hsu, Kuang-Wei; Shen, Yu-Fu

    2004-12-01

    The prevalence of hypodontia is reported to be between 1.5% to 10% in the permanent dentition. In the anterior teeth, maxillary lateral incisors and mandibular central incisors are the most frequently involved teeth. This causes esthetic problems for the patient. Several reports have focused on restoration of retained maxillary primary anterior teeth, but none have described restoration of retained mandibular primary incisors. This clinical report describes the restoration of infra-occluded retained primary mandibular central incisors of a 17 year-old girl diagnosed with hypodontia. All-ceramic crowns made with computer-aided design/ computer-aided manufacturing technology were used to restore the teeth incisally and interproximally. Due to a relatively short root length and inadequate crown-root ratio, the primary mandibular central incisors were splinted and adjusted to distribute the protrusive force evenly across the maxillary and mandibular incisors. Functional and esthetic results were achieved.

  1. National Use of Safety-Net Clinics for Primary Care among Adults with Non-Medicaid Insurance in the United States

    PubMed Central

    Nguyen, Oanh Kieu; Makam, Anil N.; Halm, Ethan A.

    2016-01-01

    Objective To describe the prevalence, characteristics, and predictors of safety-net use for primary care among non-Medicaid insured adults (i.e., those with private insurance or Medicare). Methods Cross-sectional analysis using the 2006–2010 National Ambulatory Medical Care Surveys, annual probability samples of outpatient visits in the U.S. We estimated national prevalence of safety-net visits using weighted percentages to account for the complex survey design. We conducted bivariate and multivariate logistic regression analyses to examine characteristics associated with safety-net clinic use. Results More than one-third (35.0%) of all primary care safety-net clinic visits were among adults with non-Medicaid primary insurance, representing 6,642,000 annual visits nationally. The strongest predictors of safety-net use among non-Medicaid insured adults were: being from a high-poverty neighborhood (AOR 9.53, 95% CI 4.65–19.53), being dually eligible for Medicare and Medicaid (AOR 2.13, 95% CI 1.38–3.30), and being black (AOR 1.97, 95% CI 1.06–3.66) or Hispanic (AOR 2.28, 95% CI 1.32–3.93). Compared to non-safety-net users, non-Medicaid insured adults who used safety-net clinics had a higher prevalence of diabetes (23.5% vs. 15.0%, p<0.001), hypertension (49.4% vs. 36.0%, p<0.001), multimorbidity (≥2 chronic conditions; 53.5% vs. 40.9%, p<0.001) and polypharmacy (≥4 medications; 48.8% vs. 34.0%, p<0.001). Nearly one-third (28.9%) of Medicare beneficiaries in the safety-net were dual eligibles, compared to only 6.8% of Medicare beneficiaries in non-safety-net clinics (p<0.001). Conclusions Safety net clinics are important primary care delivery sites for non-Medicaid insured minority and low-income populations with a high burden of chronic illness. The critical role of safety-net clinics in care delivery is likely to persist despite expanded insurance coverage under the Affordable Care Act. PMID:27027617

  2. Health benefits of primary care social work for adults with complex health and social needs: a systematic review.

    PubMed

    McGregor, Jules; Mercer, Stewart W; Harris, Fiona M

    2016-04-05

    The prevalence of complex health and social needs in primary care patients is growing. Furthermore, recent research suggests that the impact of psychosocial distress on the significantly poorer health outcomes in this population may have been underestimated. The potential of social work in primary care settings has been extensively discussed in both health and social work literature and there is evidence that social work interventions in other settings are particularly effective in addressing psychosocial needs. However, the evidence base for specific improved health outcomes related to primary care social work is minimal. This review aimed to identify and synthesise the available evidence on the health benefits of social work interventions in primary care settings. Nine electronic databases were searched from 1990 to 2015 and seven primary research studies were retrieved. Due to the heterogeneity of studies, a narrative synthesis was conducted. Although there is no definitive evidence for effectiveness, results suggest a promising role for primary care social work interventions in improving health outcomes. These include subjective health measures and self-management of long-term conditions, reducing psychosocial morbidity and barriers to treatment and health maintenance. Although few rigorous study designs were found, the contextual detail and clinical settings of studies provide evidence of the practice applicability of social work intervention. Emerging policy on the integration of health and social care may provide an opportunity to develop this model of care.

  3. Hepatocellular carcinoma with both fibrolamellar and classical components: an unusual morphological pattern.

    PubMed

    Castro-Villabón, Diana; Barrera-Herrera, Luis E; Rodríguez-Urrego, Paula A; Hudacko, Rachel; Vera, Alonso; Álvarez, Johanna; Andrade, Rafael; López, Rocío

    2015-01-01

    Fibrolamellar carcinoma (FLC) is an uncommon form of primary liver malignancy with unique clinical, histological, and biological characteristics. It is usually seen in young adults without underlying liver disease. Histologically, it shows large cells with abundant eosinophilic cytoplasm, large vesicular nuclei, prominent nucleoli, and lamellar type fibrosis. In contrast, classical hepatocellular carcinoma (HCC) is typically present in elderly male patients with cirrhosis. It is the most common histological subtype, and it is characterized by its resemblance to the normal liver, both in its growth pattern and its cytology. The unusual case of a liver carcinoma that presented with histological features of both FLC and classical HCC is herein reported. This was the case of a 37-year-old female complaining of diffuse abdominal discomfort and epigastric pain for two months. She was referred to us for further management after she was diagnosed with HCC in a noncirrhotic liver. She underwent a left-sided hepatectomy. A yellow nodular mass with well-defined borders and a necrotic center was present in the resection specimen. The morphological features and immunohistochemical studies were consistent with a diagnosis of FLC mixed with classical HCC. The patient was followed up for five months, and no signs of recurrence were evident.

  4. 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

  5. Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma

    PubMed Central

    Dayton, Talya L.; Gocheva, Vasilena; Miller, Kathryn M.; Israelsen, William J.; Bhutkar, Arjun; Clish, Clary B.; Davidson, Shawn M.; Luengo, Alba; Bronson, Roderick T.; Jacks, Tyler; Vander Heiden, Matthew G.

    2016-01-01

    Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase (PK), and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. To interrogate the functional requirement for PKM2 during development and tissue homeostasis, we generated germline PKM2-null mice (Pkm2−/−). Unexpectedly, despite being the primary isoform expressed in most wild-type adult tissues, we found that Pkm2−/− mice are viable and fertile. Thus, PKM2 is not required for embryonic or postnatal development. Loss of PKM2 leads to compensatory expression of PKM1 in the tissues that normally express PKM2. Strikingly, PKM2 loss leads to spontaneous development of hepatocellular carcinoma (HCC) with high penetrance that is accompanied by progressive changes in systemic metabolism characterized by altered systemic glucose homeostasis, inflammation, and hepatic steatosis. Therefore, in addition to its role in cancer metabolism, PKM2 plays a role in controlling systemic metabolic homeostasis and inflammation, thereby preventing HCC by a non-cell-autonomous mechanism. PMID:27125672

  6. Management of large hepatocellular carcinoma.

    PubMed

    Amarapurkar, D N

    2004-04-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. There is increasing incidence of HCC in India. More than 70% of HCC are not suitable for curative treatment. Majority of the HCCs are large when diagnosed all over the world. There is no standard treatment for large HCCs. Different palliative treatments like arterial embolization/chemoembolization, intraarterial lipoidol chemotherapy, hormonal compounds like tamoxifene, octerotide systemic chemotherapy, immuno therapy with interferon, internal radiation with 131I or 99Yttrium. Arterial chemoembolization is the treatment of choice with proved efficacy in selected group of patients. The newer modalities and strategies need to be tried in controlled randomized trials.

  7. 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.

  8. How grim is hepatocellular carcinoma?

    PubMed Central

    Weledji, Elroy P.; Enow Orock, George; Ngowe, Marcelin N.; Nsagha, Dickson Shey

    2014-01-01

    Hepatocellular carcinoma (HCC) is a complex disease and a major cause of death in high endemic areas of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. HCC has gone from being a universal death sentence to a cancer that can be prevented, detected at an early stage and effectively treated. Liver resection or tumour ablation techniques may be effective bridge to liver transplantation if they fulfill the Milan criteria. The areas of progress in HCC are in the control of HBV or HCV and the development of adjuvant or neoadjuvant therapies. PMID:25568791

  9. 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.

  10. 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…

  11. 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…

  12. Pediatric hepatocellular carcinoma: challenges and solutions

    PubMed Central

    Schmid, Irene; von Schweinitz, Dietrich

    2017-01-01

    Hepatocellular carcinoma (HCC) is a very rare entity in children, making it nearly impossible to orchestrate Phase II/III studies even as multinational cooperative trials. In contrast to adults, nearly 50% of the children have a response (α-fetoprotein decline and/or tumor shrinkage) to chemotherapeutic agents such as cisplatin and doxorubicin (PLADO), demonstrating that HCC in childhood can be chemotherapy sensitive. As a result, the main treatment options in pediatric HCC focus on systemic drug therapies and resection as the central therapy. In nonmetastatic patients with complete resection upfront, the 5-year event-free survival and overall survival has reached 80%–90%. In almost all reported studies, children received adjuvant chemotherapy (mostly PLADO), but it has never been proven that postoperative chemotherapy is superior to observation. No data are available for the effects of sorafenib. The 3-year survival is <20% in children with unresectable HCC independent of the chemotherapy given preoperatively. Currently, PLADO in combination with sorafenib is recommended with the goal of achieving operability status. Alternatively, data are promising for the combination of sorafenib with gemcitabine and oxaliplatin. For children with nonresectable and nonmetastastic liver tumors, it has been shown that the Milan criteria regarding liver transplantation are not applicable – individual decisions have to be made. Transarterial chemoembolization could be offered to patients with chemotherapy-resistant liver tumors for palliative care or potentially to achieve surgical resectability, and therefore cure. Information about the feasibility or effects of new agents or approaches as discussed in adult HCC patients is not available for childhood HCC. Research has to be done for characterizing the molecular and genomic mechanisms of pediatric HCC to support the development of novel therapeutic approaches and the implementation of personalized medicine. PMID:28144610

  13. A Survey of Primary Care Provider Attitudes and Behaviors Regarding Treatment of Adult Depression: What Changes After a Collaborative Care Intervention?

    PubMed Central

    Upshur, Carole; Weinreb, Linda

    2008-01-01

    Objective: To assess primary care provider (PCP) attitudes and self-reported behavior with regard to identifying and managing depression in adult patients before and after a chronic disease/collaborative care intervention. Method: A self-administered cross-sectional survey was conducted in 6 targeted practices among 39 family practice physicians, family nurse practitioners, and residents before and after implementation of a depression in primary care project. In this project, the sites received tools and training in depression screening and guideline-concordant treatment, facilitated referral services for patients to access mental health providers, psychiatric phone consultation, patient education materials, and services of a depression care manager. The project was conducted from June 2003 through June 2006. Results: Comparison of responses prior to and after the intervention showed that significantly or nearly significantly larger proportions of PCPs endorsed the importance of depression as a patient presenting problem (p = .000), increased provision of supportive counseling (p = .13), more often identified counseling or therapy as effective (p = .07), and more often referred patients to mental health services (p = .001). PCPs also reduced their perception that treating depression is time consuming (p = .000). Conclusions: After a chronic disease/collaborative care approach to depression treatment in primary care was implemented, PCP attitudes and behaviors about depression treatment were significantly modified. More guideline-concordant care, and increased collaboration with mental health services, was reported. Implications for future primary care depression intervention activities and research are discussed. PMID:18615167

  14. Do occupational exposures to vinyl chloride cause hepatocellular carcinoma and cirrhosis?

    PubMed

    Lotti, Marcello

    2017-01-07

    Controversy exists about the association between occupational exposures to vinyl chloride and hepatocellular carcinoma and cirrhosis. Two large multicentre mortality cohort studies, one American and another European, reported higher mortality for primary cancer of liver and biliary tract. However, the American study was not able to rule out misclassification, because based on death certificates and under the heading primary liver cancers, some angiosarcomas, the typical neoplasia associated with vinyl chloride, may have been included. The American study does not report on cirrhosis mortality. The European study also reports higher mortality of primary liver cancer, but contrary to the American study in a further analysis based on 10 verified cases of hepatocellular carcinoma, an exposure-response trend with duration of employment and with cumulative exposure to vinyl chloride was detected. A smaller cohort belonging to this multicentre cohort confirmed these results. Meta-analyses based on the two large cohorts concluded for a small excess of primary liver cancer, although misclassification could not be ruled out. Excess risk of cirrhosis was reported in the European cohort, in a subcohort and in a cross-sectional study. However, a meta-analysis did not confirm this excess. Several critical appraisals of the literature reached antithetical conclusions about hepatocellular carcinoma, cirrhosis and occupational exposures to vinyl chloride. For both hepatocellular carcinoma and cirrhosis, a study suggests an additive and multiplicative effect of vinyl chloride exposure with viral hepatitis and alcohol consumption respectively. Pathology reports seem to indicate a possible development of hepatocellular carcinoma but not of cirrhosis after high exposures to vinyl chloride.

  15. 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.

  16. 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

  17. 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

  18. Combination of cytogenetic classification and MRD status correlates with outcome of autologous versus allogeneic stem cell transplantation in adults with primary acute myeloid leukemia in first remission.

    PubMed

    Yao, Jianfeng; Zhang, Guixin; Liang, Chen; Li, Gang; Chen, Xin; Ma, Qiaoling; Zhai, Weihua; Yang, Donglin; He, Yi; Jiang, Erlie; Feng, Sizhou; Han, Mingzhe

    2017-04-01

    Both autologous and allogeneic stem cell transplantation (auto- and allo-SCT) are treatment choice for adults with acute myeloid leukemia (AML) after complete remission (CR). However, the decision-making remains controversial in some situations. To figure out the treatment choice, we retrospectively investigated 172 consecutive patients with primary AML who received auto- (n=46) or allo-SCT (n=126) from a single transplant center. Auto- and allo-SCT group demonstrated comparable overall survival (OS) and disease-free survival (DFS) (P=0.616, P=0.559, respectively). Cytogenetic classification and minimal residual disease (MRD) after one course of consolidation were identified as independent risk factors for DFS (hazard ratio (HR), 1.800; 95% CI, 1.172-2.763; P=0.007; HR, 2.042; 95%CI, 1.003-4.154; P=0.049; respectively). We subsequently found that auto- and allo-SCT offered comparable DFS to patients with favorable or intermediate risk and were tested MRD(neg) after one course of consolidation (P=0.270) otherwise auto-SCT were inferior due to increased risk of leukemia relapse. Our study indicated that the combination of cytogenetic classification and MRD monitoring correlated with outcome of auto- versus allo-SCT and might help the choice between the two types of SCT for adults with primary AML, which is of significance for patients with expected intermediate prognosis in the current scenario.

  19. 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…

  20. Connexin36 identified at morphologically mixed chemical/electrical synapses on trigeminal motoneurons and at primary afferent terminals on spinal cord neurons in adult mouse and rat.

    PubMed

    Bautista, W; McCrea, D A; Nagy, J I

    2014-03-28

    Morphologically mixed chemical/electrical synapses at axon terminals, with the electrical component formed by gap junctions, is common in the CNS of lower vertebrates. In mammalian CNS, evidence for morphologically mixed synapses has been obtained in only a few locations. Here, we used immunofluorescence approaches to examine the localization of the neuronally expressed gap junction forming protein connexin36 (Cx36) in relation to the axon terminal marker vesicular glutamate transporter-1 (vglut1) in the spinal cord and the trigeminal motor nucleus (Mo5) of rat and mouse. In adult rodents, immunolabeling for Cx36 appeared exclusively as Cx36-puncta, and was widely distributed at all rostro-caudal levels in most spinal cord laminae and in the Mo5. A high proportion of Cx36-puncta was co-localized with vglut1, forming morphologically mixed synapses on motoneurons, in intermediate spinal cord lamina, and in regions of medial lamina VII, where vglut1-containing terminals associated with Cx36 converged on neurons adjacent to the central canal. Unilateral transection of lumbar dorsal roots reduced immunolabeling of both vglut1 and Cx36 in intermediate laminae and lamina IX. Further, vglut1-terminals displaying Cx36-puncta were contacted by terminals labeled for glutamic acid decarboxylase65, which is known to be contained in presynaptic terminals on large-diameter primary afferents. Developmentally, mixed synapses begin to emerge in the spinal cord only after the second to third postnatal week and thereafter increase to adult levels. Our findings demonstrate that axon terminals of primary afferent origin form morphologically mixed synapses containing Cx36 in broadly distributed areas of adult rodent spinal cord and Mo5.

  1. How can we build resilience in primary school aged children? The importance of social support from adults and peers in family, school and community settings.

    PubMed

    Stewart, D; Sun, J

    2004-01-01

    This study examines the association between firstly, student resiliency and their perceptions of social support from parents/caregivers, teachers, and peers, and secondly, between student's perception of their general health status and their social support. A cross-sectional research project was designed and conducted in 2003 in an urban and remote area of Queensland, Australia. The study population comprised of 2580 students (Years three, five, and seven) across 20 primary schools. The main outcome measures were self-reported health status and resiliency behaviours. Independent variables included student perceptions of support from parents/caregivers, teachers, school peers, and prosocial groups. Students who perceived parents, teachers, and peers as supportive were more likely to have higher resiliency behaviour in communication and cooperation, self-esteem, empathy, help-seeking, goals and aspirations. Students who considered that their parents, peers at school and prosocial groups were supportive, were more likely to feel healthy. Findings suggest that providing adult and peer support to students at primary school age is a vital strategy in promoting student resiliency and general health for children of primary school age.

  2. 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.

  3. Secondary Psychopathy, but not Primary Psychopathy, is Associated with Risky Decision-Making in Noninstitutionalized Young Adults.

    PubMed

    Dean, Andy C; Altstein, Lily L; Berman, Mitchell E; Constans, Joseph I; Sugar, Catherine A; McCloskey, Michael S

    2013-01-01

    Although risky decision-making has been posited to contribute to the maladaptive behavior of individuals with psychopathic tendencies, the performance of psychopathic groups on a common task of risky decision-making, the Iowa Gambling Task (IGT; Bechara, Damasio, Damasio, & Anderson, 1994), has been equivocal. Different aspects of psychopathy (personality traits, antisocial deviance) and/or moderating variables may help to explain these inconsistent findings. In a sample of college students (N = 129, age 18 to 27), we examined the relationship between primary and secondary psychopathic features and IGT performance. A measure of impulsivity was included to investigate its potential as a moderator. In a joint model including main effects and interactions between primary psychopathy, secondary psychopathy and impulsivity, only secondary psychopathy was significantly related to risky IGT performance, and this effect was not moderated by the other variables. This finding supports the growing literature suggesting that secondary psychopathy is a better predictor of decision-making problems than the primary psychopathic personality traits of lack of empathy and remorselessness.

  4. Differential effects of long-term exposure to Aroclor 1254 on lipid secretion by primary cultures of adult rat hepatocytes

    SciTech Connect

    Mendoza-Figueroa, T.; Hernandez, A.; Lopez, L.

    1992-06-01

    PCBs produce hepatic triglyceride (TG) accumulation (fatty liver) in experimental animals and humans exposed accidentally and occupationally. It has been suggested that this effect could be due to a block in TG secretion. On the other hand, increased levels of plasmatic TG and cholesterol have been described in rats after dietary exposure to Aroclor 1254 (Aro) and other PCBs; hypertriglyceridemia and hypertension have been also described in humans exposed for long periods to low concentrations of PCBs. Since the study of hepatic lipid metabolism and its alteration by toxic chemicals is complicated in the whole animal, short term cultures of adult rat hepatocytes have been used. We have described a system for the long term culture of adult rat hepatocytes which for several weeks maintain differentiated functions, like fatty acid and TG synthesis and their export to the culture medium. In this paper we used this culture system to study the effect of long-term exposure to micromolar concentrations of Aro on the secretion of lipids by cultured hepatocytes. 27 refs., 4 figs., 1 tab.

  5. 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

  6. 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

  7. 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

  8. 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

  9. Thermal ablation for hepatocellular carcinoma.

    PubMed

    Head, Hayden W; Dodd, Gerald D

    2004-11-01

    Thermal ablation, as a form of minimally invasive therapy for hepatocellular carcinoma (HCC), has become an important treatment modality. Because of the limitations of surgery, the techniques of thermal ablation have become standard therapies for HCC in some situations. This article reviews 4 thermal ablation techniques-radiofrequency (RF) ablation, microwave ablation, laser ablation, and cryoablation. Each of these techniques may have a role in treating HCC, and the mechanisms, equipment, patient selection, results, and complications of each are considered. Furthermore, combined therapies consisting of thermal ablation and adjuvant chemotherapy also show promise for enhancing these techniques. Important areas of research into thermal ablation remain, including improving the ability of ablation to treat larger tumors, determining the indications for each thermal ablation modality, optimizing image guidance, and obtaining good outcome data on the efficacy of these techniques.

  10. Transarterial Therapies for Hepatocellular Carcinoma

    PubMed Central

    Lanza, Ezio; Donadon, Matteo; Poretti, Dario; Pedicini, Vittorio; Tramarin, Marco; Roncalli, Massimo; Rhee, Hyungjin; Park, Young Nyun; Torzilli, Guido

    2016-01-01

    Background The treatment of hepatocellular carcinoma (HCC) is still a major health issue because of its increasing incidence and because of the complexity of its management. Transarterial embolization (TAE) and transarterial chemoembolization (TACE) are two widely used locoregional therapies in the treatment of HCC, especially for unresectable intermediate and advanced HCCs. Summary The modern use of TAE and TACE opens new scenarios for the treatment of unresectable HCC and has yielded interesting results. The present work describes the role of transarterial therapies for HCC and focuses on the different Western and Eastern approaches to the study of response predictors. Key Messages Recent refinements in interventional radiology techniques and in HCC patient selection have facilitated better local control of the disease. The molecular profiling of HCC to predict the response to TACE and TAE will greatly help clinicians identify the optimum therapy. PMID:27995085

  11. Percutaneous cryoablation for hepatocellular carcinoma

    PubMed Central

    Song, Kyoung Doo

    2016-01-01

    Local ablation therapy is considered as a conventional treatment option for patients with early stage hepatocellular carcinoma (HCC). Although radiofrequency (RF) ablation is widely used for HCC, the use of cryoablation has been increasing as newer and safer cryoablation systems have developed. The thermodynamic mechanism of freezing and thawing used in cryoablation is the Joule-Thomson effect. Cryoablation destroys tissue via direct tissue destruction and vascular-related injury. A few recent comparative studies have shown that percutaneous cryoablation for HCCs is comparable to percutaneous RF ablation in terms of long term therapeutic outcomes and complications. Cryoablation has several advantages over RF ablation such as well visualization of iceball, no causation of severe pain, and lack of severe damage to great vessels and gallbladder. It is important to know the advantages and disadvantages of cryoablation compared with RF ablation for improvement of therapeutic efficacy and safety. PMID:28081593

  12. 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

  13. Incidence of adult Huntington's disease in the UK: a UK-based primary care study and a systematic review

    PubMed Central

    Wexler, Nancy S; Collett, Laura; Wexler, Alice R; Rawlins, Michael D; Tabrizi, Sarah J; Douglas, Ian; Smeeth, Liam; Evans, Stephen J

    2016-01-01

    Objectives The prevalence of Huntington's disease (HD) recorded in the UK primary care records has increased twofold between 1990 and 2010. This investigation was undertaken to assess whether this might be due to an increased incidence. We have also undertaken a systematic review of published estimates of the incidence of HD. Setting Incident patients with a new diagnosis of HD were identified from the primary care records of the Clinical Practice Research Datalink (CPRD). The systematic review included all published estimates of the incidence of HD in defined populations. Participants A total of 393 incident cases of HD were identified from the CPRD database between 1990 and 2010 from a total population of 9 282 126 persons. Primary and secondary outcome measures The incidence of HD per million person-years was estimated. From the systematic review, the extent of heterogeneity of published estimates of the incidence of HD was examined using the I2 statistic. Results The data showed that the incidence of HD has remained constant between 1990 and 2010 with an overall rate of 7.2 (95% CI 6.5 to 7.9) per million person-years. The systematic review identified 14 independent estimates of incidence with substantial heterogeneity and consistently lower rates reported in studies from East Asia compared with those from Australia, North America and some—though not all—those from Europe. Differences in incidence estimates did not appear to be explained solely by differences in case ascertainment or diagnostic methods. Conclusions The rise in the prevalence of diagnosed HD in the UK, between 1990 and 2010, cannot be attributed to an increase in incidence. Globally, estimates of the incidence of HD show evidence of substantial heterogeneity with consistently lower rates in East Asia and parts of Europe. Modifiers may play an important role in determining the vulnerability of different populations to expansions of the HD allele. PMID:26908513

  14. 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.

  15. Correlates of Opioid Use in Adults with Self-Reported Drug Use Recruited from Public Safety-Net Primary Care Clinics

    PubMed Central

    Ries, Richard; Krupski, Antoinette; West, Imara I.; Maynard, Charles; Bumgardner, Kristin; Donovan, Dennis; Dunn, Chris; Roy-Byrne, Peter

    2015-01-01

    Objectives The purpose of this study was to compare demographic, clinical, and survival characteristics of drug-using safety-net primary care patients who used or did not use opioids, and to examine treatment implications of our findings. Methods The sample consisted of 868 adults who reported illicit drug use in the 90 days prior to study enrollment, 396 (45.6%) of whom were opioid users. Results Multiple measures indicated that, as a group, opioid users were less physically and psychiatrically healthy than drug users who did not endorse using opioids, and were heavy users of medical services (e.g., emergency departments, inpatient hospitals, outpatient medical) at considerable public expense. After adjusting for age, they were 2.61 (CI, 1.48-4.61) times more likely to die in the 1 to 5 years after study enrollment and more likely to die from accidental poisoning than non-opioid users. Subgroup analyses suggested patients using any non-prescribed opioids had more serious drug problems including more intravenous drug use and greater HIV risk than patients using opioids only as prescribed. Conclusions Use of opioids adds a dimension of severity over and above illicit drug use as it presents in the primary care setting. Opioid users may benefit from psychiatric and addiction care integrated into their primary care setting, naloxone overdose prevention kits, and prevention efforts such as clean needle exchanges. Addiction or primary care providers are in a key position to facilitate change among such patients, especially the third or more opioid users having a goal of abstinence from drugs. PMID:26428361

  16. Progressive adult primary glioblastoma in the medulla oblongata with an unmethylated MGMT promoter and without an IDH mutation.

    PubMed

    Yoshikawa, Akifumi; Nakada, Mitsutoshi; Watanabe, Takuya; Hayashi, Yutaka; Sabit, Hemragul; Kato, Yukinari; Suzuki, Shioto; Ooi, Akishi; Sato, Hiroshi; Hamada, Jun-ichiro

    2013-07-01

    A 63-year-old woman presented with dizziness followed by gait disturbance and loss of appetite. Magnetic resonance image (MRI) showed that a lesion located in the medulla oblongata, appearing as hyperintense on T2-weighted image and with slight enhancement area, appeared in the ventral aspect of the mass on T1-weighted MR imaging with gadolinium. It was diagnosed as high-grade brain-stem glioma and the patient underwent chemoradiotherapy. However, she died 18 days after treatment, and autopsy was performed. The pathological diagnosis was glioblastoma (GBM) with unmethylated O-6-methylguanine-DNA methyltransferase promoter and wild isocitrate dehydrogenase 1 gene. We report an extremely short clinical course of adult GBM in medulla oblongata with genetic analysis and present a review of the literature.

  17. 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

  18. Primary hyperoxaluria in an adult presenting with end-stage renal failure together with hypercalcemia and hypothyroidism.

    PubMed

    Karadag, Serhat; Gursu, Meltem; Aydin, Zeki; Uzun, Sami; Dogan, Oner; Ozturk, Savas; Kazancioglu, Rumeyza

    2011-10-01

    Primary hyperoxaluria (PH) is a rare genetic disorder characterized by overproduction of oxalate due to specific enzyme deficiencies in glyoxylate metabolism. The primary clinical presentation is in the form of recurrent urolithiasis, progressive nephrocalcinosis, end-stage renal disease, and systemic oxalosis. Herein, we present a case of PH who was diagnosed at 47 years of age after 6 years on hemodialysis. He presented with fatigue, anorexia, weight loss, and was found to have cachexia, diffuse edema, hepatomegaly, ascites, hypercalcemia, hyperphosphatemia, hypoalbuminemia, low parathyroid hormone levels, lytic and resorptive areas in the vertebrae, diffusely increased echogenity of the liver, multiple renal stones, and bilateral nephrocalcinosis. Bone marrow biopsy showed calcium oxalate crystals and crystal granulomas. The liver biopsy could not be performed. The absence of an identifiable reason for secondary forms, the severity of the clinical presentation, and pathological findings led to the diagnosis of PH2. He died while waiting for a potential liver and kidney donor. The presented case is consistent with the literature as he had renal stone disease in the third decade and end-stage renal disease in the fifth decade. Hypercalcemia was thought to be due to osteoclast-stimulating activity of macrophages constituting the granuloma. Erythropoietin-resistant anemia and hypothyroidism were thought to be due to accumulation of oxalate in the bone marrow and thyroid gland, respectively. It is very important to keep in mind the possibility of PH when faced with a patient with nephrocalcinosis and oxalate stone disease.

  19. A Comparative Study of Intravenous Immunoglobulin and Subcutaneous Immunoglobulin in Adult Patients with Primary Immunodeficiency Diseases: A Systematic Review and Meta-Analysis.

    PubMed

    Shabaninejad, Hosein; Asgharzadeh, Asra; Rezaei, Nima; Rezapoor, Aziz

    2016-01-01

    Subcutaneous immunoglobulin (SCIG) is a new therapeutic procedure for patients with primary immunodeficiency (PI). This research is a systematic review of studies on the efficacy and safety of intravenous immunoglobulin (IVIG) and SCIG in adult patients with PI. This study includes a systematic review of cohorts and randomized clinical trials (24 articles) from 5 databases with no time limits. Random effects meta-analysis was performed for outcomes such as efficacy and safety. Standard mean difference (SMD) of serum immunoglobulin level was equal to 0.336 (P <0.01; 0.205-0.467) and the odds ratio (OR) of side effects was 0.497 (P=0.1; 0.180-1.371). The results indicate that SCIG leads to a higher level of immunoglobulin and a reduction in side effects but shows the same infection rate as IVIG. Our analysis shows that shifting from IVIG to SCIG therapy can have clinical benefits for PI patients.

  20. Evaluating the Implementation of Health Checks for Adults With Intellectual and Developmental Disabilities in Primary Care: The Importance of Organizational Context.

    PubMed

    Durbin, Janet; Selick, Avra; Casson, Ian; Green, Laurie; Spassiani, Natasha; Perry, Andrea; Lunsky, Yona

    2016-04-01

    Compared to other adults, those with intellectual and developmental disabilities have more health issues, yet are less likely to receive preventative care. One strategy that has shown success in increasing prevention activities and early detection of illness is the periodic comprehensive health assessment (the health check). Effectively moving evidence into practice is a complex process that often receives inadequate attention. This qualitative study evaluates the implementation of the health check at two primary-care clinics in Ontario, Canada, and the influence of the clinic context on implementation decisions. Each clinic implemented the same core components; however, due to contextual differences, some components were operationalized differently. Adapting to the setting context is important to ensuring successful and sustainable implementation.

  1. The Influence of Primary Care and Hospital Supply on Ambulatory Care–Sensitive Hospitalizations Among Adults in Brazil, 1999–2007

    PubMed Central

    de Oliveira, Veneza B.; Turci, Maria A.; Guanais, Frederico C.; Bonolo, Palmira F.; Lima-Costa, Maria F.

    2011-01-01

    Objectives. We assessed the influence of changes in primary care and hospital supply on rates of ambulatory care–sensitive (ACS) hospitalizations among adults in Brazil. Methods. We aggregated data on nearly 60 million public sector hospitalizations between 1999 and 2007 to Brazil's 558 microregions. We modeled adult ACS hospitalization rates as a function of area-level socioeconomic factors, health services supply, Family Health Program (FHP) availability, and health needs by using dynamic panel estimation techniques to control for endogenous explanatory variables. Results. The ACS hospitalization rates declined by more than 5% annually. When we controlled for other factors, FHP availability was associated with lower ACS hospitalization rates, whereas private or nonprofit hospital beds were associated with higher rates. Areas with highest predicted ACS hospitalization rates were those with the highest private or nonprofit hospital bed supply and with low (< 25%) FHP coverage. The lowest predicted rates were seen for areas with high (> 75%) FHP coverage and very few private or nonprofit hospital beds. Conclusions. These results highlight the contribution of the FHP to improved health system performance and reflect the complexity of the health reform processes under way in Brazil. PMID:21330584

  2. Necrotizing Fasciitis Secondary to a Primary Suture for Anoperineal Trauma by Motorcycle Accident in a Healthy Adult

    PubMed Central

    Saigusa, Susumu; Ohi, Masaki; Imaoka, Hiroki; Uratani, Ryo; Kobayashi, Minako; Inoue, Yasuhiro

    2015-01-01

    A 41-year-old man experienced a swollen scrotum three days after a motorcycle accident and presented to our hospital. He had had a primary suture repair for anoperineal trauma in an outside hospital at the time of the injury. He presented to us with general fatigue, low grade fevers, and perineal pain. Abdominal computed tomography showed subcutaneous emphysema from the scrotum to the left chest. The sutured wound had foul-smelling discharge and white exudate. We made the diagnosis of necrotizing fasciitis and immediately opened the sutured wound and performed initial debridement and lavage with copious irrigation. We continued antibiotics and lavage of the wound until the infection was controlled. Fortunately, the necrotizing fasciitis did not worsen and he was discharged after 15 days. Our experience indicates that anoperineal injuries should not be closed without careful and intensive follow-up due to the potential of developing necrotizing fasciitis. PMID:26347831

  3. 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

  4. Processing of positive-causal and negative-causal coherence relations in primary school children and adults: a test of the cumulative cognitive complexity approach in German.

    PubMed

    Knoepke, Julia; Richter, Tobias; Isberner, Maj-Britt; Naumann, Johannes; Neeb, Yvonne; Weinert, Sabine

    2017-03-01

    Establishing local coherence relations is central to text comprehension. Positive-causal coherence relations link a cause and its consequence, whereas negative-causal coherence relations add a contrastive meaning (negation) to the causal link. According to the cumulative cognitive complexity approach, negative-causal coherence relations are cognitively more complex than positive-causal ones. Therefore, they require greater cognitive effort during text comprehension and are acquired later in language development. The present cross-sectional study tested these predictions for German primary school children from Grades 1 to 4 and adults in reading and listening comprehension. Accuracy data in a semantic verification task support the predictions of the cumulative cognitive complexity approach. Negative-causal coherence relations are cognitively more demanding than positive-causal ones. Moreover, our findings indicate that children's comprehension of negative-causal coherence relations continues to develop throughout the course of primary school. Findings are discussed with respect to the generalizability of the cumulative cognitive complexity approach to German.

  5. Efficacy and safety of ClairYg®, a ready-to-use intravenous immunoglobulin, in adult patients with primary immune thrombocytopenia

    PubMed Central

    Slama, Borhane; Fain, Olivier; Maisonneuve, Hervé; Jourdan, Eric; Viallard, Jean-François; Ouaja, Rabye; Alfa-Cissé, Ousmane; Godeau, Bertrand

    2017-01-01

    Purpose: The present study was designed to assess the efficacy and safety of IGNG that is a new liquid, saccharose and maltose-free highly purified ready-to-use 5% intravenous immunoglobulin (IVIg), in primary immune thrombocytopenic patients with severe thrombocytopenia. Methods: Nineteen adults with a platelet count ≤ 25 × 109/L received a single dose of IGNG (1 g/kg) on Day 1, with a second identical dose on Day 3 if needed. Patients were followed for 30 days. Primary endpoint was the response rate, defined as the proportion of patients with a platelet count ≥ 50 × 109/L within 96 hours after the first IGNG dose. Results: All but one of the 17 evaluable patients for efficacy responded with an overall response rate of 94.1% (95% CI 71.3%-99.9%). Response was observed after only one infusion (1 g/kg boby weight) in 11 patients (59%) and the others required a second dose. Mean time to response was 2.2 days. Maximum platelet count was reached within 1 week after the first dose and lasted for approximately 2 weeks. Patients requiring a second dose had lower platelet counts at baseline than patients requiring a single dose. In the 19 evaluable patients for safety, IGNG demonstrated good safety, good hepatic and renal tolerance, and did not induce hemolysis. This trial was registered at the French Medical Agency (AFSSAPS) as #DI n°060735. PMID:28203488

  6. Clinical features, histology, and histogenesis of combined hepatocellular-cholangiocarcinoma

    PubMed Central

    Gera, Shweta; Ettel, Mark; Acosta-Gonzalez, Gabriel; Xu, Ruliang

    2017-01-01

    Combined hepatocellular-cholangiocarcinoma (CHC) is a rare tumor with poor prognosis, with incidence ranging from 1.0%-4.7% of all primary hepatic tumors. This entity will be soon renamed as hepato-cholangiocarcinoma. The known risk factors for hepatocellular carcinoma (HCC) have been implicated for CHC including viral hepatitis and cirrhosis. It is difficult to diagnose this tumor pre-operatively. The predominant histologic component within the tumor largely determines the predominant radiographic features making it a difficult distinction. Heterogeneous and overlapping imaging features of HCC and cholangiocarcinoma should raise the suspicion for CHC and multiple core biopsies (from different areas of tumor) are recommended before administering treatment. Serum tumor markers CA19-9 and alpha-fetoprotein can aid in the diagnosis, but it remains a challenging diagnosis prior to resection. There is sufficient data to support bipotent hepatic progenitor cells as the cell of origin for CHC. The current World Health Organization classification categorizes two main types of CHC based on histo-morphological features: Classical type and CHC with stem cell features. Liver transplant is one of the available treatment modalities with other management options including transarterial chemoembolization, radiofrequency ablation, and percutaneous ethanol injection. We present a review paper on CHC highlighting the risk factors, origin, histological classification and therapeutic modalities. PMID:28293379

  7. Response properties of whisker-associated primary afferent neurons following infraorbital nerve transection with microsurgical repair in adult rats

    PubMed Central

    Xiao, Bo; Zanoun, Rami R.; Carvell, George E.; Washington, Kia M.

    2016-01-01

    The rodent whisker/trigeminal system, characterized by high spatial and temporal resolution, provides an experimental model for developing new therapies for improving sensory functions of damaged peripheral nerves. Here, we use controlled whisker stimulation and single-unit recordings of trigeminal ganglion cells to examine in detail the nature and time course of functional recovery of mechanoreceptive afferents following nerve transection with microsurgical repair of the infraorbital nerve (ION) branch of the trigeminal nerve in adult rats. Response measures include rapid vs. slow adaptation, firing rate, interspike intervals, latency, and angular (directional) tuning. Whisker-evoked responses, readily observable by 3 wk post-transection, recover progressively for at least the next 5 wk. All cells in transected animals, as in control cases, responded to deflections of single whiskers only, but topography within the ganglion was clearly disrupted. The time course and extent of recovery of quantitative response measures were receptor dependent. Cells displaying slowly adapting (SA) properties recovered more quickly than rapidly adapting (RA) populations, and for some response measures—notably evoked firing rates—closely approached or attained control levels by 8 wk post-transection. Angular tuning of RA cells was slightly better than control units, whereas SA tuning did not differ from control values. Nerve conduction times and refractory periods, examined separately using electrical stimulation of the ION, were slower than normal in all transected animals and poorly reflected recovery of whisker-evoked response latencies and interspike intervals. Results underscore the need for multiple therapeutic strategies that target different aspects of functional restitution following peripheral nerve injury. PMID:26792886

  8. 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

  9. Effect of alendronate on bone mineral density in adult patients with Laron syndrome (primary growth hormone insensitivity).

    PubMed

    Eshed, Varda; Benbassat, Carlos A; Laron, Zvi

    2006-04-01

    Severe short stature resulting from a deficiency in insulin-like growth factor-I (IGF-I) is a prominent feature of Laron syndrome (LS). Whether patients with LS are osteopenic or not, and whether they need treatment with bisphosphonates, remains uncertain. The aim of this study was to investigate the action of alendronate on the IGF-I-deficient bones of adult patients with LS and osteoporosis, as determined by dual X-ray absorptiometry . Seven patients (5 women and 2 men) of mean age 40.8+/-7.6 years and mean bone mass density (BMD) 0.843+/-0.06 g/cm2 (T score -2.9+/-0.5) at the lumbar spine and 0.734+/-0.11 g/cm2 (T score -2.2+/-0.9) at the femoral neck were treated with alendronate 70 mg once/weekly over a 12-month period. Treatment led to an increase of 5.3% in BMD (p=0.038) at the femoral neck. There was a similar trend at the lumbar spine, but the difference was not statistically significant (2.3%, p=0.34). Mean total alkaline phosphatase decreased by 14% from normal range at baseline (p=0.007). Urinary deoxypyridinoline levels, which were elevated at baseline (10+/-2.3 nM/mMcre), showed a nonsignificant change during treatment. Our study suggests that treatment with alendronate may have positive effects in patients with LS and low BMD on dual X-ray absorptiometry.

  10. Seizure characteristics and outcomes in 508 Chinese adult patients undergoing primary resection of low-grade gliomas: a clinicopathological study.

    PubMed

    You, Gan; Sha, Zhi-Yi; Yan, Wei; Zhang, Wei; Wang, Yong-Zhi; Li, Shao-Wu; Sang, Lin; Wang, Zi; Li, Gui-Lin; Li, Shou-Wei; Song, Yi-Jun; Kang, Chun-Sheng; Jiang, Tao

    2012-02-01

    Seizure is a common presenting manifestation and plays an important role in the clinical presentation and quality of life for patients with low-grade gliomas (LGGs). The authors set out to identify factors that influence preoperative seizure characteristics and postoperative seizure control. Cases involving adult patients who had undergone initial surgery for LGGs in a single institution between 2005 and 2009 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to identify factors associated with preoperative seizures and postoperative seizure control. Of the 508 patients in the series, 350 (68.9%) presented with seizures. Age less than 38 years and cortical involvement of tumor were more likely to be associated with seizures (P = .003 and .001, respectively, multivariate logistic analysis). For the cohort of 350 patients with seizures, Engel classification was used to evaluate 6- and 12-month outcome after surgery: completely seizure free (Engel class I), 65.3% and 62.5%; not seizure free (Engel classes II, III, IV), 34.7% and 37.5%. After multivariate logistic analysis, favorable seizure prognosis was more common in patients with secondary generalized seizure (P = .006) and with calcification on MRI (.031). With respect to treatment-related variables, patients achieved much better seizure control after gross total resection than after subtotal resection (P < .0001). Ki67 was an independent molecular marker predicting poor seizure control in the patients with a history of seizure if overexpressed but was not a predictor for those without preoperative seizures. These factors may provide insight into developing effective treatment strategies aimed at prolonging patients' survival.

  11. Laboratory Measures as Proxies for Primary Care Encounters: Implications for Quantifying Clinical Retention Among HIV-Infected Adults in North America.

    PubMed

    Rebeiro, Peter F; Althoff, Keri N; Lau, Bryan; Gill, John; Abraham, Alison G; Horberg, Michael A; Kitahata, Mari M; Yehia, Baligh R; Samji, Hasina; Brooks, John T; Buchacz, Kate; Napravnik, Sonia; Silverberg, Michael J; Rachlis, Anita; Gebo, Kelly A; Sterling, Timothy R; Moore, Richard D; Gange, Stephen J

    2015-12-01

    Because of limitations in the availability of data on primary care encounters, patient retention in human immunodeficiency virus (HIV) care is often estimated using laboratory measurement dates as proxies for clinical encounters, leading to possible outcome misclassification. This study included 83,041 HIV-infected adults from 14 clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) who had ≥1 HIV primary care encounters during 2000-2010, contributing 468,816 person-years of follow-up. Encounter-based retention (REB) was defined as ≥2 encounters in a calendar year, ≥90 days apart. Laboratory-based retention (RLB) was defined similarly, using the dates of CD4-positive cell counts or HIV-1 RNA measurements. Percentage of agreement and the κ statistic were used to characterize agreement between RLB and REB. Logistic regression with generalized estimating equations and stabilized inverse-probability-of-selection weights was used to elucidate temporal trends and the discriminatory power of RLB as a predictor of REB, accounting for age, sex, race/ethnicity, primary HIV risk factor, and cohort site as potential confounders. Both REB and RLB increased from 2000 to 2010 (from 67% to 78% and from 65% to 77%, respectively), though REB was higher than RLB throughout (P < 0.01). RLB agreed well with REB (80%-86% agreement; κ = 0.55-0.62, P < 0.01) and had a strong, imperfect ability to discriminate between persons retained and not retained in care by REB (C statistic: C = 0.81, P < 0.05). As a proxy for REB, RLB had a sensitivity and specificity of 84% and 77%, respectively, with misclassification error of 18%.

  12. Laboratory Measures as Proxies for Primary Care Encounters: Implications for Quantifying Clinical Retention Among HIV-Infected Adults in North America

    PubMed Central

    Rebeiro, Peter F.; Althoff, Keri N.; Lau, Bryan; Gill, John; Abraham, Alison G.; Horberg, Michael A.; Kitahata, Mari M.; Yehia, Baligh R.; Samji, Hasina; Brooks, John T.; Buchacz, Kate; Napravnik, Sonia; Silverberg, Michael J.; Rachlis, Anita; Gebo, Kelly A.; Sterling, Timothy R.; Moore, Richard D.; Gange, Stephen J.

    2015-01-01

    Because of limitations in the availability of data on primary care encounters, patient retention in human immunodeficiency virus (HIV) care is often estimated using laboratory measurement dates as proxies for clinical encounters, leading to possible outcome misclassification. This study included 83,041 HIV-infected adults from 14 clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) who had ≥1 HIV primary care encounters during 2000–2010, contributing 468,816 person-years of follow-up. Encounter-based retention (REB) was defined as ≥2 encounters in a calendar year, ≥90 days apart. Laboratory-based retention (RLB) was defined similarly, using the dates of CD4-positive cell counts or HIV-1 RNA measurements. Percentage of agreement and the κ statistic were used to characterize agreement between RLB and REB. Logistic regression with generalized estimating equations and stabilized inverse-probability-of-selection weights was used to elucidate temporal trends and the discriminatory power of RLB as a predictor of REB, accounting for age, sex, race/ethnicity, primary HIV risk factor, and cohort site as potential confounders. Both REB and RLB increased from 2000 to 2010 (from 67% to 78% and from 65% to 77%, respectively), though REB was higher than RLB throughout (P < 0.01). RLB agreed well with REB (80%–86% agreement; κ = 0.55–0.62, P < 0.01) and had a strong, imperfect ability to discriminate between persons retained and not retained in care by REB (C statistic: C = 0.81, P < 0.05). As a proxy for REB, RLB had a sensitivity and specificity of 84% and 77%, respectively, with misclassification error of 18%. PMID:26578717

  13. Integrated breathing and relaxation training (the Papworth method) for adults with asthma in primary care: a randomised controlled trial

    PubMed Central

    Holloway, Elizabeth A; West, Robert J

    2007-01-01

    Background An integrated breathing and relaxation technique known as the Papworth method has been implemented by physiotherapists since the 1960s for patients with asthma and dysfunctional breathing, but no controlled trials have been reported. This study evaluated the effectiveness of the Papworth method in a randomised controlled trial. Methods Eighty‐five patients (36 men) were individually randomised to the control group (n = 46) or to the intervention group receiving five sessions of treatment by the Papworth method (n = 39). Both groups received usual medical care. Assessments were undertaken at baseline, post‐treatment (6 months after baseline) and at 12 months. The primary outcome measure was the St George's Respiratory Symptoms Questionnaire (SGRQ). Secondary outcome measures included the Hospital Anxiety and Depression Scale (HADS), the Nijmegen dysfunctional breathing questionnaire and objective measures of respiratory function. Results Post‐treatment and 12 month data were available for 78 and 72 patients, respectively. At the post‐treatment assessment the mean (SD) score on the SGRQ Symptom subscale was 21.8 (18.1) in the intervention group and 32.8 (20.1) in the control group (p = 0.001 for the difference). At the 12 month follow‐up the corresponding figures were 24.9 (17.9) and 33.5 (15.9) (p = 0.007 for the difference). SGRQ Total scores and HADS and Nijmegen scores were similarly significantly lower in the intervention group than in the control group. The groups did not differ significantly following the treatment on objective measures of respiratory function except for relaxed breathing rate. Conclusions The Papworth method appears to ameliorate respiratory symptoms, dysfunctional breathing and adverse mood compared with usual care. Further controlled trials are warranted to confirm this finding, assess the effect in other patient groups and determine whether there is some effect on objective measures of

  14. Tissue Diagnosis of Hepatocellular Carcinoma

    PubMed Central

    Jain, Deepali

    2014-01-01

    The current American Association for the Study of Liver Diseases (AASLD) guideline provides strategies for achieving the diagnosis of hepatocellular carcinoma (HCC) based on the size of liver nodules seen on surveillance imaging. For lesions less than 1 cm in size, follow-up surveillance imaging is recommended. Lesions larger than 2 cm require typical radiological hallmark on dynamic imaging. Lesions of 1–2 cm in size require typical imaging features including intense uptake of contrast during arterial phases followed by decreased enhancement during portal venous phases on at least 2 imaging modalities. In cases of atypical radiological features of the suspected lesion, tissue diagnosis either by fine needle aspiration or biopsy should be obtained. Although fine needle aspiration could give a smaller risk of seeding than biopsy, biopsy has been preferred over cytology. Percutaneous biopsy of HCC carries a potential risk of tumor seeding along the needle tract. However the risk is low and there is no clear evidence of post transplant recurrence due to needle tract seeding. Histopathologic assessment can differentiate between premalignant lesions such as dysplastic nodules and early HCC. Atypical variants of HCC can be recognized morphologically which may have associated prognostic value. PMID:25755614

  15. 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

  16. Yttrium-90 microsphere radioembolization for hepatocellular carcinoma.

    PubMed

    Edeline, Julien; Gilabert, Marine; Garin, Etienne; Boucher, Eveline; Raoul, Jean-Luc

    2015-03-01

    Yttrium-90 (Y90) radioembolization is an emerging strategy to treat liver malignancies, and clinical data supporting its use have accumulated in recent years. Y90-radioembolization has shown clinical effectiveness in intermediate and advanced hepatocellular carcinoma, with a favorable safety profile. Retrospective data show similar levels of effectiveness to transarterial chemoembolization in intermediate hepatocellular carcinoma, with some evidence of better tolerance. While phase 3 studies comparing Y90-radioembolization to chemoembolization in intermediate hepatocellular carcinoma would be difficult to conduct, studies comparing or combining Y90-radioembolization with sorafenib are under way. Questions also remain about the most suitable modalities for defining the dose to administer. Phase 3 studies are under way to clarify the place of Y90-radioembolization in the algorithm of HCC treatment.

  17. 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.

  18. A Small Motor Cortex Lesion Abolished Ocular Dominance Plasticity in the Adult Mouse Primary Visual Cortex and Impaired Experience-Dependent Visual Improvements

    PubMed Central

    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

  19. Hepatocellular carcinoma in identical twins in Chile: case report

    PubMed Central

    Caglevic, Christian; Silva, Shirley; Mahave, Mauricio; Torres, Javiera; Rolfo, Christian; Gallardo, Jorge; Carrasco, Paula

    2016-01-01

    Liver cancer is the second leading cause of cancer death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary malignant liver tumour, with a typically poor prognosis, growing incidence and a well-documented relationship with chronic inflammation factors of the liver tissue. Despite the fact that family medical history has been identified as a risk factor for the development of HCC, its significance in terms of etiopathogenesis and prognosis is not well documented. With a view to contributing to this discussion, we will report the clinical case of two identical twins with HCC, both diagnosed within a short period of time, by providing relevant clinical data, and relating this to other medical literature reports that could contribute to a deeper understanding of this illness. PMID:28105079

  20. 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

  1. 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

  2. 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

  3. TRPA1-expressing primary afferents synapse with a morphologically identified subclass of substantia gelatinosa neurons in the adult rat spinal cord.

    PubMed

    Uta, Daisuke; Furue, Hidemasa; Pickering, Anthony E; Rashid, Md Harunor; Mizuguchi-Takase, Hiroko; Katafuchi, Toshihiko; Imoto, Keiji; Yoshimura, Megumu

    2010-06-01

    The TRPA1 channel has been proposed to be a molecular transducer of cold and inflammatory nociceptive signals. It is expressed on a subset of small primary afferent neurons both in the peripheral terminals, where it serves as a sensor, and on the central nerve endings in the dorsal horn. The substantia gelatinosa (SG) of the spinal cord is a key site for integration of noxious inputs. The SG neurons are morphologically and functionally heterogeneous and the precise synaptic circuits of the SG are poorly understood. We examined how activation of TRPA1 channels affects synaptic transmission onto SG neurons using whole-cell patch-clamp recordings and morphological analyses in adult rat spinal cord slices. Cinnamaldehyde (TRPA1 agonist) elicited a barrage of excitatory postsynaptic currents (EPSCs) in a subset of the SG neurons that responded to allyl isothiocyanate (less specific TRPA1 agonist) and capsaicin (TRPV1 agonist). Cinnamaldehyde evoked EPSCs in vertical and radial but not islet or central SG cells. Notably, cinnamaldehyde produced no change in inhibitory postsynaptic currents and nor did it produce direct postsynaptic effects. In the presence of tetrodotoxin, cinnamaldehyde increased the frequency but not amplitude of miniature EPSCs. Intriguingly, cinnamaldehyde had a selective inhibitory action on monosynaptic C- (but not Adelta-) fiber-evoked EPSCs. These results indicate that activation of spinal TRPA1 presynaptically facilitates miniature excitatory synaptic transmission from primary afferents onto vertical and radial cells to initiate action potentials. The presence of TRPA1 channels on the central terminals raises the possibility of bidirectional modulatory action in morphologically identified subclasses of SG neurons.

  4. 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.

  5. 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.

  6. 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

  7. Improving the diagnostic criteria for primary liver graft non-function in adults utilizing standard and transportable laboratory parameters. An outcome based analysis.

    PubMed

    Al-Freah, Mohammad A B; McPhail, Mark J W; Dionigi, Elena; Foxton, Matthew R; Auzinger, Georg; Rela, Mohamed; Wendon, Julia A; O'Grady, John G; Heneghan, Michael A; Heaton, Nigel D; Bernal, William

    2017-02-15

    Current diagnostic criteria for primary non-function (PNF) of liver grafts are based on clinical experience rather than statistical methods. A retrospective, single centre study was conducted of all adults (n=1,286) who underwent primary liver transplant 2000-2008 in our centre. Laboratory variable during the first post-liver transplant week were analysed. Forty two patients (3.7%) had 2-week graft failure. Transplant albumin, day-1 AST, day-1 lactate, day-3 bilirubin, day-3 INR and day-7 AST were independently associated with PNF on multivariate logistic regression. PNF score =(0.000280*D1AST)+(0.361*D1 Lactate)+(0.00884*D3 Bilirubin)+(0.940*D 3 INR)+(0.00153*D7 AST)-(0.0972*TxAlbumin)-4.5503. ROC analysis showed the model AUROC of 0.912 (0.889 -0.932) was superior to the current United Kingdom (UK) PNF criteria of 0.669 (0.634-0.704, p<0.0001). When applied to a validation cohort (n=386, 34.4% patients) the model had AUROC of 0.831 (0.789 -0.867) compared to the UK EGD criteria of 0.674 (0.624-0.721). The new model performed well after exclusion of patients with marginal grafts and when modified to include variables from the first three post-LT days only (AUROC of 0.818, 0.776-0.856, p=0.001). This model is superior to the current UK PNF criteria and is based on statistical methods. The model is also applicable to recipients of all types of grafts (marginal and non-marginal). This article is protected by copyright. All rights reserved.

  8. 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

  9. Erlotinib for advanced hepatocellular carcinoma

    PubMed Central

    Zhang, Jing; Zong, Yuan; Xu, Gang-Zhu; Xing, Ke

    2016-01-01

    Objectives: To evaluate the efficacy and safety of erlotinib for the treatment of advanced hepatocellular carcinoma (HCC). Methods: A systematic literature search was undertaken in June 2015. Phase II/III trials of erlotinib for the treatment of advanced HCC were included. A descriptive analysis was applied. The study was conducted in College of Medicine, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China, between June 2015 and January 2016. Results: Ten trials, comprising 9 phase II and one phase III trial, were included in the systematic review. The tumor response rate was 0% in 4 of the phase II trials, <10% in 3 of the phase II trials and the phase III trial, and >20% in 2 of the phase II trials. The disease control rate was 42.5-79.6% in most studies. Three studies reported a median progression-free survival (PFS) of 6.5-9.0 months, although PFS was <3.5 months in most studies. Most trials reported a median overall survival of 6.25-15.65 months. The most frequent grade 3/4 toxicities were fatigue (11.9%), diarrhea (10%), increased alanine and aspartate transaminases (7.3%), and rash/desquamation (6.9%). Conclusion: Erlotinib provides efficacious and well-tolerated treatment for advanced HCC. However, more detailed investigations of HCC pathogenesis and evaluation of sensitive patient subsets are needed to improve outcomes of patients with advanced HCC. Additional well-designed, randomized, controlled trials are needed to evaluate the efficacy and safety of erlotinib as monotherapy or combination with other drugs for advanced HCC. PMID:27761555

  10. 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

  11. 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

  12. The Relationship of Diabetes and Smoking Status to Hepatocellular Carcinoma Mortality.

    PubMed

    Chiang, Chien-Hsieh; Lu, Chia-Wen; Han, Hsieh-Cheng; Hung, Shou-Hung; Lee, Yi-Hsuan; Yang, Kuen-Cheh; Huang, Kuo-Chin

    2016-02-01

    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.

  13. 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

  14. 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

  15. 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.

  16. Correlation of Exon 3 β-catenin Mutations with Glutamine Synthetase Staining Patterns in Hepatocellular Adenoma and Hepatocellular Carcinoma

    PubMed Central

    Hale, Gillian; Liu, Xinxin; Hu, Junjie; Xu, Zhong; Che, Li; Solomon, David; Tsokos, Christos; Shafizadeh, Nafis; Chen, Xin; Gill, Ryan; Kakar, Sanjay

    2016-01-01

    The current clinical practice is based on the assumption of strong correlation between diffuse glutamine synthetase expression and β-catenin activation in hepatocellular adenoma and hepatocellular carcinoma. This high correlation is based on limited data, and may represent an oversimplification as glutamine synthetase staining patterns show wide variability in clinical practice. Standardized criteria for interpreting diverse glutamine synthetase patterns, and the association between each pattern and β-catenin mutations is not clearly established. This study examines the correlation between glutamine synthetase staining patterns and β-catenin mutations in 15 typical hepatocellular adenomas, 5 atypical hepatocellular neoplasms and 60 hepatocellular carcinomas. Glutamine synthetase staining was classified into one of three patterns: (a) diffuse homogeneous: moderate to strong cytoplasmic staining in more than 90% of lesional cells, without a map-like pattern, (b) diffuse heterogeneous: moderate to strong staining in 50–90% of lesional cells, without a map-like pattern, and (c) patchy: moderate to strong staining in <50% of lesional cells (often perivascular), or weak staining irrespective of extent, and all other staining patterns (including negative cases). Sanger sequencing of CTNNB1 exon 3 was performed in all cases. Of hepatocellular tumors with diffuse glutamine synthetase staining (homogeneous or heterogeneous), an exon 3 β-catenin mutation was detected in 33% (2/6) of typical hepatocellular adenoma, 75% (3/4) of atypical hepatocellular neoplasm and 17% (8/47) of hepatocellular carcinomas. An exon 3 mutation was also observed in 15% (2/13) of hepatocellular carcinomas with patchy glutamine synthetase staining. The results show a modest correlation between diffuse glutamine synthetase immunostaining and exon 3 β-catenin mutations in hepatocellular adenoma and hepatocellular carcinoma with discrepancy rates exceeding 50% in both hepatocellular adenoma and

  17. Correlation of exon 3 β-catenin mutations with glutamine synthetase staining patterns in hepatocellular adenoma and hepatocellular carcinoma.

    PubMed

    Hale, Gillian; Liu, Xinxin; Hu, Junjie; Xu, Zhong; Che, Li; Solomon, David; Tsokos, Christos; Shafizadeh, Nafis; Chen, Xin; Gill, Ryan; Kakar, Sanjay

    2016-11-01

    The current clinical practice is based on the assumption of strong correlation between diffuse glutamine synthetase expression and β-catenin activation in hepatocellular adenoma and hepatocellular carcinoma. This high correlation is based on limited data and may represent an oversimplification as glutamine synthetase staining patterns show wide variability in clinical practice. Standardized criteria for interpreting diverse glutamine synthetase patterns, and the association between each pattern and β-catenin mutations is not clearly established. This study examines the correlation between glutamine synthetase staining patterns and β-catenin mutations in 15 typical hepatocellular adenomas, 5 atypical hepatocellular neoplasms and 60 hepatocellular carcinomas. Glutamine synthetase staining was classified into one of the three patterns: (a) diffuse homogeneous: moderate-to-strong cytoplasmic staining in >90% of lesional cells, without a map-like pattern, (b) diffuse heterogeneous: moderate-to-strong staining in 50-90% of lesional cells, without a map-like pattern, and (c) patchy: moderate-to-strong staining in <50% of lesional cells (often perivascular), or weak staining irrespective of the extent, and all other staining patterns (including negative cases). Sanger sequencing of CTNNB1 exon 3 was performed in all cases. Of hepatocellular tumors with diffuse glutamine synthetase staining (homogeneous or heterogeneous), an exon 3 β-catenin mutation was detected in 33% (2/6) of typical hepatocellular adenoma, 75% (3/4) of atypical hepatocellular neoplasm and 17% (8/47) of hepatocellular carcinomas. An exon 3 mutation was also observed in 15% (2/13) of hepatocellular carcinomas with patchy glutamine synthetase staining. The results show a modest correlation between diffuse glutamine synthetase immunostaining and exon 3 β-catenin mutations in hepatocellular adenoma and hepatocellular carcinoma with discrepancy rates >50% in both hepatocellular adenoma and hepatocellular

  18. [Multiple primary malignant tumors involving the liver].

    PubMed

    Tiszlavicz, L

    1991-11-17

    In the autopsy material of the Department of Pathology of Albert Szent-Györgyi Medical University 167 primary liver cancers were observed in 30 years, from which 13 patients (7.8%) had also other primary malignancies. The tumour-associations were mainly synchronously, there was strong male predominance. In 9 cases the hepatocellular carcinoma originated in cirrhotic liver. The most frequent extrahepatic tumours were found in the lungs (5 cases), smoking was among the anamnestic data.

  19. 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

  20. Expression of liver fatty acid binding protein in hepatocellular carcinoma☆

    PubMed Central

    Cho, Soo-Jin; Ferrell, Linda D.; Gill, Ryan M.

    2017-01-01

    Summary Loss of expression of liver fatty acid binding protein (LFABP) by immunohistochemistry has been shown to be characteristic of a subset of hepatocellular adenomas (HCAs) in which HNF1A is inactivated. Transformation to hepatocellular carcinoma is thought to be a very rare phenomenon in the HNF1A-inactivated variant of HCA. However, we recently observed 2 cases at our institution, 1 definite hepatocellular carcinoma and 1 possible hepatocellular carcinoma, with loss of LFABP staining, raising the possibility that LFABP down-regulation may be associated with hepatocellular carcinogenesis. Our aim was to evaluate hepatocellular carcinomas arising in various backgrounds and with varying degrees of differentiation for loss of LFABP staining. Twenty total cases of hepatocellular carcinoma were examined. Thirteen cases arose in a background of cirrhosis due to hepatitis C (n = 8) or steatohepatitis (n = 5); 7 cases arose in a noncirrhotic background, with 2 cases arising within HNF1A-inactivated variant HCA and 2 cases arising within inflammatory variant HCA. Complete loss of expression of LFABP was seen in 6 of 20 cases, including 2 cases of hepatocellular carcinoma arising within HNF1A-inactivated variant HCA. Thus, loss of staining for LFABP appears to be common in hepatocellular carcinoma and may be seen in well-differentiated hepatocellular carcinoma. Therefore, LFABP loss should not be interpreted as evidence for hepatocellular adenoma over carcinoma, when other features support a diagnosis of hepatocellular carcinoma. The findings raise consideration for a role of HNF1A inactivation in hepatocellular carcinogenesis, particularly in less differentiated tumors. PMID:26997447

  1. 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.

  2. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

    PubMed Central

    Dollinger, Matthias M; Behrens, Christa M; Lesske, Joachim; Behl, Susanne; Behrmann, Curd; Fleig, Wolfgang E

    2008-01-01

    Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years) not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0) with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01), a low score in the Okuda- and CLIP-classification (p < 0.001) or a low AFP-level (p < 0.001) were associated with better survival, but not therapy modalities other than thymostimulin (p = 0.1) or signs of an invasive HCC phenotype such as vascular invasion (p = 0.3) and metastases (p = 0.1). The only variables independently related to survival in the Cox's regression model were Okuda stage and presence of liver cirrhosis (p < 0.01) as well as response to thymostimulin (p < 0.05). Of 39/44 patients evaluable for response, two obtained complete responses (one after concomitant radiofrequency ablation), five partial responses (objective response 18%), twenty-four stable disease (tumor control rate 79%) and eight progressed. Median progression-free survival was 6.4 months (95% CI 0.8–12). Grade 1 local reactions following injection were the only side effects. Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage) in addition

  3. Lower rates of symptom recurrence and surgical revision after primary compared with secondary endoscopic third ventriculostomy for obstructive hydrocephalus secondary to aqueductal stenosis in adults.

    PubMed

    Sankey, Eric W; Goodwin, C Rory; Jusué-Torres, Ignacio; Elder, Benjamin D; Hoffberger, Jamie; Lu, Jennifer; Blitz, Ari M; Rigamonti, Daniele

    2016-05-01

    OBJECT Endoscopic third ventriculostomy (ETV) is the treatment of choice for obstructive hydrocephalus; however, the success of ETV in patients who have previously undergone shunt placement remains unclear. The present study analyzed 103 adult patients with aqueductal stenosis who underwent ETV for obstructive hydrocephalus and evaluated the effect of previous shunt placement on post-ETV outcomes. METHODS This study was a retrospective review of 151 consecutive patients who were treated between 2007 and 2013 with ETV for hydrocephalus. One hundred three (68.2%) patients with aqueductal stenosis causing obstructive hydrocephalus were included in the analysis. Postoperative ETV patency and aqueductal and cisternal flow were assessed by high-resolution, gradient-echo MRI. Post-ETV Mini-Mental State Examination, Timed Up and Go, and Tinetti scores were compared with preoperative values. Univariate and multivariate analyses were performed comparing the post-ETV outcomes in patients who underwent a primary (no previous shunt) ETV (n = 64) versus secondary (previous shunt) ETV (n = 39). RESULTS The majority of patients showed significant improvement in symptoms after ETV; however, no significant differences were seen in any of the quantitative tests performed during follow-up. Symptom recurrence occurred in 29 (28.2%) patients after ETV, after a median of 3.0 (interquartile range 0.8-8.0) months post-ETV failure. Twenty-seven (26.2%) patients required surgical revision after their initial ETV. Patients who received a secondary ETV had higher rates of symptom recurrence (p = 0.003) and surgical revision (p = 0.003), particularly in regard to additional shunt placement/revision post-ETV (p = 0.005). These differences remained significant after multivariate analysis for both symptom recurrence (p = 0.030) and surgical revision (p = 0.043). CONCLUSIONS Patients with obstructive hydrocephalus due to aqueductal stenosis exhibit symptomatic improvement after ETV, with a

  4. A PROSPECTIVE RANDOMIZED TRIAL OF TACROLIMUS AND PREDNISONE VERSUS TACROLIMUS, PREDNISONE AND MYCOPHENOLATE MOFETIL IN PRIMARY ADULT LIVER TRANSPLANTATION: A SINGLE CENTER REPORT1

    PubMed Central

    Jain, A.; Kashyap, R.; Dodson, F.; Kramer, D.; Hamad, I.; Khan, A.; Eghestad, B.; Starzl, T.E.; Fung, J.J.

    2010-01-01

    Background Tacrolimus (TAC) and mycophenolate mofetil (MMF) are currently approved immunosuppressants for prevention of rejection in liver transplantation (LTx). They have different modes of action and toxicity profiles, but the efficacy and safety of MMF in primary liver transplantation with TAC has not been determined. Methods An Institutional Review Board-approved, open-label, single-center, prospective randomized trial was initiated to study the efficacy and toxicity of TAC and steroids (double-drug therapy (D)) versus TAC, steroids, and MMF (triple-drug therapy (T)) in primary adult LTx recipients. Both groups of patients were started on the same doses of TAC and steroids. Patients randomized to T also received 1 gm MMF twice a day. Results Between August 1995 and May 1998, 350 patients were enrolled at a single center-175 in the D and 175 in the T groups. All patients were followed until May 1998, with a mean follow-up of 33.8±9.1 months. Using an intention-to-treat analysis, the 1-, 2-, 3-, and 4-year patient survival was 85.1%, 81.6%, 78.6%, and 75.8%, respectively, for D and 87.4%, 85.4%, 81.3%, and 79.9%, respectively, for T. The 4-year graft survival was 70% for D and 72.1% for T. Although the rate of acute rejection in the first 3 months was significantly lower for T than for D (28% for triple vs. 38.9% for double, P=0.03), the overall rate of rejection for T at the end of 1 year was not significantly lower than for the D (38.9% triple vs. 45.2% double). The median time to the first episode of rejection was 14 days for D versus 24 days for T (P=0.008). During the study period, 38 of 175 patients in D received MMF to control ongoing acute rejection, nephrotoxicity, and/or neurotoxicity. On the other hand, 103 patients in the T discontinued MMF for infection, myelosuppression, and/or gastrointestinal disturbances. The need for corticosteroids was less after 6 months for T and the perioperative need for dialysis was lower with use of MMF. Conclusion This

  5. Mechanisms of doxorubicin resistance in hepatocellular carcinoma

    PubMed Central

    Cox, Josiah; Weinman, Steven

    2015-01-01

    Hepatocellular carcinoma, one of the most common solid tumors worldwide, is poorly responsive to available chemotherapeutic approaches. While systemic chemotherapy is of limited benefit, intra-arterial delivery of doxorubicin to the tumor frequently produces tumor shrinkage. Its utility is limited, in part, by the frequent emergence of doxorubicin resistance. The mechanisms of this resistance include increased expression of multidrug resistance efflux pumps, alterations of the drug target, topoisomerase, and modulation of programmed cell death pathways. Many of these effects result from changes in miRNA expression and are particularly prominent in tumor cells with a stem cell phenotype. This review will summarize the current knowledge on the mechanisms of doxorubicin resistance of hepatocellular carcinoma and the potential for approaches toward therapeutic chemosensitization. PMID:26998221

  6. Treatment of hepatocellular carcinoma: present and future.

    PubMed

    Genco, Chiara; Cabibbo, Giuseppe; Maida, Marcello; Brancatelli, Giuseppe; Galia, Massimo; Alessi, Nicola; Butera, Giuseppe; Genova, Claudio; Romano, Piero; Raineri, Maurizio; Giarratano, Antonello; Midiri, Massimo; Cammà, Calogero

    2013-04-01

    Hepatocellular carcinoma is a major health problem. It is the sixth most common cancer worldwide and the third most common cause of cancer-related death. Despite the availability of several treatment opportunities, diagnosis is still made in an advanced phase, limiting application of most therapeutic choices that currently are based on the Barcelona Clinic Cancer Liver Classification and include surgical resection, orthotopic liver transplantation and ablative methods for very early and early disease, arterial chemoembolization for intermediate stages and systemic therapy with sorafenib for advanced hepatocellular carcinoma. Thanks to novel advancements in knowledge of molecular pathogenesis of this tumor, many new systemic agents and locoregional treatments are in different stages of clinical development and they represent an important promise of further improvements in patients' survival.

  7. Hepatocellular carcinoma: Advances in diagnostic imaging.

    PubMed

    Sun, Haoran; Song, Tianqiang

    2015-10-01

    Thanks to the growing knowledge on biological behaviors of hepatocellular carcinomas (HCC), as well as continuous improvement in imaging techniques and experienced interpretation of imaging features of the nodules in cirrhotic liver, the detection and characterization of HCC has improved in the past decade. A number of practice guidelines for imaging diagnosis have been developed to reduce interpretation variability and standardize management of HCC, and they are constantly updated with advances in imaging techniques and evidence based data from clinical series. In this article, we strive to review the imaging techniques and the characteristic features of hepatocellular carcinoma associated with cirrhotic liver, with emphasis on the diagnostic value of advanced magnetic resonance imaging (MRI) techniques and utilization of hepatocyte-specific MRI contrast agents. We also briefly describe the concept of liver imaging reporting and data systems and discuss the consensus and controversy of major practice guidelines.

  8. 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.

  9. 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

  10. Chemoembolization and Radioembolization for Hepatocellular Carcinoma

    PubMed Central

    Salem, Riad; Lewandowski, Robert J.

    2013-01-01

    Hepatocellular carcinoma (HCC) continues to represent a major worldwide problem. While treatments such as resection, transplantation and ablation may provide a chance for cure, these options are often precluded because of advanced disease presentation. Palliative treatments include transarterial embolization and systemic therapies. This review will summarize the state of the science for embolic therapies in HCC (conventional and drug-eluting chemoembolization, radioembolization), as well as discuss related topics including HCC staging, assessment of response and ongoing clinical trials. PMID:23357493

  11. Targeting Notch3 in Hepatocellular Carcinoma: Molecular Mechanisms and Therapeutic Perspectives.

    PubMed

    Giovannini, Catia; Bolondi, Luigi; Gramantieri, Laura

    2016-12-28

    The Notch signaling pathway is a very conserved system that controls embryonic cell fate decisions and the maintenance of adult stem cells through cell to cell communication. Accumulating evidence support the relevance of Notch signaling in different human diseases and it is one of the most commonly activated signaling pathways in cancer. This review focuses mainly on the role of Notch3 signaling in hepatocellular carcinoma and its potential therapeutic applications against this malignancy. In this regard, the crosstalk between Notch and p53 may play an important role.

  12. Targeting Notch3 in Hepatocellular Carcinoma: Molecular Mechanisms and Therapeutic Perspectives

    PubMed Central

    Giovannini, Catia; Bolondi, Luigi; Gramantieri, Laura

    2016-01-01

    The Notch signaling pathway is a very conserved system that controls embryonic cell fate decisions and the maintenance of adult stem cells through cell to cell communication. Accumulating evidence support the relevance of Notch signaling in different human diseases and it is one of the most commonly activated signaling pathways in cancer. This review focuses mainly on the role of Notch3 signaling in hepatocellular carcinoma and its potential therapeutic applications against this malignancy. In this regard, the crosstalk between Notch and p53 may play an important role. PMID:28036048

  13. Radiographic parameters in predicting outcome of patients with hepatocellular carcinoma treated with yttrium-90 microsphere radioembolization.

    PubMed

    Salem, Mohamed E; Jain, Nitin; Dyson, Gregory; Taylor, Stephanie; El-Refai, Sherif M; Choi, Minsig; Shields, Anthony F; Critchfield, Jeffery; Philip, Philip A

    2013-01-01

    Background. In patients with hepatocellular carcinoma, selection criteria for transarterial hepatic selective internal radiotherapy are imprecise. Additionally, radiographic parameters to predict outcome of transarterial hepatic selective internal radiotherapy have not been fully characterized. Patients and methods. Computed tomography (CT) scans of 23 patients with unresectable primary hepatocellular carcinoma before and after transarterial hepatic selective internal radiotherapy with yttrium-90 microspheres were retrospectively reviewed. Selected radiographic parameters were evaluated and correlated with progression-free survival and overall survival. Response to treatment was assessed with Response RECIST 1.1 and Morphology, Attenuation, Size, and Structure (MASS) criteria. Results. On the post-SIRT CT, 68% of tumors demonstrated decreased size (median decrease of 0.8 cm, P = 0.3); 64% had decreased attenuation (median decrease 5.7 HU, P = 0.06), and 48% demonstrated increased tumor necrosis (P < 0.001). RECIST-defined partial response was seen in 10% patients, stable disease in 80%, and 10% had disease progression. Median progression-free survival was 3.9 months (range, 3.3 to 7.3), and median overall survival was 11.2 months (7.1 to 31.1). Pretreatment lower hepatopulmonary shunt fraction, central hypervascularity, and well-defined tumor margins were associated with improved progression-free survival. Conclusion. In patients with unresectable hepatocellular carcinoma, pretreatment CT parameters may predict favorable response to SIRT and improve patient selection.

  14. Molecular Mechanisms of Hepatocellular Apoptosis Induced by Trovafloxacin-Tumor Necrosis Factor-alpha Interaction

    PubMed Central

    Roth, Robert A.

    2014-01-01

    Idiosyncratic drug-induced liver injury (IDILI) continues to be a significant human health problem. IDILI is characterized as occurring in a minority of individuals exposed to a drug, yet it accounts for as much as 17% of all cases of acute liver failure. Despite these concerns, the mechanisms underlying IDILI remain unknown. Trovafloxacin (TVX), which causes IDILI in humans, also causes hepatocellular death in vitro when combined with tumor necrosis factor-alpha (TNF) treatment. However, the molecular mechanisms involved in this toxicity are not fully characterized. The purpose of this study was to identify mechanisms by which TVX and TNF interact to cause hepatocellular death, with a focus on a human hepatocyte cell line. TVX and TNF interacted to cause cytotoxicity in HepG2 cells at drug concentrations similar to those in people undergoing TVX therapy. TVX/TNF treatment caused apoptosis and DNA damage in HepG2 cells that depended on caspase activation. Prolonged activation of JNK occurred in TVX/TNF-induced cytotoxicity, and treatment with the JNK selective inhibitor SP600125 attenuated cytotoxicity. TVX/TNF cotreatment also caused cytotoxicity in isolated primary murine hepatocytes that was dependent on caspase activation. These results increase understanding of molecular signaling pathways involved in hepatocellular death caused by a drug with idiosyncratic liability in the presence of TNF. PMID:24097668

  15. Family history influences the early onset of hepatocellular carcinoma

    PubMed Central

    Park, Chung-Hwa; Jeong, Seung-Hee; Yim, Hyeon-Woo; Kim, Jin Dong; Bae, Si Hyun; Choi, Jong Young; Yoon, Seung Kew

    2012-01-01

    AIM: To evaluate the relationship between a positive family history of primary liver cancer and hepatocellular carcinoma (HCC) development in Korean HCC patients. METHODS: We studied a total of 2242 patients diagnosed with HCC between January 1990 and July 2008, whose family history of primary liver cancer was clearly described in the medical records. RESULTS: Of the 2242 patients, 165 (7.4%) had a positive family history of HCC and 2077 (92.6%) did not. The male to female ratio was 3.6:1, and the major causes of HCC were chronic hepatitis B virus (HBV) infection in 75.1%, chronic hepatitis C virus infection in 13.2% and alcohol in 3.1%. The median ages at diagnosis in the positive- and negative-history groups were 52 years (range: 29-79 years) and 57 years (range: 18-89 years), respectively (P < 0.0001). Furthermore, among 1713 HCC patients with HBV infection, the number of patients under 45 years of age out of 136 patients with positive family history was 26 (19.1%), whereas those out of 1577 patients with negative family history was 197 (12.5%), suggesting that a positive family history may be associated with earlier development of HCC in the Korean population (P = 0.0028). CONCLUSION: More intensive surveillance maybe recommended to those with a positive family history of HCC for earlier diagnosis and proper management especially when HBV infection is present. PMID:22690075

  16. 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…

  17. 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

  18. Localization of the fourth locus (GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region.

    PubMed Central

    Sarfarazi, M; Child, A; Stoilova, D; Brice, G; Desai, T; Trifan, O C; Poinoosawmy, D; Crick, R P

    1998-01-01

    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. PMID:9497264

  19. 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

  20. Clinical trials of antiangiogenic therapy for hepatocellular carcinoma.

    PubMed

    Taketomi, Akinobu

    2016-04-01

    Angiogenesis is a promising therapeutic target to inhibit tumor growth. This review summarizes data from clinical trials of antiangiogenic agents in hepatocellular carcinoma. A systematic search of PubMed was performed to identify clinical trials of specific antiangiogenic agents in hepatocellular carcinoma treatment, particularly phase III trials involving treatment guidelines for advanced hepatocellular carcinoma. Sorafenib is the only systemic drug approved for the treatment of advanced hepatocellular carcinoma. Two large-scale, randomized phase III trials using sorafenib involving patients with unresectable HCC showed a significant survival benefit compared with placebo control groups. However, subsequent phase III trials of antiangiogenic agents in hepatocellular carcinoma have failed to improve survival compared with standard treatment protocols using sorafenib. The efficacy of antiangiogenic agents in combination with other drugs, transarterial chemoembolization, and surgical resection is currently being investigated. Future research is expected to optimize antiangiogenic therapies in combination with standard treatment with sorafenib.

  1. Differential expression of laminin receptors in human hepatocellular carcinoma

    PubMed Central

    Ozaki, I; Yamamoto, K; Mizuta, T; Kajihara, S; Fukushima, N; Setoguchi, Y; Morito, F; Sakai, T

    1998-01-01

    Background—Laminin receptors are involved in cell-extracellular matrix interactions in malignant cells that show invasion and metastasis. Hepatocellular carcinoma frequently shows early invasion into blood vessels, and intrahepatic and extrahepatic metastases. However, the role of laminin receptors in hepatocellular carcinoma is unknown. 
Aims—To examine the expression of mRNA for laminin receptors and their isoforms in hepatocellular carcinoma. 
Methods—The expression of several laminin receptors, including α1 integrin, α6 integrin and its isoforms α6A and α6B, β1 integrin and its isoforms β1A and β1B, and 32kD/67kDa laminin binding protein was examined in human hepatocellular carcinomas and non-cancerous liver tissues using the reverse transcription polymerase chain reaction. 
Results—α6 Integrin, β1 integrin, and laminin binding protein showed notably increased expression in hepatocellular carcinoma, compared with non-cancerous liver tissue, although the α1 integrin did not show a significant change. Furthermore, β1B integrin, a splicing variant of β1 integrin, was overexpressed in hepatocellular carcinoma while the β1A integrin isoform did not show significant changes between hepatocellular carcinoma and surrounding non-cancerous liver tissue. 
Conclusions—The differential upregulation of laminin receptors and their splicing isoforms was shown in hepatocellular carcinoma, suggesting that certain laminin receptors and their isoforms may be involved in the development and progression of hepatocellular carcinoma. 

 Keywords: laminin receptor; integrin α6β1; hepatocellular carcinoma PMID:9824613

  2. The role of imaging in the surveillance and diagnosis of hepatocellular cancer.

    PubMed

    Dulku, Gurjeet; Dhillon, Ravinder; Goodwin, Mark; Cheng, Wendy; Kontorinis, Nick; Mendelson, Richard

    2016-12-16

    A decision support tool has been developed as part of a suite of on-line evidence-based and consensus-based guidelines Diagnostic imaging Pathways (DIP): www.imagingpathways.health.wa.gov.au) in the form of an algorithmic flow chart with supporting evidence and consensus to inform referrers to diagnostic imaging and radiologists as to the optimum strategy for surveillance and diagnosis of primary hepatocellular cancer (HCC) in those patients with risk factors of this disease. A literature review, including reference to several international consensus-based expert guidelines, has been employed to develop this tool.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. Family Violence Among Older Adult Patients Consulting in Primary Care Clinics: Results From the ESA (Enquête sur la santé des aînés) Services Study on Mental Health and Aging

    PubMed Central

    Préville, Michel; Mechakra-Tahiri, Samia Djemaa; Vasiliadis, Helen-Maria; Mathieu, Véronique; Quesnel, Louise; Gontijo-Guerra, Samantha; Lamoureux-Lamarche, Catherine; Berbiche, Djamal

    2014-01-01

    Objective To document the reliability and construct validity of the Family Violence Scale (FVS) in the older adult population aged 65 years and older. Method: Data came from a cross-sectional survey, the Enquête sur la santé des aînés et l’utilisation des services de santé (ESA Services Study), conducted in 2011–2013 using a probabilistic sample of older adults waiting for medical services in primary care clinics (n = 1765). Family violence was defined as a latent variable, coming from a spouse and from children. Results: A model with 2 indicators of violence; that is, psychological and financial violence, and physical violence, adequately fitted the observed data. The reliability of the FVS was 0.95. According to our results, 16% of older adults reported experiencing some form of family violence in the past 12 months of their interview, and 3% reported a high level of family violence (FVS > 0.36). Our results showed that the victim’s sex was not associated with the degree of violence (β = 0.02). However, the victim’s age was associated with family violence (β = −0.12). Older adults, aged 75 years and older, reported less violence than those aged between 65 and 74 years. Conclusion: Our results lead us to conclude that family violence against older adults is common and warrants greater public health and political attention. General practitioners could play an active role in the detection of violence among older adults. PMID:25161067

  9. The Role of Autophagy in Hepatocellular Carcinoma.

    PubMed

    Lee, Yoo Jin; Jang, Byoung Kuk

    2015-11-06

    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.

  10. Hepatocellular Carcinoma: Therapeutic Guidelines and Medical Treatment

    PubMed Central

    Kudo, Masatoshi; Trevisani, Franco; Abou-Alfa, Ghassan K; Rimassa, Lorenza

    2016-01-01

    Western and Eastern perspectives on therapeutic guidelines for hepatocellular carcinoma (HCC) have many commonalities but may also differ in certain aspects, as described in this article. In view of the limited therapeutic options for advanced HCC, evidence-based therapies are few, and thus there is a dependence on consensus-based guidelines. This article focuses on the Italian Association for the Study of the Liver guidelines and the Japanese approaches to therapy, while drawing attention to certain controversies from other academic bodies where applicable and appropriate. PMID:27995084

  11. Antiangiogenic Therapies for Advanced Hepatocellular Carcinoma

    PubMed Central

    Sampat, Keeran R.

    2013-01-01

    Hepatocellular carcinoma (HCC) is a significant cause of death worldwide. HCC is a highly vascular tumor, and proangiogenic cytokines such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor may play crucial roles in this disease. Sorafenib, a multikinase inhibitor that blocks VEGF and PDGF signaling, was the first systemic therapy to demonstrate improved survival in patients with advanced HCC. Several other drugs targeting VEGF are in development. Because of the anticipation of eventual resistance to anti-VEGF therapies, drugs that also target alternative proangiogenic pathways are being investigated. Recent clinical and preclinical data along with ongoing studies are reviewed. PMID:23576483

  12. Percutaneous ablation of hepatocellular carcinoma: current status.

    PubMed

    McWilliams, Justin P; Yamamoto, Shota; Raman, Steven S; Loh, Christopher T; Lee, Edward W; Liu, David M; Kee, Stephen T

    2010-08-01

    Hepatocellular carcinoma (HCC) is an increasingly common disease with dismal long-term survival. Percutaneous ablation has gained popularity as a minimally invasive, potentially curative therapy for HCC in nonoperative candidates. The seminal technique of percutaneous ethanol injection has been largely supplanted by newer modalities, including radiofrequency ablation, microwave ablation, cryoablation, and high-intensity focused ultrasound ablation. A review of these modalities, including technical success, survival rates, and complications, will be presented, as well as considerations for treatment planning and follow-up.

  13. 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

  14. Hepatocellular carcinoma is accelerated by NASH involving M2 macrophage polarization mediated by hif-1αinduced IL-10.

    PubMed

    Ambade, Aditya; Satishchandran, Abhishek; Saha, Banishree; Gyongyosi, Benedek; Lowe, Patrick; Kodys, Karen; Catalano, Donna; Szabo, Gyongyi

    2016-01-01

    Obesity-related inflammation promotes cancer development. Tissue resident macrophages affect tumor progression and the tumor micro-environment favors polarization into alternatively activated macrophages (M2) that facilitate tumor invasiveness. Here, we dissected the role of western diet-induced NASH in inducing macrophage polarization in a carcinogen initiated model of hepatocellular carcinoma (HCC). Adult C57BL/6 male mice received diethyl nitrosamine (DEN) followed by 24 weeks of high fat-high cholesterol-high sugar diet (HF-HC-HSD). We assessed liver MRI and histology, serum ALT, AFP, liver triglycerides, and cytokines. Macrophage polarization was determined by IL-12/TNFα (M1) and CD163/CD206 (M2) expression using flow cytometry. Role of hif-1α-induced IL-10 was dissected in hepatocyte specific hif-1αKO and hif-1αdPA (over-expression) mice. The western diet-induced features of NASH and accelerated HCC development after carcinogen exposure. Liver fibrosis and serum AFP were significantly increased in DEN + HF-HC-HSD mice compared to controls. Western diet resulted in macrophage (F4/80(+)CD11b(+)) infiltration to liver and DEN + HF-HC-HSD mice showed preferential increase in M2 macrophages. Isolated hepatocytes from western diet fed mice showed significant upregulation of the hypoxia-inducible transcription factor, hif-1α, and livers from hif-1α over-expressing mice had increased proportion of M2 macrophages. Primary hepatocytes from wild-type mice treated with DEN and palmitic acid in vitro showed activation of hif-1α and induction of IL-10, a M2 polarizing cytokine. IL-10 neutralization in hepatocyte-derived culture supernatant prevented M2 macrophage polarization and silencing hif-1α in macrophages blocked their M2 polarization. Therefore, our data demonstrate that NASH accelerates HCC progression via upregulation of hif-1α mediated IL-10 polarizing M2 macrophages.

  15. 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.

  16. Glucose intolerance and hepatocellular carcinoma: recent findings for old diseases.

    PubMed

    Facciorusso, Antonio; Barone, Michele

    2014-04-01

    In the last years, an increasing number of evidences on the influence of metabolic syndrome on the occurrence of hepatocellular carcinoma (HCC) have been developed. Type 2 mellitus diabetes (T2MD) has been found to increase the occurrence of primary liver tumors and to define a more aggressive carcinogenetic process. Furthermore, several preclinical and observational studies and a recent meta-analysis have shown that anti-diabetic drugs can modify the risk of HCC development in patients with T2DM. However, despite these evidences, underlying molecular mechanisms linking both pathological conditions have to be completely cleared yet. The study published by Gao et al. has found a possible molecular link between the two conditions, describing the predisposition to T2DM and HCC given by the haploinsufficiency of nuclear receptor coactivator 5 (NCOA5) in murine models. The authors have generated Ncoa5+/- (haploinsufficient) male mice and shown that 94% of male mutant mice developed HCC within 18 months of age, this in contrast with Ncoa5+/+ and Ncoa5+/- female mice. These results suggest that NCOA5 haploinsufficiency is linked to HCC development in male mice. Moreover, mutant male mice showed significantly elevated levels of fasting blood glucose and markedly decreased glucose tolerance and insulin sensitivity compared to Ncoa5+/+ littermates. This well-constructed work sheds light on the molecular link between T2DM and HCC and opens the way to further biological and clinical studies in the field of liver tumor prevention and treatment.

  17. [Progress of epigenetics and its therapeutic application in hepatocellular carcinoma].

    PubMed

    Lingyun, Sun; Xingyu, Li; Zhiwei, Sun

    2015-06-01

    Liver cancer is a severe harmful disease. It is the fifth most frequently diagnosed cancer and second most frequent cause of cancer deaths worldwide. As the most popular histologic subtype of hepatocellular carcinoma (HCC), primary HCC is a heterogeneous disease whose management requires a multidisciplinary approach combining genetics, genomics and environmental toxicology. Although many molecular targeted therapies such as sorafenib have entered clinical application and proven effective, the cytotoxicity and other negative effects cannot be ignored. There is an urgent need to identify new therapeutic targets and drugs, which can kill HCC cells with high efficiency and specificity. Plenty of evidence suggests that occurrence and development of HCC is closely related with epigenetics. DNA methylation, histone modification, aberrant expression of miRNAs and dysregulated expression of many epigenetic regulatory genes are significantly altered in HCC. Epigenetic therapeutic drugs may reverse abnormal gene expression, thus controlling the occurrence and development of HCC. In this review, we summarize the latest research progresses in epigenetics and its therapeutic application in HCC,and the potential treatments to be used in the future.

  18. 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.

  19. Multiple ectopic hepatocellular carcinomas arising in the abdominal cavity.

    PubMed

    Miyake, Toru; Hoshino, Seiichiro; Yoshida, Yoichiro; Aisu, Naoya; Tanimura, Syu; Hisano, Satoshi; Kuno, Nobuaki; Sohda, Tetsuro; Sakisaka, Shotaro; Yamashita, Yuichi

    2012-09-01

    Ectopic hepatocellular carcinoma (HCC) is a very rare clinical entity that is defined as HCC arising from extrahepatic liver tissue. This report presents a case of ectopic multiple HCC arising in the abdominal cavity. A 42-year-old otherwise healthy male presented with liver dysfunction at a general health checkup. Both HCV antibody and hepatitis B surface antigen were negative. Laboratory examination showed elevations in serum alpha-fetoprotein and PIVKA-II. Ultrasonography and computed tomography revealed multiple nodular lesions in the abdominal cavity with ascites without a possible primary tumor. Exploratory laparoscopy was performed, which revealed bloody ascites and multiple brown nodular tumors measuring approximately 10 mm in size that were disseminated on the perineum and mesentery. A postoperative PET-CT scan was performed but it did not reveal any evidence of a tumor in the liver. The tumors resected from the peritoneum were diagnosed as HCC. The present case of HCC was thought to have possibly developed from ectopic liver on the peritoneum or mesentery.

  20. Targeting fibroblast growth factor receptor signaling in hepatocellular carcinoma.

    PubMed

    Cheng, Ann-Lii; Shen, Ying-Chun; Zhu, Andrew X

    2011-01-01

    Hepatocellular carcinoma (HCC) is the primary type of liver cancer, and both the age-adjusted incidence and mortality of HCC have steadily increased in recent years. Advanced HCC is associated with a very poor survival rate. Despite accumulating data regarding the risk factors for HCC, the mechanisms that contribute to HCC tumorigenesis remain poorly understood. Signaling through the fibroblast growth factor (FGF) family is involved in fibrosis and its progression to cirrhosis of the liver, which is a risk factor for the development of HCC. Furthermore, several alterations in FGF/FGF receptor (FGFR) signaling correlate with the outcomes of HCC patients, suggesting that signaling through this family of proteins contributes to the development or progression of HCC tumors. Currently, there are no established systemic treatments for patients with advanced HCC in whom sorafenib treatment has failed or who were unable to tolerate it. Recently, several multikinase inhibitors that target FGFRs have demonstrated some early evidence of antitumor activity in phase I/II trials. Therefore, this review discusses the molecular implications of FGFR-mediated signaling in HCC and summarizes the clinical evidence for novel FGFR-targeted therapies for HCC currently being studied in clinical trials.

  1. Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials

    PubMed Central

    Scaggiante, Bruna; Kazemi, Maryam; Pozzato, Gabriele; Dapas, Barbara; Farra, Rosella; Grassi, Mario; Zanconati, Fabrizio; Grassi, Gabriele

    2014-01-01

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the sixth most common cancer worldwide and the third leading cause of cancer-related death. The difficulty to diagnose early cancer stages, the aggressive behaviors of HCC, and the poor effectiveness of therapeutic treatments, represent the reasons for the quite similar deaths per year and incidence number. Considering the fact that the diagnosis of HCC typically occurs in the advanced stages of the disease when the therapeutic options have only modest efficacy, the possibility to identify early diagnostic markers could be of significant benefit. So far, a large number of biomarkers have been associated to HCC progression and aggressiveness, but many of them turned out not to be of practical utility. This is the reason why active investigations are ongoing in this field. Given the huge amount of published works aimed at the identification of HCC biomarkers, in this review we mainly focused on the data published in the last year, with particular attention to the role of (1) molecular and biochemical cellular markers; (2) micro-interfering RNAs; (3) epigenetic variations; and (4) tumor stroma. It is worth mentioning that a significant number of the HCC markers described in the present review may be utilized also as targets for novel therapeutic approaches, indicating the tight relation between diagnosis and therapy. In conclusion, we believe that integrated researches among the different lines of investigation indicated above should represent the winning strategies to identify effective HCC markers and therapeutic targets. PMID:24574801

  2. Lactate Dehydrogenase in Hepatocellular Carcinoma: Something Old, Something New.

    PubMed

    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.

  3. Imaging of hepatocellular carcinoma: diagnosis, staging and treatment monitoring

    PubMed Central

    Hennedige, Tiffany

    2012-01-01

    Abstract Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Imaging is important for establishing a diagnosis of HCC. Several imaging modalities including ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and angiography are used in evaluating patients with chronic liver disease and suspected HCC. CT, MRI and contrast-enhanced US have replaced biopsy for diagnosis of HCC. Dynamic multiphase contrast-enhanced CT or MRI is the current standard for imaging diagnosis of HCC. Functional imaging techniques such as perfusion CT and diffusion-weighted MRI provide additional information about tumor angiogenesis that may be useful for treatment. Techniques evaluating tissue mechanical properties such as magnetic resonance elastography, and acoustic radiation force impulse imaging are being explored for characterizing liver lesions. The role of PET in the evaluation of HCC is evolving with promise seen especially with the use of a hepatocyte-specific PET tracer. Imaging is also critical for assessment of treatment response and detection of recurrence following locoregional treatment. Knowledge of the post-treatment appearance of HCC is essential for correct interpretation. This review article provides an overview of the role of imaging in the diagnosis, staging and post-treatment follow-up of HCC. PMID:23400006

  4. Prevention of hepatocellular carcinoma: a concise review of contemporary issues.

    PubMed

    Wong, Vincent Wai-Sun; Chan, Henry Lik-Yuen

    2012-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer deaths in men. Due to differences in the prevalence of viral hepatitis, the incidence of HCC in low and middle income countries is much higher than that of high income countries. Strategies to limit the impact of HCC include primary prevention against new cases of viral hepatitis, secondary prevention of HCC in susceptible individuals, and early HCC detection. Universal hepatitis B vaccination has resulted in dramatic reduction in incident cases of chronic hepatitis B and HCC in children and adolescents, and the full effect is expected in the next 20 years. The key hurdle for universal vaccination is the cost and the accessibility in low and middle income countries. Randomized controlled trials and meta-analyses showed that successful treatment of chronic hepatitis B and C can reduce the risk of HCC and cirrhotic complications. HCC surveillance by regular ultrasound examination and alpha fetoprotein testing leads to early cancer detection and offers the opportunity for curative treatment. Since all these measures are costly and require manpower and infrastructure support, the implementation should rely on the liaison among healthcare providers and policymakers. The cost-effectiveness of various strategies should also be studied based on local situations.

  5. MicroRNAs: Emerging Novel Clinical Biomarkers for Hepatocellular Carcinomas

    PubMed Central

    Anwar, Sumadi Lukman; Lehmann, Ulrich

    2015-01-01

    The discovery of small non-coding RNAs known as microRNAs has refined our view of the complexity of gene expression regulation. In hepatocellular carcinoma (HCC), the fifth most frequent cancer and the third leading cause of cancer death worldwide, dysregulation of microRNAs has been implicated in all aspects of hepatocarcinogenesis. In addition, alterations of microRNA expression have also been reported in non-cancerous liver diseases including chronic hepatitis and liver cirrhosis. MicroRNAs have been proposed as clinically useful diagnostic biomarkers to differentiate HCC from different liver pathologies and healthy controls. Unique patterns of microRNA expression have also been implicated as biomarkers for prognosis as well as to predict and monitor therapeutic responses in HCC. Since dysregulation has been detected in various specimens including primary liver cancer tissues, serum, plasma, and urine, microRNAs represent novel non-invasive markers for HCC screening and predicting therapeutic responses. However, despite a significant number of studies, a consensus on which microRNA panels, sample types, and methodologies for microRNA expression analysis have to be used has not yet been established. This review focuses on potential values, benefits, and limitations of microRNAs as new clinical markers for diagnosis, prognosis, prediction, and therapeutic monitoring in HCC. PMID:26295264

  6. 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

  7. Hepatitis B and hepatocellular carcinoma in Eskimo/Inuit population.

    PubMed

    McMahon, B J; Lanier, A P; Wainwright, R B

    1998-01-01

    Hepatitis B virus (HBV) is major risk factor for the development of hepatocellular carcinoma (HCC) worldwide. Serologic surveys performed in the 1970s and 1980s have demonstrated that Alaskan Eskimos, Canadian Inuit, and Greenland Inuit have very high prevalence rates of HBV. In Alaska, a high incidence of HCC in Eskimos, especially males, has been reported. Alaska Natives chronically infected with HBV have a relative risk of HCC of 148 compared to Alaska Natives who are not chronically infected. In Canada the incidence of HCC is six times more frequent in elderly Inuit than in Canadians in general. However, an elevated rate of HCC has not been found in Greenland. Primary prevention programs to prevent HCC by vaccination against HBV are being conducted in Alaska, Canada, and Greenland. In addition, in Alaska a program to detect HCC earlier by screening persons chronically infected with HBV, using semiannual alpha-fetoprotein testing, has resulted in detecting over 60% of HCC early enough for surgical resection.

  8. Developments in cancer vaccines for hepatocellular carcinoma.

    PubMed

    Buonaguro, Luigi

    2016-01-01

    Hepatocellular carcinoma (HCC) accounts for about 6 % of all new cancers diagnosed worldwide and represents one of the leading causes of cancer-related death globally in men and women, respectively. The overall prognosis for HCC patients is poor, especially in the majority of patients with more advanced stage of disease. Indeed, in such cases immunotherapeutic strategies may represent a novel and effective tool. A few immunotherapy trials conducted for HCC have provided divergent results, urging the scientific community to explore additional paths to improve efficacy of immunotherapeutic approaches. The "Cancer Vaccine development for Hepatocellular Carcinoma"-HEPAVAC Consortium has been funded by the EU within the FP7 with the goal of developing a novel therapeutic peptide-based cancer vaccine strategy for HCC including both "off-the-shelf" and personalized antigens. This will be one of the very few vaccine trials for HCC and the first multi-epitope, multi-target and multi-HLA allele therapeutic cancer vaccine for such a frequent and aggressive disease with a hitherto high unmet medical need. Feasibility, safety and biological efficacy will be evaluated in a randomized, controlled European multicenter phase I/II clinical trial.

  9. Synergistic effect of puerarin and 5-fluorouracil on hepatocellular carcinoma.

    PubMed

    Zeng, Yan-Ping; Yang, Zi-Rong; Guo, Xu-Feng; Jun, Wang; Dong, Wei-Guo

    2014-12-01

    Hepatocellular carcinoma (HCC) is one of the most common types of human malignancy worldwide, which is becoming increasingly resistant to traditional drug treatments. Puerarin combined with 5-fluorouracil (5-FU) may be a useful treatment for liver cancer. The primary aim of the present study was to determine whether combined treatment with 5-FU and puerarin is more effective against the hepatocellular carcinoma (HCC) cell line, SMMC7721, than treatment with 5-FU or puerarin alone. The growth inhibition of SMMC7721 cells by puerarin or 5-FU alone or in combination was determined by the Cell Counting Kit-8 assay, in vitro. Apoptotic morphological features and the percentage of apoptotic cells were detected using Hoechst 33258 staining and an Annexin V/PI apoptosis kit, respectively. In addition, a tumor xenograft model was established in nude mice using SMMC7721 cells. Puerarin and 5-FU alone or in combination were injected into the mice, and the inhibition of tumor growth was evaluated by monitoring tumor volume and weight. Treatment with 6,400 or 640 μM 5-FU resulted in growth inhibition of 95.56±0.81 and 75.91±3.54%, respectively. The combination index values were <1 when the fraction of affected cells was between 0.2555 and 0.7420. Furthermore, the percentage of apoptotic cells was markedly increased in the combined treatment group when compared with that of the individual treatment groups, in vitro and in vivo. Individual treatment with puerarin resulted in a tumor volume inhibition rate (IR) of 70.58% and a tumor weight IR of 46.20%. Treatment with 5-FU was found to decrease the tumor volume by 76.26% and tumor weight by 49.86%. In the combined treatment group, the tumor volume and weight IRs were 93.11 and 75.21%, respectively. A marked increase in the inhibition of tumor growth and the number of apoptotic cells in response to combined treatment with puerarin and 5-FU was identified with no observed liver or renal toxicity. These results suggest that

  10. 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…

  11. Lysis of primary hepatic tumours by lymphokine activated killer cells.

    PubMed Central

    Hsieh, K H; Shu, S Y; Lee, C S; Chu, C T; Yang, C S; Chang, K J

    1987-01-01

    Lymphokine activated killer cell is a newly described lytic system against a variety of solid tumours and is distinct in several respects from the classic cytolytic T cell and the natural killer systems. This study was conducted to evaluate the lytic activity of lymphokine activated killer cells against fresh autologous and allogeneic, as well as cultured hepatocellular carcinoma cells. Lymphokine activated killer cell was generated by incubating peripheral blood mononuclear cells with various concentrations of recombinant IL-2 (rIL-2, Cetus, USA) for various periods of time. A four hour 51Cr release assay was used to measure cytotoxicity. The results show that fresh and cultured hepatocellular carcinoma cells were only slightly susceptible to natural killer cells. Normal hepatocytes were resistant to lymphokine activated killer-mediated lysis. Lymphokine activated killer cells could be generated from mononuclear cells of hepatocellular carcinoma patients and normal subjects with lytic activity against fresh autologous and allogeneic and cultured hepatocellular carcinoma cells, but lymphokine activated killer cells from the former was less efficient than that from the latter. It is concluded that the adoptive immunotherapy with combined rIL-2 and lymphokine activated killer may be worth trying in early cases of primary hepatocellular carcinoma. PMID:3030899

  12. 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

  13. Hepatocellular autophagy modulates the unfolded protein response and fasting-induced steatosis in mice.

    PubMed

    Kwanten, Wilhelmus J; Vandewynckel, Yves-Paul; Martinet, Wim; De Winter, Benedicte Y; Michielsen, Peter P; Van Hoof, Viviane O; Driessen, Ann; Timmermans, Jean-Pierre; Bedossa, Pierre; Van Vlierberghe, Hans; Francque, Sven M

    2016-10-01

    Autophagy and the unfolded protein response (UPR) are key cellular homeostatic mechanisms and are both involved in liver diseases, including nonalcoholic fatty liver disease (NAFLD). Although increasing but conflicting results link these mechanisms to lipid metabolism, their role and potential cross talk herein have been poorly investigated. Therefore, we assessed the effects of hepatocyte-specific autophagy deficiency on liver parenchyma, the UPR, and lipid metabolism. Adult hepatocellular-specific autophagy-deficient mice (Atg7(F/F)Alb-Cre(+)) were compared with their autophagy-competent littermates (Atg7(+/+)Alb-Cre(+)). Livers were analyzed by electron microscopy, histology, real-time qPCR, and Western blotting. Atg7(F/F)Alb-Cre(+) mice developed hepatomegaly with significant parenchymal injury, as shown by inflammatory infiltrates, hepatocellular apoptosis, pericellular fibrosis, and a pronounced ductular reaction. Surprisingly, the UPR exhibited a pathway-selective pattern upon autophagy deficiency. The activity of the adaptive activating transcription factor 6 (ATF6) pathway was abolished, whereas the proapoptotic protein kinase RNA-like ER kinase pathway was increased compared with Atg7(+/+)Alb-Cre(+) mice. The inositol-requiring enzyme-1α signal was unaltered. Fasting-induced steatosis was absent in Atg7(F/F)Alb-Cre(+) mice. Remarkably, some isolated islands of fat-containing and autophagy-competent cells were observed in these livers. Hepatocellular autophagy is essential for parenchymal integrity in mice. Moreover, in the case of autophagy deficiency, the three different UPR branches are pathway selectively modulated. Attenuation of the ATF6 pathway might explain the observed impairment of fasting-induced steatosis. Finally, autophagy and lipid droplets are directly linked to each other.

  14. 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

  15. Hypoxia-induced angiogenesis in human hepatocellular carcinoma.

    PubMed

    Kim, Kwang-Rok; Moon, Hyo-Eun; Kim, Kyu-Won

    2002-11-01

    Hepatocellular carcinoma is a typical hypervascular tumor. Generally, hepatocellular carcinoma is developed through liver cirrhosis induced by chronic liver injury. This chronic injury leads to changes in the cellular property of the liver and subsequently causes fibrogenesis to demolish normal liver blood system. The catastrophe of the normal liver blood system leads to the shortage of blood circulation in the liver and causes hypoxia. Moreover, the increased cellularity due to highly proliferative tumor cells also induces local hypoxia inside hepatocellular carcinoma. Hypoxia can stimulate angiogenesis to support tumor growth by induction of angiogenic factors. Thus hypoxia may be a major cause of hypervasculature of hepatocellular carcinoma. Recently it has been reported that several hypoxia-regulatory factors are closely involved in angiogenesis of hepatocellular carcinoma. The stability and function of these factors can be regulated by interaction with other protein factors and consequently modulate the expression of angiogenic factors depending on oxygen tension. Therefore induction mechanism of hypoxia and the role of hypoxia-regulatory factors could provide new insights into hepatocarcinogenesis and the treatment of hepatocellular carcinoma.

  16. Radiofrequency thermal ablation of hepatocellular carcinoma.

    PubMed

    Allgaier, H P; Galandi, D; Zuber, I; Blum, H E

    2001-01-01

    Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide. Due to advanced or decompensated liver cirrhosis, comorbidity and multicentricity of the tumor lesions, 70-80% of HCC patients are inoperable at the time of diagnosis. Radiofrequency thermal ablation (RFTA) is a new minimally invasive and sage technique for the nonsurgical treatment of HCCs. Similar to other ablation techniques, the treatment strategy depends on several factors, including the patient's clinical status, the stage of liver cirrhosis and of the HCC. RFTA can be performed percutaneously, laparoscopically or after laparotomy. Advanced RFTA equipment, refined techniques of modifying tumor tissue response to RFTA, and combined treatment strategies should lead to better response rates even in larger HCCs.

  17. Early hepatocellular carcinoma and dysplastic nodules.

    PubMed

    Kojiro, Masamichi; Roskams, Tania

    2005-01-01

    It has been established that small, equivocal nodular lesions such as dysplastic nodules (DNs) and small well-differentiated hepatocellular carcinomas (early HCCs) are frequently observed in noncancerous liver tissues resected along with HCCs and in explant cirrhotic livers. DNs are classified into low-grade DNs or high-grade DNs on the basis of cytological and architectural atypia; high-grade DNs show varying degrees of cytological or architectural atypia, or both. Early HCCs are indistinctly nodular and highly differentiated and are frequently difficult to differentiate from high-grade DNs. Although the pathological diagnosis of high-grade DNs and early HCCs is controversial, the presence of tumor cell invasion into the intratumoral portal tracts (stromal invasion) is a helpful clue for differentiating early HCC from high-grade DNs. It is highly suggested that many HCCs occurring in cirrhotic liver arise in DNs and develop to classical HCC in a multistep fashion.

  18. 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

  19. Hepatocellular carcinoma metastases to the epidural space.

    PubMed

    Somerset, Hilary; Witt, J Peter; Kleinschmidt-Demasters, Bette K

    2009-12-01

    Hepatocellular carcinoma (HCC) is relatively uncommon in the United States, although hepatitis C, one of the known risk factors for disease, is currently showing burgeoning growth in the country. Hence, it is possible that the incidence of HCC also will increase. Clinicians and pathologists in the United States are relatively unfamiliar with the patterns of metastatic spread for HCC. We report 2 US-native patients with cirrhosis and HCC who developed epidural space metastasis, a pattern of disease spread seen infrequently, even in endemic areas. Diagnostic testing was delayed in both patients because of the lowered suspicion for metastasis and the fact that neither patient had recognized metastatic spread to more common sites, such as lung or lymph nodes. New-onset neck or back pain-especially with symptoms of paresthesia, radiculopathy, or cord compression-in the setting of HCC warrants prompt investigation for metastases to the spine and epidural space.

  20. Immunological landscape and immunotherapy of hepatocellular carcinoma.

    PubMed

    Prieto, Jesús; Melero, Ignacio; Sangro, Bruno

    2015-12-01

    Advanced hepatocellular carcinoma (HCC) is a serious therapeutic challenge and targeted therapies only provide a modest benefit in terms of overall survival. Novel approaches are urgently needed for the treatment of this prevalent malignancy. Evidence demonstrating the antigenicity of tumour cells, the discovery that immune checkpoint molecules have an essential role in immune evasion of tumour cells, and the impressive clinical results achieved by blocking these inhibitory receptors, are revolutionizing cancer immunotherapy. Here, we review the data on HCC immunogenicity, the mechanisms for HCC immune subversion and the different immunotherapies that have been tested to treat HCC. Taking into account the multiplicity of hyperadditive immunosuppressive forces acting within the HCC microenvironment, a combinatorial approach is advised. Strategies include combinations of systemic immunomodulation and gene therapy, cell therapy or virotherapy.

  1. Prevention of hepatocellular carcinoma by immunization*

    PubMed Central

    1983-01-01

    The evidence for an association between the carrier state of hepatitis B virus infection and hepatocellular carcinoma (liver cell cancer) is now sufficiently strong to justify the use of a vaccine against this infection as a means of preventing this cancer. Effective vaccines are available and have been tested in feasibility studies, and their use in field trials to test their effectiveness against the long-term risk of developing this cancer is now possible. At the present time, only limited quantities of the vaccine derived from human plasma infected by the hepatitis B virus are available, and the development of other types of vaccine is discussed together with the necessary revision of the present requirements for vaccine production. As the studies to assess the prevention of this cancer would require the surveillance of subjects for some years, consideration is also given to the design of field studies with short- and medium-term objectives. PMID:6317213

  2. Hepatocellular Carcinoma: The Role of Interventional Oncology

    PubMed Central

    Donadon, Matteo; Solbiati, Luigi; Dawson, Laura; Barry, Aisling; Sapisochin, Gonzalo; Greig, Paul D; Shiina, Shuichiro; Fontana, Andrea; Torzilli, Guido

    2016-01-01

    Background Hepatocellular carcinoma (HCC) remains a major health issue because of its increasing incidence and because of the complexity of its management. In addition to the traditional potentially curative treatments, i.e., liver transplantation and surgical resection, other new and emerging local therapies have been applied with promising results. Summary Radiotherapy (RT) and interstitial treatments, such as radiofrequency ablation (RFA), microwave ablation (MWA), and irreversible electroporation (IRE), have recently opened new and interesting treatment scenarios for HCC and are associated with promising results in selected patients. Herein, we describe the emerging role of interventional oncology for the treatment of HCC and focus on the different Western and Eastern approaches. Key Messages Modern RT and modern interstitial therapies, such as RFA, MWA, and IRE, should be considered for inclusion in HCC therapy guidelines. PMID:27995086

  3. Epidemiology of Viral Hepatitis and Hepatocellular Carcinoma

    PubMed Central

    El-Serag, Hashem B.

    2012-01-01

    Most cases of hepatocellular carcinoma (HCC) are associated with cirrhosis related to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Changes in the time trends of HCC and most variations in its age-, sex-, and race-specific rates among different regions are likely to be related to differences in hepatitis viruses that are most prevalent in a population, the timing of their spread, and the ages of the individuals the viruses infect. Environmental, host genetic, and viral factors can affect the risk of HCC in individuals with HBV or HCV infection. This review summarizes the risk factors for HCC among HBV- or HCV-infected individuals, based on findings from epidemiological studies and meta-analyses, as well as determinants of patient outcome and the HCC disease burden, globally and in the US. PMID:22537432

  4. Hepatocellular carcinoma associated with noncirrhotic autoimmune hepatitis.

    PubMed

    Maeda, Chizu; Tamano, Masaya; Murohisa, Toshimitsu; Yamagishi, Toshitsugu; Hashimoto, Takashi; Kojima, Kazuo; Iijima, Makoto; Sugaya, Takeshi; Nakano, Masakazu; Akima, Takashi; Tomita, Shigeki; Fujimori, Takahiro; Hiraishi, Hideyuki

    2010-04-01

    A rare case of hepatocellular carcinoma (HCC) in a 78-year-old woman with a 10-year history of autoimmune hepatitis (AIH) without liver cirrhosis and no history of alcohol abuse, drug injection, or blood transfusion is presented. At the time HCC was diagnosed, based on imaging studies showing a 5-cm-diameter S6 liver tumor, she had normal liver function, positive anti-nuclear antibodies, negative hepatitis B and C markers, and elevated alfa-fetoprotein (AFP; 169 ng/ml) and protein-induced by vitamin K absence or antagonist II (PIVKA-II; 721 mAU/ml) levels. Following subsegmental S6 resection, no evidence of fibrosis or cirrhosis was observed.

  5. Image-guided ablation for hepatocellular carcinoma.

    PubMed

    Lencioni, Riccardo; Crocetti, Laura

    2013-01-01

    Image-guided ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma (HCC) when surgical options-including resection and transplantation-are precluded. The term image-guided tumor ablation is defined as the direct application of chemical substances or sources of energy to a focal tumor in an attempt to achieve eradication or substantial tumor destruction. Over the past 25 years, several methods for local tumor destruction have been developed and clinically tested. Radiofrequency ablation (RFA) has shown superior anticancer effect and greater survival benefit with respect to the seminal percutaneous technique, ethanol injection, in meta-analyses of randomized controlled trials, and is currently established as the standard ablative modality. Nevertheless, novel thermal and nonthermal techniques for tumor ablation-including microwave ablation and irreversible electroporation-seem to have potential to improve the efficacy of RFA and are currently undergoing clinical investigation.

  6. The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma

    PubMed Central

    Zhai, Weiwei; Lim, Tony Kiat-Hon; Zhang, Tong; Phang, Su-Ting; Tiang, Zenia; Guan, Peiyong; Ng, Ming-Hwee; Lim, Jia Qi; Yao, Fei; Li, Zheng; Ng, Poh Yong; Yan, Jie; Goh, Brian K.; Chung, Alexander Yaw-Fui; Choo, Su-Pin; Khor, Chiea Chuen; Soon, Wendy Wei-Jia; Sung, Ken Wing-Kin; Foo, Roger Sik-Yin; Chow, Pierce Kah-Hoe

    2017-01-01

    Hepatocellular carcinoma (HCC) has one of the poorest survival rates among cancers. Using multi-regional sampling of nine resected HCC with different aetiologies, here we construct phylogenetic relationships of these sectors, showing diverse levels of genetic sharing, spanning early to late diversification. Unlike the variegated pattern found in colorectal cancers, a large proportion of HCC display a clear isolation-by-distance pattern where spatially closer sectors are genetically more similar. Two resected intra-hepatic metastases showed genetic divergence occurring before and after primary tumour diversification, respectively. Metastatic tumours had much higher variability than their primary tumours, suggesting that intra-hepatic metastasis is accompanied by rapid diversification at the distant location. The presence of co-existing mutations offers the possibility of drug repositioning for HCC treatment. Taken together, these insights into intra-tumour heterogeneity allow for a comprehensive understanding of the evolutionary trajectories of HCC and suggest novel avenues for personalized therapy. PMID:28240289

  7. The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma

    NASA Astrophysics Data System (ADS)

    Zhai, Weiwei; Lim, Tony Kiat-Hon; Zhang, Tong; Phang, Su-Ting; Tiang, Zenia; Guan, Peiyong; Ng, Ming-Hwee; Lim, Jia Qi; Yao, Fei; Li, Zheng; Ng, Poh Yong; Yan, Jie; Goh, Brian K.; Chung, Alexander Yaw-Fui; Choo, Su-Pin; Khor, Chiea Chuen; Soon, Wendy Wei-Jia; Sung, Ken Wing-Kin; Foo, Roger Sik-Yin; Chow, Pierce Kah-Hoe

    2017-02-01

    Hepatocellular carcinoma (HCC) has one of the poorest survival rates among cancers. Using multi-regional sampling of nine resected HCC with different aetiologies, here we construct phylogenetic relationships of these sectors, showing diverse levels of genetic sharing, spanning early to late diversification. Unlike the variegated pattern found in colorectal cancers, a large proportion of HCC display a clear isolation-by-distance pattern where spatially closer sectors are genetically more similar. Two resected intra-hepatic metastases showed genetic divergence occurring before and after primary tumour diversification, respectively. Metastatic tumours had much higher variability than their primary tumours, suggesting that intra-hepatic metastasis is accompanied by rapid diversification at the distant location. The presence of co-existing mutations offers the possibility of drug repositioning for HCC treatment. Taken together, these insights into intra-tumour heterogeneity allow for a comprehensive understanding of the evolutionary trajectories of HCC and suggest novel avenues for personalized therapy.

  8. Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism

    PubMed Central

    Zhang, Qingyu; Liu, Jie; Liu, Bin; Xia, Juan; Chen, Nianping; Chen, Xiaofeng; Cao, Yi; Zhang, Chen; Lu, CaiJie; Li, Mingyi; Zhu, Runzhi

    2014-01-01

    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. PMID:24717393

  9. 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.

  10. Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (SF1/Ad4BP, NR5A1) in children and adults with primary adrenal failure: ten years' experience

    PubMed Central

    Lin, Lin; Gu, Wen-Xia; Ozisik, Gokhan; To, Wing S.; Owen, Catherine J.; Jameson, J. Larry; Achermann, John C.

    2007-01-01

    Context Primary adrenal failure is a life-threatening condition that can be caused by a range of etiologies, including autoimmune, metabolic, and developmental disorders. The nuclear receptors DAX1 (NR0B1) and steroidogenic factor-1 (SF1/Ad4BP, NR5A1) play an important role in adrenal development and function, and mutations in these transcription factors have been found in patients with adrenal hypoplasia. Objective To investigate the prevalence of DAX1 and SF1 mutations in children and adults with primary adrenal failure of unknown etiology (i.e., not caused by congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune disease). Patients One-hundred and seventeen patients were included. Eighty-eight individuals presented in infancy or childhood with adrenal hypoplasia or primary adrenal failure of unknown etiology (n=64, 46,XY phenotypic males; n=17, 46,XY gonadal dysgenesis/impaired androgenization; n=7, 46,XX females). Twenty-nine individuals presented in adulthood with “Addison disease” of unknown etiology. Methods Mutational analysis of DAX1 (NR0B1) (including exon 2α/1A) and SF1 (NR5A1) by direct sequencing. Results DAX1 mutations were found in 58% (37/64) of 46,XY phenotypic boys referred with adrenal hypoplasia, and in all boys (8/8) with hypogonadotropic hypogonadism and a family history suggestive of adrenal failure in males. SF1 mutations causing adrenal failure were found only in two patients with 46,XY gonadal dysgenesis. No DAX1 or SF1 mutations were identified in the adult-onset group. Conclusions DAX1 mutations are a relatively frequent cause of adrenal failure in this group of boys. SF1 mutations causing adrenal failure in humans are rare and are more likely to be associated with significant underandrogenization and gonadal dysfunction in 46,XY individuals. PMID:16684822

  11. Magnesium Elevation Promotes Neuronal Differentiation While Suppressing Glial Differentiation of Primary Cultured Adult Mouse Neural Progenitor Cells through ERK/CREB Activation

    PubMed Central

    Liao, Wang; Jiang, Mujun; Li, Mei; Jin, Congli; Xiao, Songhua; Fan, Shengnuo; Fang, Wenli; Zheng, Yuqiu; Liu, Jun

    2017-01-01

    This study aimed to explore the influence of magnesium elevation on fate determination of adult neural progenitor cells (aNPCs) and the underlying mechanism in vitro. Adult neurogenesis, which is the generation of functional neurons from neural precursors, occurs throughout life in restricted anatomical regions in mammals. Magnesium is the fourth most abundant ion in mammals, and its elevation in the brain has been shown to enhance memory and synaptic plasticity in vivo. However, the effects of magnesium on fate determination of aNPCs, which are vital processes in neurogenesis, remain unknown. NPCs isolated from the dentate gyrus of adult C57/BL6 mice were induced to differentiate in a medium with varying magnesium concentrations (0.6, 0.8, and 1.0 mM) and extracellular signal-regulated kinase (ERK) inhibitor PD0325901. The proportion of cells that differentiated into neurons and glial cells was evaluated using immunofluorescence. Quantitative real-time polymerase chain reaction and Western blot methods were used to determine the expression of β-III tubulin (Tuj1) and glial fibrillary acidic protein (GFAP). The activation of ERK and cAMP response element-binding protein (CREB) was examined by Western blot to reveal the underlying mechanism. Magnesium elevation increased the proportion of Tju1-positive cells and decreased the proportion of GFAP-positive cells. Also, the expression of Tuj1 was upregulated, whereas the expression of GFAP was downregulated. Moreover, magnesium elevation enhanced the activation of both ERK and CREB. Treatment with PD0325901 reversed these effects in a dose-dependent manner. Magnesium elevation promoted neural differentiation while suppressing glial cell differentiation, possibly via ERK-induced CREB activation. PMID:28280456

  12. Myopericarditis during a primary Epstein-Barr virus infection in an otherwise healthy young adult. An unusual and insidious complication. Case report and a 60-year literature review.

    PubMed

    Sabbatani, Sergio; Manfredi, Roberto; Ortolani, Paolo; Trapani, Fabio Filippo; Viale, Pierluigi

    2012-06-01

    An otherwise healthy young man had infectious mononucleosis detected after an atypical clinical onset, including myocarditis and pericarditis. Our patient slowly but completely recovered from his cardiac complications after the course of his primary Epstein-Barr infection, as shown by periodical electrocardiographic and ultrasonographic studies, and a simple treatment with aspirin alone. Our case report is briefly reported, and discussed with regard to the existing literature, which has recorded such complications since the mid 1940s.

  13. 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.

  14. The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis

    PubMed Central

    Arrieta, Oscar; Cacho, Bernardo; Morales-Espinosa, Daniela; Ruelas-Villavicencio, Ana; Flores-Estrada, Diana; Hernández-Pedro, Norma

    2007-01-01

    Background Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. Methods We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. Results For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. Conclusion The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach αFP levels ≥200 ng

  15. 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

  16. Hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C, and intercellular adhesion-1 molecules. Clues to pathogenesis of hepatocellular damage and response to interferon treatment in patients with chronic hepatitis C.

    PubMed Central

    Ballardini, G; Groff, P; Pontisso, P; Giostra, F; Francesconi, R; Lenzi, M; Zauli, D; Alberti, A; Bianchi, F B

    1995-01-01

    To obtain information on the mechanisms of hepatocellular damage and the determinants of response to interferon, hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C and intercellular adhesion-1 molecules, and the number of lobular T lymphocytes were studied in 38 anti-HCV-positive patients. 14 patients did not show a primary response to interferon treatment. HCV genotype 1b was detected in 11 of them. They displayed higher scores of HCV-positive hepatocytes, HLA-A,B,C, and ICAM-1 molecules expression than with the responders. HCV-infected hepatocytes maintained the capacity to express HLA-A,B,C and ICAM-1 molecules. CD8-positive T cells in contact with infected hepatocytes and Councilman-like bodies were observed. A significant correlation was found between the number of lobular CD8-positive T cells and alanine amino transferase levels. No differences were observed in clinical, biochemical, and histological features between patients with high and low number of hepatocytes containing HCV antigens. These data suggest a prominent role of T cell-mediated cytotoxicity in the genesis of hepatocellular damage. The high expression of interferon-inducible antigens like HLA-A,B,C molecules suggests the presence of strong activation of the interferon system possibly related to high HCV replication in nonresponder patients infected with genotype 1b. Images PMID:7738174

  17. 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.

  18. 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.

  19. AP-2α inhibits hepatocellular carcinoma cell growth and migration.

    PubMed

    Huang, Wenhuan; Chen, Cheng; Liang, Zhongheng; Qiu, Junlu; Li, Xinxin; Hu, Xiang; Xiang, Shuanglin; Ding, Xiaofeng; Zhang, Jian

    2016-03-01

    Transcription factor AP-2α is involved in many types of human cancers, but its role in hepatocellular carcinogenesis is largely unknown. In this study, we found that expression of AP-2α was low in 40% of human hepatocellular cancers compared with adjacent normal tissues by immunohistochemical analysis. Moreover, AP-2α expression was low or absent in hepatocellular cancer cell lines (HepG2, Hep3B, SMMC-7721 and MHHC 97-H). Human liver cancer cell lines SMMC-7721 and Hep3B stably overexpressing AP-2α were established by lentiviral infection and puromycin screening, and the ectopic expression of AP-2α was able to inhibit hepatocellular cancer cell growth and proliferation by cell viability, MTT assay and liquid colony formation in vitro and in vivo. Furthermore, AP-2α overexpression decreased liver cancer cell migration and invasion as assessed by wound healing and Transwell assays, increasing the sensitivity of liver cancer cells to cisplatin analyzed by MTT assays. Also AP-2α overexpression suppressed the sphere formation and renewed the ability of cancer stem cells. Finally, we found that AP-2α is epigenetically modified and modulates the levels of phosphorylated extracellular signal-regulated protein kinase (ERK), β-catenin, p53, EMT, and CD133 expression in liver cancer cell lines. These results suggested that AP-2α expression is low in human hepatocellular cancers by regulating multiple signaling to affect hepatocellular cancer cell growth and migration. Therefore, AP-2α might represent a novel potential target in human hepatocellular cancer therapy.

  20. Evaluation of a multidisciplinary Tier 3 weight management service for adults with morbid obesity, or obesity and comorbidities, based in primary care.

    PubMed

    Jennings, A; Hughes, C A; Kumaravel, B; Bachmann, M O; Steel, N; Capehorn, M; Cheema, K

    2014-10-01

    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.

  1. 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

  2. Outcomes utilizing imported liver grafts for recipients with hepatocellular carcinoma.

    PubMed

    Battula, Narendra; Reichman, Trevor W; Amiri, Yamah; Carmody, Ian C; Galliano, Gretchen; Seal, John; Bugeaud, Emily; Bohorquez, Humberto; Bruce, David; Cohen, Ari; Loss, George E

    2017-03-01

    Liver transplantation (LT) offers the best chance of survival in selected patients with hepatocellular carcinoma (HCC). Wait-list mortality or dropout due to tumor progression can be significant, and therefore, timely transplantation is critical. Liver grafts discarded by outside organ procurement organizations are a potential source of grafts for low Model for End-Stage Liver Disease tumor patients. The primary aim of this study was to assess the disease-free and overall survival of patients with HCC transplanted with imported liver grafts (ILGs). Review of all patients transplanted for HCC between June 2005 and December 2014 was performed. Data on demographics, survival, and HCC recurrence were analyzed. During this time period, 59 out of 190 (31%) recipients with HCC received ILG. Of these 59 grafts, 54 were imported from within the region and 5 were from national offers (outside the region). The mean cold ischemia time for local liver grafts (LLGs) was 4.1 ± 1.5 hours versus 5.1 ± 1.4 hours for ILG (P < 0.001). The 1-, 3-, and 5-year patient survival was 90%, 85%, and 83% and 85%, 80%, and 79% for LLG and ILG (P = 0.08), respectively. The observed disease recurrence rate for both LLG and ILG recipients was equivalent. The median wait-list time for HCC recipients was 43 days (range, 2-1167 days). In conclusion, with careful graft assessment, the use of ILGs results in comparable outcomes following LT and no increased risk of HCC recurrence. Use of ILGs maximizes the donor pool and results in a higher rate of transplantation for HCC recipients. Liver Transplantation 23 299-304 2017 AASLD.

  3. Targeted therapy for hepatocellular carcinoma: novel agents on the horizon

    PubMed Central

    Cervello, Melchiorre; McCubrey, James A.; Cusimano, Antonella; Lampiasi, Nadia; Azzolina, Antonina; Montalto, Giuseppe

    2012-01-01

    Hepatocellular carcinoma (HCC) is the most common liver cancer, accounting for 90% of primary liver cancers. In the last decade it has become one of the most frequently occurring tumors worldwide and is also considered to be the most lethal of the cancer systems, accounting for approximately one third of all malignancies. Although the clinical diagnosis and management of early-stage HCC has improved significantly, HCC prognosis is still extremely poor. Furthermore, advanced HCC is a highly aggressive tumor with a poor or no response to common therapies. Therefore, new effective and well-tolerated therapy strategies are urgently needed. Targeted therapies have entered the field of anti-neoplastic treatment and are being used on their own or in combination with conventional chemotherapy drugs. Molecular-targeted therapy holds great promise in the treatment of HCC. A new therapeutic opportunity for advanced HCC is the use of sorafenib (Nexavar). On the basis of the recent large randomized phase III study, the Sorafenib HCC Assessment Randomized Protocol (SHARP), sorafenib has been approved by the FDA for the treatment of advanced HCC. Sorafenib showed to be able to significantly increase survival in patients with advanced HCC, establishing a new standard of care. Despite this promising breakthrough, patients with HCC still have a dismal prognosis, as it is currently the major cause of death in cirrhotic patients. Nevertheless, the successful results of the SHARP trial underscore the need for a comprehensive understanding of the molecular pathogenesis of this devastating disease. In this review we summarize the most important studies on the signaling pathways implicated in the pathogenesis of HCC, as well as the newest emerging drugs and their potential use in HCC management. PMID:22470194

  4. Living donor liver transplantation for hepatocellular carcinoma achieves better outcomes

    PubMed Central

    Lin, Chih-Che

    2016-01-01

    Liver transplantation (LT) for hepatocellular carcinoma (HCC) at Kaohsiung Chang Gung Memorial Hospital mainly relies on live donor LT (LDLT). Owing to taking the risk of LD, we are obligated to adopt strict selection criteria for HCC patients and optimize the pre-transplant conditions to ensure a high disease-free survival similar to those without HCC, even better than deceased donor LT (DDLT). Better outcomes are attributed to excellent surgical results and optimal patient selection. The hospital mortality of primary and salvage LDLT are lower than 2% in our center. Although Taiwan Health Insurance Policy extended the Milan to University of California, San Francisco (UCSF) criteria in 2006, selection criteria will not be consolidated to take into account only by the morphologic size/number of tumors but also by their biology. The criteria are divided into modifiable image morphology, alpha fetoprotein (AFP), and positron emission tomography (PET) scan with standard uptake value (SUV) and unmodifiable unfavorable pathology such as HCC combined with cholangiocarcinoma (CC), sarcomatoid type, and poor differentiation. Downstaging therapy is necessary for HCC patients beyond criteria to fit all modifiable standards. The upper limit of downstaging treatment seems to be extended by more effective drug eluting transarterial chemoembolization in cases without absolute contraindications. In contrast, the pitfall of unmodifiable tumor pathology should be excluded by the findings of pretransplant core biopsy/resection if possible. More recently, achieving complete tumor necrosis in explanted liver could almost predict no recurrence after transplant. Necrotizing therapy is advised if possible before transplant even the tumor status within criteria to minimize the possibility of tumor recurrence. LDLT with low surgical mortality in experienced centers provides the opportunities of optimizing the pre-transplant tumor conditions and timing of transplant to achieve better

  5. 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.

  6. 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

  7. 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

  8. Short-term effects of unilateral lesion of the primary motor cortex (M1) on ipsilesional hand dexterity in adult macaque monkeys.

    PubMed

    Bashir, Shahid; Kaeser, Mélanie; Wyss, Alexander; Hamadjida, Adjia; Liu, Yu; Bloch, Jocelyne; Brunet, Jean-François; Belhaj-Saif, Abderraouf; Rouiller, Eric M

    2012-01-01

    Although the arrangement of the corticospinal projection in primates is consistent with a more prominent role of the ipsilateral motor cortex on proximal muscles, rather than on distal muscles involved in manual dexterity, the role played by the primary motor cortex on the control of manual dexterity for the ipsilateral hand remains a matter a debate, either in the normal function or after a lesion. We, therefore, tested the impact of permanent unilateral motor cortex lesion on the manual dexterity of the ipsilateral hand in 11 macaque monkeys, within a time window of 60 days post-lesion. For comparison, unilateral reversible pharmacological inactivation of the motor cortex was produced in an additional monkey. Manual dexterity was assessed quantitatively based on three motor parameters derived from two reach and grasp manual tasks. In contrast to the expected dramatic, complete deficit of manual dexterity of the contralesional hand that persists for several weeks, the impact on the manual dexterity of the ipsilesional hand was generally moderate (but statistically significant) and, when present, lasted less than 20 days. Out of the 11 monkeys, only 3 showed a deficit of the ipsilesional hand for 2 of the 3 motor parameters, and 4 animals had a deficit for only one motor parameter. Four monkeys did not show any deficit. The reversible inactivation experiment yielded results consistent with the permanent lesion data. In conclusion, the primary motor cortex exerts a modest role on ipsilateral manual dexterity, most likely in the form of indirect hand postural control.

  9. 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.

  10. 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. PMID:27818805

  11. Hepatocellular carcinoma first presenting as a tumor of the oral cavity.

    PubMed

    Alrumaih, Redha Ali; Arian, Asif Ali; Alhedyani, Alanoud A; Al-Zaher, Nabil; Dababo, M Anas

    2015-09-01

    Hepatocellular carcinoma (HCC) is the sixth most common neoplasm worldwide; HCC metastasis is common affecting 50% of cases. However, metastasis to the oral cavity is extremely infrequent. We present a case of hepatocellular cancer first presenting as a mass lesion at the upper alveolus and review metastatic hepatocellular carcinoma to the oral cavity in 73-year-old male patient.

  12. Endobronchial metastasis from hepatocellular carcinoma – a case description with literature review

    PubMed Central

    Szumera-Ciećkiewicz, Anna; Olszewski, Włodzimierz T; Piech, Krzysztof; Głogowski, Maciej; Prochorec-Sobieszek, Monika

    2013-01-01

    Endobronchial metastases from hepatocellular carcinoma are very rare. Up to date, no more than 7 cases were reported. The authors present a case of 20-year old female with metastatic hepatocellular carcinoma to superior lobar bronchus. Examination of cytological and small biopsy specimens obtained from bronchoscopy revealed characteristic microscopic features and immunohistochemical profile of hepatocellular carcinoma. PMID:24040462

  13. The therapeutic potential of bone marrow-derived mesenchymal stromal cells on hepatocellular carcinoma.

    PubMed

    Bayo, Juan; Marrodán, Mariano; Aquino, Jorge B; Silva, Marcelo; García, Mariana G; Mazzolini, Guillermo

    2014-03-01

    Mesenchymal stromal cells (MSCs) are more often obtained from adult and extraembryonic tissues, with the latter sources being likely better from a therapeutic perspective. MSCs show tropism towards inflamed or tumourigenic sites. Mechanisms involved in MSC recruitment into tumours are comprehensively analysed, including chemoattractant signalling axes, endothelial adhesion and transmigration. In addition, signals derived from hepatocellular carcinoma (HCC) tumour microenvironment and their influence in MSC tropism and tumour recruitment are dissected, as well as the present controversy regarding their influence on tumour growth and/or metastasis. Finally, evidences available on the use of MSCs and other selected progenitor/stem cells as vehicles of antitumourigenic genes are discussed. A better knowledge of the mechanisms involved in progenitor/stem cell recruitment to HCC tumours is proposed in order to enhance their tumour targeting which may result in improvements in cell-based gene therapy strategies.

  14. Fibroblast growth factor family as a potential target in the treatment of hepatocellular carcinoma

    PubMed Central

    Coleman, Stacey J; Grose, Richard P; Kocher, Hemant M

    2014-01-01

    Hepatocellular cancer (HCC) is currently the third leading cause of cancer death worldwide. The prognosis of patients diagnosed with late-stage disease is dismal due to high resistance to conventional systemic therapies. The introduction of sorafenib, despite its limited efficacy, as the standard systemic therapy for advanced HCC has paved a way for targeted molecular therapies for HCC. Fibroblast growth factor (FGF) signaling plays an important role in the developing embryo and the adult. The FGF signaling pathway is often hijacked by cancer cells, including HCC. Several alterations in FGF signaling correlate with poor outcome in HCC patients, suggesting that this family of signaling molecules plays an important role in the development of HCC. Multikinase inhibitors targeting FGF signaling are currently under investigation in clinical trials. This review discusses the current understanding of the biological and clinical implications of aberrant FGF signaling in the prognosis, diagnosis, and treatment of HCC. PMID:27508175

  15. Can primary care team-based transition to insulin improve outcomes in adults with type 2 diabetes: the stepping up to insulin cluster randomized controlled trial protocol

    PubMed Central

    2014-01-01

    Background Type 2 diabetes (T2D) brings significant human and healthcare costs. Its progressive nature means achieving normoglycaemia is increasingly difficult, yet critical to avoiding long term vascular complications. Nearly one-half of people with T2D have glycaemic levels out of target. Insulin is effective in achieving glycaemic targets, yet initiation of insulin is often delayed, particularly in primary care. Given limited access to specialist resources and the size of the diabetes epidemic, primary care is where insulin initiation must become part of routine practice. This would also support integrated holistic care for people with diabetes. Our Stepping Up Program is based on a general practitioner (GP) and practice nurse (PN) model of care supported appropriately by endocrinologists and credentialed diabetes educator-registered nurses. Pilot work suggests the model facilitates integration of the technical work of insulin initiation within ongoing generalist care. Methods This protocol is for a cluster randomized controlled trial to examine the effectiveness of the Stepping Up Program to enhance the role of the GP-PN team in initiating insulin and improving glycaemic outcomes for people with T2D. 224 patients between the ages of 18 and 80 years with T2D, on two or more oral hypoglycaemic agents and with an HbA1c ≥7.5% in the last six months will be recruited from 74 general practices. The unit of randomization is the practice. Primary outcome is change in glycated haemoglobin HbA1c (measured as a continuous variable). We hypothesize that the intervention arm will achieve an absolute HbA1c mean difference of 0.5% lower than control group at 12 months follow up. Secondary outcomes include the number of participants who successfully transfer to insulin and the proportion who achieve HbA1c measurement of <7.0%. We will also collect data on patient psychosocial outcomes and healthcare utilization and costs. Discussion The study is a pragmatic translational

  16. SERUM LEPTIN LEVENS AND HEPATOCELLULAR CARCINOMA: REVIEW ARTICLE

    PubMed Central

    ANDRIGHETTO, Luiza Vitelo; POZIOMYCK, Aline Kirjner

    2016-01-01

    ABSTRACT Introduction: Hepatocellular carcinoma is one of the most frequent types of malignant tumors in the world. There is growing evidence of the relationship between it development and obesity. The mechanism that links obesity to cancer is still not fully understood; however, it is essential to the understanding the adipose tissue in metabolic changes related to obesity and hepatocellular carcinoma. Objective: To review the influence of serum leptin levels in patients with hepatocelular carcinoma. Method: Systematic review of the literature based on the methodology of the Cochrane Institute. The search for articles was in the database: Science Direct, Scielo, Medline, Lilacs e Pubmed. The key words used were hepatocellular carcinoma, leptin, adipokine. Results: After evaluation of individual studies, were selected seven studies. The results previously studied are still inconsistent and contradictory, and leptin can be effectively involved in the occurrence and development of hepatocellular carcinoma. Conclusion: Therefore, it is necessary to develop prospective, well-designed and conducted focusing on the role and specific mechanisms of this hormone in patients with hepatocellular carcinoma, so that new correlations can be properly supported. PMID:28076486

  17. IT-36PHASE 1/2 STUDY OF THE COMBINATION OF INDOXIMOD AND TEMOZOLOMIDE FOR ADULT PATIENTS WITH TEMOZOLOMIDE-REFRACTORY PRIMARY MALIGNANT BRAIN TUMORS

    PubMed Central

    Zakharia, Yousef; Johnson, Theodore; Colman, Howard; Vahanian, Nicholas; Link, Charles; Kennedy, Eugene; Sadek, Ramses; Kong, Feng-Ming; Vender, John; Munn, David; Rixe, Olivier

    2014-01-01

    BACKGROUND: Indoleamine 2, 3-dioxygenase (IDO) is a key immune-modulatory enzyme that inhibits CD8+ T cells and enhances the suppressor activity of Tregs. IDO is expressed in 50 to 90% of glioblastoma (GBM) and is correlated with poor prognosis. IDO pathway inhibitors such as indoximod (1-Methyl-D-tryptophan) can improve anti-tumor T cell response slowing the tumor growth in vivo. We have demonstrated a synergistic effect of indoximod when combined with temozolomide (TMZ) and radiation in a syngeneic orthotopic brain tumor model. This phase 1 study is designed to determine maximal tolerated dose (MTD) of indoximod in combination with TMZ in GBM followed by an expansion phase 2 testing the preliminary activity of the combination in relevant situations with the addition of bevacizumab or stereotactic radiosurgery. METHODS: After progression to standard front line-therapy, patients with GBM are enrolled in a dose escalation study of indoximod (600, 1000 or 1200 mg twice daily given orally) with a standard fixed dose of TMZ. In the phase 2 part, patients are separated into 3 cohorts: cohort 2a: indoximod with TMZ, cohort 2b: indoximod with TMZ and bevacizumab (for patients who are currently on bevacizumab), cohort 2c: indoximod with TMZ and stereotactic radiosurgery. STATISTICAL ANALYSIS: The study uses a 3 + 3 dose escalation design, until reaching the MTD or the maximal specified dose. Sample size in phase 2 is based on the primary endpoint of 6 months progression free survival (PFS). CORRELATIVE STUDIES: Assessment of primary tumor samples for IDO expression, evaluation of serum for potential biomarkers of IDO pathway activity (kynurenine and tryptophan) and a pharmacokinetic analysis will be performed. RESULTS: Study is ongoing. Updates are to be presented at the meeting.

  18. Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular carcinoma

    PubMed Central

    2012-01-01

    Background The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ABCG2 in adult human hepatocellular carcinoma (HCC) in both in vivo and in vitro models with different degree of malignancy. Methods In cell lines derived from human hepatocellular carcinoma, ABCG2 gene expression was assessed by reverse transcription quantitative real time PCR and function by Hoechst 33342 efflux assay; protein content was assessed by SDS-PAGE Western blot. Results ABCG2 expression was found to be highest in the most undifferentiated cell lines, and this was related with a higher functional activity. ABCG2 expression was sensitive to antineoplastic drugs since exposure to 5 μM doxorubicin for 24 hours resulted in significant up-regulations of ABCG2 in all cell lines, particularly in those lines with low basal ABCG2 expression (p<0.01). The gene expression was also investigated in 51 adult liver tissues with HCC and related cirrhosis; normal liver tissue was used as control. ABCG2 gene expression was higher in HCC than both cirrhotic paired tissue and normal tissue. This up-regulation was greater (p<0.05) in pathological poorly differentiated grade G3/G4 than in well-differentiated G1/G2 HCC. Conclusions Our results suggest a correlation of ABCG2 gene expression and differentiation stage both in human and HCC derived cell lines. The rapid up-regulation of ABCG2 to exposure to doxorubicin emphasizes the importance of this transporter in accounting for drug resistance in liver tumors. PMID:23153066

  19. Amenorrhea - primary

    MedlinePlus

    ... of periods - primary Images Primary amenorrhea Normal uterine anatomy (cut section) Absence of menstruation (amenorrhea) References Bulun SE. The physiology and pathology of the female reproductive axis. In: ...

  20. Schistosoma mansoni infection of Syrian golden hamsters: the host humoral immune response in relation to the adult worm burdens after primary infection.

    PubMed

    Yong, W K; Das, P K; Dachlan, Y P

    1983-01-01

    Seven-week-old female Syrian golden hamsters (Mesocricetus auratus) showed different degrees of susceptibility to Schistosoma mansoni, as assessed by the percentage of cercariae recovered as adult worms 6 weeks after infection. Plasma of the low (A), medium (B) and high (C) susceptibility groups were tested immunochemically. No differences were observed in the concentrations of albumin, alpha 1-, alpha 2-, beta- and gamma-globulins as measured by cellulose acetate electrophoresis. However, a significantly higher percentage of animals in groups A and B than in group C had an S. mansoni specific "beforked" IgG precipitin band and specific antibodies against a worm tegumental antigen preparation (AWT). Conversely, more animals in group C made antibodies against a "denuded" worm-body antigen preparation (AWB) than in groups A and B. However, by using the enzyme-linked immunosorbent assay, no significant differences in antibody titres against AWT, AWB and a total worm antigen (AVA) were observed in the animals in groups A, B and C. Upon consideration of the immunochemical data in relation to the distribution pattern of susceptibility to infection, we propose that the intensity of S. mansoni infection in the hamster is a polygene-controlled phenomenon and depends upon the presentation of differing parasite antigenic component(s) to the host.

  1. Gene expression analyses of hepatocellular adenoma and hepatocellular carcinoma from the marine flatfish Limanda limanda.

    PubMed

    Small, Hamish J; Williams, Timothy D; Sturve, Joachim; Chipman, James K; Southam, Andrew D; Bean, Tim P; Lyons, Brett P; Stentiford, Grant D

    2010-01-25

    At selected sites around the UK, the offshore sentinel flatfish species dab Limanda limanda are found to contain elevated levels of macroscopic liver tumors. Previous proteomic and metabolomic studies have demonstrated that differences exist between tumor and non-tumor tissues; however, these differing features were not identified, and little is known about the changes at the gene expression level, or whether prognostic markers are present and can be identified. A flounder Platichthys flesus custom cDNA microarray and RT-PCR were used to investigate hepatic mRNA expression in the histologically confirmed tumors, hepatocellular adenoma (HA) and hepatocellular carcinoma (HC) from dab, and in adjacent normal tissue from the same fish. Differences in gene expression were observed between tumor and normal tissues, and between tumor types. A class-prediction approach using 50 transcripts revealed sufficient group-specific expression profiles to allow segregation of samples dependent on their tumor type or the sex of the host. Vitellogenins were found to display the greatest induction (up to 500-fold induction) in some HC tumors from female fish and in both HA and HC tumors from males. To the best of our knowledge, this is the first report of the association of vitellogenin expression with tumors of wild fish.

  2. 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

  3. Promising new strategies for hepatocellular carcinoma.

    PubMed

    Nakamoto, Yasunari

    2016-08-25

    Hepatocellular carcinoma (HCC) is one of the most common causes of cancer death worldwide. It usually arises based on a background of chronic liver diseases, defined as the hypercarcinogenic state. The current treatment options for HCC ranging from locoregional treatments to chemotherapies, including sorafenib, effectively regulate the limited sizes and numbers of the nodules. However, these treatments remain unsatisfactory because they have insufficient antitumor effects on the large and numerous nodules associated with HCC and because of a high recurrence rate in the surrounding inflamed liver. To develop novel and promising therapies with higher antitumor effects, recent progress in identifying molecular targets and developing immunological procedures for HCC are reviewed. The molecular targets discussed include the intracellular signaling pathways of protein kinase B/mammalian target of rapamycin and RAS/RAF/mitogen-activated protein kinase, Wnt/β-catenin and glutamine synthetase, insulin-like growth factor, signal transducer and activator of transcription 3, nuclear factor-κB and telomerase reverse transcriptase, and c-MET. Immunological studies have focused mainly on target identification, T cells, natural killer cells, dendritic cells, natural killer T cells, and vaccine development.

  4. 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.

  5. Local Ablation for Hepatocellular Carcinoma in Taiwan

    PubMed Central

    Lin, Shi-Ming

    2013-01-01

    Hepatocellular carcinoma (HCC) is the second commonest cancer in Taiwan. The national surveillance program can detect HCC in its early stages, and various curative modalities (including surgical resection, orthotopic liver transplantation, and local ablation) are employed for the treatment of small HCC. Local ablation therapies are currently advocated for early-stage HCC that is unresectable because of co-morbidities, the need to preserve liver function, or refusal of resection. Among the various local ablation therapies, the most commonly used modalities include percutaneous ethanol injection and radiofrequency ablation (RFA); percutaneous acetic acid injection and microwave ablation are used less often. RFA is more commonly employed than other local ablative modalities in Taiwan because the technique is highly effective, minimally invasive, and requires fewer sessions. RFA is therefore advocated in Taiwan as the first-line curative therapy for unresectable HCC or even for resectable HCC. However, current RFA procedures are less effective against tumors that are in high-risk or difficult-to-ablate locations, are poorly visualized on ultrasonography (US), or are large. Recent advancements in RFA in Taiwan can resolve these issues by the creation of artificial ascites or pleural effusion, application of real-time virtual US assistance, use of combination therapy before RFA, or use of switching RF controllers with multiple electrodes. This review article provides updates on the clinical outcomes and advances in local ablative modalities (mostly RFA) for HCC in Taiwan. PMID:24159599

  6. Current and future treatments for hepatocellular carcinoma

    PubMed Central

    Schlachterman, Alexander; Craft Jr, Willie W; Hilgenfeldt, Eric; Mitra, Avir; Cabrera, Roniel

    2015-01-01

    Hepatocellular carcinoma (HCC) represents a unique challenge for physicians and patients. There is no definitively curative treatment. Rather, many treatment and management modalities exist with differing advantages and disadvantages. Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC. In addition, quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies. Thus, considering all the options and their various pros and cons can quickly become complex for both clinicians and patients. In this review, we systematically discuss the current treatment modalities available for HCC, detailing relevant clinical data, risks and rewards and overall outcomes for each approach. Surgical options discussed include resection, transplantation and ablation. We also discuss the radiation modalities: conformal radiotherapy, yttrium 90 microspheres and proton and heavy ion radiotherapy. The biologic agent Sorafenib is discussed as a promising new approach, and recent clinical trials are reviewed. We then detail currently described molecular pathways implicated in the initiation and progression of HCC, and we explore the potential of each pathway as an avenue for drug exploitation. We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease. PMID:26229392

  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. 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

  9. Status of hepatocellular carcinoma in Gulf region.

    PubMed

    Rasul, Kakil Ibrahim; Al-Azawi, Safaa H; Chandra, Prem; Abou-Alfa, Ghassan K; Knuth, Alexander

    2013-12-01

    Hepatocellular carcinoma (HCC) has a unique geographic distribution that is likely to be determined by specific etiologic factors. There is a distinctive difference in sex and age related occurrence of disease. In the Gulf region, there are contradicting data on the prevalence and death rates due to HCC. In this review we highlight some aspects of HCC specific to the Gulf region. A retrospective analysis of 150 patient's data is presented, including demographic, epidemiological, aetiological disease status assessment with child Pugh criteria, modes of treatment and treatment related outcome. Hepatitis C virus (HCV) infection was the most common (45%) documented etiology, similar to Western European countries, followed by hepatitis B virus (HBV) infection in 27% of cases, alcoholic liver disease only in six patients (4%). Child-Pugh assessment was A in 33%, B in 37% and C in 30% of observed patients. Surgery (liver resection or transplantation) was performed in 12% and local ablation in 5% of cases. The others were treated by chemo-embolization in 17% and by systemic therapy with sorafenib in 13% of patients. Nearly half of the patients (53%) were in advanced stages and received palliative treatment. To improve the outcome of treatment in HCC patients in the Gulf region, an effective and strategic screening program must be implemented for early diagnosis and treatment to improve the outcome of this mostly fatal disease.

  10. Hepatitis B virus and hepatocellular carcinoma

    PubMed Central

    Arbuthnot, Patrick; Kew, Michael

    2001-01-01

    Chronic hepatitis B virus (HBV) infection is a major global cause of hepatocellular carcinoma (HCC). Individuals who are chronic carriers have a greater than 100-fold increased relative risk of developing the tumour. Several mechanisms of HBV-induced HCC have been proposed. Integration of HBV DNA into the genome of hepatocytes occurs commonly, although integration at cellular sites that are important for regulation of hepatocyte proliferation appears to be a rare event. Functions of the HBx protein are also potentially oncogenic. These include transcriptional activation of cellular growth regulatory genes, modulation of apoptosis and inhibition of nucleotide excision repair of damaged cellular DNA. The effects of HBx are mediated by interaction with cellular proteins and activation of cell signalling pathways. Variations in HBV genome sequences may be important in hepatocarcinogenesis, although their significance has not yet been completely elucidated. Necroinflammatory hepatic disease, which often accompanies chronic HBV infection, may contribute indirectly to hepatocyte transformation in a number of ways, including by facilitating HBV DNA integration, predisposing to the acquisition of cellular mutations and generating mutagenic oxygen reactive species. Although HCC is a malignancy with a poor prognosis, the availability of an effective vaccine against HBV infection, and its inclusion in the Expanded Programme of Immunization of many countries, augurs well for the eventual elimination of HBV-associated HCC. PMID:11454100

  11. Current and future treatments for hepatocellular carcinoma.

    PubMed

    Schlachterman, Alexander; Craft, Willie W; Hilgenfeldt, Eric; Mitra, Avir; Cabrera, Roniel

    2015-07-28

    Hepatocellular carcinoma (HCC) represents a unique challenge for physicians and patients. There is no definitively curative treatment. Rather, many treatment and management modalities exist with differing advantages and disadvantages. Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC. In addition, quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies. Thus, considering all the options and their various pros and cons can quickly become complex for both clinicians and patients. In this review, we systematically discuss the current treatment modalities available for HCC, detailing relevant clinical data, risks and rewards and overall outcomes for each approach. Surgical options discussed include resection, transplantation and ablation. We also discuss the radiation modalities: conformal radiotherapy, yttrium 90 microspheres and proton and heavy ion radiotherapy. The biologic agent Sorafenib is discussed as a promising new approach, and recent clinical trials are reviewed. We then detail currently described molecular pathways implicated in the initiation and progression of HCC, and we explore the potential of each pathway as an avenue for drug exploitation. We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease.

  12. 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

  13. Relation between sex hormones and hepatocellular carcinoma.

    PubMed

    El Mahdy Korah, T; Abd Elfatah Badr, E; Mohamed Emara, M; Ahmed Samy Kohla, M; Gamal Saad Michael, G

    2016-11-01

    Males have higher incidence of hepatocellular carcinoma (HCC) than females. Sex hormones may be a risk factor. The aim was to determine the levels of sex hormones in male and female patients with HCC and cirrhosis versus controls and its possible relationship with HCC. This study was conducted on 90 subjects divided into 40 patients with HCC, 30 patients with liver cirrhosis and 20 apparently healthy subjects complete blood picture, liver function tests. Determination of AFP levels and hormonal assay of oestrogen, progesterone, total testosterone, prolactin, FSH and LH were performed on all subjects. Total testosterone levels were significantly decreased in the two patients groups compared with controls. While oestrogen levels were significantly decreased in the HCC group in comparison with other two groups, prolactin levels were significantly decreased in the HCC group compared with the liver cirrhosis group and increased in the liver cirrhosis group when compared to controls. FSH and LH levels were significantly increased in the HCC group when compared to controls. There is no significant correlation between sex hormones assay and both the size of HCC and degree of cirrhosis in both patient groups. It is concluded that there is no strong relation between sex hormones and HCC when the study was carried out on the levels of sex hormones in patients with HCC.

  14. Liver resection for intermediate hepatocellular carcinoma

    PubMed Central

    Yi, Peng-Sheng; Zhang, Ming; Zhao, Ji-Tong; Xu, Ming-Qing

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. The Barcelona Clinic Liver Cancer (BCLC) staging system is regarded as the gold standard staging system for HCC, classifying HCC as early, intermediate, or advanced. For intermediate HCC, trans-catheter arterial chemoembolization (TACE) is recommended as the optimal strategy by the BCLC guideline. This review investigates whether liver resection is better than TACE for intermediate HCC. Based on published studies, we compare the survival benefits and complications of liver resection and TACE for intermediate HCC. We also compare the survival benefits of liver resection in early and intermediate HCC. We find that liver resection can achieve better or at least comparable survival outcomes compared with TACE for intermediate HCC; however, we do not observe a significant difference between liver resection and TACE in terms of safety and morbidity. We conclude that liver resection may improve the short- and long-term survival of carefully selected intermediate HCC patients, and the procedure may be safely performed in the management of intermediate HCC. PMID:27190577

  15. Repeated proton beam therapy for hepatocellular carcinoma

    SciTech Connect

    Hashimoto, Takayuki |. E-mail: hashimoto@pmrc.tsukuba.ac.jp; Tokuuye, Koichi |; Fukumitsu, Nobuyoshi |; Igaki, Hiroshi |; Hata, Masaharu |; Kagei, Kenji |; Sugahara, Shinji; Ohara, Kiyoshi; Matsuzaki, Yasushi; Akine, Yasuyuki |

    2006-05-01

    Purpose: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). Methods and Materials: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. Results: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. Conclusions: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A.

  16. Association Between Hepatitis C and Hepatocellular Carcinoma

    PubMed Central

    de Oliveria Andrade, Luis Jesuino; D'Oliveira, Argemiro; Melo, Rosangela Carvalho; De Souza, Emmanuel Conrado; Costa Silva, Carolina Alves; Paraná, Raymundo

    2009-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer, the third most common cause for cancer death in the world, a major cause of death in patients with chronic hepatitis C virus infection, and responsible for approximately one million deaths each year. Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of HCC. The incidence of HCC is expected to increase in the next two decades, largely due to hepatitis C infection and secondary cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. Potential preventive strategies in the development of HCC are being recognized. The natural history of HCC is highly variable and the clinical management choices for HCC can be complex, hence patient assessment and treatment planning have to take the severity of the nonmalignant liver disease into account. This review summarizes the inter-relationship between HCV and liver carcinogenesis. PMID:20300384

  17. Genomic and epigenomic heterogeneity of hepatocellular carcinoma.

    PubMed

    Lin, De-Chen; Mayakonda, Anand; Dinh, Huy Q; Huang, Pinbo; Lin, Lehang; Liu, Xiaoping; Ding, Ling-Wen; Wang, Jie; Berman, Benjamin; Song, Erwei; Yin, Dong; Koeffler, H Phillip

    2017-02-20

    Understanding the intratumoral heterogeneity of hepatocellular carcinoma (HCC) is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 HCC cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2. Similar with other cancer types, TP53 mutations were always shared between all tumor regions i.e. located on the "trunk" of the evolutionary tree. In addition, we found that variants within several drug targets such as KIT, SYK and PIK3CA were mutated in a fully clonal manner, indicating their therapeutic potentials for HCC. Temporal dissection of mutational signatures suggested that mutagenic processes associated with exposure to aristolochic acid and aflatoxin might play a more important role in early, as opposed to late, stages of HCC development. Moreover, we observed extensive intratumoral epigenetic heterogeneity in HCC based on multiple independent analytical methods and showed that intratumoral methylation heterogeneity might play important roles in the biology of HCC cells. Our results also demonstrated prominent heterogeneity of intratumoral methylation even in a stable HCC genome. Together, these findings highlight widespread intratumoral heterogeneity at both the genomic and epigenomic levels in HCC and provide an important molecular foundation for better understanding the pathogenesis of this malignancy.

  18. Genetic alterations in hepatocellular carcinoma: An update

    PubMed Central

    Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Wen-Hong

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC. PMID:27895396

  19. 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

  20. Senescence and immortality in hepatocellular carcinoma.

    PubMed

    Ozturk, Mehmet; Arslan-Ergul, Ayca; Bagislar, Sevgi; Senturk, Serif; Yuzugullu, Haluk

    2009-12-01

    Cellular senescence is a process leading to terminal growth arrest with characteristic morphological features. This process is mediated by telomere-dependent, oncogene-induced and ROS-induced pathways, but persistent DNA damage is the most common cause. Senescence arrest is mediated by p16(INK4a)- and p21(Cip1)-dependent pathways both leading to retinoblastoma protein (pRb) activation. p53 plays a relay role between DNA damage sensing and p21(Cip1) activation. pRb arrests the cell cycle by recruiting proliferation genes to facultative heterochromatin for permanent silencing. Replicative senescence that occurs in hepatocytes in culture and in liver cirrhosis is associated with lack of telomerase activity and results in telomere shortening. Hepatocellular carcinoma (HCC) cells display inactivating mutations of p53 and epigenetic silencing of p16(INK4a). Moreover, they re-express telomerase reverse transcriptase required for telomere maintenance. Thus, senescence bypass and cellular immortality is likely to contribute significantly to HCC development. Oncogene-induced senescence in premalignant lesions and reversible immortality of cancer cells including HCC offer new potentials for tumor prevention and treatment.

  1. 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

  2. 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.

  3. Disease monitoring of hepatocellular carcinoma through metabolomics

    PubMed Central

    Fitian, Asem I; Cabrera, Roniel

    2017-01-01

    We elucidate major pathways of hepatocarcinogenesis and accurate diagnostic metabolomic biomarkers of hepatocellular carcinoma (HCC) identified by contemporary HCC metabolomics studies, and delineate a model HCC metabolomics study design. A literature search was carried out on Pubmed for HCC metabolomics articles published in English. All relevant articles were accessed in full text. Major search terms included “HCC”, “metabolomics”, “metabolomics”, “metabonomic” and “biomarkers”. We extracted clinical and demographic data on all patients and consolidated the lead candidate biomarkers, pathways, and diagnostic performance of metabolomic expression patterns reported by all studies in tables. Where reported, we also extracted and summarized the metabolites and pathways most highly associated with the development of cirrhosis in table format. Pathways of lysophospholipid, sphingolipid, bile acid, amino acid, and reactive oxygen species metabolism were most consistently associated with HCC in the cited works. Several studies also elucidate metabolic alterations strongly associated with cirrhosis, with γ-glutamyl peptides, bile acids, and dicarboxylic acids exhibiting the highest capacity for stratifying cirrhosis patients from appropriately matched controls. Collectively, global metabolomic profiles of the referenced works exhibit a promising diagnostic capacity for HCC at a capacity greater than that of conventional diagnostic biomarker alpha-fetoprotein. Metabolomics is a powerful strategy for identifying global metabolic signatures that exhibit potential to be leveraged toward the screening, diagnosis, and management of HCC. A streamlined study design and patient matching methodology may improve concordance among metabolomic datasets in future works. PMID:28105254

  4. Genomic analysis of fibrolamellar hepatocellular carcinoma

    PubMed Central

    Xu, Lei; Hazard, Florette K.; Zmoos, Anne-Flore; Jahchan, Nadine; Chaib, Hassan; Garfin, Phillip M.; Rangaswami, Arun; Snyder, Michael P.; Sage, Julien

    2015-01-01

    Pediatric tumors are relatively infrequent, but are often associated with significant lethality and lifelong morbidity. A major goal of pediatric cancer research has been to identify key drivers of tumorigenesis to eventually develop targeted therapies to enhance cure rate and minimize acute and long-term toxic effects. Here, we used genomic approaches to identify biomarkers and candidate drivers for fibrolamellar hepatocellular carcinoma (FL-HCC), a very rare subtype of pediatric liver cancer for which limited therapeutic options exist. In-depth genomic analyses of one tumor followed by immunohistochemistry validation on seven other tumors showed expression of neuroendocrine markers in FL-HCC. DNA and RNA sequencing data further showed that common cancer pathways are not visibly altered in FL-HCC but identified two novel structural variants, both resulting in fusion transcripts. The first, a 400 kb deletion, results in a DNAJB1-PRKCA fusion transcript, which leads to increased cAMP-dependent protein kinase (PKA) activity in the index tumor case and other FL-HCC cases compared with normal liver. This PKA fusion protein is oncogenic in HCC cells. The second gene fusion event, a translocation between the CLPTM1L and GLIS3 genes, generates a transcript whose product also promotes cancer phenotypes in HCC cell lines. These experiments further highlight the tumorigenic role of gene fusions in the etiology of pediatric solid tumors and identify both candidate biomarkers and possible therapeutic targets for this lethal pediatric disease. PMID:25122662

  5. Obesity, insulin resistance, NASH and hepatocellular carcinoma.

    PubMed

    Yu, Jun; Shen, Jiayun; Sun, Ting Ting; Zhang, Xiang; Wong, Nathalie

    2013-12-01

    Epidemiological and clinical data have clearly demonstrated that non-alcoholic steatohepatitis (NASH) predisposes risk to the development of hepatocellular carcinoma (HCC). NASH is the liver manifestation of metabolic syndrome, which constellates obesity, insulin resistance and dyslipidemia. Although the percentage of patients diagnosed annually with NASH-associated HCC is still relatively low, this number signifies a large population due to the rapidly increasing incidence of obesity and diabetes globally. Fundamental studies on lipid storage, regulation of adipose factors, inflammatory cytokine recruitments and oxidative stress have provided insights into NASH as well as metabolic syndrome. Recent evidence also indicates the significant role of genetic factors in contributing to the pathogenesis of NASH and induced hepatic malignancy. In this review, we attempt to collate current research on NASH biology that lead to our understandings on how metabolic disorders may intersect with cancer development. We also discuss study models that have supported discoveries of molecular and cellular defects, and offered a perspective on therapeutic developments. These studies have collectively increased our knowledge on the complex signaling pathways involved in NASH and cancer, and provided the foundation for improved clinical management of patients with metabolic diseases.

  6. Rare Gingival Metastasis by Hepatocellular Carcinoma

    PubMed Central

    Xue, Li-Jun; Geng, Jian; Chen, Ya-Nan; Wang, Qian

    2017-01-01

    Hepatocellular carcinoma (HCC) uncommonly metastasizes to the gingiva, which always means a poor outcome. We reported a rare HCC case with multiple metastases to gingiva, lungs, and brain. A 60-year-old man was initially diagnosed as HCC with metastases to double lungs. He was subjected to a transarterial chemoembolization (TACE) (5-fluorouracil, 750 mg) and two cycles of intravenous chemotherapy (gemcitabine 1.8 g at days 1 and 8, oxaliplatin 200 mg at day 2, every 4 weeks). However, the volume of liver tumor still increased. A bean-size gingival nodule growing with occasional bleeding was also found. TACE (5-fluorouracil 750 mg, perarubicin 40 mg, cisplatin 20 mg) was performed again and an oral sorafenib therapy (400 mg, twice per day) was adopted. The disease maintained relatively stable for about 6 months until a second obvious progress. The gingival nodule was then palliatively excised and identified as a poorly differentiated metastatic HCC by histopathological examination. Best supportive treatments were made since the performance score was too bad. Finally, cerebral metastases occurred and the patient died of systemic failure. Upon review of previous reports, we discussed risk factors, clinical and pathological characteristics, treatments, and prognosis of gingival metastasis by HCC. PMID:28386283

  7. Low Birth Weight Is Associated with a Decreased Overall Adult Health Status and Reproductive Capability – Results of a Cross-Sectional Study in Primary Infertile Patients

    PubMed Central

    Boeri, Luca; Ventimiglia, Eugenio; Capogrosso, Paolo; Ippolito, Silvia; Pecoraro, Angela; Paciotti, Marco; Scano, Roberta; Galdini, Alessandro; Valsecchi, Luca; Papaleo, Enrico; Montorsi, Francesco; Salonia, Andrea

    2016-01-01

    Individuals born with low birth weight (LBW) risk cardiometabolic complications later in life. However the impact of LBW on general health status and male reproductive function has been scantly analysed. We investigated the clinical and seminal impact of different birth weights (BW) in white-European men presenting for primary couple’s infertility. Demographic, clinical, and laboratory data from 827 primary infertile men were compared with those of 373 consecutive fertile men. Patients with BW ≤2500, 2500–4200, and ≥4200gr were classified as having LBW, normal (NBW), and high BW (HBW), respectively. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Testicular volume was assessed with a Prader orchidometer. Semen analysis values were assessed based on 2010 WHO reference criteria. Descriptive statistics and regression models tested associations between semen parameters, clinical characteristics and BW categories. LBW, NBW and HBW were found in 71 (8.6%), 651 (78.7%) and 105 (12.7%) infertile men, respectively. LBW was more frequent in infertile patients than fertile men (p = 0.002). Infertile patients with LBW had a higher rate of comorbidities (p = 0.003), lower mean testicular volume (p = 0.007), higher FSH (p = 0.02) and lower tT levels (p = 0.04) compared to other BW groups. Higher rates of asthenozoospermia (p = 0.02) and teratozoospermia (p = 0.03) were also found in LBW men. At logistic regression models, LBW was univariably associated with pathologic progressive motility (p≤0.02) and pathologic sperm morphology (p<0.005). At multivariable logistic regression analysis, LBW achieved independent predictor status for both lower sperm motility and pathologic sperm morphology (all p≤0.04). Only LBW independently predicted higher CCI values (p<0.001). In conclusion, we found that LBW was more frequent in infertile than in fertile men. Infertile individuals with LBW showed a higher rate of comorbidities and

  8. Unusual presentation; seeding of tumor after biopsy for hepatocellular carcinoma

    PubMed Central

    Aksoy, Asude; Karabulut, Koray; Artas, Hakan; Kilicarslan, Ahmet; Usta, Sertac; Bahcecioglu, Ibrahim Halil

    2016-01-01

    Hepatocellular cancer is one of the most common and fatal cancer tumor worldwide. However, the obtained results are questionable in terms of medical treatment of hepatocellular cancer. The muscle, soft tissue and cutaneous metastases of hepatocellular cancer, for instance, are rare and may result from interventional procedures. Seeding of tumor along the biopsy needle upon percutaneous biopsy is a very rare phenomenon. We report a very rare case of a 79 -year- old man, known to be hepatitis C virus carrier with a metastatic tumor in abdominal wall caused by seeding of tumor after three years following a percutaneous biopsy procedure. Even years later, after a biopsy procedure for diagnostic purposes and may be soft tissue metastases. This complication is a very rare condition that should not be ignored but can be observed. The biopsy requirement should be questioned closely and avoided unnecessary biopsy procedures. PMID:28083068

  9. Successful Liver Transplantation for Hyperammonemic Fibrolamellar Hepatocellular Carcinoma

    PubMed Central

    Alsina, Angel E.; Franco, Edson; Nakshabandi, Ahmad; Albers, Christopher; Kemmer, Nyingi; Finan, Jon

    2016-01-01

    Fibrolamellar hepatocellular carcinoma is a rare hepatocellular tumor usually arising in noninfected and noncirrhotic livers. Only 2 cases accompanied by hyperammonemia due to intrahepatic shunting have been reported. A 23-year-old white woman presented with a 2-week history of nausea, vomiting, generalized weakness, and intermittent right upper quadrant pain. Abdominal computerized tomography revealed a 13 x 9-cm hepatic mass. Core-needle biopsy revealed fibrolamellar hepatocellular carcinoma. She presented with coma due to hyperammonemia levels (peak at 437 mcg/dL) but without metastatic disease. She was urgently transplanted, started on daily sorafenib 8 weeks after transplantation, and was free of disease at 1 year after transplantation. PMID:27807568

  10. Bridging and downstaging therapy in patients suffering from hepatocellular carcinoma waiting on the list of liver transplantation

    PubMed Central

    She, Wong Hoi

    2016-01-01

    Hepatocellular carcinoma (HCC) is a common primary malignancy worldwide especially in the patients with the background of chronic liver disease. Liver transplantation (LT) is the only curative treatment effective for both malignancy as well as the cirrhosis and portal hypertension. Unfortunately, living donor is not always possible and the deceased graft is scarce. Neoadjuvant therapies, therefore, have been developed as a downstaging treatment to try to downstage the tumor within the transplant criteria, or as a bridging therapy to control the tumor growth in patients while waiting in the transplant list. This paper reviewed the common modalities used as bridging and downstaging therapies for patients suffering from HCC before undergoing LT. PMID:28138601

  11. RUNX3 Promoter Methylation Is Associated with Hepatocellular Carcinoma Risk: A Meta-Analysis.

    PubMed

    Zhang, Xueyan; He, Hairong; Zhang, Xu; Guo, Wenjie; Wang, Yueqi

    2015-04-01

    Runt-related transcription factor 3 (RUNX3) has been reported to be a tumor-suppressing gene in hepatocellular carcinoma. Association between hepatocellular carcinoma and RUNX3 promoter methylation has been investigated in studies with specific ethnic backgrounds and small sample sizes. In this study, a meta-analysis was adopted to combine the data from 11 studies of association between RUNX3 promoter methylation and hepatocellular carcinoma. Pooled odds ratio for RUNX3 promoter methylation status in hepatocellular carcinoma versus control liver tissue was 24.37 (95%CI: 12.14, 48.92), p < .00001, indicates a strong association between methylation of the RUNX3 promoter and hepatocellular carcinoma.

  12. Combinatorial analysis of calcium-binding proteins in larval and adult zebrafish primary olfactory system identifies differential olfactory bulb glomerular projection fields.

    PubMed

    Kress, Sigrid; Biechl, Daniela; Wullimann, Mario F

    2015-07-01

    In the zebrafish (Danio rerio) olfactory epithelium, the calcium-binding proteins (CBPs) calretinin and S100/S100-like protein are mainly expressed in ciliated or crypt olfactory sensory neurons (OSNs), respectively. In contrast parvalbumin and calbindin1 have not been investigated. We present a combinatorial immunohistological analysis of all four CBPs, including their expression in OSNs and their axonal projections to the olfactory bulb in larval and adult zebrafish. A major expression of calretinin and S100 in ciliated and crypt cells, respectively, with some expression of S100 in microvillous cells is confirmed. Parvalbumin and calbindin1 are strongly expressed in ciliated and microvillous cells, but not in crypt cells. Moreover, detailed combinatorial double-label experiments indicate that there are eight subpopulations of zebrafish OSNs: S100-positive crypt cells (negative for all other three CBPs), parvalbumin only, S100 and parvalbumin, parvalbumin and calbindin1, and parvalbumin and calbindin1 and calretinin-positive microvillous OSNs, as well as a major parvalbumin and calbindin1 and calretinin, and minor parvalbumin and calbindin1 and calretinin-only-positive ciliated OSN populations. CBP-positive projections to olfactory bulb are consistent with previous reports of ciliated OSNs projecting to dorsal and ventromedial glomerular fields and microvillous OSNs to ventrolateral glomerular fields. We newly describe parvalbumin-positive fibers to the mediodorsal field which is calretinin free, with its anterior part showing additionally calbindin1-positive fibers, but absence thereof in the posterior part, indicating an origin from microvillous OSNs in both parts. One singular glomerulus (mdG2) exhibits S100 and parvalbumin-positive fibers, apparently originating from all crypt cells plus some microvillous OSNs. Arguments for various olfactory labeled lines are discussed.

  13. 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

  14. Pravastatin reduces the risk for cardiovascular disease in Japanese hypercholesterolemic patients with impaired fasting glucose or diabetes: diabetes subanalysis of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study.

    PubMed

    Tajima, Naoko; Kurata, Hideaki; Nakaya, Noriaki; Mizuno, Kyoichi; Ohashi, Yasuo; Kushiro, Toshio; Teramoto, Tamio; Uchiyama, Shinichiro; Nakamura, Haruo

    2008-08-01

    Diabetes mellitus (DM) is a major risk factor for cardiovascular disease (CVD) in patients with no history of CVD. Evidence for the effect of statins on CVD in the diabetic population in low-risk populations (e.g., Japanese) is limited. We evaluated the effect of pravastatin on risk reduction of CVD related to baseline glucose status in a primary prevention setting. The Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study, in patients with mild-to-moderate hypercholesterolemia (220-270 mg/dL), showed that low-dose pravastatin significantly reduced the risk for CVD by 26%. This exploratory subanalyses examined the efficacy of diet plus pravastatin on CVD in 2210 patients with abnormal fasting glucose (AFG, including 1746 patients with DM and 464 patients with impaired fasting glucose (IFG) at 5 years in the MEGA Study. CVD was threefold higher in AFG patients (threefold higher in DM, and twofold higher in IFG) compared with normal fasting glucose (NFG) patients in the diet group. Diet plus pravastatin treatment significantly reduced the risk of CVD by 32% (hazard ratio 0.68, 95% CI 0.48-0.96, number needed to treat, 42) in the AFG group compared with the diet alone group, and no significant interaction between AFG and NFG (interaction P=0.85) was found. Safety problems were not observed during long-term treatment with pravastatin. In conclusion, pravastatin reduces the risk of CVD in subjects with hypercholesterolemia and abnormal fasting glucose in the primary prevention setting in Japan.

  15. 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.

  16. 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

  17. Needle track seeding following percutaneous procedures for hepatocellular carcinoma

    PubMed Central

    Cabibbo, Giuseppe; Craxì, Antonio

    2009-01-01

    Neoplastic seeding may arise after diagnostic or therapeutic percutaneous procedures for hepatocellular carcinoma. The true incidence of seeding with hepatocellular carcinoma is difficult to assess precisely, but a significant risk of seeding exists and is greater when performing diagnostic biopsy as compared to therapeutic percutaneous procedures [radiofrequency ablation, radiofrequency ablation (RFA); percutaneous ethanol injection, Percutaneous ethanol injection (PEI)]. Whenever liver transplantation is feasible, diagnostic needle biopsies should be avoided, but RFA and PEI are often needed as “bridge” treatments. The role of adjuvant treatments in reducing the incidence of seeding following RFA or PEI requires further evaluation. PMID:21160966

  18. Role of surveillance in prevention of hepatocellular carcinoma.

    PubMed

    Panda, Dipanjan

    2014-08-01

    Hepatocellular carcinoma is a common malignancy and one of the important public health problems in India. The surveillance of hepatocellular carcinoma (HCC) is an established approach to detect early cancers in patients with defined risks. However, there are still controversies and issues to be addressed regarding the optimal surveillance methods and interval. The current level of awareness among physicians in India about surveillance is low and the need and most cost effective surveillance strategy in developing country like ours is unclear. This article has tried to discuss these issues in their appropriate perspective. To address this complicated issue, a multicenter randomized prospective study however may be required.

  19. [Hepatocellular carcinoma with cardiovascular invasion. Report of five cases].

    PubMed

    Valera, José M; Merino, Roberto; Palavecino, Patricio; Sepúlveda, Luis; Smok, Gladys; Fernández, Manuel; Brahm, Javier

    2004-12-01

    The diagnosis of hepatocellular carcinoma in cirrhotic patients has increased, mainly due to early detection using newer imaging techniques. The therapeutic approach depends on the tumor staging and the liver function. Cardiac involvement has a very bad prognosis. We report three males aged 59, 75 and 76 years and two females, aged 64 and 79 years. All had cirrhosis of diverse aetiologies with hepatocellular carcinoma and tumoral invasion of the inferior vena cava and right atrium. Three patients died during hospital stay and two were discharged for conservative management at home. This rare complication has to be considered in cirrhosis.

  20. Inhibitory effects of xanthohumol from hops (Humulus lupulus L.) on human hepatocellular carcinoma cell lines.

    PubMed

    Ho, Yi-Chien; Liu, Chi-Hsien; Chen, Chien-Nan; Duan, Kow-Jen; Lin, Ming-Tse

    2008-11-01

    Xanthohumol is one of the main flavonoids in hop extracts and in beer. Very few investigations of xanthohumol have studied hepatocellular carcinoma. In this study, the inhibitory effects of xanthohumol on human hepatocellular carcinoma cell lines were investigated. The IC(50) values of xanthohumol for two hepatocellular carcinoma cell lines and one normal hepatocyte cell line were 108, 166 and 211 microm, respectively. Normal murine hepatocyte cell line had more resistance to xanthohumol than hepatocellular carcinoma cell lines. Besides, the inhibitory effects of xanthohumol on human hepatocellular carcinoma cell lines were attributed to apoptosis as indicated in the results of flow cytometry, fluorescent nuclear staining and electrophoresis of oligonucleosomal DNA fragments. Hop xanthohumol was more efficient in the growth inhibition of hepatocellular carcinoma cell lines than the flavonoids silibinin and naringin from thistle and citrus. It was shown for the first time that xanthohumol from hops effectively inhibits proliferation of human hepatocellular carcinoma cells in vitro.

  1. Body-mass index and risk of advanced chronic kidney disease: Prospective analyses from a primary care cohort of 1.4 million adults in England

    PubMed Central

    Bankhead, Clare; Matsushita, Kunihiro; Stevens, Sarah; Holt, Tim; Hobbs, F. D. Richard; Coresh, Josef; Woodward, Mark

    2017-01-01

    Background It is uncertain whether being overweight, but not obese, is associated with advanced chronic kidney disease (CKD) and how the size and shape of associations between body-mass index (BMI) and advanced CKD differs among different types of people. Methods We used Clinical Practice Research Datalink records (2000–2014) with linkage to English secondary care and mortality data to identify a prospective cohort with at least one BMI measure. Cox models adjusted for age, sex, smoking and social deprivation and subgroup analyses by diabetes, hypertension and prior cardiovascular disease assessed relationships between BMI and CKD stages 4–5 and end-stage renal disease (ESRD). Findings 1,405,016 adults aged 20–79 with mean BMI 27.4kg/m2 (SD 5.6) were followed for 7.5 years. Compared to a BMI of 20 to <25kg/m2, higher BMI was associated with a progressively increased risk of CKD stages 4–5 (hazard ratio 1.34, 95% CI 1.30–1.38 for BMI 25 to <30kg/m2; 1.94, 1.87–2.01 for BMI 30 to <35kg/m2; and 3.10, 2.95–3.25 for BMI ≥35kg/m2). The association between BMI and ESRD was shallower and reversed at low BMI. Current smoking, prior diabetes, hypertension or cardiovascular disease all increased risk of CKD, but the relative strength and shape of BMI-CKD associations, which were generally log-linear above a BMI of 25kg/m2, were similar among those with and without these risk factors. There was direct evidence that being overweight was associated with increased risk of CKD stages 4–5 in these subgroups. Assuming causality, since 2000 an estimated 39% (36–42%) of advanced CKD in women and 26% (22–30%) in men aged 40–79 resulted from being overweight or obese. Conclusions This study provides direct evidence that being overweight increases risk of advanced CKD, that being obese substantially increases such risk, and that this remains true for those with and without diabetes, hypertension or cardiovascular disease. Strategies to reduce weight among those

  2. Association between Modified Shuttle Walk Test and cardiorespiratory fitness in overweight/obese adults with primary hypertension: EXERDIET-HTA study.

    PubMed

    Jurio-Iriarte, Borja; Gorostegi-Anduaga, Ilargi; Aispuru, G Rodrigo; Pérez-Asenjo, Javier; Brubaker, Peter H; Maldonado-Martín, Sara

    2017-02-07

    The aims of the study were to evaluate the relationship between Modified Shuttle Walk Test (MSWT) with peak oxygen uptake (V˙O2peak) in overweight/obese people with primary hypertension (HTN) and to develop an equation for the MSWT to predict V˙O2peak. Participants (N = 256, 53.9 ± 8.1 years old) with HTN and overweight/obesity performed a cardiorespiratory exercise test to peak exertion on an upright bicycle ergometer using an incremental ramp protocol and the 15-level MSWT. The formula of Singh et al was used as a template to predict V˙O2peak, and a new equation was generated from the measured V˙O2peak-MSWT relationship in this investigation. The correlation between measured and predicted V˙O2peak for Singh et al equation was moderate (r = 0.60, P < .001) with a standard error of the estimate (SEE) of 4.92 mL·kg(-1) minute(-1), SEE% = 21%. The correlation between MSWT and measured V˙O2peak as well as for the new equation was strong (r = 0.72, P < .001) with a SEE of 4.35 mL·kg(-1) minute(-1), SEE% = 19%. These results indicate that MSWT does not accurately predict functional capacity in overweight/obese people with HTN and questions the validity of using this test to evaluate exercise intolerance. A more accurate determination from a new equation in the current study incorporating more variables from MSWT to estimate V˙O2peak has been performed but still results in substantial error.

  3. Combined use of heat-shock protein 70 and glutamine synthetase is useful in the distinction of typical hepatocellular adenoma from atypical hepatocellular neoplasms and well-differentiated hepatocellular carcinoma

    PubMed Central

    Nguyen, Thuy B; Roncalli, Massimo; Tommaso, Luca Di; Kakar, Sanjay

    2017-01-01

    Well-differentiated hepatocellular carcinoma can mimic high-grade dysplastic nodule in cirrhotic liver and hepatocellular adenoma in non-cirrhotic liver. This study evaluates the efficacy of combined use of heat-shock protein 70 (HSP70), glutamine synthetase (GS) and glypican-3 in this setting. Immunohistochemistry for these three markers was done in 17 typical hepatocellular adenoma, 15 high-grade dysplastic nodules, 20 atypical hepatocellular neoplasms (14 clinically atypical and 6 pathologically atypical), 14 very well-differentiated hepatocellular carcinoma, and 43 well-differentiated hepatocellular carcinoma. All three markers were negative in typical adenomas. HSP70 was positive in 10, 71, and 67% of atypical neoplasms, very well-differentiated and well-differentiated HCC, respectively, while GS was positive in 60, 50, and 60% of atypical neoplasms, very well-differentiated and well-differentiated hepatocellular carcinoma, respectively. Glypican-3 was negative in all atypical neoplasms and very well-differentiated hepatocellular carcinoma, and was positive in 27% of well-differentiated hepatocellular carcinoma. Positive staining with at least one marker (HSP70 and/or GS) was seen in 85% of very well-differentiated hepatocellular carcinoma, which was similar to well-differentiated hepatocellular carcinoma (78%, P = 0.4), and pathologically atypical cases (100%, P = 0.5), but significantly higher compared with clinically atypical cases (43%. P = 0.03) and none of typical adenomas (P < 0.001). Positive staining with both GS and HSP70 was seen significantly more often in hepatocellular carcinoma compared with atypical neoplasms (45 vs 10%, P = 0.004). Both these markers were also more often expressed in very well-differentiated hepatocellular carcinoma compared with atypical cases (38 vs 10%, P = 0.06). In conclusion, the combined use of GS and HSP70 can be useful in the diagnosis of very well-differentiated hepatocellular carcinoma. These stains can also help in

  4. Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

    PubMed Central

    Li, Min; Zhang, Weiyue; Wang, Birong; Gao, Yang; Song, Zifang; Zheng, Qi Chang

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high morbidity and mortality worldwide. Chemotherapy is recommended to patients with intermediate or advanced stage cancer. However, the conventional chemotherapy yields low desired response rates due to multidrug resistance, fast clearance rate, nonspecific delivery, severe side effects, low drug concentration in cancer cells, and so on. Nanoparticle-mediated targeted drug delivery system can surmount the aforementioned obstacles through enhanced permeability and retention effect and active targeting as a novel approach of therapeutics for HCC in recent years. The active targeting is triggered by ligands on the delivery system, which recognize with and internalize into hepatoma cells with high specificity and efficiency. This review focuses on the latest targeted delivery systems for HCC and summarizes the ligands that can enhance the capacity of active targeting, to provide some insight into future research in nanomedicine for HCC. PMID:27920520

  5. Design, Synthesis and Evaluation of Naphthalimide Derivatives as Potential Anticancer Agents for Hepatocellular Carcinoma.

    PubMed

    Ge, Chaochao; Chang, Liping; Zhao, Ying; Chang, Congcong; Xu, Xiaojuan; He, Haoying; Wang, Yuxia; Dai, Fujun; Xie, Songqiang; Wang, Chaojie

    2017-02-22

    Two kinds of naphthalimide derivatives were synthesized and evaluated for in vitro their anti-hepatocellular carcinoma properties. Compound 3a with a fused thiazole fragment to naphthalimide skeleton inhibited cell migration of SMMC-7721 and HepG2, and further in vivo trials with two animal models confirmed that compound 3a moderately inhibited primary H22 tumor growth (52.6%) and potently interrupted lung metastasis (75.7%) without obvious systemic toxicity at the therapeutic dose. Mechanistic research revealed that compound 3a inhibited cancerous liver cell growth mostly by inducing G2/M phase arrest. Western blotting experiments corroborated that 3a could up-regulate the cell cycle related protein expression of cyclin B1, CDK1 and p21, and inhibit cell migration by elevating the E-cadherin and attenuating integrin α6 expression. Our study showed that compound 3a is a valuable lead compound worthy of further investigation.

  6. Molecular alterations in hepatocellular carcinoma associated with hepatitis B and hepatitis C infections

    PubMed Central

    Izzo, Francesco; Buonaguro, Franco M.

    2016-01-01

    Chronic infections with hepatitis B (HBV) and hepatitis C viruses (HCV) are the leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. Both viruses encode multifunctional regulatory proteins activating several oncogenic pathways, which induce accumulation of multiple genetic alterations in the infected hepatocytes. Gene mutations in HBV- and HCV-induced HCCs frequently impair the TP53, Wnt/b-catenin, RAS/RAF/MAPK kinase and AKT/mTOR pathways, which represent important anti-cancer targets. In this review, we highlight the molecular mechanisms underlying the pathogenesis of primary liver cancer, with particular emphasis on the host genetic variations identified by high-throughput technologies. In addition, we discuss the importance of genetic alterations, such as mutations in the telomerase reverse transcriptase (TERT) promoter, for the diagnosis, prognosis, and tumor stratification for development of more effective treatment approaches. PMID:26943571

  7. Laparoscopic and robotic approach for hepatocellular carcinoma—state of the art

    PubMed Central

    de Werra, Edoardo; Mascianà, Gianluca; Colasanti, Marco; Santoro, Roberto; D’Andrea, Vito; Ettorre, Giuseppe Maria

    2016-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor worldwide and the most common primary liver cancer, in over 80% of cases HCC grown on a cirrhotic liver. Laparoscopic liver resection (LLR) is now worldwide accepted considering the excellent results shown. Minimally invasive surgical approach for HCC is increasing continuously and in specialized centers seems to become the first-line approach for those patients. The aim of this review presents and discusses state of the art in the laparoscopic and robotic surgical treatment of HCC. An electronic search was performed to identify all studies dealing with HCC resected with laparoscopy or robotic approach. Indications for laparoscopic resection, robotic assisted and totally robotic resection of HCC will be doubtless increased in future years. LLR and robotic approach for HCC is safe and feasible. PMID:28124002

  8. FEM simulation of tapered cap floating sleeve antenna for hepatocellular carcinoma therapy.

    PubMed

    Maini, Surita

    2016-01-01

    Malignant liver tumors are the sixth most common and deadly cancer in the world and the third most common cause of cancer mortality. Hepatocellular carcinoma (primary liver cancer) is one of the most common malignancies worldwide with one of the highest mortality rates. Microwave ablation (MWA) is a new, promising, and multidisciplinary technology designed to destroy unhealthy tissue of various natures by radiating electromagnetic waves with microwave antennas. The finite element method (FEM) has been used in the present work to generate the simulated models of tapered cap floating sleeve antenna for validation of its design concepts, because FEM allows modeling of complex geometries that cannot be solved by analytical methods or finite difference models. The performances have been evaluated in terms of objective metrics, ablation zone, antenna matching, power absorption and SAR pattern.

  9. 2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma

    PubMed Central

    2015-01-01

    The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC. PMID:25918260

  10. Living donor liver transplantation with abdominal wall reconstruction for hepatocellular carcinoma with needle track seeding

    PubMed Central

    Yang, Horng-Ren; Thorat, Ashok; Gesakis, Kanellos; Li, Ping-Chun; Kiranantawat, Kidakorn; Chen, Hung Chi; Jeng, Long-Bin

    2015-01-01

    Malignant cell seeding in subcutaneous tissues along the needle track and/or percutaneous biliary drainage catheters is rare complication, but pose various technical issues in planning surgical treatment of such patients. If underlying primary hepatic malignancy can be treated, an aggressive resection of subcutaneous tissue bearing cancer cell with subsequent abdominal wall reconstruction has been sporadically reported. But, when hepatic resection is not possible due to underlying advanced cirrhosis, liver transplantation along with abdominal wall resection and subsequent reconstruction remains only feasible option. Herein, we describe our successful experience of living donor liver transplantation for hepatocellular carcinoma with full-thickness abdominal wall resection bearing the tumor seeding followed by reconstruction in single stage surgery. PMID:26722665

  11. Therapeutic potential of small interfering RNAs/micro interfering RNA in hepatocellular carcinoma.

    PubMed

    Farra, Rossella; Grassi, Mario; Grassi, Gabriele; Dapas, Barbara

    2015-08-14

    Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and represents the third leading cause of cancer-related death worldwide. Current available therapeutic approaches are poorly effective, especially for the advanced forms of the disease. In the last year, short double stranded RNA molecules termed small interfering RNAs (siRNAs) and micro interfering RNAs (miRNA), emerged as interesting molecules with potential therapeutic value for HCC. The practical use of these molecules is however limited by the identification of optimal molecular targets and especially by the lack of effective and targeted HCC delivery systems. Here we focus our discussion on the most recent advances in the identification of siRNAs/miRNAs molecular targets and on the development of suitable siRNA/miRNAs delivery systems.

  12. Treatment Algorithms for Managing Hepatocellular Carcinoma

    PubMed Central

    Saraswat, Vivek A.; Pandey, Gaurav; Shetty, Sachin

    2014-01-01

    Early diagnosis and aggressive therapy improves outcome in hepatocellular carcinoma (HCC). Several potentially curative as well as palliative treatment options are available for patients. The choice of therapy is influenced by factors such as extent of tumor and severity of underlying liver dysfunction as well as availability of resources and of expertise. A systematic, algorithmic approach would ensure optimal therapy for each patient and is likely to improve outcomes. Even after receiving therapy for HCC, patients remain at risk for recurrent HCC as well as progression of underlying cirrhosis. Proper assessment and monitoring is needed for the underlying liver disease, which may progress to liver failure and have a major impact on long-term survival. Comprehensive care for patients with cirrhosis includes interventions such as antiviral therapy for HBV and HCV, abstention from alcohol, management of fatty liver disease, endoscopic surveillance and treatment for complications of portal hypertension and, if indicated, immunization against HAV and HBV. An algorithmic approach is useful for choosing the most appropriate treatment option for the individual patient from among the various options that are available. The general consensus is that the BCLC system should be preferred for staging HCC as it is useful in predicting outcomes and planning treatment. The BCLC system classifies patients with HCC into five categories: very early, early, intermediate, advanced, and terminal. It incorporates data on tumor status (number and size of nodules, vascular invasion, extra-hepatic spread), liver function (CTP status, presence of portal hypertension) and overall health status (constitutional symptoms, cancer symptoms, performance status). Treatment allocation according to sub-class of patients is a merit of the BCLC system; a few limitations have been noted, particularly with respect to patients with BCLC stage B and C disease. The treatment algorithm as per BCLC system is

  13. Survival of Hepatocellular Carcinoma in Puerto Rico

    PubMed Central

    MARRERO, CARLOS ROMERO; ORTIZ, ANA P.; PÉREZ, CYNTHIA M.; PÉREZ, JAVIER; TORRES, ESTHER A.

    2013-01-01

    Background Blacks and Hispanics in the United States (US) have the lowest survival rates of hepatocellular carcinoma (HCC), mainly associated to the presence of advanced disease at diagnosis when intervention is least beneficial. This study compared the survival distribution and relative survival of HCC in Puerto Rico (PR) during 1988-1992 and 1998-2002. Methods All HCC cases in the PR Central Cancer Registry database for 1988-1992 (n=306) and 1998-2002 (n=333) were identified. Patient characteristics and clinical variables were compared between study periods. Survival by age at diagnosis, sex, tumor stage and treatment was estimated using the Kaplan-Meier method, and survival curves were compared using the Wilcoxon test. A Cox proportional hazards model was employed to assess the effect of period of diagnosis on survival, after adjusting for confounders. One- and three-year survival rates were also calculated. Results Patients diagnosed during 1998-2002 (median: 3.08 months, 95% CI: 2.30-4.16) had a longer observed survival than those diagnosed from 1988-1992 (median: 1.80 months, 95% CI: 1.44-2.52). A significant interaction was observed between the variables age and period of diagnosis, where only among persons aged ≥ 60 years the risk of HCC death was lower (sex-adjusted HR=O.72; 95%CI: 0.59-0.88) in patients diagnosed during 1998-2002 as compared to those diagnosed during 1988-1992. The overall one- and three-year relative survival during 1998-2002 was approximately 6% (22.4% vs.16.6%) and 2% higher (9.0% vs. 6.7%) respectively, as compared to 1988-1992. Conclusion We observed a temporal improvement in the survival of HCC in PR during the last decade. However, this survival is inferior to the one observed in the US population. Further studies are needed to identify factors that explain these disparities. PMID:19530551

  14. How to detect hepatocellular carcinoma in cirrhosis.

    PubMed

    Ward, Janice; Robinson, Philip J

    2002-09-01

    Cirrhosis predisposes to hepatocellular carcinoma (HCC) which develops by sequential steps of de-differentiation of hepatocytes from regenerative nodules via borderline (dysplastic) nodules to frankly malignant HCC. Effective treatment depends on early recognition of HCC, so the key tasks for imaging are firstly recognising the presence of a suspicious lesion, and secondly differentiating between benign, borderline and malignant nodules. Screening of high-risk cirrhotic patients with sonography and measurement of alpha fetoprotein (AFP) is helpful but will not reliably differentiate small HCC from benign or dysplastic nodules. Large HCCs can usually be recognised by their characteristic morphology on imaging, but the appearances of smaller benign and malignant nodules show considerable overlap on unenhanced sonography, CT and MRI. Increasing degrees of histological malignancy are associated with increasing arterialisation and loss of portal blood supply, so the recognition of HCC requires the use of dynamic imaging with contrast-enhanced CT or T1-weighted MRI with gadolinium enhancement. Sonography with microbubble contrast media now offers another method for detecting arterialised nodules; however, some non-malignant nodules show arterial hypervascularity and a minority of HCCs are hypovascular, so the assessment of perfusion does not conclusively distinguish benign from malignant lesions. Kupffer cell function is another attribute of liver tissue which can be explored using MRI with superparamagnetic iron oxide particles (SPIO). Experience thus far suggests that uptake of SPIO is an effective discriminator between benign and malignant nodules. The combination of SPIO with gadolinium-enhanced MRI offers the opportunity for imaging characterisation of cirrhotic nodules by cellular function as well as by blood supply, and this approach is now proposed as the examination of choice for detecting HCC in cirrhosis.

  15. The Eltrombopag antitumor effect on hepatocellular carcinoma

    PubMed Central

    KUROKAWA, TOMOHIRO; MURATA, SOICHIRO; ZHENG, YUN-WEN; IWASAKI, KENICHI; KOHNO, KEISUKE; FUKUNAGA, KIYOSHI; OHKOHCHI, NOBUHIRO

    2015-01-01

    Currently, sorafenib is the only available chemotherapeutic agent for advanced hepatocellular carcinoma (HCC), but it cannot be used in patients with liver cirrhosis (LC) or thrombocytopenia. In these cases, sorafenib is likely effective if given in combination with treatments that increase the number of platelets, such as thrombopoietin (TPO) receptor agonists. Increasing the platelet count via TPO treatment resulted in reduction of LC. Eltrombopag (EP), a TPO receptor agonist, has been reported to have antitumor effects against certain cancers, despite their lack of TPO receptor expression. We hypothesized that EP may possess antitumor activity against HCC in addition to its ability to suppress hepatic fibrosis by increasing the platelet count. In the present study, the antitumor activity of EP was examined by assessing the inhibition of cell proliferation and then ascertaining the ability of iron supplementation to reverse these effects in HepG2, Hep3B and Huh7 cells. In addition, a cell cycle assay was performed using flow cytometry, and signal transduction was evaluated by analyzing cell cycle-related protein expression. The results of EP were compared with those of the most common iron chelator, deferoxamine (DFO). The combined effect of EP and sorafenib was also assessed. The results revealed that EP exerts antitumor activity in HCC that is mediated by the modulation of intracellular iron content. EP suppressed the expression of the cell cycle-related protein cyclin D1 and elicited cell cycle arrest in the G0/G1 phase. The activity of EP was comparable to that of DFO in HCC, and EP did not compete with sorafenib at low concentrations. In conclusion, our findings suggest that EP is a good candidate chemotherapeutic agent for the treatment of HCC in patients with LC and thrombocytopenia. PMID:26397763

  16. Treatment algorithms for managing hepatocellular carcinoma.

    PubMed

    Saraswat, Vivek A; Pandey, Gaurav; Shetty, Sachin

    2014-08-01

    Early diagnosis and aggressive therapy improves outcome in hepatocellular carcinoma (HCC). Several potentially curative as well as palliative treatment options are available for patients. The choice of therapy is influenced by factors such as extent of tumor and severity of underlying liver dysfunction as well as availability of resources and of expertise. A systematic, algorithmic approach would ensure optimal therapy for each patient and is likely to improve outcomes. Even after receiving therapy for HCC, patients remain at risk for recurrent HCC as well as progression of underlying cirrhosis. Proper assessment and monitoring is needed for the underlying liver disease, which may progress to liver failure and have a major impact on long-term survival. Comprehensive care for patients with cirrhosis includes interventions such as antiviral therapy for HBV and HCV, abstention from alcohol, management of fatty liver disease, endoscopic surveillance and treatment for complications of portal hypertension and, if indicated, immunization against HAV and HBV. An algorithmic approach is useful for choosing the most appropriate treatment option for the individual patient from among the various options that are available. The general consensus is that the BCLC system should be preferred for staging HCC as it is useful in predicting outcomes and planning treatment. The BCLC system classifies patients with HCC into five categories: very early, early, intermediate, advanced, and terminal. It incorporates data on tumor status (number and size of nodules, vascular invasion, extra-hepatic spread), liver function (CTP status, presence of portal hypertension) and overall health status (constitutional symptoms, cancer symptoms, performance status). Treatment allocation according to sub-class of patients is a merit of the BCLC system; a few limitations have been noted, particularly with respect to patients with BCLC stage B and C disease. The treatment algorithm as per BCLC system is

  17. Epidemiology of Hepatocellular Carcinoma in India

    PubMed Central

    Acharya, Subrat K.

    2014-01-01

    Indian data on epidemiology of HCC is not available. Cancer is not a reportable disease in India and the cancer registries in India are mostly urban. National cancer registry program of the Indian Council of Medical Research (ICMR) has been recently expanded to include 21 population based and 6 hospital based cancer registries. The last published registry data by ICMR available in the cancer registry website (www.ncrpindia.org) was in 2008 which provides information on various cancers from 2006 to 2008. The other source of information was the report published by International Agency for Research on Cancer (WHO). According to these available data the age adjusted incidence rate of hepatocellular carcinoma (HCC) in India for men ranges from 0.7 to 7.5 and for women 0.2 to 2.2 per 100,000 population per year. The male:female ratio for HCC in India is 4:1. The age of presentation varies from 40 to 70 years. According to a study conducted by verbal autopsy in 1.1 million homes representing the whole country, the age standardized mortality rate for HCC in India for men is 6.8/100,000 and for women is 5.1/100,000. According to another study the incidence of HCC in cirrhotics in India is 1.6% per year. The unpublished data from various tertiary care centers suggest that the incidence of HCC is increasing in India. There is a need for a multi-centric HCC registry under the aegis of INASL. PMID:25755607

  18. Epidemiology of hepatocellular carcinoma in India.

    PubMed

    Acharya, Subrat K

    2014-08-01

    Indian data on epidemiology of HCC is not available. Cancer is not a reportable disease in India and the cancer registries in India are mostly urban. National cancer registry program of the Indian Council of Medical Research (ICMR) has been recently expanded to include 21 population based and 6 hospital based cancer registries. The last published registry data by ICMR available in the cancer registry website (www.ncrpindia.org) was in 2008 which provides information on various cancers from 2006 to 2008. The other source of information was the report published by International Agency for Research on Cancer (WHO). According to these available data the age adjusted incidence rate of hepatocellular carcinoma (HCC) in India for men ranges from 0.7 to 7.5 and for women 0.2 to 2.2 per 100,000 population per year. The male:female ratio for HCC in India is 4:1. The age of presentation varies from 40 to 70 years. According to a study conducted by verbal autopsy in 1.1 million homes representing the whole country, the age standardized mortality rate for HCC in India for men is 6.8/100,000 and for women is 5.1/100,000. According to another study the incidence of HCC in cirrhotics in India is 1.6% per year. The unpublished data from various tertiary care centers suggest that the incidence of HCC is increasing in India. There is a need for a multi-centric HCC registry under the aegis of INASL.

  19. Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Ur Rahman, Zia; Hurairah, Abu

    2016-01-01

    Our objective was to study nonalcoholic fatty liver disease (NAFLD) as a relevant risk factor associated with hepatocellular carcinoma (HCC) in patients with and without cirrhosis. HCC is a common cancer worldwide that predominantly involves patients with hepatic cirrhosis. HCC has recently been linked to NAFLD, the hepatic manifestation of obesity and related metabolic disorders. This association is alarming due to the high prevalence of NAFLD globally, which may contribute to the rising incidence of HCC. A 31-year-old female with a history of dyslipidemia, hypertension, and diabetes mellitus presented with abdominal pain that persisted for six months. The pain was associated with gastrointestinal symptoms and weight loss. She was drug-free and a nonalcoholic and a nonsmoker. The physical examination was unremarkable. The abdominal exam showed a soft and non-tender abdomen, with no organomegaly or ascites. The laboratory evaluation was unremarkable. The imaging studies showed a hypodense lesion in the right hepatic lobe with strong arterial enhancement. Subsequently, the patient underwent a liver biopsy. The histopathology results were consistent with HCC. The patient underwent an uneventful segment VI liver resection and tumor-free margins were achieved. In our patient, NAFLD was designated as an independent etiology for HCC, without cirrhosis. Our patient recovered well and has been disease free for over a year. HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk of HCC. These results provide new targets for surveillance, prevention, early recognition, and effective treatment of HCC associated with NAFLD. PMID:27733959

  20. Gene replacement therapy for genetic hepatocellular jaundice.

    PubMed

    van Dijk, Remco; Beuers, Ulrich; Bosma, Piter J

    2015-06-01

    Jaundice results from the systemic accumulation of bilirubin, the final product of the catabolism of haem. Inherited liver disorders of bilirubin metabolism and transport can result in reduced hepatic uptake, conjugation or biliary secretion of bilirubin. In patients with Rotor syndrome, bilirubin (re)uptake is impaired due to the deficiency of two basolateral/sinusoidal hepatocellular membrane proteins, organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3. Dubin-Johnson syndrome is caused by a defect in the ATP-dependent canalicular transporter, multidrug resistance-associated protein 2 (MRP2), which mediates the export of conjugated bilirubin into bile. Both disorders are benign and not progressive and are characterised by elevated serum levels of mainly conjugated bilirubin. Uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) is responsible for the glucuronidation of bilirubin; deficiency of this enzyme results in unconjugated hyperbilirubinaemia. Gilbert syndrome is the mild and benign form of inherited unconjugated hyperbilirubinaemia and is mostly caused by reduced promoter activity of the UGT1A1 gene. Crigler-Najjar syndrome is the severe inherited form of unconjugated hyperbilirubinaemia due to mutations in the UGT1A1 gene, which can cause kernicterus early in life and can be even lethal when left untreated. Due to major disadvantages of the current standard treatments for Crigler-Najjar syndrome, phototherapy and liver transplantation, new effective therapeutic strategies are under development. Here, we review the clinical features, pathophysiology and genetic background of these inherited disorders of bilirubin metabolism and transport. We also discuss the upcoming treatment option of viral gene therapy for genetic disorders such as Crigler-Najjar syndrome and the possible immunological consequences of this therapy.

  1. Hepatocellular Cancer: New Kids on the Block

    PubMed Central

    Hoffmann, Andreas-Claudius; Gerken, Guido G.H.

    2014-01-01

    Background With over 600,000 newly diagnosed hepatocellular cancer (HCC) patients worldwide every year and ongoing clinical research, it is surprising that many