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Sample records for acute hepatocellular necrosis

  1. Therapy for acute retinal necrosis.

    PubMed

    Kawaguchi, Tatsushi; Spencer, Doran B; Mochizuki, Manabu

    2008-01-01

    Acute retinal necrosis is a progressive necrotizing retinopathy caused by herpes simplex virus (HSV) or varicella zoster virus (VZV). The mainstay of its treatment is antiviral therapy against these pathogenic organisms, such as intravenous acyclovir or oral valacyclovir. Systemic and topical corticosteroids together with antiviral therapy are used as an anti-inflammatory treatment to minimize damages to the optic nerve and retinal blood vessels. Because the majority of severe cases of the disease show occlusive retinal vasculitis, a low dosage of aspirin is used as anti-thrombotic treatment. Vitreo-retinal surgery is useful to repair rhegmatogenous retinal detachment, one of the main late-stage complications. Moreover, recent articles have reported some encouraging results of prophylactic vitrectomy before rhegmatogenous retinal detachment occurs. The efficacy of laser photocoagulation to prevent the development or extension of rhegmatogenous retinal detachment is controversial. Despite these treatments, the visual prognosis of acute retinal necrosis is still poor, in particular VZV-induced acute retinal necrosis.

  2. Acute oesophageal necrosis (black oesophagus).

    PubMed

    Galtés, Ignasi; Gallego, María Ángeles; Esgueva, Raquel; Martin-Fumadó, Carles

    2016-03-01

    A 54-year-old man was admitted to hospital after being found unconscious in his home. He had a history of alcoholism, multiple drug addictions, and type I diabetes mellitus. At admission, he had hyperglycaemia (550 mg/dL) with glucosuria and ketone bodies in the urine, along with septic shock refractory to bilateral alveolar infiltrates and severe respiratory failure. The patient died 24 hours post admission due to multiple organ failure, with diabetic ketoacidosis decompensated by possible respiratory infection in a patient with polytoxicomania. The autopsy confirmed the presence of acute bilateral bronchopneumonia, chronic pancreatitis, severe hepatic steatosis, and generalized congestive changes. At the oesophagus, acute oesophageal necrosis was evident.

  3. Acute Necrotizing Esophagitis Followed by Duodenal Necrosis.

    PubMed

    Del Hierro, Piedad Magdalena

    2011-12-01

    Acute Necrotizing Esophagitis is an uncommon pathology, characterized by endoscopic finding of diffuse black coloration in esophageal mucosa and histological presence of necrosis in patients with upper gastrointestinal bleeding. The first case of acute necrotizing esophagitis followed by duodenal necrosis, in 81 years old woman with a positive history of Type 2 Diabetes Mellitus, Hypertension, and usual intake of Nonsteroidal Anti-inflammatory drugs, is reported. Although its etiology remains unknown, the duodenal necrosis suggests that ischemia could be the main cause given that the branches off the celiac axis provide common blood supply to the distal esophageal and duodenal tissue. The massive gastroesophagic reflux and NSAID intake could be involved.

  4. 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

  5. Black esophagus (acute esophageal necrosis) after spinal anesthesia.

    PubMed

    Román Fernández, A; López Álvarez, A; Fossati Puertas, S; Areán González, I; Varela García, O; Viaño López, P M

    2014-01-01

    Acute esophagic necrosis or black esophagus is an uncommon clinical entity that owes its name to the endoscopic view of the necrotic esophageal mucosa. It is always related with a critical medical condition and usually has an ischemic etiology. We report the first case of acute esophageal necrosis after a spinal anesthetic for partial hip joint arthroplasty. We discuss the underlying pathophysiological mechanisms.

  6. The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis

    PubMed Central

    Günther, Claudia; He, Gui-Wei; Kremer, Andreas E.; Murphy, James M.; Petrie, Emma J.; Amann, Kerstin; Linkermann, Andreas; Poremba, Christopher; Schleicher, Ulrike; Dewitz, Christin; Neurath, Markus F.; Becker, Christoph; Wirtz, Stefan

    2016-01-01

    Although necrosis and necroinflammation are central features of many liver diseases, the role of programmed necrosis in the context of inflammation-dependent hepatocellular death remains to be fully determined. Here, we have demonstrated that the pseudokinase mixed lineage kinase domain–like protein (MLKL), which plays a key role in the execution of receptor-interacting protein (RIP) kinase–dependent necroptosis, is upregulated and activated in human autoimmune hepatitis and in a murine model of inflammation-dependent hepatitis. Using genetic and pharmacologic approaches, we determined that hepatocellular necrosis in experimental hepatitis is driven by an MLKL-dependent pathway that occurs independently of RIPK3. Moreover, we have provided evidence that the cytotoxic activity of the proinflammatory cytokine IFN-γ in hepatic inflammation is strongly connected to induction of MLKL expression via activation of the transcription factor STAT1. In summary, our results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases. PMID:27756058

  7. Thioacetamide-induced Hepatocellular Necrosis Is Attenuated in Diet-induced Obese Mice

    PubMed Central

    Shirai, Makoto; Arakawa, Shingo; Miida, Hiroaki; Matsuyama, Takuya; Kinoshita, Junzo; Makino, Toshihiko; Kai, Kiyonori; Teranishi, Munehiro

    2013-01-01

    To assess modification of thioacetamide-induced hepatotoxicity in mice fed a high-fat diet, male C57BL/6J mice were fed a normal rodent diet or a high-fat diet for 8 weeks and then treated once intraperitoneally with thioacetamide at 50 mg/kg body weight. At 24 and 48 hours after administration, massive centrilobular hepatocellular necrosis was observed in mice fed the normal rodent diet, while the necrosis was less severe in mice fed the high-fat diet. In contrast, severe swelling of hepatocytes was observed in mice fed the high-fat diet. In addition, mice fed the high-fat diet displayed more than a 4-fold higher number of BrdU-positive hepatocytes compared with mice fed the normal rodent diet at 48 hours after thioacetamide treatment. To clarify the mechanisms by which the hepatic necrosis was attenuated, we investigated exposure to thioacetamide and one of its metabolites, the expression of CYP2E1, which converts thioacetamide to reactive metabolites, and the content of glutathione S-transferases in the liver. However, the reduced hepatocellular necrosis noted in mice fed the high-fat diet could not be explained by the differences in exposure to thioacetamide or thioacetamide sulfoxide or by differences in the expression of drug-metabolizing enzymes. On the other hand, at 8 hours after thioacetamide administration, hepatic total glutathione in mice fed the high-fat diet was significantly lower than that in mice fed the normal diet. Hence, decreased hepatic glutathione amount is a candidate for the mechanism of the attenuated necrosis. In conclusion, this study revealed that thioacetamide-induced hepatic necrosis was attenuated in mice fed the high-fat diet. PMID:23914059

  8. Necrosis and Apoptosis in Hepatocellular Carcinoma Following Low-Dose Versus High-Dose Preoperative Chemoembolization

    SciTech Connect

    Lu Wei Li Yanhao He Xiaofeng; Zhao Jianbo; Chen Yong; Mei Quelin

    2008-11-15

    Our purpose was to study necrosis and apoptosis of hepatocellular carcinoma (HCC) cells after preoperative transcatheter arterial chemoembolization (TACE) with use of low-dose and high-dose anticancer drugs in HCCs. Fifty-four patients with advanced but surgically resectable HCC were studied. Thirty-four patients who elected to undergo preoperative superselective TACE were randomized to low- and high-dose TACE. Patients in group A (n = 16) received low-dose anticancer drugs: 2 mg mitomycin C (MMC), 10 mg epirubicin (EPI), and 100 mg carboplatin (CBP). Patients in group B (n = 18) were given high doses of anticancer drugs (10 mg MMC, 40 mg EPI, and 300 mg CBP). Hepatic resection was subsequently performed. Group C comprised 20 patients who underwent resection without TACE. In all patients the necrosis rates and apoptosis index of tumor cells were evaluated by pathologic examinations and terminal deoxynucleotidyl transferase-mediated nick-end labeling assay. There was no significant difference between group A and group B in tumor response (p > 0.05) after TACE. Necrosis rates in groups A, B, and C were 88.4 {+-} 11.1%, 87.1 {+-} 12.5%, and 7.3 {+-} 3.5%, respectively. There was no significant difference between group A and group B (p > 0.05), while statistical difference was found between group A and group C (p < 0.001) and between group B and group C (p < 0.001). Apoptosis indexes in the three groups were 11.0 {+-} 4.0%, 10.7 {+-} 3.9%, and 5.6 {+-} 2.6%, respectively. Statistical difference exhibited between group A and group C (p < 0.001) and group B versus group C (p < 0.001). No significant difference was observed between group A and group B (p > 0.05). In conclusion, superselective TACE with low- and high-dose chemotherapeutic agents induced similar degrees of cellular apoptosis and necrosis.

  9. Acute Bladder Necrosis after Pelvic Arterial Embolization for Pelvic Trauma: Lessons Learned from Two Cases of Immediate Postembolization Bladder Necrosis

    PubMed Central

    Osterberg, E. Charles; Elliott, Sean P.; Hittelman, Adam B.

    2016-01-01

    We report two cases of acute bladder injury with bladder neck necrosis identified during the initial operative evaluation and within the early postprocedural period in patients with significant pelvic trauma requiring pelvic vascular embolization. To our knowledge, this is the first report of bladder neck necrosis found during the initial intraoperative surgical evaluation or early postoperative setting. PMID:27656309

  10. Clinical Manifestation of Self-Limiting Acute Retinal Necrosis

    PubMed Central

    Brydak-Godowska, Joanna; Borkowski, Piotr; Szczepanik, Szymon; Moneta-Wielgoś, Joanna; Kęcik, Dariusz

    2014-01-01

    Background The purpose of this paper was to present a case series of self-limiting, peripheral acute retinal necrosis and to demonstrate efficacy of treatment with valacyclovir in patients resistant to acyclovir. The diagnosis was made on ophthalmoscopic examination and positive serum tests for herpes viruses. Material/Methods Ten patients (6F and 4M) aged 19–55 years were diagnosed and treated for self-limiting acute retinal necrosis (ARN). The following endpoints were reported: visual outcomes, clinical features, disease progression, treatment, and complications. Patients received only symptomatic treatment because they did not consent to vitreous puncture. Results Peripheral, mild retinitis was diagnosed in all eyes at baseline. Initially, all patients were treated with systemic acyclovir (800 mg, 5 times a day), prednisone (typically 40–60 mg/day), and aspirin in an outpatient setting. In 6 patients, treatment was discontinued at 6 months due to complete resolution of the inflammatory process. Four patients with immune deficiency showed signs and symptoms of chronic inflammation. Two patients did not respond to acyclovir (2 non-responders); however, those patients were successfully treated with valacyclovir. Complete resolution of inflammatory lesions was observed in 8 patients. In 2 patients, the disease progressed despite treatment – 1 female patient after kidney transplant who stopped the prescribed medications, and 1 male patient with SLE and antiphospholipid syndrome who experienced breakthrough symptoms on-treatment. He died due to cerebral venous sinus thrombosis. Neurological complications (encephalitis and meningitis) were observed in 2 female patients. Prophylactic laser photocoagulation was performed in 1 subject. Conclusions A series of cases of self-limiting acute retinal necrosis (ARN) is presented. This clinical form of ARN can resemble toxoplasmic retinitis in some cases. Oral antiviral medications provide an effective alternative to

  11. [Protocol for the treatment of severe acute pancreatitis with necrosis].

    PubMed

    Barreda, Luis; Targarona, Javier; Rodriguez, César

    2005-01-01

    The Severe Acute Pancreatic Unit of Edgardo Rebagliati Martins National Hospital was officially created in the year 2000. Up to date, we have cared for more than 195 patients with Pancreatic Necrosis. All of them have been treated under a management protocol presented by us. This has helped us to standardize treatment and also to compare results with work groups around the world. This Protocol comes from our own experience and that of our colleagues abroad with a wide knowledge in this kind of pathology abroad, with whom we maintain close ties.

  12. Early onset acute tubular necrosis following single infusion of zoledronate

    PubMed Central

    Yachoui, Ralph

    2016-01-01

    Summary Zoledronate is a highly potent bisphosphonate widely used in the treatment of postmenopausal osteoporosis. We report the first occurrence of toxic acute tubular necrosis (ATN) following treatment with zoledronate in a patient with osteoporosis. A 63-year-old Caucasian female with rheumatoid arthritis on anti-immune agents received a single dose of zoledronic acid (reclast) for worsening osteoporosis. Twelve days later, she developed renal failure with a rise in serum creatinine from a baseline level of 1.1 mg/dL to 5.5 mg/dL. Renal biopsy showed toxic ATN. Zoledronate was discontinued and the patient had subsequent gradual improvement in renal function with final serum creatinine of 1.8 mg/dL at 1 month of follow up. Careful monitoring of serum creatinine and awareness of the potential nephrotoxicity may avert the development of acute renal failure in osteoporosis patients treated with this agent. PMID:27920815

  13. Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

    PubMed Central

    Noel, Pawan; Patel, Krutika; Durgampudi, Chandra; Trivedi, Ram N; de Oliveira, Cristiane; Crowell, Michael D; Pannala, Rahul; Lee, Kenneth; Brand, Randall; Chennat, Jennifer; Slivka, Adam; Papachristou, Georgios I; Khalid, Asif; Whitcomb, David C; DeLany, James P; Cline, Rachel A; Acharya, Chathur; Jaligama, Deepthi; Murad, Faris M; Yadav, Dhiraj; Navina, Sarah; Singh, Vijay P

    2016-01-01

    Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP. PMID:25500204

  14. Prognostic and Therapeutic Values of Tumor Necrosis Factor-Alpha in Hepatocellular Carcinoma

    PubMed Central

    Wang, Hongmei; Liu, Jianmin; Hu, Xuemei; Liu, Shanshan; He, Baojun

    2016-01-01

    Background Hepatocellular carcinoma (HCC) causes many deaths worldwide every year, especially in Asia. It is characterized by high malignancy, recurrence, and short survival time. Inflammation is closely related to the initiation and development of HCC. Tumor necrosis factor-α (TNF-α), an essential inflammatory mediator, has been studied as a potential therapy target in many cancers. However, its potential role in HCC diagnosis and therapy is still unclear. Material/Methods In our study, we detected the TNF-α expression in both human HCC tumor tissue and HCC cell lines HepG2 and HuH7. Then, we detected the effect of anti-TNF-α treatment and it synergistic function with 5-FU in an HCC xenograft mouse model and in HCC cell lines. Results Survival analysis and Cox regression analysis based on 97 HCC patients indicated that a high level of TNF-α is an independent predictor of poor survival in HCC patients. Anti-TNF-α treatment by infliximab synergizes with Fluorouracil (5-FU) by promoting apoptosis of HCC tumor cells through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) effects. Conclusions Based on these data, we conclude that anti-TNF-α treatment could be a good way to increase the effect of classic chemotherapy of HCC patients, especially for the patients who have modest response to classic chemotherapy, such as 5-FU. TNF-α could also be used as a biomarker to help in early diagnosis of HCC. PMID:27739418

  15. Prognostic markers in acute pancreatitis: can pancreatic necrosis be predicted?

    PubMed Central

    Leese, T.; Shaw, D.; Holliday, M.

    1988-01-01

    The value of six prognostic markers was assessed prospectively in 198 attacks of acute pancreatitis with specific attention to their ability to predict pancreatic necrosis. The Imrie Prognostic Score (IPS) was recorded within 48 h of diagnosis. The serum C-reactive protein (CRP) alpha 1 antiprotease (A1AP), alpha 2 macroglobulin (A2M), amylase and white cell count (WCC) were measured on days 1, 3 and 7. When comparing all severe clinical outcomes to mile outcomes, serum CRP concentrations were higher on all three days (P less than 0.02, less than 0.001, less than 0.001), A1AP concentrations were higher on day 3 (P less than 0.05), A2M concentrations were lower on day 7 (P less than 0.01) and WCC was higher on all three days (P less than 0.001, less than 0.001, less than 0.001). Serum amylase concentrations showed no significant differences. None of the measured parameters were helpful in distinguishing patients who subsequently developed pancreatic necrosis from patients who had other severe outcomes. Multivariate analysis revealed that the initial IPS showed greatest independent significance in predicting severe outcome followed by the WCC (days 1 and 7) and CRP (day 3). CRP and WCC may be clinically useful predictors of severe outcome to supplement the initial IPS. These methods are unlikely to distinguish pancreatic necrosis from other severe outcomes, but they may supplement clinical judgment in selecting a high risk group of patients for contrast enhanced computed tomography. PMID:2458063

  16. Antiviral selection in the management of acute retinal necrosis

    PubMed Central

    Tam, Patrick MK; Hooper, Claire Y; Lightman, Susan

    2010-01-01

    There is no consensus on the optimal antiviral regimen in the management of acute retinal necrosis, a disease caused by herpetic viruses with devastating consequences for the eye. The current gold standard is based on retrospective case series. Because the incidence of disease is low, few well-designed, randomized trials have evaluated treatment dosage and duration. Newer oral antiviral agents are emerging as alternatives to high-dose intravenous acyclovir, avoiding the need for inpatient intravenous treatment. Drug resistance is uncommon but may also be difficult to identify. Antiviral drugs have few side effects, but special attention needs to be paid to patients who have underlying renal disease, are pregnant or are immunocompromised. PMID:20169044

  17. Three polymorphisms of tumor necrosis factor-alpha and hepatitis B virus related hepatocellular carcinoma

    PubMed Central

    Xiao, Qi; Fu, BiQi; Chen, Ping; Liu, Zhong Zhong; Wang, Wei; Ye, QiFa

    2016-01-01

    Abstract Background: To assess the association between tumor necrosis factor-alpha (TNF-α) G308A, G238A and C863T polymorphisms and hepatitis B virus related hepatocellular carcinoma (HBV-HCC) susceptibility. Methods: We interrogated the databases of Pubmed, Sciencedirect and Viley online library up to March 8, 2016. Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated in a fixed-effects model or a random-effects model when appropriate. Results: In total, 12 case–control studies which containing 1580 HBV-HCC cases, 2033 HBV carrier controls, 395 HBV spontaneously recovered (SR) controls and 1116 healthy controls were included. Compared with GG genotype, the genotypes GA/AA of G308A were associated with a significantly increased HBV-HCC risk when the controls were all healthy individuals (AA vs. GG, OR 2.483, 95%CI 1.243 to 4.959; GA vs. GG, OR 1.383, 95%CI 1.028 to 1.860; GA/AA vs. GG, OR 1.381, 95%CI 1.048 to 1.820). Meanwhile, only the AA vs. GG model of G238A and HBV-HCC showed a statistic significance when the controls were healthy individuals (OR 4.776, 95%CI 1.280 to 17.819). CT genotype of TNF-α C863T could increase HBV-HCC risk whenever the controls were healthy individuals, HBV carriers or HBV recovers. Conclusion: This meta-analysis shows that AA genotype in TNF-α G308A and TNF-α G238A and CT genotype in TNF-α C863T may increase HBV-HCC risk. Therefore, HBV infection seemed to be a more important factor for tumorigenesis of HCC than genetic predisposition in G308A of TNF-α, and interaction between TNF-α C863T polymorphisms and HBV infection might be associated with increased HCC risk. PMID:27977601

  18. Detection of acute hepatopancreatic necrosis disease (AHPND) in Mexico.

    PubMed

    Nunan, Linda; Lightner, Donald; Pantoja, Carlos; Gomez-Jimenez, Silvia

    2014-08-21

    Acute hepatopancreatic necrosis disease (AHPND), which has also been referred to as early mortality syndrome (EMS), initially emerged as a destructive disease of cultured shrimp species in Asia in 2009. The pathogen associated with the disease, Vibrio parahaemolyticus, subsequently spread to the Western Hemisphere and emerged in Mexico in early 2013. The spread to the Western Hemisphere is a major concern to shrimp producers in the region. To date, the only peer-reviewed published method for determining whether mortalities are due to AHPND is through histological examination. A novel PCR detection method was employed to assess samples from Mexico in order to confirm the presence of the pathogen in this country. This manuscript details the detection methods used to confirm the presence of AHPND in Mexico. Both immersion and per os challenge studies were used to expose the Penaeus vannamei to the bacteria in order to induce the disease. Histological analysis confirmed AHPND status following the challenge studies. Also provided are the details of the molecular test by PCR that was used for screening candidate V. parahaemolyticus isolates. A rapid PCR assay for detection of AHPND may help with early detection and help prevent the spread of AHPND to other countries.

  19. Human tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 suppresses hepatocellular carcinoma metastasis through inhibiting Rac1

    PubMed Central

    2013-01-01

    Background Tumor invasion and metastasis are the major reasons for leading death of patients with hepatocellular carcinoma (HCC). Therefore, to identify molecules that can suppress invasion and metastasis of tumor will provide novel targets for HCC therapies. Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2, TIPE2, is a novel immune negative molecule and an inhibitor of the oncogenic Ras in mice but its function in human is unclear. Our previous research has shown that TIPE2 is downregulated in human primary HCC compared with the paired adjacent non-tumor tissues. Results In present study, we provide evidence that TIPE2 inhibits effectively human hepatocellular carcinoma metastasis. The forced expression of TIPE2 in HCC-derived cell lines markedly inhibits tumor cell growth, migration and invasion in vitro and suppresses growth and metastasis of HCC in vivo. Clinical information from a cohort of 112 patients reveals that loss or reduced expression of TIPE2 in primary HCC tissues is significantly associated with tumor metastasis. Mechanically, TIPE2 inhibits the migration and invasion through targeting Rac1 and then reduces F-actin polymerization and expression of matrix metallopeptidase 9 (MMP9) and urokinase plasminogen activator (uPA). Conclusion Our results indicate that human TIPE2 is endogenous inhibitor of Rac1 in HCC by which it attenuates invasion and metastasis of HCC. The data suggest that TIPE2 will be a new target for HCC therapy. PMID:24274578

  20. An Unusual Cause of Acute Upper Gastrointestinal Bleeding: Acute Esophageal Necrosis

    PubMed Central

    Tokala, Madhusudhan R.; Dhillon, Sonu; Pisoh, Watcoun-Nchinda; Walayat, Saqib; Vanar, Vishwas; Puli, Srinivas R.

    2016-01-01

    Acute esophageal necrosis (AEN), also called “black esophagus,” is a condition characterized by circumferential necrosis of the esophagus with universal distal involvement and variable proximal extension with clear demarcation at the gastroesophageal junction. It is an unusual cause of upper gastrointestinal bleeding and is recognized with distinct and striking mucosal findings on endoscopy. The patients are usually older and are critically ill with shared comorbidities, which include atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, chronic renal insufficiency, and malnutrition. Alcoholism and substance abuse could be seen in younger patients. Patients usually have systemic hypotension along with upper abdominal pain in the background of clinical presentation of hematemesis and melena. The endoscopic findings confirm the diagnosis and biopsy is not always necessary unless clinically indicated in atypical presentations. Herein we present two cases with distinct clinical presentation and discuss the endoscopic findings along with a review of the published literature on the management of AEN. PMID:27642529

  1. Disseminated intravascular coagulation and acute myocardial necrosis caused by lightning.

    PubMed

    Ekoé, J M; Cunningham, M; Jaques, O; Balague, F; Baumann, R P; Humair, L; de Torrenté, A

    1985-01-01

    A 24-year-old woman was struck by lightning and suffered 20% second degree burns. She was admitted after cardiac and respiratory arrest. Despite intensive supportive care she died 24 h later of cardiogenic shock complicated by disseminated intravascular coagulation. At autopsy there was myocardial necrosis. Disseminated intravascular coagulation and myocardial necrosis are only rarely described as complications of lightning.

  2. Does the Degree of Hepatocellular Carcinoma Tumor Necrosis following Transarterial Chemoembolization Impact Patient Survival?

    PubMed Central

    Haywood, Nathan; Gennaro, Kyle; Obert, John; Sauer, Paul F.; Redden, David T.; Zarzour, Jessica; Smith, J. Kevin; Bolus, David; Saddekni, Souheil; Aal, Ahmed Kamel Abdel; Gray, Stephen; White, Jared; Eckhoff, Devin E.; DuBay, Derek A.

    2016-01-01

    Purpose. The association between transarterial chemoembolization- (TACE-) induced HCC tumor necrosis measured by the modified Response Evaluation Criteria In Solid Tumors (mRECIST) and patient survival is poorly defined. We hypothesize that survival will be superior in HCC patients with increased TACE-induced tumor necrosis. Materials and Methods. TACE interventions were retrospectively reviewed. Tumor response was quantified via dichotomized (responders and nonresponders) and the four defined mRECIST categories. Results. Median survival following TACE was significantly greater in responders compared to nonresponders (20.8 months versus 14.9 months, p = 0.011). Survival outcomes also significantly varied among the four mRECIST categories (p = 0.0003): complete, 21.4 months; partial, 20.8; stable, 16.8; and progressive, 7.73. Only progressive disease demonstrated significantly worse survival when compared to complete response. Multivariable analysis showed that progressive disease, increasing total tumor diameter, and non-Child-Pugh class A were independent predictors of post-TACE mortality. Conclusions. Both dichotomized (responders and nonresponders) and the four defined mRECIST responses to TACE in patients with HCC were predictive of survival. The main driver of the survival analysis was poor survival in the progressive disease group. Surprisingly, there was small nonsignificant survival benefit between complete, partial, and stable disease groups. These findings may inform HCC treatment decisions following first TACE. PMID:26949394

  3. Acute hepatic encephalopathy presenting as cortical laminar necrosis: case report.

    PubMed

    Choi, Jong Mun; Kim, Yoon Hee; Roh, Sook Young

    2013-01-01

    We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.

  4. Binge Eating Leading to Acute Gastric Dilatation, Ischemic Necrosis and Rupture –A Case Report

    PubMed Central

    Khare, Manish Kumar; Mishra, Sumanta; Marhual, Jogesh Chandra

    2016-01-01

    Acute gastric dilatation is a rarely encountered clinical scenario in our day to day practice. This is very rapidly progressing condition and can lead to ischemic necrosis and perforation/rupture of the stomach. It could be fatal if not timely intervened. We report such a case of a 17-year-old, otherwise healthy boy, who presented with pain and distension of abdomen following binge eating episode after 24 hours of prolonged fasting. On exploration, stomach was dilated with necrosis and perforation at fundus near greater curvature. He was managed with excision of all the devitalized area and primary repair with feeding jejunostomy. The case is presented due to its rarity. Acute gastric dilatation (AGD) leading to ischemic necrosis and perforation because of binge eating episode in an otherwise healthy person is an exceptional occurrence with only few cases reported in literature. The clinician should be aware of this condition for prompt and appropriate management. PMID:27134932

  5. Caffeine protects human skin fibroblasts from acute reactive oxygen species-induced necrosis.

    PubMed

    Silverberg, Jonathan I; Patel, Mital; Brody, Neil; Jagdeo, Jared

    2012-11-01

    Oxidative damage by reactive oxygen species (ROS) plays a major role in aging and carcinogenesis. Little is known about either the effects of acute ROS in necrosis and inflammation of skin or the therapeutic agents for prevention and treatment. Previously, our laboratory identified caffeine as an inhibitor of hydrogen peroxide (H2O2)-generated lipid peroxidation products in human skin fibroblasts. Here, we study effects of caffeine on acute ROS-mediated necrosis. Human skin fibroblasts were incubated with caffeine, followed by H2O2 challenge. Flow cytometry was used to analyze cell morphology, counts, apoptosis and necrosis, and ROS. We found that caffeine protects from H2O2 cell damage at lower (0.01 mM) and intermediate (0.1 mM) doses. The beneficial effects of caffeine appear to be mediated by a mechanism other than antioxidant function.

  6. Haemorrhagic necrosis of small intestine and acute pancreatitis following open-heart surgery

    PubMed Central

    Horton, E. H.; Murthy, S. K.; Seal, R. M. E.

    1968-01-01

    Five cases of haemorrhagic necrosis of the small intestine occurring after valve replacement under cardiopulmonary bypass are described. In one case, in addition to the above, there was an unusual complication, namely acute pancreatitis. The possible causes are discussed. The importance of hypotension before, during, or after bypass, or in the post-operative phase, is stressed. Images PMID:5664708

  7. Tumor Necrosis Factor-α-308 G/A Polymorphisms and Risk of Hepatocellular Carcinoma: A Meta-Analysis

    PubMed Central

    Tavakolpour, Soheil; Sali, Shahnaz

    2016-01-01

    Context Hepatocellular carcinoma (HCC) is a common disorder throughout the world that can develop due to various factors, including genetics. Tumor necrosis factor-α (TNF-α) is the most frequently studied cytokine related to the risk of developing HCC, and an association between the 308 position of the TNF-α promoter (TNF-α-308) and HCC risk has been confirmed in various reports. Evidence Acquisition The PubMed, Scopus, and Google Scholar databases were searched through July 12, 2015, for studies on associations between TNF-α-308 and the risk of HCC. To determine this association, odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results A total of 23 case-control studies were investigated, involving 3,389 cases and 4,235 controls. The overall conclusion was that the A allele was more frequent in case groups compared to control groups (13.4% vs. 8.4%). Thus, the A allele was significantly associated with increased HCC risk (OR = 1.77; 95% CI = [1.26-2.50]; P value < 0.002). In addition to the allelic model, the dominant model (AA + AG vs. GG) was significantly associated with HCC risk (OR = 1.80; CI = [1.29-2.51]; P value < 0.001). In the sensitivity analysis for co-dominant (AA vs. GG) and recessive models (AA vs. AG + GG), no trustworthy associations with the risk of HCC development were observed. Conclusions This meta-analysis indicated that the TNF-α-308 G/A polymorphism is significantly associated with increased susceptibility to HCC. However, to confirm this finding, more studies are needed on TNF-α-308 G/A polymorphisms associated with HCC. PMID:27257425

  8. Regulatory mechanisms of interleukin-8 production induced by tumour necrosis factor-α in human hepatocellular carcinoma cells

    PubMed Central

    Wang, Yaohui; Wang, Weimin; Wang, Lingyan; Wang, Xiangdong; Xia, Jinglin

    2012-01-01

    Abstract Interleukin (IL)-8 plays the critical role in the initiation of micro-environmental inflammation responsible for tumour growth and patient prognosis. This study aimed at investigating the molecular mechanisms of IL-8 production from human hepatocellular carcinoma (HCC) cells. The levels of IL-8 and phosphorylation of p38 mitogen-activated protein kinase (MAPK), ERK1/2 and Akt in MHCC-97H cells were measured by ELISA, Western blot and immunofluorescence. NF-κB p65 protein nuclear translocation was determined by non-radioactive NF-κB p50/p65 transcription factor activity kit and cell bio-behaviours were detected by the real-time cell-monitoring system. Tumour necrosis factor-α (TNF-α) significantly induced phosphorylation of p38 MAPK, ERK, Akt and production of IL-8 from HCC cells, which were prevented by SB203580 (p38 MAPK inhibitor), PD98059 (ERK inhibitor), LY294002 and Wortmannin (PI3K inhibitor) and SB328437 (CCR3 inhibitor). TNF-α could significantly increase the translocation of NF-κB p65 protein into the nucleus in a dose-dependent manner, while SB203580 partially inhibited. In inflammatory micro-environment, HCC auto-produced IL-8 through p38 MAPK, ERK and PI3K/Akt signalling pathways, where the p38 MAPK is a central factor to activate the NF-κB pathway and regulate the expression of IL-8 production. There was a potential cross-talking between receptors. PMID:21545687

  9. Acute necrosis after Gamma Knife surgery in vestibular schwannoma leading to multiple cranial nerve palsies.

    PubMed

    Kapitza, Sandra; Pangalu, Athina; Horstmann, Gerhard A; van Eck, Albert T; Regli, Luca; Tarnutzer, Alexander A

    2016-08-01

    We discuss a rare acute complication after Gamma Knife therapy (Elekta AB, Stockholm, Sweden) in a single patient. A 52-year-old woman presented with vertigo, facial weakness and hearing loss emerging 48hours following Gamma Knife radiosurgery for a right-sided vestibular schwannoma. Neurological examination 6days after symptom onset showed right-sided facial palsy, spontaneous left-beating nystagmus and pathologic head-impulse testing to the right. Pure-tone audiogram revealed right-sided sensorineural hearing loss. A diagnosis of acute vestibulocochlear and facial neuropathy was made. Brain MRI demonstrated focal contrast sparing within the schwannoma, likely related to acute radiation necrosis. Acute multiple cranial neuropathies of the cerebellopontine angle after Gamma Knife treatment should raise suspicion of acute tissue damage within the schwannoma and should result in urgent MRI. Treatment with steroids may be considered based on accompanying swelling and edema.

  10. Acute Retinal Necrosis Presenting in Developmentally-delayed Patients with Neonatal Encephalitis: A Case Series and Literature Review.

    PubMed

    Okafor, Kingsley; Lu, Jonathan; Thinda, Sumeer; Schwab, Ivan; Morse, Lawrence S; Park, Susanna S; Moshiri, Ala

    2016-05-18

    We report three cases of patients with developmental-delay from neonatal herpetic encephalitis and/or meningitis who presented years later with acute retinal necrosis due to herpes simplex virus. The diagnosis was delayed in all cases due to the patients' inability to verbalize their ocular complaints and cooperate with eye examinations. This case series documents the clinical course, pathophysiologic mechanism, and treatment of acute retinal necrosis in this patient population. Clinicians should understand the importance of prudent consideration of acute retinal necrosis in patients with a history of neonatal herpetic encephalitis and/or meningitis presenting with a red eye.

  11. Walled-off pancreatic necrosis and other current concepts in the radiological assessment of acute pancreatitis.

    PubMed

    Cunha, Elen Freitas de Cerqueira; Rocha, Manoel de Souza; Pereira, Fábio Payão; Blasbalg, Roberto; Baroni, Ronaldo Hueb

    2014-01-01

    Acute pancreatitis is an inflammatory condition caused by intracellular activation and extravasation of inappropriate proteolytic enzymes determining destruction of pancreatic parenchyma and peripancreatic tissues. This is a fairly common clinical condition with two main presentations, namely, endematous pancreatitis - a less severe presentation -, and necrotizing pancreatitis - the most severe presentation that affects a significant part of patients. The radiological evaluation, particularly by computed tomography, plays a fundamental role in the definition of the management of severe cases, especially regarding the characterization of local complications with implications in the prognosis and in the definition of the therapeutic approach. New concepts include the subdivision of necrotizing pancreatitis into the following presentations: pancreatic parenchymal necrosis with concomitant peripancreatic tissue necrosis, and necrosis restricted to peripancreatic tissues. Moreover, there was a systematization of the terms acute peripancreatic fluid collection, pseudocyst, post-necrotic pancreatic/peripancreatic fluid collections and walled-off pancreatic necrosis. The knowledge about such terms is extremely relevant to standardize the terminology utilized by specialists involved in the diagnosis and treatment of these patients.

  12. [Atypical case of acute retinal necrosis secondary to the primary herpes simplex infection].

    PubMed

    Terelak-Borys, Barbara; Krzyźewska-Niedzialek, Aldona; Jamrozy-Witkowska, Agnieszka; Borkowski, Piotr K; Ulińska, Magdalena; Grabska-Liberek, Iwona

    2015-01-01

    Acute retinal necrosis is a rare manifestation of viral chorioretinitis, accompanied by occlusive vasculitis, which is associated with poor visual prognosis. The main causal factors include varicella-zoster virus in older patients and herpes simplex in younger ones. The disease typically manifests as a reactivation of latent infections. We present a case of a 57-year-old female with atypical clinical manifestation of acute retinal necrosis secondary to the primary viral infection with herpes simplex. The serology panel of vitreous tap and blood sample confirmed viral aetiology (H. simplex). The initial clinical signs included optic disc edema with retinitis presenting as self-limiting, slowly progressing, peripheral lesions, later followed by uveitis. The antiviral therapy resolved the symptoms of uveitis and enabled healing of retinal lesions, however the natural course of disease was later complicated with retinal detachment. It was successfully treated with vitreoretinal surgery. Despite aggressive treatment, the final visual outcome was unfavourable, due to optic nerve atrophy.

  13. Acute Esophageal Necrosis Presenting With Henoch-Schönlein Purpura.

    PubMed

    Iorio, Natalya; Bernstein, Gregory R; Malik, Zubair; Schey, Ron

    2015-10-01

    A 63-year-old woman with abdominal pain and melena developed a palpable, purpuric rash and acute kidney injury. Skin and kidney biopsy confirmed Henoch-Schönlein purpura. Upper endoscopy revealed diffuse, circumferential, black-appearing mucosa of the esophagus consistent with acute esophageal necrosis (AEN), also known as black esophagus. AEN is a very rare cause of gastrointestinal hemorrhage with a high mortality risk. To our knowledge, there have been no prior reports of AEN associated with Henoch-Schonlein purpura or other vasculitis.

  14. Acute Esophageal Necrosis Presenting With Henoch-Schönlein Purpura

    PubMed Central

    Bernstein, Gregory R.; Malik, Zubair; Schey, Ron

    2015-01-01

    A 63-year-old woman with abdominal pain and melena developed a palpable, purpuric rash and acute kidney injury. Skin and kidney biopsy confirmed Henoch-Schönlein purpura. Upper endoscopy revealed diffuse, circumferential, black-appearing mucosa of the esophagus consistent with acute esophageal necrosis (AEN), also known as black esophagus. AEN is a very rare cause of gastrointestinal hemorrhage with a high mortality risk. To our knowledge, there have been no prior reports of AEN associated with Henoch-Schonlein purpura or other vasculitis. PMID:26504868

  15. [Acute kidney failure due to kidney cortex necrosis. 2 clinical cases of surviving patients].

    PubMed

    Fuenzalida, E

    1991-07-01

    A 22 year old female developed preeclampsia with fetal death in utero. After cesarean section she developed uterine inertia and acute hemorrhagic anemia complicated by sepsis, disseminated intravascular coagulation and total anuria for 4 weeks. She was treated with hemodialysis. The second patient, a 49 year old man developed sepsis and intravascular coagulation after a dog bite. Acute renal failure with a 3 week total anuria followed. He was initially treated with peritoneo dialysis. Renal biopsy showed evidence of renal cortical necrosis in both patients.

  16. Aspirin Protects against Acinar Cells Necrosis in Severe Acute Pancreatitis in Mice

    PubMed Central

    Lu, Guotao; Tong, Zhihui; Ding, Yanbing; Liu, Jinjiao; Pan, Yiyuan; Gao, Lin; Tu, Jianfeng; Liu, George

    2016-01-01

    Aspirin has a clear anti-inflammatory effect and is used as an anti-inflammatory agent for both acute and long-term inflammation. Previous study has indicated that aspirin alleviated acute pancreatitis induced by caerulein in rat. However, the role of aspirin on severe acute pancreatitis (SAP) and the necrosis of pancreatic acinar cell are not yet clear. The aim of this study was to determine the effects of aspirin treatment on a SAP model induced by caerulein combined with Lipopolysaccharide. We found that aspirin reduced serum amylase and lipase levels, decreased the MPO activity, and alleviated the histopathological manifestations of pancreas and pancreatitis-associated lung injury. Proinflammatory cytokines were decreased and the expression of NF-κB p65 in acinar cell nuclei was suppressed after aspirin treatment. Furthermore, aspirin induced the apoptosis of acinar cells by TUNEL assay, and the expression of Bax and caspase 3 was increased and the expression of Bcl-2 was decreased. Intriguingly, the downregulation of critical necrosis associated proteins RIP1, RIP3, and p-MLKL was observed; what is more, we additionally found that aspirin reduced the COX level of pancreatic tissue. In conclusion, our data showed that aspirin could protect pancreatic acinar cell against necrosis and reduce the severity of SAP. Clinically, aspirin may potentially be a therapeutic intervention for SAP. PMID:28119929

  17. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

    PubMed Central

    Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called “second pathway of liver regeneration.” The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin. PMID:26136687

  18. Involvement of thrombopoietin in acinar cell necrosis in L-arginine-induced acute pancreatitis in mice.

    PubMed

    Shen, Jiaqing; Wan, Rong; Hu, Guoyong; Wang, Feng; Shen, Jie; Wang, Xingpeng

    2012-10-01

    Thrombopoietin (TPO) plays an important role in injuries of different tissues. However, the role of TPO in acute pancreatitis (AP) is not yet known. The aim of the study was to determine the involvement of TPO in AP. Serum TPO was assayed in necrotizing pancreatitis induced by L-arginine in mice. Recombinant TPO and anti-TPO antibody were given to mice with necrotizing pancreatitis. Amylase, lipase, lactate dehydrogenase, myeloperoxidase activity and pancreatic water content were assayed in serum and tissue samples. Pancreas and lung tissue samples were also collected for histological evaluation. Immunohistochemistry of amylase α and PCNA were applied for the study of acinar regeneration and TUNEL assay for the detection of apoptosis in the pancreas. Increased levels of serum TPO were found in necrotizing pancreatitis. After TPO administration, more severe acinar necrosis was found and blockade of TPO reduced the acinar necrosis in this AP model. Acinar regeneration and apoptosis in the pancreas were affected by TPO and antibody treatment in necrotizing pancreatitis. The severity of pancreatitis-associated lung injury was worsened after TPO treatment, but attenuated after Anti-TPO antibody treatment. In conclusion, serum TPO is up-regulated in the necrotizing pancreatitis induced by L-arginine in mice and may be a risk factor for the pancreatic acinar necrosis in AP. As a pro-necrotic factor, blockade of TPO can attenuate the acinar necrosis in AP and may be a possible therapeutic intervention for AP.

  19. Contrast-Enhanced Ultrasonography of Hepatocellular Carcinoma After Chemoembolisation Using Drug-Eluting Beads: A Pilot Study Focused on Sustained Tumor Necrosis

    SciTech Connect

    Moschouris, Hippocrates; Malagari, Katerina; Papadaki, Marina Georgiou; Kornezos, Ioannis Matsaidonis, Dimitrios

    2010-10-15

    The purpose of this study was to assess the use of contrast-enhanced ultrasonography (CEUS) and the sustained antitumor effect of drug-eluting beads used for transarterial chemoembolisation (TACE) of unresectable hepatocellular carcinoma (HCC). Ten patients with solitary, unresectable HCC underwent CEUS before, 2 days after, and 35 to 40 days after TACE using a standard dose (4 ml) of drug-eluting beads (DC Beads; Biocompatibles, Surrey, UK) preloaded with doxorubicin (25 mg doxorubicin/ml hydrated beads). For CEUS, a second-generation contrast agent (SonoVue, Bracco, Milan, Italy) and a low mechanical-index technique were used. A part of the tumor was characterized as necrotic if it showed complete lack of enhancement. The percentage of necrosis was calculated at the sonographic section that depicted the largest diameter of the tumor. Differences in the extent of early (2 days after TACE) and delayed (35 to 40 days after TACE) necrosis were quantitatively and subjectively assessed. Early post-TACE tumor necrosis ranged from 21% to 70% (mean 43.5% {+-} 19%). There was a statistically significant (p = 0.0012, paired Student t test) higher percentage of delayed tumor necrosis, which ranged from 24% to 88% (mean 52.3% {+-} 20.3%). Subjective evaluation showed a delayed obvious increase of the necrotic areas in 5 patients. In 2 patients, tumor vessels that initially remained patent disappeared on the delayed follow-up. A part of tumor necrosis after chemoembolisation of HCC with DEB seems to take place later than 2 days after TACE. CEUS may provide evidence for the sustained antitumor effect of DEB-TACE. Nevertheless, the ideal time for the imaging evaluation of tumor response remains to be defined.

  20. Gallbladder Volvulus: A Rare Emergent Cause of Acute Cholecystitis, if Untreated, Progresses to Necrosis and Perforation

    SciTech Connect

    Justin L, Regner Angela, Lomas

    2016-03-25

    An 86 year-old woman with a past medical history significant for abdominal hernia and Alzheimer dementia presented to the Emergency Department with a 24 hour history of acute right upper quadrant pain associated with nausea and non-bilious emesis. Physical exam revealed right sided abdominal tenderness with associated mass. All laboratory values were within normal ranges. Both abdominal ultrasound and computed tomography of the abdomen/pelvis revealed a large distended gallbladder with wall thickening and gallstones. Based on presentation and radiologic findings, the emergency general surgery service was consulted for suspected acute cholecystitis. The patient was then admitted for intravenous antibiotics and scheduled for laparoscopic cholecystectomy the following day. Intra-operative findings revealed volvulus with acute necrosis of the entire gallbladder. The gallbladder had a long pedunculated cystic duct and artery that was detorsed before proceeding with resection. Postoperatively, the patient did well and was discharged a few days later tolerating a regular diet.

  1. Lipolysis of Visceral Adipocyte Triglyceride by Pancreatic Lipases Converts Mild Acute Pancreatitis to Severe Pancreatitis Independent of Necrosis and Inflammation

    PubMed Central

    Patel, Krutika; Trivedi, Ram N.; Durgampudi, Chandra; Noel, Pawan; Cline, Rachel A.; DeLany, James P.; Navina, Sarah; Singh, Vijay P.

    2016-01-01

    Visceral fat necrosis has been associated with severe acute pancreatitis (SAP) for over 100 years; however, its pathogenesis and role in SAP outcomes are poorly understood. Based on recent work suggesting that pancreatic fat lipolysis plays an important role in SAP, we evaluated the role of pancreatic lipases in SAP-associated visceral fat necrosis, the inflammatory response, local injury, and outcomes of acute pancreatitis (AP). For this, cerulein pancreatitis was induced in lean and obese mice, alone or with the lipase inhibitor orlistat and parameters of AP induction (serum amylase and lipase), fat necrosis, pancreatic necrosis, and multisystem organ failure, and inflammatory response were assessed. Pancreatic lipases were measured in fat necrosis and were overexpressed in 3T3-L1 cells. We noted obesity to convert mild cerulein AP to SAP with greater cytokines, unsaturated fatty acids (UFAs), and multisystem organ failure, and 100% mortality without affecting AP induction or pancreatic necrosis. Increased pancreatic lipase amounts and activity were noted in the extensive visceral fat necrosis of dying obese mice. Lipase inhibition reduced fat necrosis, UFAs, organ failure, and mortality but not the parameters of AP induction. Pancreatic lipase expression increased lipolysis in 3T3-L1 cells. We conclude that UFAs generated via lipolysis of visceral fat by pancreatic lipases convert mild AP to SAP independent of pancreatic necrosis and the inflammatory response. PMID:25579844

  2. A case of acute oesophageal necrosis (AEN) in a hypothermic patient. The grave prognosis of the black oesophagus.

    PubMed

    Salem, George A; Ahluwalia, Sumit; Guild, Ralph T

    2015-01-01

    Acute oesophageal necrosis, also known as black oesophagus, is a rare, and potentially lethal syndrome which is often diagnosed incidentally during upper endoscopy for evaluation of upper gastrointestinal bleed. It is characterised by diffuse circumferential black mucosal discolouration in the distal oesophagus secondary to necrosis that may extend proximally to involve variable length of the oesophagus. One theory of pathogenesis is that the relatively low perfusion state in the distal areas of the oesophagus makes it susceptible to mucosal injury. We present a case of acute oesophageal necrosis in a 62year-old lady with history of alcoholic cirrhosis who presented with haematemesis and severe hypothermia, and was eventually found to have acute oesophageal necrosis.

  3. Duration of injury correlates with necrosis in caerulein-induced experimental acute pancreatitis: implications for pathophysiology.

    PubMed

    Jacob, Tony G; Raghav, Rahul; Kumar, Ajay; Garg, Pramod K; Roy, Tara S

    2014-06-01

    Pancreatic acinar cell necrosis is indicative of severe pancreatitis and the degree of necrosis is an index of its outcome. We studied whether the dose and duration of injury correlates with severity, particularly in terms of necrosis, in caerulein-induced acute pancreatitis (AP) in Swiss albino mice. In addition to control group 1 (G1), groups 2 and 3 received four injections of caerulein every hour but were sacrificed at five hours (G2) and nine hours (G3) respectively, and group 4 received eight injections and was sacrificed at nine hours (G4). The severity of pancreatitis was assessed histopathologically and biochemically. The histopathological scores of pancreatitis in groups 3 and 4 were significantly higher than in groups 1 and 2 (4 vs. 1, 4 vs. 2, 3 vs. 1, 3 vs. 2; P < 0.05). TUNEL-positive apoptotic cells were significantly higher in groups 2 and 3 compared with groups 1 and 4 (P < 0.05). Necrosis was significantly more in group 4 than other groups (37.49% (4.68) vs. 19.97% (1.60) in G2; 20.36% (1.56) in G3; P = 0.006 for G 2 vs. 4 and P = 0.019 for G 3 vs. 4). Electron microscopy revealed numerous autophagosomes in groups 2 and 3 and mitochondrial damage and necrosis in group 4. The pancreatic and pulmonary myeloperoxidase activity in group 4 was significantly higher than that in the other groups (P < 0.01). Hence, severity of pancreatitis is a function of the dose of injurious agent, while inflammation is both dose and duration dependent, which may also explain the wide spectrum of severity of AP seen in clinical practice.

  4. Abdominal compartment syndrome after endovascular repair for ruptured abdominal aortic aneurysm leads to acute intestinal necrosis

    PubMed Central

    Chen, Xiyang; Zhao, Jichun; Huang, Bin; Yuan, Ding; Yang, Yi; Ma, Yukui

    2016-01-01

    Abstract Introduction: Abdominal compartment syndrome (ACS) after endovascular repair (EVAR) of rupture abdominal aortic aneurysm (rAAA) is a rare emergency situation, which has a high mortality. However, the progression of ACS is rapid and the diagnosis is usually been delayed, which increase the difficulties in treatment and affect the prognosis. We describe a case of a sever complication (acute intestinal necrosis) resulting from ACS after endovascular repair of rAAA. Clinical Finding: An elderly man, 81 years old, complained a sudden lower abdominal and back pain without any predisposing cause. He had a history of hypertension for 20 years without any regular anti-hypertensive therapy. Physical Examination revealed that the blood pressure was 89/54 mmHg, pulse was 120/min, oxygen saturation was 91%. The abdominal ultrasound and the CTA (computed tomography angiography) scan revealed a rAAA. Emergency EVAR under general anesthesia was performed for this patient. Diagnosis: Fourteen hours after endovascular repair, sudden decreased of blood pressure (70/50 mmHg) and oxygen saturation (70%) was observed. ACS or bleeding of retroperitoneal space was diagnosed. Interventions: Abdominal laparotomy was immediately performed. ACS was verified and a severe complication (acute intestinal necrosis) was observed, intestinal resection was performed for this patient. Outcomes: Unfortunately, this patient died after operation because of multi-organ failure in a very short period, which is very rare regarding to this condition. Surgical pathology, diagnosis and management were discussed. Conclusion: ACS was occurred with a severe complication (acute intestinal necrosis) in a very short period, which is very rare regarding to this condition after EVAR, it reminds us the severe result of ACS and more methods to prevent it happened after surgical management. PMID:27893667

  5. Acute pancreatitis as a complication of trans-arterial chemoembolization of hepatocellular cancer—case report and review of literature

    PubMed Central

    Brown, Mathew; Agrawal, Sangeeta; Short, Robert F.

    2017-01-01

    Transarterial chemoembolization (TACE) is a therapeutic procedure often performed for hepatocellular carcinoma (HCC). Local complications, though generally uncommon, can arise from arterial ischemia and local cytotoxicity from the chemotherapeutic delivery. We present a case of acute pancreatitis as a rare complication of the TACE procedure along with a review of literature of this uncommon adverse effect. PMID:28280633

  6. Acute retinal necrosis complicating chicken pox in a healthy adult: a case report and review of literature.

    PubMed

    Tajunisah, Iqbal; Reddy, Sagili Chandrasekhara

    2007-01-01

    We report a case of unilateral acute retinal necrosis (ARN) with marked vitritis and retinal necrosis leading to retinal breaks following chicken pox successfully treated with intravenous acyclovir followed by oral acyclovir, orbital floor triamcinolone injections to contain the inflammation, and barrier laser therapy to secure the retinal breaks with good visual outcome. This case is unusual in its severity and the novel use orbital floor triamcinolone therapy to contain ARN inflammation.

  7. TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events.

    PubMed

    Cavassani, Karen A; Ishii, Makoto; Wen, Haitao; Schaller, Matthew A; Lincoln, Pamela M; Lukacs, Nicholas W; Hogaboam, Cory M; Kunkel, Steven L

    2008-10-27

    Ligands from dying cells are a source of Toll-like receptor (TLR) activating agents. Although TLR3 is known to respond to RNA from necrotic cells, the relative importance of this response in vivo during acute inflammatory processes has not been fully explored. We observed the involvement of TLR3 activation during experimental polymicrobial septic peritonitis and ischemic gut injury in the absence of an exogenous viral stimulus. In TLR3-deficient mice, increased chemokine/cytokine levels and neutrophil recruitment characterized the initial inflammatory responses in both injury models. However, the levels of inflammatory chemokines and tumor necrosis factor alpha quickly returned to baseline in tlr3(-/-) mice, and these mice were protected from the lethal effects of sustained inflammation. Macrophages from tlr3(-/-) mice responded normally to other TLR ligands but did not respond to RNA from necrotic neutrophils. Importantly, an immunoneutralizing antibody directed against TLR3 attenuated the generation of inflammatory chemokines evoked by byproducts from necrotic neutrophils cultured with wild-type macrophages. In vivo, anti-TLR3 antibody attenuated the tissue injury associated with gut ischemia and significantly decreased sepsis-induced mortality. Collectively, these data show that TLR3 is a regulator of the amplification of immune response and serves an endogenous sensor of necrosis, independent of viral activation.

  8. Tumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis

    PubMed Central

    Oliveira, Marina C.; Tavares, Luciana P.; Vago, Juliana P.; Batista, Nathália V.; Queiroz-Junior, Celso M.; Vieira, Angelica T.; Menezes, Gustavo B.; Sousa, Lirlândia P.; van de Loo, Fons A. J.; Teixeira, Mauro M.; Amaral, Flávio A.; Ferreira, Adaliene V. M.

    2016-01-01

    Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines. PMID:26742100

  9. Tumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis.

    PubMed

    Oliveira, Marina C; Tavares, Luciana P; Vago, Juliana P; Batista, Nathália V; Queiroz-Junior, Celso M; Vieira, Angelica T; Menezes, Gustavo B; Sousa, Lirlândia P; van de Loo, Fons A J; Teixeira, Mauro M; Amaral, Flávio A; Ferreira, Adaliene V M

    2016-01-01

    Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines.

  10. Liver necrosis induced by acute intraperitoneal ethanol administration in aged rats.

    PubMed

    Giavarotti, Leandro; D'Almeida, Vania; Giavarotti, Karin A S; Azzalis, Ligia A; Rodrigues, Luciano; Cravero, Amerys A M; Videla, Luis A; Koch, Osvaldo R; Junqueira, Virginia B C

    2002-03-01

    It is generally agreed that the deleterious pathophysiological effects of ethanol are caused, at least partially by an increase in free radical production. However, little attention has been directed to the effects of ethanol upon elderly organisms. Male Wistar rats at ages 3, 6, 12, 18 and 24 months were treated either with a single i.p. dose of 35% ethanol (v/v) at 3 g ethanol/kg body weight or an isovolumetric amount of 0.9% saline solution. We then assessed the plasma levels of transaminases and hepatic levels of oxidative stress-related parameters, followed by liver histological evaluation. The younger rats (3 months old) were not affected by the treatment with ethanol with respect to any of the studied parameters except for a lowering of total hepatic GSH and an increase in hepatic thiobarbituric acid reactants (TBARS) formation, while animals older than 3 months were increasingly more affected by the treatment. Acute ethanol treatment elicited the similar responses to those in the 3 months-old group, plus a decrease in the hepatic and plasma levels of beta-carotene and the plasma level of alpha-tocopherol, as well as an increase in the activity of plasma transaminases. In the 12,18 and 24 months old groups, there was increasing liver necrosis. These findings suggest that liver damage induced by acute ethanol administration in elderly rats may involve a lack of antioxidants.

  11. Determination of the infectious nature of the agent of acute hepatopancreatic necrosis syndrome affecting penaeid shrimp.

    PubMed

    Tran, Loc; Nunan, Linda; Redman, Rita M; Mohney, Leone L; Pantoja, Carlos R; Fitzsimmons, Kevin; Lightner, Donald V

    2013-07-09

    A new emerging disease in shrimp, first reported in 2009, was initially named early mortality syndrome (EMS). In 2011, a more descriptive name for the acute phase of the disease was proposed as acute hepatopancreatic necrosis syndrome (AHPNS). Affecting both Pacific white shrimp Penaeus vannamei and black tiger shrimp P. monodon, the disease has caused significant losses in Southeast Asian shrimp farms. AHPNS was first classified as idiopathic because no specific causative agent had been identified. However, in early 2013, the Aquaculture Pathology Laboratory at the University of Arizona was able to isolate the causative agent of AHPNS in pure culture. Immersion challenge tests were employed for infectivity studies, which induced 100% mortality with typical AHPNS pathology to experimental shrimp exposed to the pathogenic agent. Subsequent histological analyses showed that AHPNS lesions were experimentally induced in the laboratory and were identical to those found in AHPNS-infected shrimp samples collected from the endemic areas. Bacterial isolation from the experimentally infected shrimp enabled recovery of the same bacterial colony type found in field samples. In 3 separate immersion tests, using the recovered isolate from the AHPNS-positive shrimp, the same AHPNS pathology was reproduced in experimental shrimp with consistent results. Hence, AHPNS has a bacterial etiology and Koch's Postulates have been satisfied in laboratory challenge studies with the isolate, which has been identified as a member of the Vibrio harveyi clade, most closely related to V. parahemolyticus.

  12. Renal cortical necrosis and acute kidney injury associated with Plasmodium vivax: a neglected human malaria parasite.

    PubMed

    Kute, Vivek B; Vanikar, Aruna V; Ghuge, Pramod P; Goswami, Jitendra G; Patel, Mohan P; Patel, Himanshu V; Gumber, Manoj R; Shah, Pankaj R; Trivedi, Hargovind L

    2012-11-01

    Plasmodium vivax is causing increasingly more cases of severe malaria worldwide. There is an urgent need to reexamine the clinical spectrum and burden of P. vivax so that adequate control measures can be implemented against this emerging but neglected disease. Herein, we report a case of renal acute cortical necrosis and acute kidney injury (AKI) associated with P. vivax monoinfection. Her initial serum creatinine was 7.3 mg/dL on admission. Modification of Diet in Renal Disease (MDRD) Study glomerular filtration rate (GFR) value was 7 mL/min/1.73 m(2) (normal kidney function-GFR above 90 mL/min/1.73 m(2) and no proteinuria). On follow-up, 5 months later, her SCr. was 2.43 mg/dl with no proteinuria. MDRD GFR value was 24 mL/min/1.73 m(2) suggesting severe chronic kidney disease (CKD; GFR less than 60 or kidney damage for at least 3 months), stage 4. Our case report highlights the fact that P. vivax malaria is benign by name but not always by nature. AKI associated with P. vivax malaria can lead to CKD. Further studies are needed to determine why P. vivax infections are becoming more severe.

  13. Changing picture of renal cortical necrosis in acute kidney injury in developing country

    PubMed Central

    Prakash, Jai; Singh, Vijay Pratap

    2015-01-01

    Renal cortical necrosis (RCN) is characterized by patchy or diffuse ischemic destruction of all the elements of renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. In addition, direct endothelial injury particularly in setting of sepsis, eclampsia, haemolytic uremic syndrome (HUS) and snake bite may lead to endovascular thrombosis with subsequent renal ischemia. Progression to end stage renal disease is a rule in diffuse cortical necrosis. It is a rare cause of acute kidney injury (AKI) in developed countries with frequency of 1.9%-2% of all patients with AKI. In contrast, RCN incidence is higher in developing countries ranging between 6%-7% of all causes of AKI. Obstetric complications (septic abortion, puerperal sepsis, abruptio placentae, postpartum haemorrhage and eclampsia) are the main (60%-70%) causes of RCN in developing countries. The remaining 30%-40% cases of RCN are caused by non-obstetrical causes, mostly due to sepsis and HUS. The incidence of RCN ranges from 10% to 30% of all cases of obstetric AKI compared with only 5% in non-gravid patients. In the developed countries, RCN accounts for 2% of all cases of AKI in adults and more than 20% of AKI during the third trimester of pregnancy. The reported incidence of RCN in obstetrical AKI varies between 18%-42.8% in different Indian studies. However, the overall incidence of RCN in pregnancy related AKI has decreased from 20%-30% to 5% in the past two decades in India. Currently RCN accounts for 3% of all causes of AKI. The incidence of RCN in obstetrical AKI was 1.44% in our recent study. HUS is most common cause of RCN in non-obstetrical group, while puerperal sepsis is leading cause of RCN in obstetric group. Because of the catastrophic sequelae of RCN, its prevention and aggressive management should always be important for the better renal outcome and prognosis of the patients. PMID:26558184

  14. Changing picture of renal cortical necrosis in acute kidney injury in developing country.

    PubMed

    Prakash, Jai; Singh, Vijay Pratap

    2015-11-06

    Renal cortical necrosis (RCN) is characterized by patchy or diffuse ischemic destruction of all the elements of renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. In addition, direct endothelial injury particularly in setting of sepsis, eclampsia, haemolytic uremic syndrome (HUS) and snake bite may lead to endovascular thrombosis with subsequent renal ischemia. Progression to end stage renal disease is a rule in diffuse cortical necrosis. It is a rare cause of acute kidney injury (AKI) in developed countries with frequency of 1.9%-2% of all patients with AKI. In contrast, RCN incidence is higher in developing countries ranging between 6%-7% of all causes of AKI. Obstetric complications (septic abortion, puerperal sepsis, abruptio placentae, postpartum haemorrhage and eclampsia) are the main (60%-70%) causes of RCN in developing countries. The remaining 30%-40% cases of RCN are caused by non-obstetrical causes, mostly due to sepsis and HUS. The incidence of RCN ranges from 10% to 30% of all cases of obstetric AKI compared with only 5% in non-gravid patients. In the developed countries, RCN accounts for 2% of all cases of AKI in adults and more than 20% of AKI during the third trimester of pregnancy. The reported incidence of RCN in obstetrical AKI varies between 18%-42.8% in different Indian studies. However, the overall incidence of RCN in pregnancy related AKI has decreased from 20%-30% to 5% in the past two decades in India. Currently RCN accounts for 3% of all causes of AKI. The incidence of RCN in obstetrical AKI was 1.44% in our recent study. HUS is most common cause of RCN in non-obstetrical group, while puerperal sepsis is leading cause of RCN in obstetric group. Because of the catastrophic sequelae of RCN, its prevention and aggressive management should always be important for the better renal outcome and prognosis of the patients.

  15. Novel Synthetic Biscoumarins Target Tumor Necrosis Factor-α in Hepatocellular Carcinoma in Vitro and in Vivo*

    PubMed Central

    Keerthy, Hosadurga Kumar; Mohan, Chakrabhavi Dhananjaya; Siveen, Kodappully Sivaraman; Fuchs, Julian E.; Rangappa, Shobith; Sundaram, Mahalingam S.; Li, Feng; Girish, Kesturu S.; Sethi, Gautam; Basappa; Bender, Andreas; Rangappa, Kanchugarakoppal Subbegowda

    2014-01-01

    TNF is a pleotropic cytokine known to be involved in the progression of several pro-inflammatory disorders. Many therapeutic agents have been designed to counteract the effect of TNF in rheumatoid arthritis as well as a number of cancers. In the present study we have synthesized and evaluated the anti-cancer activity of novel biscoumarins in vitro and in vivo. Among new compounds, BIHC was found to be the most cytotoxic agent against the HepG2 cell line while exhibiting less toxicity toward normal hepatocytes. Furthermore, BIHC inhibited the proliferation of various hepatocellular carcinoma (HCC) cells in a dose- and time-dependent manner. Subsequently, using in silico target prediction, BIHC was predicted as a TNF blocker. Experimental validation was able to confirm this hypothesis, where BIHC could significantly inhibit the recombinant mouse TNF-α binding to its antibody with an IC50 of 16.5 μm. Furthermore, in silico docking suggested a binding mode of BIHC similar to a ligand known to disrupt the native, trimeric structure of TNF, and also validated with molecular dynamics simulations. Moreover, we have demonstrated the down-regulation of p65 phosphorylation and other NF-κB-regulated gene products upon BIHC treatment, and on the phenotypic level the compound shows inhibition of CXCL12-induced invasion of HepG2 cells. Also, we demonstrate that BIHC inhibits infiltration of macrophages to the peritoneal cavity and suppresses the activity of TNF-α in vivo in mice primed with thioglycollate broth and lipopolysaccharide. We comprehensively validated the TNF-α inhibitory efficacy of BIHC in an inflammatory bowel disease mice model. PMID:25231984

  16. Acute Cadmium Fume Poisoning: Five Cases with one Death from Renal Necrosis

    PubMed Central

    Beton, D. C.; Andrews, G. S.; Davies, H. J.; Howells, Leonard; Smith, G. F.

    1966-01-01

    This paper describes the accidental poisoning of five workers by cadmium fume. The men were dismantling a frame of girders in a confined space by cutting bolts with an oxyacetylene burner. They were unaware at the time that the bolts were cadmium-plated or that this presented a serious industrial hazard. The paper sets out to give an appreciation of acute cadmium poisoning, the characteristics and uses of cadmium, and a review of the literature. The clinical picture of these cases is described, with the pathology of the fatal case which showed severe pulmonary oedema, alveolar metaplasia of the lung, and bilateral cortical necrosis of the kidneys. The lungs contained 0·25 g. cadmium oxide (CdO) per 100 g. wet specimen. An attempted estimation of the fatal dose of CdO fume is made. From the post-mortem findings, using an assumption that 11% of inhaled CdO will be retained in the lungs, approximately 51·7 mg. CdO fume must have been inhaled by the fatal case. As he worked for five hours with a probable ventilatory rate of 20 l./min. the concentration of CdO in the air breathed would be of the order of 8·6 mg./m.3. An estimation of the dose from a study of the working conditions proved unsatisfactory due to certain variables listed in the text. Images PMID:5928153

  17. Prognostic significance of ligands belonging to tumour necrosis factor superfamily in acute lymphoblastic leukaemia.

    PubMed

    Bolkun, L; Lemancewicz, D; Jablonska, E; Szumowska, A; Bolkun-Skornicka, U; Moniuszko, M; Dzieciol, J; Kloczko, J

    2015-03-01

    Altered activities of ligands belonging to tumour necrosis factor (TNF) superfamily, namely B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and apoptosis inducing ligand (TRAIL) were demonstrated in several haematological diseases including acute lymphoblastic leukaemia (ALL). BAFF, APRIL and TRAIL provide crucial survival signals to immature, naive and activated B cells. These ligands are capable of activating a broad spectrum of intracellular signalling cascades that can either induce apoptosis or protect from programmed cell death. BAFF and APRIL, which can directly activate the NF-κB pathway, have been identified as crucial survival factors for ALL cells. Here, we have analyzed serum BAFF, APRIL and TRAIL concentrations in 48 patients with newly diagnosed ALL and 44 healthy volunteers. The levels of APRIL and BAFF were significantly higher in ALL patients as compared to healthy volunteers. In contrast, concentrations of TRAIL were significantly lower in ALL patients. Moreover, following induction, the levels of APRIL, but not BAFF or TRAIL, were significantly lower in a group of patients with complete remission (CR) as compared to non-respondent (NR) ALL patients. Furthermore, we demonstrated statistically significant differences in concentrations of APRIL between CR MRD-negative and CR, MRD-positive ALL patients. Notably detection of higher concentrations of APRIL was associated with shorter leukaemia-free survival and overall survival. Altogether, our data indicate that APRIL can play an important role in the pathogenesis of ALL and the measurement of APRIL levels can improve prognostication in ALL patients.

  18. Acute retinal necrosis in the United Kingdom: results of a prospective surveillance study

    PubMed Central

    Cochrane, T F; Silvestri, G; McDowell, C; Foot, B; McAvoy, C E

    2012-01-01

    Background To determine the incidence of acute retinal necrosis (ARN) in the United Kingdom and to describe the demographics, management, and visual outcome in these patients. Methods This was a prospective study carried out by the British Ophthalmological Surveillance Unit (BOSU) between September 2007 and October 2008. Initial and 6-month questionnaires were sent to UK ophthalmologists who reported cases of ARN via the monthly BOSU report card system. Results In all, 45 confirmed cases (52 eyes) of ARN were reported in the 14-month study period, giving a minimum incidence of 0.63 cases per million population per year. There were 20 females and 25 males. Age ranged from 10 to 94 years. Eight patients had a history of herpetic CNS disease. Aqueous sampling was carried out in 13 patients, vitreous in 27, and cerebrospinal fluid (CSF) in 4. Varicella-zoster virus followed by herpes simplex were the most common causative agents. Treatment in 76% of the cases was with intravenous antivirals; however, 24% received only oral antivirals. In all, 47% of patients had intravitreal antiviral therapy. Visual outcome at 6 months was <6/60 in 48% of the affected eyes. Conclusion The minimum incidence of ARN in the UK is 0.63 cases per million. Patients with a history of herpetic CNS disease should be warned to immediately report any visual symptoms. There is increased use of oral and intravitreal antivirals in initial treatment. PMID:22281865

  19. Acute Retinal Necrosis Associated with Epstein-Barr Virus in a Patient Undergoing Immunosuppressive Therapy

    PubMed Central

    Oe, Chiaki; Hiraoka, Miki; Tanaka, Sachie; Ohguro, Hiroshi

    2016-01-01

    Acute retinal necrosis (ARN) is a rapidly progressive and severe retinitis resulting in a poor visual outcome. Infections caused by herpes viruses such as herpes simplex virus (HSV) types 1 and 2 or the varicella zoster virus (VZV) are known to be implicated in the development of ARN. In the present study, an 80-year-old female with ARN was examined. She had been affected with rheumatoid arthritis and had taken methotrexate for over 10 years. Her right eye showed clinical features of ARN, and her left eye showed mild retinitis. The genomic DNA in the aqueous humor and vitreous fluid from her right eye were analyzed by a comprehensive polymerase chain reaction (PCR) assay to screen infectious pathogens including viruses. The Epstein-Barr virus (EBV) was detected from both specimens, but neither HSV or VZV nor cytomegalovirus was detected. She underwent intraocular surgery following systemic corticosteroid and acyclovir applications. However, although the retinitis of her right eye was extinguished, the final visual outcome was blindness due to optic nerve atrophy. There are few reports indicating that EBV is associated with ARN development. The present findings suggest that EBV alone can be the causative agent of ARN. PMID:27194989

  20. Acute Respiratory Failure Caused by Hepatopulmonary Fistula in a Patient with Hepatocellular Carcinoma

    PubMed Central

    Lee, Jungsil; Kim, Yoon Jun; Kim, Hyung-Jun; Kim, Jee-Min; Kim, Young-Chan

    2016-01-01

    A 59-year-old man presented with acute dyspnea following sudden productive cough and expectoration of a full cup of "blood-tinged" sputum. He had been diagnosed with hepatitis B virus–related hepatocellular carcinoma and had received transarterial chemoembolization 5 years ago for a 20-cm hepatic mass; he denied any history of hematemesis and the last esophagogastroduodenoscopy from a year ago showed absence of varix. Chest computed tomography (CT) with angiography showed new appearance of right basal lung consolidation but no bleeding focus. Despite the use of systemic antibiotics, the patient developed respiratory failure on day 7 of hospitalization. After intubation, a massive amount of brown sputum with anchovy-paste-like consistency was suctioned via the endotracheal tube. Bronchoscopic toileting was performed and the patient was extubated. In the ward, he continued to expectorate the brown sputum. On day 25 of hospitalization, a repeat CT scan showed simultaneous disappearance of the pneumonic consolidation and the necrotic fluid within the hepatic mass, suggesting the presence of a fistula. He has continued to receive systemic antibiotics, sorafenib, and entecavir, and follow up by respiratory and hepato-oncology specialists. PMID:27433178

  1. An insight into the hepatocellular death induced by amphetamines, individually and in combination: the involvement of necrosis and apoptosis.

    PubMed

    Dias da Silva, Diana; Carmo, Helena; Lynch, Adam; Silva, Elisabete

    2013-12-01

    The liver is a vulnerable target for amphetamine toxicity, but the mechanisms involved in the drug's hepatotoxicity remain poorly understood. The purpose of the current research was to characterize the mode of death elicited by four amphetamines and to evaluate whether their combination triggered similar mechanisms in immortalized human HepG2 cells. The obtained data revealed a time- and temperature-dependent mortality of HepG2 cells exposed to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy; 1.3 mM), methamphetamine (3 mM), 4-methylthioamphetamine (0.5 mM) and D-amphetamine (1.7 mM), alone or combined (1.6 mM mixture). At physiological temperature (37 °C), 24-h exposures caused HepG2 death preferentially by apoptosis, while a rise to 40.5 °C favoured necrosis. ATP levels remained unaltered when the drugs where tested at normothermia, but incubation at 40.5 °C provoked marked ATP depletion for all treatments. Further investigations on the apoptotic mechanisms triggered by the drugs (alone or combined) showed a decline in BCL-2 and BCL- XL mRNA levels, with concurrent upregulation of BAX, BIM, PUMA and BID genes. Elevation of Bax, cleaved Bid, Puma, Bak and Bim protein levels was also seen. To the best of our knowledge, Puma, Bim and Bak have never been linked with the toxicity induced by amphetamines. Time-dependent caspase-3/-7 activation, but not mitochondrial membrane potential (∆ψm) disruption, also mediated amphetamine-induced apoptosis. The cell dismantling was confirmed by poly(ADP-ribose)polymerase proteolysis. Overall, for all evaluated parameters, no relevant differences were detected between individual amphetamines and the mixture (all tested at equieffective cytotoxic concentrations), suggesting that the mode of action of the amphetamines in combination does not deviate from the mode of action of the drugs individually, when eliciting HepG2 cell death.

  2. Acute retinal necrosis (ARN) in the context of neonatal HSV-2 exposure and subconjunctival dexamethasone: case report and literature review.

    PubMed

    McGrath, Lindsay; Woods, Marion; Lee, Lawrence; Conrad, Diana

    2013-01-01

    HSV-2 is an important cause of the acute retinal necrosis (ARN) syndrome in younger patients. We describe an atypical case of HSV-2 ARN in the context of neonatal exposure and subconjunctival steroid injection. Clinicians should be aware of the association of neonatal or congenital exposure to HSV-2 as a risk factor for this disease because early treatment may improve outcome and/or avoid involvement of both eyes.

  3. EVALUATION OF THE RENAL TOXICITY OF HEME PROTEINS AND THEIR DERIVATIVES: A ROLE IN THE GENESIS OF ACUTE TUBULE NECROSIS

    PubMed Central

    Braun, Sheldon R.; Weiss, Frederick R.; Keller, Allen I.; Ciccone, J. Richard; Preuss, Harry G.

    1970-01-01

    This investigation studies the toxicity of heme proteins and/or their break-down products on renal function. Heme proteinemia precedes acute tubule necrosis at a frequency great enough to suggest a causal relationship between the two events. Physiological and metabolic functions of kidney slices are investigated in several models of acute tubule necrosis. Organic acid and organic base transport is depressed earliest. These alterations in tubule function cannot be explained by ischemia or obstruction alone. Heme proteinemia in rats or incubation of renal slices in medium containing heme proteins yields several interesting observations. Neither in vivo or in vitro do hemoglobin and methemoglobin alone produce a depressive effect on the transport systems studied. However, parallel to many clinical situations, when such secondary insults as hypoxia and elevated ammonia concentrations are included in the experimental design, transport functions are depressed. Ferrihemate, a molecule smaller than hemoglobin or methemoglobin, depresses transport function without secondary insults. From these studies it is concluded that heme proteins play a role in tubule dysfunction seen in acute tubule necrosis. A model is presented that collates these data with other factors known to play a part in the pathogenesis of this renal syndrome. PMID:5413325

  4. [Minor bcr/abl positive acute lymphoblastic leukemia preceded by knee joint pain due to bone marrow necrosis].

    PubMed

    Sato, Kazuya; Mori, Masaki; Meguro, Akiko; Miyoshi, Takuji; Nagai, Tadashi; Muroi, Kazuo; Komatsu, Norio; Ozawa, Keiya

    2004-11-01

    A 16-year-old male was referred to our hospital in April 2003 due to severe knee joint pain from five months previously. Lymphoblasts were identified in his peripheral blood, resulting in a diagnosis of acute lymphoblastic leukemia (ALL). Bone marrow examination revealed massive necrosis with clusters of lymphoblasts and the bcr/abl fusion gene. Magnetic resonance imaging (MRI) of the knee joint showed low signal intensity on T1-weighted images, and peripheral rim enhancement on Gd-DTPA enhanced fat suppression images, which was compatible with bone marrow necrosis. After the patient achieved complete remission (CR), the knee joint pain has disappeared. He was treated with an allogeneic bone marrow transplantation (BMT) from an HLA-identical unrelated donor and has been in CR for 26 months after the diagnosis of ALL. In the knee joint, the replacement of fatty marrow after BMT has been confirmed with MRI. Hematological malignancies including ALL should be considered in the cases of bone marrow necrosis and adequate treatment may improve necrosis.

  5. Shock, acute disseminated intravascular coagulation, and microvascular thrombosis: is 'shock liver' the unrecognized provocateur of ischemic limb necrosis?

    PubMed

    Warkentin, T E; Pai, M

    2016-02-01

    For unknown reasons, a small minority of critically ill patients with septic or cardiogenic shock, multiorgan failure, and disseminated intravascular coagulation develop symmetrical acral (distal extremity) limb loss due to microvascular thrombosis ('limb gangrene with pulses'). Case reports have described preceding 'shock liver' in some critically ill patients who developed such a picture of ischemic limb necrosis. This suggests that profoundly disturbed procoagulant-anticoagulant balance featuring uncontrolled generation of thrombin-resulting from failure of the protein C and antithrombin natural anticoagulant systems due to insufficient hepatic synthesis of these crucial proteins-could explain the microvascular thrombosis and associated limb loss. We hypothesize that shock liver is the key predisposing risk factor underlying ischemic limb necrosis in the majority of patients who develop this complication in the setting of acute disseminated intravascular coagulation complicating septic or cardiogenic shock. As shock liver precedes onset of limb ischemia by several days, therapeutic intervention may be possible.

  6. Myocardial uptake of indium-111-labeled antimyosin in acute subendocardial infarction: Clinical, histochemical, and autoradiographic correlation of myocardial necrosis

    SciTech Connect

    Hendel, R.C.; McSherry, B.A.; Leppo, J.A. )

    1990-11-01

    Indium-111-labeled antimyosin has been utilized in the diagnosis and localization of acute transmural myocardial infarction. The present report describes a patient who presented with a massive subendocardial infarction. Two days after the injection of antimyosin, the patient's clinical status markedly deteriorated and he expired. Postmortem examination demonstrated severe three-vessel coronary artery disease with extensive myocyte death in the endocardium. Autoradiography and histochemical staining of the prosected heart demonstrated high correlation for myocardial necrosis and corresponded to clinical evidence for diffuse subendocardial infarction.

  7. Increased taurine in pre-weaned juvenile mdx mice greatly reduces the acute onset of myofibre necrosis and dystropathology and prevents inflammation

    PubMed Central

    Terrill, Jessica R.; Grounds, Miranda D; Arthur, Peter G.

    2016-01-01

    Background: The mdx mouse model for the fatal muscle wasting disease Duchenne Muscular Dystrophy (DMD) shows a very mild pathology once growth has ceased, with low levels of myofibre necrosis in adults. However, from about 3 weeks of post-natal age, muscles of juvenile mdx mice undergo an acute bout of severe necrosis and inflammation: this subsequently decreases and stabilises to lower adult levels by about 6 weeks of age. Prior to the onset of this severe dystropathology, we have shown that mdx mice are deficient in the amino acid taurine (potentially due to weaning), and we propose that this exacerbates myofibre necrosis and inflammation in juvenile mdx mice. Objectives: The purpose of this study was to increase taurine availability to pre-weaned juvenile mdx mice (from 14 days of age), to evaluate the impact on levels of myofibre necrosis and inflammation (at 22 days) during the acute period of severe dystropathology. Results: Untreated 22 day old mdx muscle was not deficient in taurine, with similar levels to normal C57 control muscle. However taurine treatment, which increased the taurine content of young dystrophic muscle (by 40%), greatly reduced myofibre necrosis (by 75%) and prevented significant increases in 3 markers of inflammation. Conclusion: Taurine was very effective at preventing the acute phase of muscle damage that normally results in myofibre necrosis and inflammation in juvenile mdx mice, supporting continued research into the use of taurine as a therapeutic intervention for protecting growing muscles of young DMD boys PMID:27679740

  8. Evidence for a protective role of tumor necrosis factor in the acute phase of Trypanosoma cruzi infection in mice.

    PubMed Central

    Lima, E C; Garcia, I; Vicentelli, M H; Vassalli, P; Minoprio, P

    1997-01-01

    A possible role for tumor necrosis factor (TNF) alpha during Trypanosoma cruzi infection was explored by using transgenic mice expressing in blood high levels of a soluble TNFR1-FcIgG3 fusion protein, which neutralizes the effects of TNF in vivo. Nontransgenic littermates were used as controls. The transgenic mice showed high susceptibility to T. cruzi infection. Inocula sublethal for control mice resulted in over 80% mortality associated with higher levels of parasites in the blood. In histological sections of the hearts of transgenic mice, large parasitic clusters without inflammatory cell infiltrates around the parasites were seen, while smaller parasitic clusters associated with leukocytes were seen in control mice. No difference in specific antibody response or lymphocyte composition of the spleen was found between transgenic and control mice, although the unresponsiveness of spleen cells to concanavalin A stimulation in vitro, typical of the acute phase of T. cruzi infection, was less pronounced in transgenic mice. Infected transgenic mice produced higher levels of gamma interferon than did control mice. These results confirm that TNF is involved in mechanisms leading to parasite clearance and protection from death in the acute phase of T. cruzi infection. More importantly, the data reveal that TNF is necessary for the establishment of effective tissue inflammation and parasite load control in acute experimental Chagas' disease myocarditis. PMID:9009297

  9. Acute retinal necrosis results in low vision in a young patient with a history of herpes simplex virus encephalitis.

    PubMed

    Shahi, Sanjeet K

    2016-08-31

    Acute retinal necrosis (ARN), secondary to herpes simplex encephalitis, is a rare syndrome that can present in healthy individuals, as well as immuno-compromised patients. Most cases are caused by a secondary infection from the herpes virus family, with varicella zoster virus being the leading cause of this syndrome. Potential symptoms include blurry vision, floaters, ocular pain and photophobia. Ocular findings may consist of severe uveitis, retinal vasculitis, retinal necrosis, papillitis and retinal detachment. Clinical manifestations of this disease may include increased intraocular pressure, optic disc oedema, optic neuropathy and sheathed retinal arterioles. A complete work up is essential to rule out cytomegalovirus retinitis, herpes simplex encephalitis, herpes virus, syphilis, posterior uveitis and other conditions. Depending on the severity of the disease, the treatment options consist of anticoagulation therapy, cycloplegia, intravenous acyclovir, systemic steroids, prophylactic laser photocoagulation and pars plana vitrectomy with silicon oil for retinal detachment. An extensive history and clinical examination is crucial in making the correct diagnosis. Also, it is very important to be aware of low vision needs and refer the patients, if expressing any sort of functional issues with completing daily living skills, especially reading. In this article, we report one case of unilateral ARN 20 years after herpetic encephalitis.

  10. Detecting Acute Myocardial Infarction by Diffusion-Weighted versus T2-Weighted Imaging and Myocardial Necrosis Markers.

    PubMed

    Jin, Jiyang; Chen, Min; Li, Yongjun; Wang, YaLing; Zhang, Shijun; Wang, Zhen; Wang, Lin; Ju, Shenghong

    2016-10-01

    We used a porcine model of acute myocardial infarction to study the signal evolution of ischemic myocardium on diffusion-weighted magnetic resonance images (DWI). Eight Chinese miniature pigs underwent percutaneous left anterior descending or left circumflex coronary artery occlusion for 90 minutes followed by reperfusion, which induced acute myocardial infarction. We used DWI preprocedurally and hourly for 4 hours postprocedurally. We acquired turbo inversion recovery magnitude T2-weighted images (TIRM T2WI) and late gadolinium enhancement images from the DWI slices. We measured the serum myocardial necrosis markers myoglobin, creatine kinase-MB isoenzyme, and cardiac troponin I at the same time points as the magnetic resonance scanning. We used histochemical staining to confirm injury. All images were analyzed qualitatively. Contrast-to-noise ratio (the contrast between infarcted and healthy myocardium) and relative signal index were used in quantitative image analysis. We found that DWI identified myocardial signal abnormity early (<4 hr) after acute myocardial infarction and identified the infarct-related high signal more often than did TIRM T2WI: 7 of 8 pigs (87.5%) versus 3 of 8 (37.5%) (P=0.046). Quantitative image analysis yielded a significant difference in contrast-to-noise ratio and relative signal index between infarcted and normal myocardium on DWI. However, within 4 hours after infarction, the serologic myocardial injury markers were not significantly positive. We conclude that DWI can be used to detect myocardial signal abnormalities early after acute myocardial infarction-identifying the infarction earlier than TIRM T2WI and widely used clinical serologic biomarkers.

  11. Detecting Acute Myocardial Infarction by Diffusion-Weighted versus T2-Weighted Imaging and Myocardial Necrosis Markers

    PubMed Central

    Chen, Min; Li, Yongjun; Wang, YaLing; Zhang, Shijun; Wang, Zhen; Wang, Lin; Ju, Shenghong

    2016-01-01

    We used a porcine model of acute myocardial infarction to study the signal evolution of ischemic myocardium on diffusion-weighted magnetic resonance images (DWI). Eight Chinese miniature pigs underwent percutaneous left anterior descending or left circumflex coronary artery occlusion for 90 minutes followed by reperfusion, which induced acute myocardial infarction. We used DWI preprocedurally and hourly for 4 hours postprocedurally. We acquired turbo inversion recovery magnitude T2-weighted images (TIRM T2WI) and late gadolinium enhancement images from the DWI slices. We measured the serum myocardial necrosis markers myoglobin, creatine kinase-MB isoenzyme, and cardiac troponin I at the same time points as the magnetic resonance scanning. We used histochemical staining to confirm injury. All images were analyzed qualitatively. Contrast-to-noise ratio (the contrast between infarcted and healthy myocardium) and relative signal index were used in quantitative image analysis. We found that DWI identified myocardial signal abnormity early (<4 hr) after acute myocardial infarction and identified the infarct-related high signal more often than did TIRM T2WI: 7 of 8 pigs (87.5%) versus 3 of 8 (37.5%) (P=0.046). Quantitative image analysis yielded a significant difference in contrast-to-noise ratio and relative signal index between infarcted and normal myocardium on DWI. However, within 4 hours after infarction, the serologic myocardial injury markers were not significantly positive. We conclude that DWI can be used to detect myocardial signal abnormalities early after acute myocardial infarction—identifying the infarction earlier than TIRM T2WI and widely used clinical serologic biomarkers. PMID:27777517

  12. A diagnostic dilemma: acute abdomen presenting as segmental arterial mediolysis masked by a ruptured hepatocellular carcinoma.

    PubMed

    Liao, Chen-Yi; Kuo, Wu-Hsien; Huang, En-Hua; Hsieh, An-Tie; Le, Ching-Chang; Tsai, Chi-Chang; Hsueh, Chao-Wen

    2015-07-10

    A 65-year-old male was brought to our hospital with right upper abdominal fullness sensation and recent body weight loss of about 3 kg. The patient had developed episodes of melena following progressive abdominal muscular guarding and drop of haemoglobin level to 6.3 g/dL. An abdominal computed tomography scan disclosed a ruptured hepatocellular cell carcinoma. A segmental arterial mediolysis was found on the superior mesenteric artery in the process of repairing the ruptured right hepatic artery with the assistance of angiography. Transarterial embolization was carried out and permanent haemostasis was achieved.

  13. One compound of saponins from Disocorea zingiberensis protected against experimental acute pancreatitis by preventing mitochondria-mediated necrosis

    PubMed Central

    Zhang, Rui; Wen, Li; Shen, Yan; Shi, Na; Xing, Zhihua; Xia, Qing; Niu, Hai; Huang, Wen

    2016-01-01

    Acute pancreatitis (AP) is a painful inflammatory disorder of the exocrine pancreas, ranking as the most common gastrointestinal reasons for hospitalization with no specific therapy currently. Diosgenyl saponins extracted from natural products and diosgenin or its derivatives have been shown to exert anti-inflammatory effects in various diseases. However, the therapeutic effects of diosgenyl saponins from Dioscorea zingiberensis C. H. Wright in AP have not yet been determined. Five compounds were extracted and screened for taurocholate-induced necrosis in mouse pancreatic acinar cells. Particularly, 26-O-β-d-glucopyranosyl-3β, 22α, 26-trihydroxy-25(R)-furosta-5-en-3-O-[α-L-rhamnopyranosyl-(1 → 4)]-β-d-glucopyranoside (compound 1) exhibited the best protective effects with no toxicity observed. Next, we showed compound 1 concentration-dependently inhibited necrotic cell death pathway activation and 2.5 mM compound 1 also prevented the loss of mitochondrial membrane potential, adenosine triphosphate production, and reactive oxygen species generation in mouse pancreatic acinar cells. Finally, we showed compound 1 protected against three clinically representative murine models of AP and significantly improved pancreatitis-associated acute lung injury. These data provide in vitro and in vivo evidence that one compound of diosgenyl saponins can be potential treatment for AP. This study suggests natural saponins may serve as fruitful sources for exploring/identifying potential therapies for inflammatory diseases. PMID:27779235

  14. Tubular Peroxiredoxin 3 as a Predictor of Renal Recovery from Acute Tubular Necrosis in Patients with Chronic Kidney Disease.

    PubMed

    Wu, Chia-Lin; Su, Tzu-Cheng; Chang, Chia-Chu; Kor, Chew-Teng; Chang, Chung-Ho; Yang, Tao-Hsiang; Chiu, Ping-Fang; Tarng, Der-Cherng

    2017-02-27

    Peroxiredoxin 3 (PRX3) is a mitochondrial antioxidant that regulates apoptosis in various cancers. However, whether tubular PRX3 predicts recovery of renal function following acute kidney injury (AKI) remains unknown. This retrospective cohort study included 54 hospitalized patients who had AKI with biopsy-proven acute tubular necrosis (ATN). The study endpoint was renal function recovery within 6 months. Of the 54 enrolled patients, 25 (46.3%) had pre-existing chronic kidney disease (CKD) and 33 (61%) recovered renal function. Tubular PRX3 expression was higher in patients with ATN than in those without renal function recovery. The level of tubular but not glomerular PRX3 expression predicted renal function recovery from AKI (AUROC = 0.76). In multivariate Cox regression analysis, high PRX3 expression was independently associated with a higher probability of renal function recovery (adjusted hazard ratio = 8.99; 95% CI 1.13-71.52, P = 0.04). Furthermore, the discriminative ability of the clinical model for AKI recovery was improved by adding tubular PRX3. High tubular PRX3 expression was associated with a higher probability of renal function recovery from ATN. Therefore, tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD.

  15. Tubular Peroxiredoxin 3 as a Predictor of Renal Recovery from Acute Tubular Necrosis in Patients with Chronic Kidney Disease

    PubMed Central

    Wu, Chia-Lin; Su, Tzu-Cheng; Chang, Chia-Chu; Kor, Chew-Teng; Chang, Chung-Ho; Yang, Tao-Hsiang; Chiu, Ping-Fang; Tarng, Der-Cherng

    2017-01-01

    Peroxiredoxin 3 (PRX3) is a mitochondrial antioxidant that regulates apoptosis in various cancers. However, whether tubular PRX3 predicts recovery of renal function following acute kidney injury (AKI) remains unknown. This retrospective cohort study included 54 hospitalized patients who had AKI with biopsy-proven acute tubular necrosis (ATN). The study endpoint was renal function recovery within 6 months. Of the 54 enrolled patients, 25 (46.3%) had pre-existing chronic kidney disease (CKD) and 33 (61%) recovered renal function. Tubular PRX3 expression was higher in patients with ATN than in those without renal function recovery. The level of tubular but not glomerular PRX3 expression predicted renal function recovery from AKI (AUROC = 0.76). In multivariate Cox regression analysis, high PRX3 expression was independently associated with a higher probability of renal function recovery (adjusted hazard ratio = 8.99; 95% CI 1.13–71.52, P = 0.04). Furthermore, the discriminative ability of the clinical model for AKI recovery was improved by adding tubular PRX3. High tubular PRX3 expression was associated with a higher probability of renal function recovery from ATN. Therefore, tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD. PMID:28240739

  16. Tumor necrosis factor participates in the pathogenesis of acute immune complex alveolitis in the rat.

    PubMed Central

    Warren, J S; Yabroff, K R; Remick, D G; Kunkel, S L; Chensue, S W; Kunkel, R G; Johnson, K J; Ward, P A

    1989-01-01

    We have examined the role of intrapulmonary TNF in a rat model of acute immune complex-triggered alveolitis. Intratracheal instillation of IgG anti-bovine serum albumin (anti-BSA) followed by intravenous infusion of BSA results in acute alveolitis. Over the 4-h course of evolving lung injury, a 10-fold increase in TNF activity occurred in bronchoalveolar lavage (BAL) fluid. Immunohistochemical analysis of lung sections and BAL cells revealed that alveolar macrophages are the chief source of TNF. Antibodies that specifically neutralize rat TNF activity were raised in rabbits immunized with recombinant mouse TNF alpha. When administered into the lungs with anti-BSA, anti-TNF resulted in a marked reduction (up to 61%) in lung injury. Intratracheal instillation of exogenous TNF alone, or in combination with anti-BSA, resulted in an increase in lung injury compared to controls. Morphometric analysis and measurements of myeloperoxidase activities in whole lung extracts from rats treated with anti-TNF revealed a marked reduction in neutrophils compared to positive controls. The anti-TNF antibody preparation did not inhibit in vitro complement activation or diminish neutrophil chemotactic activity present in activated rat serum. These data indicate that intrapulmonary TNF activity is required for the full development of acute immune complex-triggered alveolitis, that alveolar macrophages are the primary source of this cytokine, and that TNF participates in the pathogenesis of immune complex alveolitis through a mechanism involving neutrophil recruitment. Images PMID:2531759

  17. Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-α) pathways.

    PubMed

    Dal Bó, Wladmir; Luiz, Ana Paula; Martins, Daniel F; Mazzardo-Martins, Leidiane; Santos, Adair R S

    2013-10-01

    Eugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro-inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3-300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 ± 10% and 90 ± 6% of the acetic acid-induced nociception, with ID₅₀ values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3-100 mg/kg, i.p.) reduced the response behavior by 62 ± 5% with an ID₅₀ of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 ± 9%), kainic (acid kainite) (41 ± 12%), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (55 ± 5%), and substance P (SP) (39 ± 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF-α, 65 ± 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF-α. Thus, eugenol could represent an important compound in the treatment for acute pain.

  18. Protection against Acute Hepatocellular Injury Afforded by Liver Fibrosis Is Independent of T Lymphocytes

    PubMed Central

    Lacoste, Benoit; Raymond, Valérie-Ann; Lapierre, Pascal; Bilodeau, Marc

    2016-01-01

    Collagen produced during the process of liver fibrosis can induce a hepatocellular protective response through ERK1 signalling. However, the influence of T cells and associated cytokine production on this protection is unknown. In addition, athymic mice are frequently used in hepatocellular carcinoma xenograft experiments but current methods limit our ability to study the impact of liver fibrosis in this setting due to high mortality. Therefore, a mouse model of liver fibrosis lacking T cells was developed using Foxn1 nu/nu mice and progressive oral administration of thioacetamide (TAA) [0.01–0.02%] in drinking water. Fibrosis developed over a period of 16 weeks (alpha-SMA positive area: 20.0 ± 2.2%, preCol1a1 mRNA expression: 11.7 ± 4.1 fold changes, hydroxyproline content: 1041.2 ± 77μg/g of liver) at levels comparable to that of BALB/c mice that received intraperitoneal TAA injections [200 μg/g of body weight (bw)] (alpha-SMA positive area: 20.9 ± 2.9%, preCol1a1 mRNA expression: 13.1 ± 2.3 fold changes, hydroxyproline content: 931.6 ± 14.8μg/g of liver). No mortality was observed. Athymic mice showed phosphorylation of ERK1/2 during fibrogenesis (control 0.03 ± 0.01 vs 16 weeks 0.22 ± 0.06AU; P<0.05). The fibrosis-induced hepatoprotection against cytotoxic agents, as assessed histologically and by serum AST levels, was not affected by the absence of circulating T cells (anti-Fas JO2 [0.5μg/g bw] for 6h (fibrotic 4665 ± 2596 vs non-fibrotic 13953 ± 2260 U/L; P<0.05), APAP [750 mg/kg bw] for 6 hours (fibrotic 292 ± 66 U/L vs non-fibrotic 4086 ± 2205; P<0.01) and CCl4 [0.5mL/Kg bw] for 24h (fibrotic 888 ± 268 vs non-fibrotic 15673 ± 2782 U/L; P<0.001)). In conclusion, liver fibrosis can be induced in athymic Foxn1 nu/nu mice without early mortality. Liver fibrosis leads to ERK1/2 phosphorylation. Finally, circulating T lymphocytes and associated cytokines are not involved in the hepatocellular protection afforded by liver fibrosis. PMID

  19. Acute hemorrhagic pancreatic necrosis in mice: the activity of lysosomal enzymes in the pancreas and the liver.

    PubMed Central

    Rao, K. N.; Zuretti, M. F.; Baccino, F. M.; Lombardi, B.

    1980-01-01

    The activity of lysosomal enzymes of the pancreas and the liver has been studied during induction and onset of acute hemorrhagic pancreatic necrosis with fat necrosis (AHPN) in mice. We induced AHPN by feeding the animals a choline-deficient (CD) diet containing 0.5% DL-ethionine (CDE). Control animals were fed either laboratory chow or a plain CD DIET. Increased total activities of cathespin B1, beta-galactosidase, and acid phosphatase were found to occur in pancreas homogenates of mice fed the CDE diet for 2 and 3 days. Release of cathespin B1 into pancreas cytosol was observed after 1 day of feeding. beta-galactosidase and acid phosphatase were increased in pancreas cytosol after 2 and 3 days of feeding. Changes in total activity and location of the lysosomal enzymes did not occur in the liver. Feeding the CD and CDE diets resulted in an increase in the free activity of lysosomal enzymes of both the pancreas and the liver, suggesting the existence of alterations in the lysosomal membrane. Pancreas and liver homogenates were stored on ice up to 3 hours, and the free activity of acid phosphatase and beta-galactosidase were determined at various time intervals. The free activity of both enzymes increased progressively for 3 hours in the pancreas but not in the liver. It is concluded that: 1) induction of AHPN in mice is accompanied by an increase in the activity of lysosomal enzymes of the acinar cells of the pancreas; 2) cathepsin B1 may be responsible for triggering an intraparenchymal activation of zymogens, and 3) pancreatic lysosomes are labilized more easily than liver lysosomes. PMID:7350817

  20. Role of interleukin-1 and tumour necrosis factor in leukocyte recruitment to acute dermal inflammation

    PubMed Central

    Lopes, Nancy; Issekutz, Thomas B.

    1992-01-01

    The cytokines IL-1 and TNF-α are involved in inflammation and their production is stimulated by various agents, especially endotoxin (LPS). Here, using the human IL-1 receptor antagonist (IL-1RA) and a new monoclonal antibody (mAb 7F11) to rabbit TNF, the role of endogenous IL-l and TNF production in acute (3h) leukocyte (PMNL) recruitment to dermal inflammation in rabbits has been studied. IL-1RA inhibited by 27% the PMNL accumulation in reactions induced by killed Escherichia coli (p < 0.05) but not by LPS. The monoclonal antibody to TNF inhibited by 27% and 38% (p < 0.002) the PMNL accumulation in LPS and E. coli reactions respectively, but a combination of the mAb with IL-1RA was not more effective. Treatment of human umbilical vein endothelium with LPS for 3 h activated endothelium to induce PMNL transendothelial migration in vitro, which was not inhibited by IL-1RA, antibody to TNF-α, IL-1 or to IL-8. In conclusion, TNF and IL-1 may partially mediate acute PMNL infiltration in vivo to LPS and Gram negative bacteria, but there is a major IL-1/TNF independent mechanism, at least in dermal inflammation, which may be due to direct LPS activation of the microvasculature or perhaps the generation of cytokines other than IL-1 and TNF. PMID:18475483

  1. Preconditioning with Triiodothyronine Improves the Clinical Signs and Acute Tubular Necrosis Induced by Ischemia/Reperfusion in Rats

    PubMed Central

    Ferreyra, Carla; Vargas, Félix; Rodríguez-Gómez, Isabel; Pérez-Abud, Rocío; O'Valle, Francisco; Osuna, Antonio

    2013-01-01

    Background Renal ischemia/reperfusion (I/R) injury is manifested by acute renal failure (ARF) and acute tubular necrosis (ATN). The aim of this study was to evaluate the effectiveness of preconditioning with 3, 3, 5 triiodothyronine (T3) to prevent I/R renal injury. Methodology/Principal Findings The rats were divided into four groups: sham-operated, placebo-treated (SO-P), sham-operated T3- treated (SO- T3), I/R-injured placebo-treated (IR-P), and I/R-injured T3-treated (IR- T3) groups. At 24 h before ischemia, the animals received a single dose of T3 (100 μg/kg). Renal function and plasma, urinary, and tissue variables were studied at 4, 24, and 48 h of reperfusion, including biochemical, oxidative stress, and inflammation variables, PARP-1 immunohistochemical expression, and ATN morphology. In comparison to the SO groups, the IR-P groups had higher plasma urea and creatinine levels and greater proteinuria (at all reperfusion times) and also showed: increased oxidative stress-related plasma, urinary, and tissue variables; higher plasma levels of IL6 (proinflammatory cytokine); increased glomerular and tubular nuclear PARP-1 expression; and a greater degree of ATN. The IR-T3 group showed a marked reduction in all of these variables, especially at 48 h of reperfusion. No significant differences were observed between SO-P and SO-T3 groups. Conclusions This study demonstrates that preconditioning rats with a single dose of T3 improves the clinical signs and ATN of renal I/R injury. These beneficial effects are accompanied by reductions in oxidative stress, inflammation, and renal PARP-1 expression, indicating that this sequence of factors plays an important role in the ATN induced by I/R injury. PMID:24086411

  2. Successful Resolution of Gastric Outlet Obstruction Caused by Pancreatic Pseudocyst or Walled-Off Necrosis After Acute Pancreatitis

    PubMed Central

    Zhang, Yun; Zhang, Shao-Yang; Gao, Shun-Liang; Liang, Zhong-Yan; Yu, Wen-Qiao; Liang, Ting-Bo

    2015-01-01

    Objective Delayed gastric emptying (DGE) in patients with acute pancreatitis (AP) can be caused by gastroparesis or gastric outlet obstruction, which may occur when pancreatic pseudocyst (PP) or walled-off necrosis (WON) compresses the stomach. The aim of the study was to explore a proper surgical treatment. Methods From June 2010 to June 2013, 25 of 148 patients with AP suffered DGE. Among them, 12 were caused by gastroparesis, 1 was a result of obstruction from a Candida albicans plug, and 12 were gastric outlet obstruction (GOO) compressed by PP (n = 8) or WON (n = 4), which were treated by percutaneous catheter drainage (PCD). Results All 12 cases of compressing GOO achieved resolution by PCD after 6 [1.86] and 37.25 [12.02] days for PP and WON, respectively. Five cases developed intracystic infection, 3 cases had pancreatic fistulae whereas 2 achieved resolution and 1 underwent a pseudocyst jejunostomy. Conclusions Gastric outlet obstruction caused by a PP or WON is a major cause of DGE in patients with AP. Percutaneous catheter drainage with multiple sites, large-bore tubing, and lavage may be a good therapy due to high safety and minimal invasiveness. PMID:26465954

  3. Complete genome sequence of acute viral necrosis virus associated with massive mortality outbreaks in the Chinese scallop, Chlamys farreri

    PubMed Central

    2013-01-01

    Background Acute viral necrosis virus (AVNV) is the causative agent of a serious disease resulting in high mortality in cultured Chinese scallops, Chlamys farreri. We have sequenced and analyzed the complete genome of AVNV. Results The AVNV genome is a linear, double-stranded DNA molecule of 210,993 bp with a nucleotide composition of 38.5% G + C. A total of 123 open reading frames were predicted to encode functional proteins, ranging from 41 to 1,878 amino acid residues. The DNA sequence of AVNV is 97% identical to that of ostreid herpesvirus 1 (OsHV-1), and the amino acid sequences of the encoded proteins of these two viruses are 94-100% identical. The genomic organization of AVNV is similar to that of OsHV-1, and consists of two unique regions (170.4 kb and 3.4 kb, respectively), each flanked by two inverted repeats (7.6 kb and 10.2 kb, respectively), with a third unique region (1.5 kb) situated between the two internal repeats. Conclusions Our results indicate that AVNV is a variant of OsHV-1. The AVNV genome sequence provides information useful for understanding the evolution and divergence of OsHV-1 in marine molluscs. PMID:23566284

  4. Acute retinal necrosis caused by herpes simplex virus type 2 in children: reactivation of an undiagnosed latent neonatal herpes infection.

    PubMed

    Grose, Charles

    2012-09-01

    Herpes simplex virus type 2 (HSV-2) is known to cause acute retinal necrosis (ARN). The availability of HSV-2-specific polymerase chain reaction tests for diagnostic analysis has greatly increased our ability to discriminate ARN caused by HSV-2 from ARN caused by either herpes simplex virus type 1 or varicella zoster virus (VZV). Of great interest, HSV-2 appears to be the most common cause of viral ARN in children and adolescents. Although a few children with ARN are known to have had neonatally acquired herpes infection, most children lack a history of known herpes disease. Thus, the origin of the HSV-2 infection is a mystery. The hypothesis of this review is that HSV-2 ARN in children and adolescents may be the first sign of a previously undiagnosed and asymptomatic neonatal HSV-2 infection, which has reactivated several years later from latency in a cranial nerve and entered the retina. The review brings together 7 previously published ARN cases, plus one new case is added. Thus, this review also expands the spectrum of complications from neonatal HSV-2 infection.

  5. Patients with ischaemic, mixed and nephrotoxic acute tubular necrosis in the intensive care unit – a homogeneous population?

    PubMed Central

    Santos, Wilson JQ; Zanetta, Dirce MT; Pires, Antonio C; Lobo, Suzana MA; Lima, Emerson Q; Burdmann, Emmanuel A

    2006-01-01

    Introduction Acute tubular necrosis (ATN) is usually studied as a single entity, without distinguishing between ischaemic, nephrotoxic and mixed aetiologies. In the present study we evaluated the characteristics and outcomes of patients with ATN by aetiological group. Method We conducted a retrospective comparison of clinical features, mortality rates and risk factors for mortality for the three types of ATN in patients admitted to the general intensive care unit of a university hospital between 1997 and 2000. Results Of 593 patients with acute renal failure, 524 (88%) were classified as having ATN. Their mean age was 58 years, 68% were male and 52% were surgical patients. The overall mortality rate was 62%. A total of 265 patients (51%) had ischaemic ATN, 201 (38%) had mixed ATN, and 58 (11%) had nephrotoxic ATN. There were no differences among groups in terms of age, sex, APACHE II score and reason for ICU admission. Multiple organ failure was more frequent among patients with ischaemic (46%) and mixed ATN (55%) than in those with nephrotoxic ATN (7%; P < 0.0001). The complications of acute renal failure (such as, gastrointestinal bleeding, acidosis, oliguria and hypervolaemia) were more prevalent in ischaemic and mixed ATN patients. Mortality was higher for ischaemic (66%; P = 0.001) and mixed ATN (63%; P = 0.0001) than for nephrotoxic ATN (38%). When ischaemic ATN patients, mixed ATN patients and all patients combined were analyzed by multivariate logistic regression, the independent factors for mortality identified were different except for oliguria, which was the only variable universally associated with death (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.64–5.49 [P = 0.0003] for ischaemic ATN; OR 1.96, 95% CI 1.04–3.68 [P = 0.036] for mixed ATN; and OR 2.53, 95% CI 1.60–3.76 [P < 0.001] for all patients combined]). Conclusion The frequency of isolated nephrotoxic ATN was low, with ischaemic and mixed ATN accounting for almost 90% of cases. The

  6. High-Quality Draft Genomes of Two Vibrio parahaemolyticus Strains Aid in Understanding Acute Hepatopancreatic Necrosis Disease of Cultured Shrimps in Mexico

    PubMed Central

    Noriega-Orozco, Lorena; Sotelo-Mundo, Rogerio R.; Cantu-Robles, Vito A.; Cobian-Guemes, Ana G.; Cota-Verdugo, Rosario G.; Gamez-Alejo, Luis A.; del Pozo-Yauner, Luis; Guevara-Hernandez, Eduardo; Garcia-Orozco, Karina D.; Lopez-Zavala, Alonso A.

    2014-01-01

    The high-quality draft genomes of two Vibrio parahaemolyticus strains, one that causes the acute hepatopancreatic necrosis disease (AHPND) in cultured shrimps (FIM-S1708+), and another that does not (FIM-S1392−) are reported. A chromosome-scale assembly for the FIM-S1392− genome is reported here. The analysis of the two genomes gives some clues regarding the genomic differences between the strains. PMID:25125645

  7. Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2

    PubMed Central

    Huang, Bee-Piao; Lin, Chun-Shiang; Wang, Chau-Jong; Kao, Shao-Hsuan

    2017-01-01

    Tumor necrosis factor alpha (TNFα) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNFα on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNFα stimulus. We observed that HepG2 cell revealed a higher resistance to TNFα-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By using a label-free quantitative proteomic analysis, we found that 520 proteins were differentially expressed in the HepG2 cells exposed to TNFα, including 211 up-regulated and 309 down-regulated proteins. We further confirmed several proteins with significant expression change (TNFα/control ratio>2.0 or <0.5) by immunoblotting using specific antibodies. We also analyzed the differential expressed proteins using Gene ontology and KEGG annotations, and the results implicated that TNFα might regulate ribosome, spliceosome, antigen processing and presentation, and energy metabolism in HepG2 cells. Moreover, we demonstrated that upregulation of heat shock protein 70 (HSP70) was involved in both the promoted migration and the inhibited apoptosis of HepG2 cells in response to TNFα. Collectively, these findings indicate that TNFα alters protein expression such as HSP70, which triggering specific molecular processes and signaling cascades that promote migration and inhibit apoptosis of HepG2 cells. PMID:28367089

  8. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α–Mediated Apoptosis

    PubMed Central

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W.; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N.; Gonzalez, Frank J.

    2016-01-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics–pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factor α (TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics–pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL’s protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  9. Acute tubular necrosis

    MedlinePlus

    ... Liver disease and kidney damage caused by diabetes ( diabetic nephropathy ) may make a person more susceptible to the ... Urine sodium Urine specific gravity and osmolarity urine Treatment In most people, ATN is reversible. The goal ...

  10. Radiofrequency and microwave ablation in combination with transarterial chemoembolization induce equivalent histopathologic coagulation necrosis in hepatocellular carcinoma patients bridged to liver transplantation

    PubMed Central

    Ginsburg, Michael; Ahmed, Osman; Doshi, Taral; Hart, John; Te, Helen; Van Ha, Thuong Gustav

    2016-01-01

    Background Bridging therapy plays an increasingly important role in the management of patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). Combination therapy with drug-eluting bead transarterial chemoembolization (DEB-TACE) and percutaneous thermal ablation, such as radiofrequency ablation (RFA) or microwave ablation (MWA), has shown success at prolonging survival and bridging patients to LT. However, few studies have evaluated the two combination therapy regimens head-to-head at a single institution, and fewer have compared histopathology. This retrospective study compares tumor coagulation on explanted livers in patients with HCC treated with DEB-TACE sequentially combined with RFA versus MWA. Methods From 2005 to 2015, 42 sequential patients underwent combination therapy prior to LT by Milan criteria, with 11 patients (11 tumors; mean, 2.9 cm; range, 1.8–4.3 cm) in the DEB-TACE/RFA cohort and 31 patients (40 tumors; mean, 2.4 cm; range, 1.1–5.4 cm) in the DEB-TACE/MWA cohort. The mean TACE procedures in the RFA and MWA cohorts were 1.3 (range, 1–2) and 1.3 (range, 1–3), respectively. The mean thermal ablations in the RFA and MWA cohorts were 1.2 (range, 1–2) and 1.3 (range, 1–3), respectively. Tumor coagulation was evaluated on explanted livers. Results Mean tumor coagulation in the RFA and MWA cohorts were 88.9% (range, 0–100%) and 90.5% (range, 30–100%), respectively (P=0.82). Rates of complete tumor coagulation in the RFA and MWA cohorts were 45% and 53%, respectively (P=0.74). No difference in tumor coagulation was found between the cohorts when separating tumors <3 cm (P=0.21) and >3 cm (P=0.09). Among all 51 tumors, the 36 in complete response (CR) on imaging at LT demonstrated mean tumor coagulation of 95.8%. No correlation was found between tumor coagulation and initial tumor size or time interval to LT. No tumor seeding was seen along the ablation tracts. Conclusions RFA and MWA in sequential combination

  11. Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro

    PubMed Central

    1986-01-01

    Human hepatoma cells mimic the acute phase response after treatment with monocyte-conditioned medium. Levels of secreted fibrinogen, alpha- 1 acid glycoprotein, C-reactive protein, haptoglobin, and the third component of complement were elevated compared with control levels after 48 h of incubation with conditioned supernatant medium from an enriched fraction of normal peripheral monocytes. Albumin levels declined and alpha-1 antitrypsin remained unchanged. Levels of specific mRNA were measured by hybridization to slot blots and Northern blots and changed in correspondence with protein alterations. Interleukin-1 and tumor necrosis factor stimulated the third component of complement, but did not elevate any other member of the acute phase group and were therefore only partially active in this system. The identification of an in vitro model of the human acute phase response will permit analysis of the molecular basis for coordinate regulation of this group of facultative genes. PMID:3017995

  12. Review of hepatocellular cancer, hypertension and renal impairment as late complications of acute porphyria and recommendations for patient follow-up.

    PubMed

    Stewart, Mary Felicity

    2012-11-01

    This review critically appraises the data emerging from small retrospective and prospective cohort studies suggesting that patients with the autosomal dominant acute porphyrias may be at increased risk of hepatocellular cancer (HCC), hypertension (HT) and renal impairment. The most striking finding is a marked excess risk of HCC in Swedish patients with acute intermittent porphyria (AIP). As Sweden has a relatively high prevalence of AIP due to a founder effect, it is uncertain to what extent the finding is generalisable to other populations or other acute porphyrias and whether early intervention through screening can improve outcomes. As yet there is no evidence for the cost-effectiveness of systematic surveillance for HCC in acute porphyria outside Sweden. Data from several populations also suggest a high prevalence of chronic sustained HT and renal impairment in AIP, but it is uncertain if this represents a true excess risk, in particular for asymptomatic patients. As these long-term complications are important and potentially treatable, a pragmatic recommendation is that symptomatic patients with acute porphyria should be offered specialist long-term follow-up and, for those aged >50 years, annual liver ultrasound may be considered following discussion of the likely risks and benefits. Opportunistic cardiovascular risk assessment can readily be incorporated into a structured annual review so that appropriate drugs safe for use in acute porphyria are prescribed promptly. As these diseases are rare, collaborative international epidemiological studies such as those being coordinated through the European Porphyria Network are essential to inform best clinical practice.

  13. Effects of 28Si Ions, 56Fe Ions, and Protons on the Induction of Murine Acute Myeloid Leukemia and Hepatocellular Carcinoma

    PubMed Central

    Weil, Michael M.; Ray, F. Andrew; Genik, Paula C.; Yu, Yongjia; McCarthy, Maureen; Fallgren, Christina M.; Ullrich, Robert L.

    2014-01-01

    Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n 28Si or 600 MeV/n 56Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n 28Si ions, 600 MeV/n 56Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with 137Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that 28Si or 56Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, 28Si or 56Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the 28Si and 56Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members. PMID:25126721

  14. In vitro acute effects of tobacco smoke on tumor necrosis factor alpha and interleukin-6 production by alveolar macrophages.

    PubMed

    Dubar, V; Gosset, P; Aerts, C; Voisin, C; Wallaert, B; Tonnel, A B

    1993-01-01

    Tobacco smoke is a usual form of oxidant aggression present in the domestic environment. In the present study, the in vitro acute effects of a 2-cigarette smoke gas phase were evaluated on cell viability and cytokine secretion by alveolar macrophages (AM) from guinea pigs and human healthy subjects. Cell injury was estimated immediately after smoke exposure by evaluation of ATP cell content (measured by bioluminescence) and lactic dehydrogenase (LDH) release in the culture medium. LDH release was also measured when the interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) activities were evaluated. No cytotoxic effect was found: The ATP cell content of both guinea pig AM and human AM did not significantly change after tobacco smoke exposure. Similarly, the LDH release in the culture medium was unchanged both immediately after tobacco smoke exposure and at the time of the cytokine evaluation (18-20 h later) compared to cells cultured in the air. The total protein synthesis by the guinea pig AM evaluated by 35S-L-methionine labeling was unaffected by tobacco smoke exposure. The production of IL-6 and TNF activities was evaluated 18-20 h after smoke exposure. The IL-6 activity was measured by the proliferation test of 7TD1 hybridoma cell line; the TNF activity was evaluated by the L929 mouse fibroblast cytotoxic test and by an immunoradiometric assay (for human AM). A 2-cigarette smoke exposure decreased both activities significantly. The exposure of the guinea pig AM reduced IL-6 activity by 24.3 +/- 6.7%, 42.4 +/- 7.8%, and 39.7 +/- 9.6% and TNF activity by 33.8 +/- 10.4%, 35.1 +/- 10.7%, and 38.8 +/- 9.9% (respectively unstimulated cells and AM activated by 0.1 and 10 micrograms LPS/mL). The decrease in monokine production by the human AM was, respectively, 57.8 +/- 8.8%, 59.7 +/- 11.4%, and 49.9 +/- 10.5% of IL-6 activity and 37.4 +/- 14.6%, 17.6 +/- 9.6%, and 37.2 +/- 6.3% of TNF activity. The possible release of cytokine inhibitors was also investigated

  15. The major acute-phase protein, serum amyloid P component, in mice is not involved in endogenous resistance against tumor necrosis factor alpha-induced lethal hepatitis, shock, and skin necrosis.

    PubMed

    Van Molle, W; Hochepied, T; Brouckaert, P; Libert, C

    2000-09-01

    The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) induces lethal hepatitis when injected into D-(+)-galactosamine-sensitized mice on the one hand or systemic inflammatory response syndrome (SIRS) in normal mice on the other hand. We studied whether serum amyloid P component (SAP), the major acute-phase protein in mice, plays a protective role in both lethal models. For this purpose, we used SAP(0/0) mice generated by gene targeting. We studied the lethal response of SAP(0/0) or SAP(+/+) mice to both lethal triggers but found no differences in the sensitivity of both types of mice. We also investigated whether SAP is involved in establishing two types of endogenous protection: one using a single injection of interleukin-1beta (IL-1beta) for desensitization and clearly involving a liver protein, the other by tolerizing mice for 5 days using small doses of human TNF-alpha. Although after IL-1beta or after tolerization the SAP levels in the serum had risen fourfold in the control mice and not in the SAP(0/0) mice, the same extents of desensitization and tolerization were achieved. Finally, we observed that the induction of hemorrhagic necrosis in the skin of mice by two consecutive local injections with TNF-alpha was not altered in SAP(0/0) mice. We conclude that the presence or absence of SAP has no influence on the sensitivity of mice to TNF-alpha-induced hepatitis, SIRS, and hemorrhagic necrosis or on the endogenous protective mechanisms of desensitization or tolerization.

  16. Fat necrosis.

    PubMed

    Canteli, B; Saez, F; de los Ríos, A; Alvarez, C

    1996-04-01

    We report the MR appearance of a case of subcutaneous fat necrosis, which is a previously unreported etiology for knee mass. The role of MR imaging in differentiating fat necrosis from other causes of soft tissue masses is discussed. We conclude that MR characteristics of subcutaneous fat necrosis are typical and allow its differentiation from other types of soft tissue lesions.

  17. The anti-necrosis role of hypoxic preconditioning after acute anoxia is mediated by aldose reductase and sorbitol pathway in PC12 cells.

    PubMed

    Wu, Li-Ying; Ma, Zi-Min; Fan, Xue-Lai; Zhao, Tong; Liu, Zhao-Hui; Huang, Xin; Li, Ming-Ming; Xiong, Lei; Zhang, Kuan; Zhu, Ling-Ling; Fan, Ming

    2010-07-01

    It has been demonstrated that hypoxic preconditioning (HP) enhances the survival ability of the organism against the subsequent acute anoxia (AA). However, it is not yet clear whether necrosis induced by AA can be prevented by HP, and what are the underlying mechanisms. In this study, we examined the effect of HP (10% O(2), 48 h) on necrosis induced by AA (0% O(2), 24 h) in PC12 cells. We found that HP delayed the regulatory volume decrease and reduced cell swelling after 24 h of exposure to AA. Since aldose reductase (AR) is involved in cell volume regulation, we detected AR mRNA expression with reverse transcription-polymerase chain reaction (RT-PCR) techniques. The AR mRNA level was dramatically elevated by HP. Furthermore, an HP-induced decrease in cell injury was reversed by berberine chloride (BB), the inhibitor of AR. In addition, sorbitol synthesized from glucose catalyzed by AR is directly related to cell volume regulation. Subsequently, we tested sorbitol content in the cytoplasm. HP clearly elevated sorbitol content, while BB inhibited the elevation induced by HP. Further study showed that a strong inhibitor of sorbitol permease, quinidine, completely reversed the protection induced by HP after AA. These data provide evidence that HP prevents necrosis induced by AA and is mediated by AR and sorbitol pathway.

  18. 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.

  19. Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident postinfectious glomerulonephritis

    PubMed Central

    Kim, Kyung Min; Sung, Kyoung; Yang, Hea Koung; Kim, Seong Heon; Kim, Hye Young; Ban, Gil Ho; Park, Su Eun; Lee, Hyoung Doo

    2016-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature. PMID:27186222

  20. Acute hemorrhagic myocardial necrosis and sudden death of rats exposed to a combination of ephedrine and caffeine.

    PubMed

    Nyska, Abraham; Murphy, Elizabeth; Foley, Julie F; Collins, Bradley J; Petranka, John; Howden, Reuben; Hanlon, Paul; Dunnick, June K

    2005-02-01

    Because of possible side effects of herbal medicines containing ephedrine and guarana-derived caffeine, including increased risk of stroke, myocardial infarction, and sudden death, the Food and Drug Administration recently banned the sale of ephedra-containing products, specifically over-the-counter dietary supplements. We report cardiac in 7- and 14-week-old male F344 rats exposed by gavage to ephedrine(25 mg/kg) and caffeine (30 mg/kg) administered in combination for one or two days. The ephedrine-caffeine dosage was approximately 12- and 1.4-fold, respectively, above average human exposure, based on a mg/m2 body surface-area comparison. Several (5/7) of the exposed 14-week-old rats died or were sacrificed in extremis 4-5 h after the first dosing. In these hearts, changes were observed chiefly in the interventricular septum but also left and right ventricular walls. Massive interstitial hemorrhage, with degeneration of myofibers, occurred at the subendocardial myocardium of the left ventricle and interventricular septum. Immunostaining for cleaved caspase-3 and hyperphosphorylated H2A.X, a histone variant that becomes hyperphosphorylated during apoptosis, indicated multifocal generalized positive staining of degenerating myofibers and fragmenting nuclei, respectively. The Barbeito-Lopez trichrome stain revealed generalized patchy yellow myofibers consistent with degeneration and/or coagulative necrosis. In ephedrine-caffeine-treated animals terminated after the second dosing, foci of myocardial degeneration and necrosis were already infiltrated by mixed inflammatory cells. The myocardial necrosis may occur secondarily to intense diffuse vasoconstriction of the coronary arterial system with decreased myocardial perfusion. Our work shows the direct relationship between combined ephedrine and caffeine exposure and cardiac pathology.

  1. Rare combination of bilateral putaminal necrosis, optic neuritis, and polyneuropathy in a case of acute methanol intoxication among patients met with hooch tragedy in Gujarat, India

    PubMed Central

    Jarwani, Bhavesh S; Motiani, Puja; Divetia, Ruchir; Thakkar, Gurudutta

    2012-01-01

    Methanol poisoning is a rare but extremely hazardous form of intoxication, generally occurring after suicidal or accidental events. Methanol is a cheap and potent adulterant of illicit liquors. In India, we have witnessed number of mass emergencies due to adulterated alcohol consumption. Although Gujarat State had banned alcohol consumption since 1961, worse hooch tragedies have often taken place. The most severe consequences of methanol intoxication are blindness, a profound metabolic acidosis and various forms of neurological impairment; which occur characteristically after a latent period of several hours or days after ingestion. We present a unique case of acute methanol intoxication presented with, apart from metabolic acidosis and optic neuritis, involvement of central nervous system and peripheral nervous system. He had bilateral optic neuritis, delayed onset polyneuropathy with axonopathy, and radiculopathy. Magnetic resonance imaging findings were consistent with bilateral putaminal necrosis. PMID:23248510

  2. 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.

  3. [Indices of tissue necrosis markers in acute pyo-destructive diseases of organs of the abdominal cavity].

    PubMed

    Ostrovskiĭ, V K; Makarov, S V; Rodionov, P N; Kochetkov, L N

    2011-01-01

    Investigation of indices of lactate dehydrogenase (LDG) and creatine phosphokinase (CPK) in a group of patients with extensive necrotic alterations in organs of the abdominal cavity and in a group of patients without extensive necroses has shown that in the first group there were higher levels of LDG and CPK. It shows that the LDG and CPK indices may be used as markers of tissue necrosis of the abdominal organs. In addition, in patients who died against the background of growing polyorganic insufficiency the LDG and CPK level by the end of treatment was statistically reliably higher than on admission of the same patients that may be an indicator of growing phenomena of dystrophy and micronecroses in vitals, so the indices of LDG and CPK may show the degree of severity of polyorganic insufficiency and determine its prognosis.

  4. Avascular Necrosis

    MedlinePlus

    ... blood flow and leading to avascular necrosis. Excessive alcohol use. Consuming several alcoholic drinks a day for several years also can cause fatty deposits to form in your blood vessels. Bisphosphonate ...

  5. A Case of Acute Ischemic Duodenal Ulcer Associated with Superior Mesenteric Artery Dissection After Transarterial Chemoembolization for Hepatocellular Carcinoma

    SciTech Connect

    Jang, Eun Sun; Jeong, Sook-Hyang Kim, Jin Wook; Lee, Sang Hyub; Yoon, Chang Jin; Kang, Sung Gwon

    2009-03-15

    We report a case of transarterial chemoembolization (TACE)-related acute ischemic duodenal ulcer that developed in association with dissection of the superior mesenteric artery. We conclude that the acute duodenal ulcer was developed by ischemia related to superior mesenteric artery dissection during TACE. TACE should be conducted carefully with continuous observation of abdominal arteries.

  6. Minimally invasive treatment of infected pancreatic necrosis

    PubMed Central

    Cebulski, Włodzimierz; Słodkowski, Maciej; Krasnodębski, Ireneusz W.

    2014-01-01

    Infected pancreatic necrosis is a challenging complication that worsens prognosis in acute pancreatitis. For years, open necrosectomy has been the mainstay treatment option in infected pancreatic necrosis, although surgical debridement still results in high morbidity and mortality rates. Recently, many reports on minimally invasive treatment in infected pancreatic necrosis have been published. This paper presents a review of minimally invasive techniques and attempts to define their role in the management of infected pancreatic necrosis. PMID:25653725

  7. Post-pancreatitis Fat Necrosis Mimicking Carcinomatosis.

    PubMed

    Smith, Joshua P; Arnoletti, J Pablo; Varadarajulu, Shyam; Morgan, Desiree E

    2008-01-01

    Acute pancreatitis can result in retroperitoneal fat necrosis, typically occurring in the peripancreatic region, with extension into the transverse mesocolon, omentum and mesenteric root. When evaluated with contrast enhanced computed tomography (CECT), acute peripancreatic post necrotic collections typically become lower in attenuation over time, and often appear as homogeneous fluid collections. Saponification as a complication of fat necrosis in patients with acute pancreatitis is a well recognized clinical entity. While retroperitonal fat necrosis is commonly seen on CECT, saponification is not a prominent imaging feature. We present a case of acute pancreatitis complicated by extensive saponification of fat throughout the retroperitoneum and peritoneal lining, mimicking carcinomatosis.

  8. Evaluation of plasma leptin, tumor necrosis factor-α, and prealbumin as prognostic biomarkers during clinical recovery from acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Mohan, Anant; Arora, Sneh; Uniyal, Arvind; Poulose, Rosemary; Luthra, Kalpana; Pandey, RM; Guleria, Randeep

    2017-01-01

    Background: Inflammatory and nutritional biomarkers have an important bearing on outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but the temporal profile of these compounds during an acute episode is unclear. Patients and Methods: Plasma leptin, prealbumin, and tumor necrosis factor-alpha (TNF-α) were estimated at baseline and before hospital discharge in patients with AECOPD. Results: A total of 82 patients were evaluated (66 males; mean (standard deviation) age, 61.6 (10.1) years. Of these, 74 subjects (90.2%) were current or former smokers, with median (range) pack-years of 15 (0–96), duration of COPD of 8 years (range, 2–25 years) and duration of current symptoms being 5 days (range, 1–30 days). Majority (41.5%) had type I (severe) exacerbation. During the current episode, 46 patients (58.9%) required mechanical ventilation for a median of 6 days (range, 1–34). The median duration of hospital stay was 13 days, (range, 1–110). At discharge, significant reduction was observed in dyspnea, total leukocyte count, erythrocyte sedimentation rate (ESR), partial pressure of carbon dioxide, hemoglobin, urea, creatinine, potassium, aspartate transferase, and TNF-α levels compared to baseline, whereas arterial pH, PO2, serum albumin, prealbumin, and leptin significantly improved. No difference was seen in leptin, prealbumin, and TNF-α between patients with mild/moderate and severe exacerbation, or between patients who required or did not require mechanical ventilation. Change in leptin correlated with body mass index and change in ESR; no associations were observed between leptin, prealbumin, and TNF-α with other clinico-laboratory variables. Conclusion: Plasma levels of novel inflammatory and nutritional biomarkers, i.e., leptin, TNF-α, and prealbumin are altered in AECOPD episodes and lag behind other parameters during recovery. These biomarkers are not reliable predictors of clinical outcomes in these patients. PMID

  9. Field and Experimental Evidence of Vibrio parahaemolyticus as the Causative Agent of Acute Hepatopancreatic Necrosis Disease of Cultured Shrimp (Litopenaeus vannamei) in Northwestern Mexico

    PubMed Central

    Gomez-Gil, Bruno; Lozano-Olvera, Rodolfo; Betancourt-Lozano, Miguel; Morales-Covarrubias, Maria Soledad

    2014-01-01

    Moribund shrimp affected by acute hepatopancreatic necrosis disease (AHPND) from farms in northwestern Mexico were sampled for bacteriological and histological analysis. Bacterial isolates were molecularly identified as Vibrio parahaemolyticus by the presence of the tlh gene. The tdh-negative, trh-negative, and tlh-positive V. parahaemolyticus strains were further characterized by repetitive extragenic palindromic element-PCR (rep-PCR), and primers AP1, AP2, AP3, and AP and an ems2 IQ2000 detection kit (GeneReach, Taiwan) were used in the diagnostic tests for AHPND. The V. parahaemolyticus strains were used in immersion challenges with shrimp, and farmed and challenged shrimp presented the same clinical and pathological symptoms: lethargy, empty gut, pale and aqueous hepatopancreas, and expanded chromatophores. Using histological analysis and bacterial density count, three stages of AHNPD (initial, acute, and terminal) were identified in the affected shrimp. The pathognomonic lesions indicating severe desquamation of tubular epithelial cells of the hepatopancreas were observed in both challenged and pond-infected shrimp. The results showed that different V. parahaemolyticus strains have different virulences; some of the less virulent strains do not induce 100% mortality, and mortality rates also rise more slowly than they do for the more virulent strains. The virulence of V. parahaemolyticus strains was dose dependent, where the threshold infective density was 104 CFU ml−1; below that density, no mortality was observed. The AP3 primer set had the best sensitivity and specificity. Field and experimental results showed that the V. parahaemolyticus strain that causes AHPND acts as a primary pathogen for shrimp in Mexico compared with the V. parahaemolyticus strains reported to date. PMID:25548045

  10. The role of slow and persistent TTX-resistant sodium currents in acute tumor necrosis factor-α-mediated increase in nociceptors excitability

    PubMed Central

    Gudes, Sagi; Barkai, Omer; Caspi, Yaki; Katz, Ben; Lev, Shaya

    2014-01-01

    Tetrodotoxin-resistant (TTX-r) sodium channels are key players in determining the input-output properties of peripheral nociceptive neurons. Changes in gating kinetics or in expression levels of these channels by proinflammatory mediators are likely to cause the hyperexcitability of nociceptive neurons and pain hypersensitivity observed during inflammation. Proinflammatory mediator, tumor necrosis factor-α (TNF-α), is secreted during inflammation and is associated with the early onset, as well as long-lasting, inflammation-mediated increase in excitability of peripheral nociceptive neurons. Here we studied the underlying mechanisms of the rapid component of TNF-α-mediated nociceptive hyperexcitability and acute pain hypersensitivity. We showed that TNF-α leads to rapid onset, cyclooxygenase-independent pain hypersensitivity in adult rats. Furthermore, TNF-α rapidly and substantially increases nociceptive excitability in vitro, by decreasing action potential threshold, increasing neuronal gain and decreasing accommodation. We extended on previous studies entailing p38 MAPK-dependent increase in TTX-r sodium currents by showing that TNF-α via p38 MAPK leads to increased availability of TTX-r sodium channels by partial relief of voltage dependence of their slow inactivation, thereby contributing to increase in neuronal gain. Moreover, we showed that TNF-α also in a p38 MAPK-dependent manner increases persistent TTX-r current by shifting the voltage dependence of activation to a hyperpolarized direction, thus producing an increase in inward current at functionally critical subthreshold voltages. Our results suggest that rapid modulation of the gating of TTX-r sodium channels plays a major role in the mediated nociceptive hyperexcitability of TNF-α during acute inflammation and may lead to development of effective treatments for inflammatory pain, without modulating the inflammation-induced healing processes. PMID:25355965

  11. Serum and urinary insulin-like growth factor-1 and tumor necrosis factor in neonates with and without acute renal failure.

    PubMed

    Kornhauser, Carlos; Dubey, Luis-Antonio; Garay, M-Eugenia; Pérez-Luque, Elva-Leticia; Malacara, Juan-Manuel; Vargas-Origel, Arturo

    2002-05-01

    Acute renal failure (ARF) in neonates may occur after renal ischemia. Growth factors participate in the tubular regeneration process. Insulin-like growth factor-1 (IGF-1) is produced in the kidney during the recovery phase of ARF. Tumor necrosis factor-alpha (TNFalpha) may play a role in renal apoptosis. We examined serum and urinary IGF-1 and TNFalpha in neonates with or without ARF after asphyxia, in order to assess their possible use as markers of renal damage and recovery. We studied 20 full-term asphyxiated neonates, 10 with ARF and 10 without ARF, and compared them with 13 normal newborns for 7 days after birth. Blood urea, creatinine, pH, base deficit, and serum and urine IGF-1 and TNFalpha were assessed. Neonates with ARF had more-severe acidosis than patients without ARF. All patients had lower serum IGF-1 values immediately after birth than control children. Serum IGF-1 remained low in the ARF patients. The initial urinary IGF-1 was higher in all patients compared with control newborns, and remained elevated for the rest of the study only in the ARF neonates. Serum and urinary TNFalpha concentrations were similar for all healthy and diseased neonates. Measurement of serum and urinary IGF-1 levels in ARF neonates might be of additional value for clinical assessment of ARF.

  12. Genetic diversity of Vibrio parahaemolyticus strains isolated from farmed Pacific white shrimp and ambient pond water affected by acute hepatopancreatic necrosis disease outbreak in Thailand.

    PubMed

    Chonsin, Kaknokrat; Matsuda, Shigeaki; Theethakaew, Chonchanok; Kodama, Toshio; Junjhon, Jiraphan; Suzuki, Yasuhiko; Suthienkul, Orasa; Iida, Tetsuya

    2016-01-01

    Acute hepatopancreatic necrosis disease (AHPND) is an emerging shrimp disease that causes massive die-offs in farmed shrimps. Recent outbreaks of AHPND in Asia have been causing great losses for shrimp culture and have become a serious socioeconomic problem. The causative agent of AHPND is Vibrio parahaemolyticus, which is typically known to cause food-borne gastroenteritis in humans. However, there have been few reports of the epidemiology of V. parahaemolyticus AHPND strains, and the genetic relationship among AHPND strains is unclear. Here, we report the genetic characterization of V. parahaemolyticus strains isolated from AHPND outbreaks in Thailand. We found eight isolates from AHPND-suspected shrimps and pond water that were positive for AHPND markers AP1 and AP2. PCR analysis confirmed that none of these eight AP-positive AHPND strains possesses the genes for the conventional virulence factors affecting to humans, such as thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH) and type III secretion system 2. Phylogenetic analysis by multilocus sequence typing showed that the AHPND strains are genetically diverse, suggesting that AHPND strains were not derived from a single genetic lineage. Our study represents the first report of molecular epidemiology of AHPND-causing V. parahaemolyticus strains using multilocus sequence typing, and provides an insight into their evolutionary mechanisms.

  13. Impact of farm management on expression of early mortality syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND) on penaeid shrimp farms in Thailand.

    PubMed

    Boonyawiwat, V; Patanasatienkul, T; Kasornchandra, J; Poolkhet, C; Yaemkasem, S; Hammell, L; Davidson, J

    2016-09-05

    Asian shrimp farming industry has experienced massive production losses due to a disease caused by toxins of Vibrio bacteria, known as early mortality syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND) for the last 5 years. The disease can cause up to 100% cumulative pond mortality within a week. The objective of this study was to identify factors associated with AHPND occurrence on shrimp farms. A case-control study was carried out on shrimp farms in four provinces of Thailand. Factors related to farm characteristics, farm management, pond and water preparation, feed management, post-larvae (PL) shrimp and stock management were evaluated. Multivariable logistic regression analysis identified factors affecting AHPND occurrence at the pond level. Chlorine treatment, reservoir availability, use of predator fish in the water preparation, culture of multiple shrimp species in one farm and increased PL stocking density contributed to an increased risk of AHPND infection, while delayed first day of feeding, polyculture and water ageing were likely to promote outbreak protection. Additionally, the source of PL was found to be associated with AHPND occurrence in shrimp ponds, which requires further study at the hatchery level. Identification of these factors will facilitate the development of effective control strategies for AHPND on shrimp farms.

  14. Beneficial effects of post-transfusional hepatitis in acute myelogenous leukemia may be mediated by lipopolysaccharides, tumor necrosis factor alpha and interferon gamma.

    PubMed

    Treon, S P; Broitman, S A

    1992-10-01

    Post-transfusional hepatitis is often a complication in patients with acute myelogenous leukemia (AML) in whom survival is paradoxically prolonged. The etiology is unknown. In previous studies, we showed that impaired hepatic endotoxin (lipopolysaccharide, LPS) clearance in patients with acute viral hepatitis A, B, or C versus controls results in endotoxemia and tumor necrosis factor alpha (TNF-alpha) release. TNF-alpha mediates anti-proliferative and differentiating effects in AML cell lines. Interferon-gamma (IFN-gamma) released in acute viral hepatitis, acts in synergy with TNF-alpha. HL60, KG1, and U937 AML cells treated 3, 6, and 9 days with physiologically attainable TNF-alpha (10 U/ml), IFN-gamma (100 U/ml) and LPS (10 ng/ml) levels, have significantly diminished viability and cell growth versus controls. Treatment of HL60 AML cells with LPS/TNF-alpha/IFN-gamma also resulted in significantly increased monocytic pathway differentiation not seen with KG1 or U937 AML cells. HL60 AML cells treated with TNF-alpha/IFN-gamma for 6 days released endogenous TNF-alpha (1.57 U/10(6) cells) upon LPS stimulation compared to less than 0.01 U/10(6) cells in non-LPS-stimulated TNF-alpha/IFN-gamma-treated cells or untreated cells (p less than 0.0001). Untreated HL60 AML cells co-cultured with HL60 cells pretreated for 6 days with TNF-alpha/IFN-gamma and then subjected to LPS stimulation had significantly diminished cell growth compared to controls (p less than 0.0001). This effect could be reversed with anti-TNF-alpha antibody, supporting the concept that endogenous TNF-alpha release by LPS/TNF-alpha/IFN-gamma treated HL60 AML cells may act by paracrine means to suppress growth of other AML cells. The beneficial effects of post-transfusional hepatitis in AML patients may be mediated via LPS/TNF-alpha/IFN-gamma-induced AML cell growth suppression and/or terminal differentiation in which AML cells participate by releasing TNF-alpha after being acted upon by LPS

  15. The role of necrosis, acute hypoxia and chronic hypoxia in 18F-FMISO PET image contrast: a computational modelling study

    NASA Astrophysics Data System (ADS)

    Warren, Daniel R.; Partridge, Mike

    2016-12-01

    Positron emission tomography (PET) using 18F-fluoromisonidazole (FMISO) is a promising technique for imaging tumour hypoxia, and a potential target for radiotherapy dose-painting. However, the relationship between FMISO uptake and oxygen partial pressure ({{P}{{\\text{O}2}}} ) is yet to be quantified fully. Tissue oxygenation varies over distances much smaller than clinical PET resolution (<100 μm versus  ˜4 mm), and cyclic variations in tumour perfusion have been observed on timescales shorter than typical FMISO PET studies (˜20 min versus a few hours). Furthermore, tracer uptake may be decreased in voxels containing some degree of necrosis. This work develops a computational model of FMISO uptake in millimetre-scale tumour regions. Coupled partial differential equations govern the evolution of oxygen and FMISO distributions, and a dynamic vascular source map represents temporal variations in perfusion. Local FMISO binding capacity is modulated by the necrotic fraction. Outputs include spatiotemporal maps of {{P}{{\\text{O}2}}} and tracer accumulation, enabling calculation of tissue-to-blood ratios (TBRs) and time-activity curves (TACs) as a function of mean tissue oxygenation. The model is characterised using experimental data, finding half-maximal FMISO binding at local {{P}{{\\text{O}2}}} of 1.4 mmHg (95% CI: 0.3-2.6 mmHg) and half-maximal necrosis at 1.2 mmHg (0.1-4.9 mmHg). Simulations predict a non-linear non-monotonic relationship between FMISO activity (4 hr post-injection) and mean tissue {{P}{{\\text{O}2}}} : tracer uptake rises sharply from negligible levels in avascular tissue, peaking at  ˜5 mmHg and declining towards blood activity in well-oxygenated conditions. Greater temporal variation in perfusion increases peak TBRs (range 2.20-5.27) as a result of smaller predicted necrotic fraction, rather than fundamental differences in FMISO accumulation under acute hypoxia. Identical late FMISO uptake can occur in regions with differing

  16. Tumour necrosis factor-α plus interleukin-10 low producer phenotype predicts acute kidney injury and death in intensive care unit patients.

    PubMed

    Dalboni, M A; Quinto, B M R; Grabulosa, C C; Narciso, R; Monte, J C; Durão, M; Rizzo, L; Cendoroglo, M; Santos, O P; Batista, M C

    2013-08-01

    Genetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of -308 G < A tumour necrosis factor (TNF)-α, -174 G > C interleukin (IL)-6 and -1082 G > A IL-10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case-control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF-α (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF-α/IL-10 combinations, it was observed that low TNF-α plus low IL-10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF-α producer plus low IL-10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16-4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19-12·23; P = 0·02). In this study, the combination of low TNF-α plus low IL-10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long-term follow-up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients.

  17. Tumour necrosis factor-α plus interleukin-10 low producer phenotype predicts acute kidney injury and death in intensive care unit patients

    PubMed Central

    Dalboni, M A; Quinto, B M R; Grabulosa, C C; Narciso, R; Monte, J C; Durão, M; Rizzo, L; Cendoroglo, M; Santos, O P; Batista, M C

    2013-01-01

    Genetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of −308 G < A tumour necrosis factor (TNF)-α, −174 G > C interleukin (IL)-6 and −1082 G > A IL-10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case–control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF-α (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF-α/IL-10 combinations, it was observed that low TNF-α plus low IL-10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF-α producer plus low IL-10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16–4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19–12·23; P = 0·02). In this study, the combination of low TNF-α plus low IL-10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long-term follow-up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients. PMID:23607333

  18. [The association study of the promoter polymorphism -308G>A of tumor necrosis factor gene with the development and severity of acute pancreatitis in Russian population of Kursk region].

    PubMed

    Samgina, T A; Bushueva, O Iu; Ivanov, V P; Solodilova, M A; Nazarenko, P M; Polonikov, A V

    2014-01-01

    The aim of this study was to investigate the relationship between the polymorphism -308G>A of tumor necrosis factor (TNF) gene and the risk and severity of acute pancreatitis (AP) in unrelated Russians from Kursk region. DNA samples were obtained from 190 AP patients and 217 healthy controls for genotyping the polymorphism through a TaqMan allelic discrimination assay. Although -308G>A genotypes did not show a significant association with disease risk, the genotype -308GA was found to be associated only with non-severe type of acute alcohol-related pancreatitis (odds ratio 1.81 (95% CI 1.02-3.23 p=0.04).

  19. 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 ...

  20. 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 ...

  1. Role of Fibrinogen and Protease-Activated Receptors in Acute Xenobiotic-Induced Cholestatic Liver Injury

    PubMed Central

    Luyendyk, James P.; Mackman, Nigel; Sullivan, Bradley P.

    2011-01-01

    Alpha-naphthylisothiocyanate (ANIT)–induced cholestatic liver injury causes tissue factor (TF)–dependent coagulation in mice, and TF deficiency reduces ANIT-induced liver injury. However, the mechanism whereby TF contributes to hepatotoxicity in this model is not known. Utilizing pharmacological and genetic strategies, we evaluated the contribution of fibrinogen and two distinct receptors for thrombin, protease-activated receptor-1 (PAR-1) and PAR-4, in a model of acute ANIT hepatotoxicity. ANIT administration (60 mg/kg, po) caused a marked induction of the genes encoding the three fibrinogen chains (α, β, and γ) in liver, an increase in plasma fibrinogen, and concurrent deposition of thrombin-cleaved fibrin in liver. Partial depletion of circulating fibrinogen with ancrod did not impact ANIT hepatotoxicity. However, complete fibrin(ogen) deficiency significantly reduced serum alanine aminotransferase activity and hepatocellular necrosis in ANIT-treated mice. ANIT-induced hepatocellular necrosis was similar in PAR-1−/− mice compared with PAR-1+/+ mice. Interestingly, the progression of ANIT-induced hepatocellular necrosis was significantly reduced in PAR-4−/− mice and by administration of an inhibitory PAR-4 pepducin (P4Pal-10, 0.5 mg/kg, sc) to wild-type mice 8 h after ANIT treatment. Interestingly, a distinct lesion, parenchymal-type peliosis, was also observed in PAR-4−/− mice treated with ANIT and in mice that were given P4Pal-10 prior to ANIT administration. The results suggest that fibrin(ogen), but not PAR-1, contributes to the progression of ANIT hepatotoxicity in mice. Moreover, the data suggest a dual role for PAR-4 in ANIT hepatotoxicity, both mediating an early protection against peliosis and contributing to the progression of hepatocellular necrosis. PMID:20974703

  2. 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.

  3. Cortical necrosis in a renal transplant

    SciTech Connect

    Blumhardt, R.; Growcock, G.; Lasher, J.C.

    1983-07-01

    The /sup 99m/Tc-DTPA renogram is a well extabished noninvasive method for evaluating and following transplanted kidneys. The examination is useful in distinguishing rejection from acute tubular necrosis as well as demonstrating several less common complications such as vascular occlusion, urinary extravasation, obstruction, and lymphocele. A previously unreported condition involving a transplant kidney (i.e., renal cortical necrosis) is described which was diagnosed with renal scintigraphy in combination with sonography.

  4. Regulated necrosis-related molecule mRNA expression in humans and mice and in murine acute tissue injury and systemic autoimmunity leading to progressive organ damage, and progressive fibrosis

    PubMed Central

    Honarpisheh, Mohsen; Desai, Jyaysi; Marschner, Julian A.; Weidenbusch, Marc; Lech, Maciej; Vielhauer, Volker; Anders, Hans-Joachim; Mulay, Shrikant R.

    2016-01-01

    The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of tumour necrosis factor receptor-1 (TNFR1), receptor activated protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL), CASP8, Fas-associated protein with death domain (FADD), cellular inhibitor of apoptosis protein (CIAP)1, CIAP2, glutathione peroxidase-4 (GPX4), cyclophilin D (CYPD), CASP1, NLRP3 and poly(ADP-ribose) polymerase-1 (PARP1) in human and mouse solid organs. We observed significant differences in expression of these molecules between human and mice. In addition, we characterized their expression profiles in acute as well as persistent tissue injury and chronic tissue remodelling using acute and chronic kidney injury models. We observed that the degree and pattern of induction of RN-related molecules were highly dependent on the trigger and disease pathogenesis. Furthermore, we studied their expression patterns in mice with lupus-like systemic autoimmunity, which revealed that the expression of MLKL, GPX4 and PARP1 significantly increased in the spleen along disease progression and CASP1, RIPK1, RIPK3 and CYPD were higher at the earlier stages but were significantly decreased in the later stages. In contrast, in the kidney, the expression of genes involved in pyroptosis, e.g. NLRP3 and CASP1 were significantly increased and TNFR1, RIPK1, RIPK3, CIAP1/2 and GPX4 were significantly decreased along the progression of lupus nephritis (LN). Thus, the organ- and species-specific expression of RN-related molecules should be considered during designing experiments, interpreting the results as well as extrapolating the conclusions from one species or organ to another species or organ respectively. PMID:27811014

  5. ROLE OF THE MATERNAL ACUTE PHASE RESPONSE AND TUMOR NECROSIS FACTOR ALPHA IN THE DEVELOPMENTAL TOXICITY OF LIPOPOLYSACCHARIDE IN THE CD-1 MOUSE

    EPA Science Inventory

    ABSTRACT
    The acute phase response (APR) functions to reset metabolic homeostasis following infectious, toxic or traumatic insult. TNF- , a putative mediator of the APR, has been associated with fetal death in rodents and preterm labor and delivery in humans. We hypothesized...

  6. Molecular MRI of Acute Necrosis with a Novel DNA-Binding Gadolinium Chelate: Kinetics of Cell Death and Clearance in Infarcted Myocardium

    PubMed Central

    Huang, Shuning; Chen, Howard H.; Yuan, Hushan; Dai, Guangping; Schuhle, Daniel T.; Mekkaoui, Choukri; Ngoy, Soeun; Liao, Ronglih; Caravan, Peter; Josephson, Lee; Sosnovik, David E.

    2012-01-01

    Background Current techniques to image cell death in the myocardium are largely non-specific. Here we report the use of a novel DNA-binding gadolinium chelate (Gd-TO) to specifically detect the exposed DNA in acutely necrotic (ruptured) cells in vivo. Methods and Results In vivo MRI was performed in 20 mice with myocardial infarction (MI). The mice were injected with Gd-TO or Gd-DTPA at varying time points post-MI. MRI was performed 2 hours after probe injection, to avoid nonspecific signal from the late gadolinium enhancement effect. Cell rupture (Gd-TO uptake) was present within 2 hours of infarction, but peaked 9–18 hours after the onset of injury. A significant increase in the longitudinal relaxation rate (R1) in the infarct was seen in mice injected with Gd-TO within 48 hours of MI, but not in those injected more than 72 hours post MI (R1 = 1.24 ± 0.08 and 0.92 ± 0.03 s−1, respectively, p < 0.001). Gd-DTPA, unlike Gd-TO, washed completely out of acute infarcts within 2 hours of injection (p < 0.001). The binding of Gd-TO to exposed DNA in acute infarcts was confirmed with fluorescence microscopy. Conclusions Gd-TO specifically binds to acutely necrotic cells and can be used to image the mechanism and chronicity of cell death in injured myocardium. Cell rupture in acute MI begins early but peaks many hours after the onset of injury. The ruptured cells are efficiently cleared by the immune system and are no longer present in the myocardium 72 hours after injury. PMID:21836081

  7. Effect of tumor necrosis factor-α induced protein 8 like-2 on immune function of dendritic cells in mice following acute insults

    PubMed Central

    Tong, Sen; Dong, Ning; Sheng, Zhi-yong; Yao, Yong-ming

    2016-01-01

    Tumor necrosis factor-α induced protein 8 like-2 (TNFAIP8L2, TIPE2) is a lately discovered negative regulator of innate immunity and cellular immunity. The present study was designed to investigate whether naturally occurring dendritic cells (DCs) could express TIPE2 mRNA/protein and its potential significance. Expressions of co-stimulatory molecules on DC surface and cytokines were analyzed to assess the functional role of TIPE2 in controlling DC maturation as well as activation. The activated DCs were assessed for their capacity to stimulate the proliferation and differentiation of T cells. It was found that TIPE2 was a cytoplasmic protein expressed in DCs, and the percentage of DCs which expressed co-stimulatory molecules and cytokines were obviously up-regulated when TIPE2 gene silenced by siRNA in vitro and in vivo. DCs undergone TIPE2 knockdown were found to promote the maturation of DCs, T-cell proliferation as well as differentiation, and they were significantly elevated IL-2 level and intranuclear NF-AT activation. Conversely, in over-expressing TIPE2 DC cells, it could inhibit T-cell proliferation and differentiation, and markedly down-regulate IL-2 expression and intranuclear NF-AT activation after scald injury. The results suggested that TIPE2 appeared to be a critical immunoregulatory molecule which affected DC maturation and subsequent T-cell mediated immunity. PMID:27029075

  8. Draft genome sequence of pathogenic bacteria Vibrio parahaemolyticus strain Ba94C2, associated with acute hepatopancreatic necrosis disease isolate from South America.

    PubMed

    Restrepo, Leda; Bayot, Bonny; Betancourt, Irma; Pinzón, Andres

    2016-09-01

    Vibrio parahaemolyticus is a pathogenic bacteria which has been associated to the early mortality syndrome (EMS) also known as hepatopancreatic necrosis disease (AHPND) causing high mortality in shrimp farms. Pathogenic strains contain two homologous genes related to insecticidal toxin genes, PirA and PirB, these toxin genes are located on a plasmid contained within the bacteria. Genomic sequences have allowed the finding of two strains with a divergent structure related to the geographic region from where they were found. The isolates from the geographic collection of Southeast Asia and Mexico show variable regions on the plasmid genome, indicating that even though they are not alike they still conserve the toxin genes. In this paper, we report for the first time, a pathogenic V. parahaemolyticus strain in shrimp from South America that showed symptoms of AHPND. The genomic analysis revealed that this strain of V. parahaemolyticus found in South America appears to be more related to the Southeast Asia as compared to the Mexican strains. This finding is of major importance for the shrimp industry, especially in regards to the urgent need for disease control strategies to avoid large EMS outbreaks and economic loss, and to determine its dispersion in South America. The whole-genome shotgun project of V. parahaemolyticus strain Ba94C2 have been deposited at DDBJ/EMBL/GenBank under the accession PRJNA335761.

  9. Tumor necrosis factor-α regulates glucocorticoid synthesis in the adrenal glands of Trypanosoma cruzi acutely-infected mice. the role of TNF-R1.

    PubMed

    Villar, Silvina R; Ronco, M Teresa; Fernández Bussy, Rodrigo; Roggero, Eduardo; Lepletier, Ailin; Manarin, Romina; Savino, Wilson; Pérez, Ana Rosa; Bottasso, Oscar

    2013-01-01

    Adrenal steroidogenesis is under a complex regulation involving extrinsic and intrinsic adrenal factors. TNF-α is an inflammatory cytokine produced in response to tissue injury and several other stimuli. We have previously demonstrated that TNF-R1 knockout (TNF-R1(-/-)) mice have a dysregulated synthesis of glucocorticoids (GCs) during Trypanosoma cruzi acute infection. Since TNF-α may influence GCs production, not only through the hypothalamus-pituitary axis, but also at the adrenal level, we now investigated the role of this cytokine on the adrenal GCs production. Wild type (WT) and TNF-R1(-/-) mice undergoing acute infection (Tc-WT and Tc-TNF-R1(-/-) groups), displayed adrenal hyperplasia together with increased GCs levels. Notably, systemic ACTH remained unchanged in Tc-WT and Tc-TNF-R1(-/-) compared with uninfected mice, suggesting some degree of ACTH-independence of GCs synthesis. TNF-α expression was increased within the adrenal gland from both infected mouse groups, with Tc-WT mice showing an augmented TNF-R1 expression. Tc-WT mice showed increased levels of P-p38 and P-ERK compared to uninfected WT animals, whereas Tc-TNF-R1(-/-) mice had increased p38 and JNK phosphorylation respect to Tc-WT mice. Strikingly, adrenal NF-κB and AP-1 activation during infection was blunted in Tc-TNF-R1(-/-) mice. The accumulation of mRNAs for steroidogenic acute regulatory protein and cytochrome P450 were significantly increased in both Tc-WT and Tc-TNF-R1(-/-) mice; being much more augmented in the latter group, which also had remarkably increased GCs levels. TNF-α emerges as a potent modulator of steroidogenesis in adrenocortical cells during T. cruzi infection in which MAPK pathways, NF-κB and AP-1 seem to play a role in the adrenal synthesis of pro-inflammatory cytokines and enzymes regulating GCs synthesis. These results suggest the existence of an intrinsic immune-adrenal interaction involved in the dysregulated synthesis of GCs during murine Chagas disease.

  10. Intravenous hMSCs Ameliorate Acute Pancreatitis in Mice via Secretion of Tumor Necrosis Factor-α Stimulated Gene/Protein 6

    PubMed Central

    He, Zhigang; Hua, Jie; Qian, Daohai; Gong, Jian; Lin, Shengping; Xu, Chenglei; Wei, Ge; Meng, Hongbo; Yang, Tingsong; Zhou, Bo; Song, Zhenshun

    2016-01-01

    The administration of mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs) to enhance tissue repair is currently undergoing clinical trials. Some studies, including our previous work, have also revealed the beneficial effect of MSCs in severe acute pancreatitis (SAP); however, their mechanisms or mode of action remain controversial. In this study, we demonstrated that intravenously (i.v.)-administered human MSCs (hMSCs) remarkably promoted recovery from experimental SAP without significant engraftment of hMSCs in the damaged pancreas. Interestingly, we found that i.v.-administered hMSCs with knockdown of TSG-6 expression lost most of their anti-inflammatory effects and thus could not significantly ameliorate SAP. As expected, the effects of hMSCs were also duplicated by i.v. infusion of recombinant TSG-6. Furthermore, our results showed that the increase of oxidative stress, activation of the NLRP3 inflammasome and NF-κB signaling in SAP was substantially inhibited following administration of hMSCs or TSG-6, which was dependent on the presence of CD-44 receptors in acinar cells. In conclusion, our study, for the first time, revealed that novel mechanisms are responsible for the immunomodulatory effect of i.v. hMSCs. PMID:27917949

  11. Adjusting effects of baicalin for nuclear factor-kappaB and tumor necrosis factor-alpha on rats with caerulein-induced acute pancreatitis.

    PubMed

    Xue, Dongbo; Zhang, Weihui; Zhang, Yingmei; Wang, Haiyang; Zheng, Biao; Shi, Xingye

    2006-01-01

    Forty Wistar rats were divided into 5 groups, including the control group, the acute pancreatitis group (AP group, induced by intraperitoneal injections of caerulein), and the AP group treated with baicalin, the AP group treated with LPS, and the AP group treated with LPS and baicalin. Pathological damage of pancreatic tissue was scored with hematoxylin and eosin (HE) staining. The mRNA expression of TNF-alpha was measured with semiquantitative RT-PCR, and activation of NF-kappaB was detected with flow cytometry assay. It was shown in the results that the expression of TNF-alpha mRNA, activation of NF-kappaB, and pathological score of AP group were all obviously higher than those of control group (P < .01). In AP group treated with LPS, further rise of these values were observed (P < .01). In the AP group treated with baicalin, activation of NF-kappaB decreased (P < .05), and expression of TNF-alpha mRNA also obviously decreased (P < .01), while pancreatic pathological damage was alleviated at the same time (P < .01); similar results were observed in AP group treated with LPS and baicalin (P < .01), which indicated that baicalin might be applied to inhibit NF-kappaB activating and TNF-alpha expressing so as to treat AP.

  12. Human Alpha-1-Antitrypsin (hAAT) therapy reduces renal dysfunction and acute tubular necrosis in a murine model of bilateral kidney ischemia-reperfusion injury

    PubMed Central

    Maicas, Nuria; van der Vlag, Johan; Bublitz, Janin; Florquin, Sandrine; Bakker-van Bebber, Marinka; Dinarello, Charles A.; Verweij, Vivienne; Masereeuw, Roos; Joosten, Leo A.

    2017-01-01

    Several lines of evidence have demonstrated the anti-inflammatory and cytoprotective effects of alpha-1-antitrypsin (AAT), the major serum serine protease inhibitor. The aim of the present study was to investigate the effects of human AAT (hAAT) monotherapy during the early and recovery phase of ischemia-induced acute kidney injury. Mild renal ischemia-reperfusion (I/R) injury was induced in male C57Bl/6 mice by bilateral clamping of the renal artery and vein for 20 min. hAAT (80 mg/kg, Prolastin®) was administered daily intraperitoneally (i.p.) from day -1 until day 7 after surgery. Control animals received the same amount of human serum albumin (hAlb). Plasma, urine and kidneys were collected at 2h, 1, 2, 3, 8 and 15 days after reperfusion for histological and biochemical analysis. hAAT partially preserved renal function and tubular integrity after induction of bilateral kidney I/R injury, which was accompanied with reduced renal influx of macrophages and a significant decrease of neutrophil gelatinase-associated lipocalin (NGAL) protein levels in urine and plasma. During the recovery phase, hAAT significantly decreased kidney injury molecule-1 (KIM-1) protein levels in urine but showed no significant effect on renal fibrosis. Although the observed effect size of hAAT administration was limited and therefore the clinical relevance of our findings should be evaluated carefully, these data support the potential of this natural protein to ameliorate ischemic and inflammatory conditions. PMID:28235038

  13. 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 ...

  14. Renal papillary necrosis

    MedlinePlus

    ... ureters. Causes Renal papillary necrosis often occurs with analgesic nephropathy . This is damage to one or both ... Treatment depends on the cause. For example, if analgesic nephropathy is the cause, your doctor will recommend ...

  15. 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.

  16. Inhibition of γ-secretase activity synergistically enhances tumour necrosis factor-related apoptosis-inducing ligand induced apoptosis in T-cell acute lymphoblastic leukemia cells via upregulation of death receptor 5

    PubMed Central

    Greene, Lisa M.; Nathwani, Seema M.; Zisterer, Daniela M.

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive hematopoietic malignancy prone to relapse and drug resistance. Half of all T-ALL patients exhibit mutations in Notch1, which leads to aberrant Notch1 associated signaling cascades. Notch1 activation is mediated by the γ-secretase cleavage of the Notch1 receptor into the active intracellular domain of Notch1 (NCID). Clinical trials of γ-secretase small molecule inhibitors (GSIs) as single agents for the treatment of T-ALL have been unsuccessful. The present study demonstrated, using immunofluorescence and western blotting, that blocking γ-secretase activity in T-ALL cells with N-[(3,5-difluorophenyl) acetyl]-L-alanyl-2-phenyl] glycine-1,1-dimethylethyl ester (DAPT) downregulated NCID and upregulated the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor 5 (DR5). Upregulation of DR5 restored the sensitivity of T-ALL cells to TRAIL. Combination index revealed that the combined treatment of DAPT and TRAIL synergistically enhanced apoptosis compared with treatment with either drug alone. TRAIL combined with the clinically evaluated γ-secretase inhibitor 3-[(1r, 4s)-4-(4-chlorophenylsulfonyl)-4-(2, 5-difluorophenyl) cyclohexyl] propanoic acid (MK-0752) also significantly enhanced TRAIL-induced cell death compared with either drug alone. DAPT/TRAIL apoptotic synergy was dependent on the extrinsic apoptotic pathway and was associated with a decrease in BH3 interacting-domain death agonist and x-linked inhibitor of apoptosis. In conclusion, γ-secretase inhibition represents a potential therapeutic strategy to overcome TRAIL resistance for the treatment of T-ALL. PMID:27698877

  17. Relationship between coumarin-induced hepatocellular toxicity and mitochondrial function in rats.

    PubMed

    Tanaka, Yasuhiro; Fujii, Wataru; Hori, Hisako; Kitagawa, Yoshinori; Ozaki, Kiyokazu

    2016-04-01

    The manifestation of coumarin-induced hepatocellular toxicity may differ and depends on the frequency of administration to rats. A single coumarin dose induces hepatocellular necrosis while repeated doses induce only hepatocyte degeneration. However, the mechanism underlying these effects remains unclear. Therefore, we investigated the mechanism of coumarin-induced hepatotoxicity in rats. Coumarin was administered to male rats as a single dose or for 4 consecutive days, and samples were obtained 4 or 24 h after a single dose or 24 h after the repeated doses. A single coumarin dose significantly induced hepatocellular necrosis in rats; however, toxicity was attenuated after repeated dosing. With a single dose, hepatocellular necrosis was preceded by increased mitochondrial number and size and decreased mitochondrial function. An increased expression of granular cytochrome P450 (CYP) 2E1 protein was observed in the cytoplasm and mitochondria of coumarin-treated rats compared to the expression in the untreated controls. Nevertheless, repeated dosing showed mitochondrial function that was equivalent to that of the control while enlarged CYP2E1 protein droplets were distributed outside the mitochondria. These results suggest that mitochondrial function and CYP2E1 expression might be involved in coumarin-induced hepatocellular toxicity in rats. A reduction in mitochondrial CYP2E1 might be implicated in the acquisition of coumarin resistance after repeated doses.

  18. 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.

  19. Circulating lysosomal enzymes and acute hepatic necrosis.

    PubMed Central

    Gove, C D; Wardle, E N; Williams, R

    1981-01-01

    The activities of the lysosomal enzymes acid and neutral protease, N-acetylglucosaminidase, and acid phosphatase were measured in the serum of patients with fulminant hepatic failure. Acid protease (cathepsin D) activity was increased about tenfold in patients who died and nearly fourfold in those who survived fulminant hepatic failure after paracetamol overdose, whereas activities were increased equally in patients with fulminant hepatic failure due to viral hepatitis whether or not they survived. A correlation was found between serum acid protease activity and prothrombin time, and the increase in cathepsin D activity was sustained over several days compared with aspartate aminotransferase, which showed a sharp early peak and then a fall. Circulating lysosomal proteases can damage other organs, and measurement of their activity may therefore be of added value in assessing prognosis in this condition. PMID:7007443

  20. Strangulated adenoma of the liver: a unique cause of acute abdomen.

    PubMed

    Portinari, Mattia; Liboni, Alberto; Feo, Carlo V

    2014-03-20

    Hepatic adenomas are uncommon benign tumours of the liver which may eventually present with acute onset following rupture of the lesion and haemorrhage. We present here a unique case of strangulated adenoma of the liver presenting as acute abdomen. A 27-year-old woman taking oral contraceptives, presented to the emergency department with abdominal pain, palpable abdominal mass, fever, and neutrophilia. An abdominal ultrasound showed a 3-cm hepatic nodule and an 11-cm mesogastric mass. Computed tomography of the abdomen revealed a 2.3-cm liver adenoma and a 13-cm pedunculated mass of the liver showing no contrast enhancement suggestive of pedicle torsion with ischemia of the mass. The patient underwent an emergent open resection of the strangulated liver mass, she recovered without complications, and was discharged home after three days. Final pathology confirmed an hepatocellular adenoma with areas of necrosis and hemorrhage. The clinical significance of the disease is discussed.

  1. Renal cortical necrosis: A rare complication of Plasmodium vivax malaria.

    PubMed

    Kumar, R; Bansal, N; Jhorawat, R; Kimmatkar, P D; Malhotra, V

    2014-11-01

    A young female with Plasmodium vivax malaria presented with anemia, hyperbilirubinemia, thrombocytopenia, and advanced renal failure. She remained anuric for more than 3 weeks. Kidney biopsy confirmed the diagnosis of acute cortical necrosis. During follow-up, she became dialysis independent, but remained in stage 4 chronic kidney disease (CKD) at 3 month. P. vivax is supposed to be benign in nature, but can lead to rare and severe complication like renal cortical necrosis and progress to CKD.

  2. Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy

    PubMed Central

    Guo, Rui; Lin, Bin; Pan, Jing Fei; Liong, Emily C.; Xu, Ai Min; Youdim, Moussa; Fung, Man Lung; So, Kwok Fai; Tipoe, George L.

    2016-01-01

    Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury. PMID:27580936

  3. Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy.

    PubMed

    Guo, Rui; Lin, Bin; Pan, Jing Fei; Liong, Emily C; Xu, Ai Min; Youdim, Moussa; Fung, Man Lung; So, Kwok Fai; Tipoe, George L

    2016-09-01

    Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury.

  4. Oligodendroglial degeneration in distemper: apoptosis or necrosis?

    PubMed

    Schobesberger, M; Zurbriggen, A; Summerfield, A; Vandevelde, M; Griot, C

    1999-03-01

    Canine distemper virus (CDV) causes a multifocal demyelinating disease in dogs. It was previously shown that the initial demyelinating lesions are directly virus induced since a correlation between the occurrence of demyelination and CDV replication in white matter cells was observed. During the course of infection oligodendrocytes undergo distinct morphological alterations, partly due to a restricted CDV infection of these cells, and eventually disappear from the lesions. This phenomenon has been described in vivo as well as in vitro. However, the reason for the morphological alterations and the following oligodendroglial depletion remained unclear. Since virus infection can induce cell death, it was investigated whether apoptosis or necrosis plays a role in the pathogenesis of demyelination in canine distemper. In brain tissue sections from dogs with acute distemper apoptotic cells were not detected within the demyelinating lesions using morphological and biochemical cell death criteria. In chronic distemper, apoptotic cells - presumably inflammatory cells - were seen within the perivascular cuffs. These in vivo findings were correlated to the in vitro situation using CDV-infected primary dog brain cell cultures as well as Vero cells. Infection with culture-adapted CDV lead to massive necrosis but not to apoptosis. After infection with virulent CDV neither apoptosis nor necrosis was a predominant feature in either culture system. These findings suggest that virus-induced demyelination in canine distemper is not the direct consequence of apoptosis or necrosis. It is speculated that another mechanism must be responsible for the observed morphological alterations of oligodendrocytes, ultimately leading to demyelination.

  5. Hepatic necrosis following halothane anesthesia in goats.

    PubMed

    O'Brien, T D; Raffe, M R; Cox, V S; Stevens, D L; O'Leary, T P

    1986-12-15

    One goat anesthetized with thiamylal sodium, xylazine, and halothane for repair of an abominal hernia, and 7 of 29 goats similarly anesthetized for an experiment unrelated to considerations of anesthesia, developed signs of hepatic failure within 24 hours of anesthesia. Affected goats had high values for serum aspartate transaminase and serum total bilirubin by 12 to 24 hours after induction of anesthesia. Necropsy of the 8 affected goats revealed centrilobular to massive hepatic necrosis (8 of 8), brain lesions consistent with hepatic encephalopathy (3 of 4), and acute renal tubular necrosis (6 of 6). Two unaffected goats had no hepatic necrosis. Causes of hepatic necrosis other than those related to anesthesia (eg, infectious agents, toxins) were ruled out by lack of supporting necropsy findings or were considered unlikely because of lack of opportunity for exposure. Hepatic lesions in these goats closely resembled those described in human beings with halothane-associated hepatic injury, although in both species these lesions are nonspecific at the gross and light microscopic levels. The pathogenesis of halothane-associated hepatic injury in goats, as in human beings, remains to be determined.

  6. Tumor necrosis factor.

    PubMed

    Chu, Wen-Ming

    2013-01-28

    Tumor necrosis factor (TNF) is a critical cytokine, which contributes to both physiological and pathological processes. This mini-review will briefly touch the history of TNF discovery, its family members and its biological and pathological functions. Then, it will focus on new findings on the molecular mechanisms of how TNF triggers activation of the NF-κB and AP-1 pathways, which are critical for expression of pro-inflammatory cytokines, as well as the MLKL cascade, which is critical for the generation of ROS in response to TNF. Finally, this review will briefly summarize recent advances in understanding TNF-induced cell survival, apoptosis and necrosis (also called necroptosis). Understanding new findings and emerging concepts will impact future research on the molecular mechanisms of TNF signaling in immune disorders and cancer-related inflammation.

  7. Necrosis in yeast.

    PubMed

    Eisenberg, Tobias; Carmona-Gutierrez, Didac; Büttner, Sabrina; Tavernarakis, Nektarios; Madeo, Frank

    2010-03-01

    Necrosis was long regarded as an accidental cell death process resulting from overwhelming cellular injury such as chemical or physical disruption of the plasma membrane. Such a definition, however, proved to be inapplicable to many necrotic scenarios. The discovery that genetic manipulation of several proteins either protected or enhanced necrotic cell death argued in favor of a regulated and hence programmed process, as it is the case for apoptosis. For more than a decade, yeast has served as a model for apoptosis research; recently, evidence accumulated that it also harbors a necrotic program. Here, we summarize the current knowledge about factors that control necrotic cell death in yeast. Mitochondria, aging and a low pH are positive regulators of this process while cellular polyamines (e.g. spermidine) and endonuclease G as well as homeostatic organelles like the vacuole or peroxisomes are potent inhibitors of necrosis. Physiological necrosis may stimulate intercellular signaling via the release of necrotic factors that promote viability of healthy cells and, thus, assure survival of the clone. Together, the data obtained in yeast argue for the existence of a necrotic program, which controls longevity and whose physiological function may thus be aging.

  8. Transarterial embolization for large hepatocellular carcinoma with use of superabsorbent polymer microspheres: initial experience.

    PubMed

    Osuga, Keigo; Khankan, Azzam Anwar; Hori, Shinichi; Okada, Atsuya; Sugiura, Takashi; Maeda, Munehiro; Nagano, Hiroaki; Yamada, Akira; Murakami, Takamichi; Nakamura, Hironobu

    2002-09-01

    The authors report the initial experience with transarterial embolization of large hepatocellular carcinoma (HCC) with use of superabsorbent polymer microsphere (SAP-MS) particles. Six patients with nine HCCs (mean diameter, 8.2 cm) underwent 10 embolization procedures. Two patients underwent surgery later. In follow-up, tumor necrosis, postembolization syndrome, and laboratory data were assessed. Complete necrosis in three nodules, nearly complete necrosis in three nodules, and partial necrosis in three nodules were observed. Histologically, SAP-MS occluded intratumoral vessels tightly without ischemic damage of normal hepatic tissue. Postprocedural pain was minimal. No deterioration of liver function occurred. Our initial experience suggests that embolization with use of SAP-MS leads to extensive tumor necrosis of large nodular HCC, sparing use of chemotherapeutic agents.

  9. Imaging Manifestations of Mediastinal Fat Necrosis

    PubMed Central

    Bhatt, Malay Y.; Martínez-Jiménez, Santiago; Rosado-de-Christenson, Melissa L.; Watson, Kenneth R.; Walker, Christopher M.; Kunin, Jeffrey R.

    2013-01-01

    Mediastinal fat necrosis (MFN) or epipericardial fat necrosis, as it is commonly referred to in the literature, is a rare self-limiting cause of chest pain of unclear etiology. MFN affects previously healthy individuals who present with acute pleuritic chest pain. Characteristic computed tomography (CT) findings include a fat attenuation lesion with intrinsic and surrounding increased attenuation stranding. There is often associated thickening of the adjacent pericardium and/or pleural effusions. We present two cases of MFN manifesting as ovoid fat attenuation lesions demarcated by a soft tissue attenuation rim with intrinsic and surrounding soft tissue attenuation stranding and review the clinical and pathologic features of these lesions. Knowledge of the clinical presentation of patients with MFN and familiarity with the characteristic imaging findings of these lesions should allow radiologists to prospectively establish the correct diagnosis and suggest conservative management and follow-up. PMID:24369521

  10. Radiologic-Pathologic Correlation of Hepatocellular Carcinoma Treated with Chemoembolization

    SciTech Connect

    Riaz, Ahsun; Lewandowski, Robert J.; Kulik, Laura; Ryu, Robert K.; Mulcahy, Mary F.; Baker, Talia; Gates, Vanessa; Nayar, Ritu; Wang, Ed; Miller, Frank H.; Sato, Kent T.; Omary, Reed A.; Abecassis, Michael; Salem, Riad

    2010-12-15

    To correlate posttreatment radiologic and pathologic findings in patients who underwent transarterial chemoembolization before transplantation or resection. Thirty-five patients with postchemoembolization follow-up imaging underwent liver transplantation/resection. Pre- and posttreatment contrast-enhanced magnetic resonance imaging were used to evaluate radiologic findings. Imaging characteristics using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria after treatment were evaluated. Treated lesions were examined by pathology (gold standard) for the assessment of necrosis. Radiologic findings on magnetic resonance imaging were correlated to pathologic findings to assess the predictability by imaging of actual necrosis. Kappa ({kappa}) statistics were used to determine intermethod agreement between WHO and EASL criteria. Fourteen (40%) of 35 lesions had biopsy-proven hepatocellular carcinoma. Thirteen (37%) of 35 target lesions showed complete pathologic necrosis. Complete pathologic necrosis was seen in 35% of lesions with pretreatment size <3 cm. Complete pathologic necrosis was seen in 1 (100%) of 1, 6 (67%) of 9, 6 (33%) of 18, and 0 (0%) of 7 of the lesions that exhibited complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by WHO criteria, respectively. Complete pathologic necrosis was seen in 9 (82%) of 11, 4 (36%) of 11, 0 (0%) of 8, and 0 (0%) of 5 of the lesions that showed CR, PR, SD, or PD by EASL criteria, respectively. EASL CR and WHO response were shown to have {>=}85% specificity for predicting complete pathologic necrosis. The {kappa} coefficient for agreement between WHO and EASL was 0.29. EASL and WHO criteria had minimal intermethod agreement. EASL CR and WHO response were able to predict pathologic necrosis.

  11. Prognostic significance of differentiating necrosis from fluid collection on endoscopic ultrasound in patients with presumed isolated extrapancreatic necrosis

    PubMed Central

    Rana, Surinder S.; Chhabra, Puneet; Sharma, Ravi; Sharma, Vishal; Gupta, Rajesh; Bhasin, Deepak K.

    2017-01-01

    Background Extrapancreatic necrosis is diagnosed on computed tomography (CT) as extrapancreatic changes that are more than fat stranding; both fluid collections and necrosis would have a similar appearance. The aim of this study was to determine the prognostic significance of differentiating peripancreatic necrosis from fluid collection on endoscopic ultrasound (EUS) in patients with presumed isolated extrapancreatic necrosis. Methods We carried out a retrospective analysis of prospectively collected data from 36 patients (25 males; age range 19-65 years) with acute pancreatitis (AP) and isolated extrapancreatic necrosis. On EUS, peripancreatic anechoic areas were labeled as peripancreatic fluid collections and peripancreatic heterogeneously echotextured areas as peripancreatic necrosis. Results The etiology of AP was alcohol in 16 (44.4%) patients, gallstone disease in 13 (36.1%), and other in 7 (19.4%). On EUS, 25 (69.4%) patients had peripancreatic necrosis and 11 (30.6%) patients had peripancreatic fluid collections. Compared with patients who had peripancreatic fluid collections, patients with peripancreatic necrosis had a significantly higher frequency of pleural effusion (88% vs. 55%; P=0.04), organ failure (OF) (68% vs. 27%; P=0.03), and persistent OF (48% vs. 9%; P=0.03). The patients with peripancreatic necrosis also had a higher frequency of ascites (20% vs. 9%), need for intervention (20% vs. nil), surgery (8% vs. nil) and mortality (8% vs. nil), but these differences were not statistically significant. Conclusion Isolated extrapancreatic necrosis on contrast-enhanced CT comprises a heterogeneous group, with patients who show peripancreatic fluid collections on EUS having a less severe disease course compared to patients with peripancreatic necrosis. PMID:28243045

  12. Renal papillary necrosis: an update.

    PubMed

    Eknoyan, G; Qunibi, W Y; Grissom, R T; Tuma, S N; Ayus, J C

    1982-03-01

    The clinical and diagnostic features of renal papillary necrosis (RPN) of 27 patients were studied. Diabetes mellitus was the most frequent (56%) condition associated with RPN. Analgesic abuse, sickle hemoglobinopathy and urinary tract obstruction were present in 4 patients each; in 6 of these 12 patients these conditions were present as a coexistent disease with diabetes mellitus. There was evidence of an acute or chronic infection of the urinary tract in 18 patients, as a coexistent condition with another underlying disease that itself can cause RPN in 14 patients and as the only cause of RPN in another 4. Thus, the presence of more than one diagnostic condition which might be implicated in the causation of RPN was present in 15 patients or 55% of the cases in this series. When infection was excluded, six patients or 22% of the cases had two coexisting diseases, each of which has been implicated as a cause of RPN. This observation underlines the multifactorial nature of this entity and might explain why RPN is not encountered more frequently in each of the various primary diseases with which it has been associated. The average age of the patients at the time of diagnosis was 53 years for women and 56 years for men. Only six of the patients were younger than 40 years, and three of these had sickle hemoglobinopathy. The diagnosis of RPN was based on x-ray findings in eight patients, on the histologic examination of papillary tissue in urine in one, and on autopsy findings in the rest. Papillary necrosis was bilateral in three-fourths of the cases. The clinical picture varied. Most of the patients (67%) presented with chills and fever. Flank pain and dysuria were present in 11 patients (41%). As a rule oliguria was rare and progressive uremia was uncommon. In cases diagnosed at post-mortem, the patients had succumbed to infection or to a primary severe extrarenal disorder with the possibility of RPN having been entertained clinically in only half these cases prior

  13. 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

  14. Arthroscopic assessment of avascular necrosis.

    PubMed

    Bain, Gregory I; Durrant, Adam W

    2011-08-01

    Avascular necrosis of the lunate is a process that is not well understood. The cause is uncertain, but a common theory persists that it is caused by disruption of the vascular supply to the lunate. This article discusses an approach to assessment that respects the articular cartilage and places at the front of the decision-making process the pathoanatomic components of the articular cartilage. It primarily respects the articular cartilage in the patient with avascular necrosis. This approach was developed for avascular necrosis of the lunate, but in principle applies to other joints with avascular necrosis as well.

  15. Nasal Skin Necrosis: An Unexpected New Finding in Severe Chikungunya Fever.

    PubMed

    Torres, Jaime R; Córdova, Leopoldo G; Saravia, Víctor; Arvelaez, Joanne; Castro, Julio S

    2016-01-01

    Three adult Venezuelan patients with virologically confirmed Chikungunya fever, who developed extensive acute nasal skin necrosis early in the course of a life-threatening illness characterized by shock and multiple organ dysfunction syndrome, are discussed. One patient survived and fully recovered. Nasal necrosis has not previously been associated with the disease.

  16. Necrosis Avidity: A Newly Discovered Feature of Hypericin and its Preclinical Applications in Necrosis Imaging

    PubMed Central

    Jiang, Binghu; Wang, Jichen; Ni, Yicheng; Chen, Feng

    2013-01-01

    Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been discovered to have a specific avidity for necrotic tissue. This affinity is also observed in a series of radiolabeled derivatives of hypericin, including [123I]iodohypericin, [124I]iodohypericin, and [131I]iodohypericin. Hypericin, along with other necrosis-avid contrast agents, has been investigated for use in noninvasively targeting necrotic tissues in numerous disorders. Potential clinical applications of hypericin include the identification of acute myocardial infarction, evaluation of tissue viability, assessment of therapeutic responses to treatments, and interventional procedures for solid tumors. The mechanisms of necrosis avidity in hypericin remain to be fully elucidated, although several hypotheses have been suggested. In particular, it has been proposed that the necrosis avidity of hypericin is compound specific; for instance, cholesterol, phosphatidylserine, or phosphatidylethanolamine components in the phospholipid bilayer of cellular membranes may be the major targets for its observed selectivity. Further investigations are needed to identify the specific binding moiety that is responsible for the necrosis avidity of hypericin. PMID:24052807

  17. Epipericardial fat necrosis: an underdiagnosed condition

    PubMed Central

    Costa, A N; Bachion, G H; Apanavicius, A; Filho, J R P; Kairalla, R A; Lynch, D A

    2014-01-01

    Objective: Epipericardial fat necrosis (EFN) is an uncommon benign and self-limited condition that leads patients to the emergency department (ED) owing to the onset of acute pleuritic chest pain. The aim of this study was to describe the cases of this disease in our institution and to illustrate the associated clinical and radiological findings. Methods: We reviewed 3604 chest scans referred by the ED from November 2011 to July 2013. Patients diagnosed with epipericardial necrosis had their medical records and original tomography reports analysed. Results: Chest pain was the primary complaint in 426 patients; 11 of them had definitive EFN findings characterized by a round soft-tissue attenuation lesion with a varying degree of strands. All patients presented with pleuritic chest pain on the same side as the lesion. Pericardial thickening, pleural effusion and mild atelectasis were the associated tomography findings. Cardiac enzyme and D-dimer tests performed during the episode were normal in all cases. 27% of the cases only were correctly diagnosed with EFN at the time of presentation. Conclusion: EFN is a benign inflammatory condition frequently overlooked in the ED by physicians and radiologists but is an important factor in the differential diagnosis of patients with acute chest pain. Advances in knowledge: The article adds clinically and radiologically useful information about the condition and displays the importance of making the correct diagnosis to avoid unnecessary examinations. PMID:24707937

  18. 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

  19. Hepatocellular carcinoma in variegate porphyria: a case report and literature review.

    PubMed

    Luvai, Ahai; Mbagaya, Wycliffe; Narayanan, Deepa; Degg, Tim; Toogood, Giles; Wyatt, Judith I; Swinson, Daniel; Hall, Claire J; Barth, Julian H

    2015-05-01

    Variegate porphyria is an autosomal dominant acute hepatic porphyria characterized by photosensitivity and acute neurovisceral attacks. Hepatocellular carcinoma has been described as a potential complication of variegate porphyria in case reports. We report a case of a 48-year-old woman who was diagnosed with hepatocellular carcinoma following a brief history of right upper quadrant pain which was preceded by a few months of blistering lesions in sun-exposed areas. She was biochemically diagnosed with variegate porphyria, and mutational analysis confirmed the presence of a heterozygous mutation in the protoporphyrinogen oxidase gene. Despite two hepatic resections, she developed pulmonary metastases. She responded remarkably well to Sorafenib and remains in remission 16 months after treatment. A review of the literature revealed that hepatocellular carcinoma in variegate porphyria has been described in at least eight cases. Retrospective and prospective cohort studies have suggested a plausible association between hepatocellular carcinoma and acute hepatic porphyrias. Hepatic porphyrias should be considered in the differential diagnoses of hepatocellular carcinoma of uncertain aetiology. Patients with known hepatic porphyrias may benefit from periodic monitoring for this complication.

  20. Protective effects of Parinari curatellifolia flavonoids against acetaminophen-induced hepatic necrosis in rats

    PubMed Central

    Olaleye, Mary Tolulope; Amobonye, Ayodeji Emmannuel; Komolafe, Kayode; Akinmoladun, Afolabi Clement

    2014-01-01

    In the present study, we investigated the hepatoprotective potential of Parinari curatellifolia Planch (Chrysobalanaceae) in experimental rats in order to ascertain the validity of folkloric claims of its effectiveness in the treatment of hepatic-related disorders. Flavonoid extract of P. curatellifolia seed, PCF (10-, 20- or 30 mg/kg body weight) or silymarin (25 mg/kg), dissolved in corn oil, was administered by gavage to experimental animals once daily for 14 consecutive days before liver damage was chemically induced through the administration of acetaminophen (2 g/kg p.o.) on the 14th day. Hepatoprotection was assessed by analyzing liver homogenate and serum for markers of hepatotoxicity – alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) activities as well as prothrombin time (PT). Evaluation of biochemical indices of oxidative stress – level of lipid peroxides (LPO), activities of superoxide dismutase (SOD) and catalase, along with histological assessment of hepatic tissue sections were also carried out. Results revealed that all doses of PCF significantly (P < 0.001) and dose dependently prevented acetaminophen-induced increase in serum activities of hepatic enzymes (ALT, AST, GGT, LDH) and PT. Furthermore, PCF (10- and 20 mg/kg) significantly (P < 0.001) reduced lipid peroxidation in liver tissue and restored the activities of the antioxidant enzymes SOD and catalase toward normal levels. Histopathology of the liver tissue showed that PCF mitigated the toxicant-induced hepatocellular necrosis, reduced inflammatory cell infiltration and enhanced hepatocyte regeneration. The results indicated that P. curatellifolia flavonoids demonstrated remarkable hepatoprotective activity in acute liver injury caused by acetaminophen. PMID:25313285

  1. 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).

  2. 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

  3. 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

  4. 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

  5. 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

  6. Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development

    PubMed Central

    Nayeb-Hashemi, Hamed; Desai, Anal; Demchev, Valeriy; Bronson, Roderick T.; Hornick, Jason L.; Cohen, David E.; Ukomadu, Chinweike

    2015-01-01

    Fibrinogen like protein-1 (Fgl1) is a predominantly liver expressed protein that has been implicated as both a hepatoprotectant and a hepatocyte mitogen. Fgl1 expression is decreased in hepatocellular carcinoma (HCC) and its loss correlates with a poorly differentiated phenotype. To better elucidate the role of Fgl1 in hepatocarcinogenesis, we treated mice wild type or null for Fgl1 with diethyl nitrosamine and monitored for incidence of hepatocellular cancer. We find that mice lacking Fgl1 develop HCC at more than twice the rate of wild type mice. We show that hepatocellular cancers from Fgl1 null mice are molecularly distinct from those of the wild type mice. In tumors from Fgl1 null mice there is enhanced activation of Akt and downstream targets of the mammalian target of rapamycin (mTOR). In addition, there is paradoxical up regulation of putative hepatocellular cancer tumor suppressors; tripartite motif-containing protein 35 (Trim35) and tumor necrosis factor super family 10b (Tnfrsf10b). Taken together, these findings suggest that Fgl1 acts as a tumor suppressor in hepatocellular cancer through an Akt dependent mechanism and supports its role as a potential therapeutic target in HCC. PMID:26225745

  7. 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 ...

  8. 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 ...

  9. An Unusual Complication Following Transarterial Chemoembolization: Acute Myocardial Infarction

    SciTech Connect

    Lai Yiliang; Chang Weichou; Kuo Wuhsien; Huang Tienyu; Chu Hengcheng; Hsieh Tsaiyuan; Chang Weikuo

    2010-02-15

    Transarterial chemoembolization has been widely used to treat unresectable hepatocellular carcinoma. Various complications have been reported, but they have not included acute myocardial infarction. Acute myocardial infarction results mainly from coronary artery occlusion by plaques that are vulnerable to rupture or from coronary spasm, embolization, or dissection of the coronary artery. It is associated with significant morbidity and mortality. We present a case report that describes a patient with hepatocellular carcinoma who underwent transarterial chemoembolization and died subsequently of acute myocardial infarction. To our knowledge, there has been no previous report of this complication induced by transarterial chemoembolization for hepatocellular carcinoma. This case illustrates the need to be aware of acute myocardial infarction when transarterial chemoembolization is planned for the treatment of hepatocellular carcinoma, especially in patients with underlying coronary artery disease.

  10. Apoptosis and Necrosis in the Liver

    PubMed Central

    Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

    2013-01-01

    Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

  11. 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

  12. 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.

  13. Spontaneous Necrosis of Choroidal Melanoma

    PubMed Central

    Thareja, Shalini; Rashid, Alia; Grossniklaus, Hans E.

    2014-01-01

    Background/Aims The purpose of this study was to examine the clinical presentations and pathological features of spontaneously necrotic choroidal melanomas. Methods The clinical and histological features of patients who underwent enucleation for uveal melanoma from 1989 to 2012 at Emory University and were found to have spontaneously necrotic choroidal melanomas were retrospectively analyzed. Results A total of 6 cases were identified. All cases had 90-100% tumor necrosis and also exhibited marked ischemic necrosis of the iris and ciliary body; 5 of 6 cases exhibited marked ischemic necrosis of the retina. The tumor consisted of melanoma ghost cells often surrounded by a zone of pigmented macrophages. Thrombi were not found in any of the cases. All of the tumors in our cases were centered around the equatorial choroid and 2 extended into the ciliary body. One of the cases exhibited a wedge-shaped infarct in a lateral aspect of the tumor. In most of the cases, microscopic areas of intact tumor cells were present in the peripheries of the tumors. Conclusions Spontaneous necrosis may occur in uveal melanoma. We believe that this occurs secondary to tumor hypoxia in the center of the tumor, followed by secondary inflammation, generalized ischemia and finally complete tumor necrosis. PMID:27175363

  14. [Nephrocalcinosis and subcutaneous fat necrosis].

    PubMed

    Gomes, Cláudia; Lobo, Luísa; Azevedo, António Siborro; Simão, Carla

    2015-01-01

    Subcutaneous fat necrosis of the newborn is an uncommon, transient and self-healing panniculits. This entity generally follows an uncomplicated course, however there are rare and important complications. The authors present a case of a newborn with subcutaneous fat necrosis complicated by hypercalcemia and nephrocalcinosis. The pathogenesis of hypercalcemia is not fully understood and the nephrocalcinosis can evolve to chronic kidney disease. Clinicians should be aware of subcutaneous fat necrosis as a possible risk factor for hypercalcemia and patients should have serial serum and urinary calcium determinations for up to 6 months after the appearance of the skin lesions. The early diagnosis and prompt treatment of hypercalcemia are essential to prevent severe complications.

  15. 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

  16. Avascular necrosis of carpal bones.

    PubMed

    Golimbu, C N; Firooznia, H; Rafii, M

    1995-05-01

    MR imaging is extremely well suited to detection of early phases of avascular necrosis, permitting diagnosis before collapse of the carpal bones has occurred. The sensitivity of this imaging modality allows differentiation of subtle changes in the bone marrow signal. This is used as criteria for a new stage classification of Kienböck's disease based on MR imaging appearance. The prognosis of scaphoid fractures and estimation of likelihood of avascular necrosis of the proximal fragment can be inferred by using gadolinium enhancement to evaluate the bone marrow vascularity.

  17. Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice

    PubMed Central

    Hudcovic, T; Kolinska, J; Klepetar, J; Stepankova, R; Rezanka, T; Srutkova, D; Schwarzer, M; Erban, V; Du, Z; Wells, J M; Hrncir, T; Tlaskalova-Hogenova, H; Kozakova, H

    2012-01-01

    One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms – bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression. PMID:22236013

  18. 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

  19. Inflammatory duodenal necrosis complicating gastroschisis

    PubMed Central

    Fouad, Dina; Lee, Geraint J.; Upadhyaya, Manasvi; Drake, David

    2016-01-01

    Babies with gastroschisis have an increased risk of necrotizing enterocolitis (NEC) that can lead to short bowel syndrome, a long-term parenteral nutrition requirement, and its associated complications. To our knowledge, this is the first case report of recurrent duodenal ischemia and necrosis associated with gastroschisis in the absence of NEC totalis. PMID:27695214

  20. Tumor Microenvironment, a Paradigm in Hepatocellular Carcinoma Progression and Therapy

    PubMed Central

    Tahmasebi Birgani, Maryam; Carloni, Vinicio

    2017-01-01

    Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers in the human population. Different etiological factors such as hepatitis B and C virus, alcohol and diabetes cause liver injury followed by inflammation, necrosis and hepatocytes proliferation. Continuous cycles of this destructive–regenerative process culminates in liver cirrhosis which is characterized by regenerating nodules that progress to dysplastic nodules and ultimately HCC. Despite its significance, there is only an elemental understanding of the pathogenetic mechanisms, and there are only limited therapeutic options. Therefore, the study of the involved molecular mechanisms can open a new insight to define more effective treatment strategies. A variety of alterations have been reported in HCC patients, particularly the cancer-associated microenvironment components including immune cells, fibroblast cells, endothelial cells and extracellular matrix can support the neoplastic cells to proliferate, growth and invade. This review summarizes the current state of knowledge and highlights the principal challenges that are relevant to controlling this milieu. PMID:28216578

  1. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2).

    PubMed

    Lambert, Daniel W; Yarski, Mike; Warner, Fiona J; Thornhill, Paul; Parkin, Edward T; Smith, A Ian; Hooper, Nigel M; Turner, Anthony J

    2005-08-26

    Angiotensin-converting enzyme-2 (ACE2) is a critical regulator of heart function and a cellular receptor for the causative agent of severe-acute respiratory syndrome (SARS), SARS-CoV (coronavirus). ACE2 is a type I transmembrane protein, with an extracellular N-terminal domain containing the active site and a short intracellular C-terminal tail. A soluble form of ACE2, lacking its cytosolic and transmembrane domains, has been shown to block binding of the SARS-CoV spike protein to its receptor. In this study, we examined the ability of ACE2 to undergo proteolytic shedding and investigated the mechanisms responsible for this shedding event. We demonstrated that ACE2, heterologously expressed in HEK293 cells and endogenously expressed in Huh7 cells, undergoes metalloproteinase-mediated, phorbol ester-inducible ectodomain shedding. By using inhibitors with differing potency toward different members of the ADAM (a disintegrin and metalloproteinase) family of proteases, we identified ADAM17 as a candidate mediator of stimulated ACE2 shedding. Furthermore, ablation of ADAM17 expression using specific small interfering RNA duplexes reduced regulated ACE2 shedding, whereas overexpression of ADAM17 significantly increased shedding. Taken together, these data provided direct evidence for the involvement of ADAM17 in the regulated ectodomain shedding of ACE2. The identification of ADAM17 as the protease responsible for ACE2 shedding may provide new insight into the physiological roles of ACE2.

  2. 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.

  3. 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

  4. [Latest advances in acute pancreatitis].

    PubMed

    de-Madaria, Enrique

    2015-09-01

    The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition.

  5. Bilateral putaminal necrosis in a comatose patient with metabolic acidosis

    PubMed Central

    Kumar, Sudhir; Reddy, Chenna Rajesh; Prabhakar, Subhashini

    2016-01-01

    We present a case of acute-onset coma in a young woman, associated with metabolic acidosis, respiratory distress, and hypotension. Magnetic resonance imaging of the brain done on day 2 of admission showed features of bilateral putaminal necrosis. History of methanol ingestion, though not forthcoming at admission, was confirmed later after the patient regained consciousness. A final diagnosis of methyl alcohol toxicity resulting in severe metabolic acidosis, coma, and bilateral blindness was made. This case is reported to emphasize the point that the finding of bilateral putaminal necrosis in a patient with coma and metabolic acidosis is virtually diagnostic of methyl alcohol toxicity even in the absence of any positive history. PMID:28149036

  6. [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

  7. The imprint of radiofrequency in the management of hepatocellular carcinoma

    PubMed Central

    Bramis, Ioannis; Triantopoulou, Charikleia; Madariaga, Juan; Dervenis, Christos

    2006-01-01

    Background. This article reviews the current results of radiofrequency application in the management of hepatocellular carcinoma (HCC) with reference to the comparison between the different surgical modalities. Method. An electronic search was performed for studies on the treatment of HCC. Results. Thermoablation by means of radiofrequency (RFA), microwave coagulation therapy (MCT) and laser-induced thermotherapy (LITT) provides tumor necrosis with a low complication rate. These methods are still not predictable and it is difficult to monitor the extent of necrosis in a real-time manner. Combined transarterial embolization and RF ablation is a promising strategy for large HCCs. Radiofrequency-assisted liver resection is unique and has become very popular recently because it permits parenchymal transection with minimal blood loss. Conclusion. Many alternative techniques have been applied recently for the management of HCC but their exact roles need to be defined by randomized studies. Advances in technology and refinements in technique may provide an effective and predictable way to ablate liver tumors using radiofrequency devices. PMID:18333136

  8. Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development

    SciTech Connect

    Nayeb-Hashemi, Hamed; Desai, Anal; Demchev, Valeriy; Bronson, Roderick T.; Hornick, Jason L.; Cohen, David E.; Ukomadu, Chinweike

    2015-09-18

    Fibrinogen like protein-1 (Fgl1) is a predominantly liver expressed protein that has been implicated as both a hepatoprotectant and a hepatocyte mitogen. Fgl1 expression is decreased in hepatocellular carcinoma (HCC) and its loss correlates with a poorly differentiated phenotype. To better elucidate the role of Fgl1 in hepatocarcinogenesis, we treated mice wild type or null for Fgl1 with diethyl nitrosamine and monitored for incidence of hepatocellular cancer. We find that mice lacking Fgl1 develop HCC at more than twice the rate of wild type mice. We show that hepatocellular cancers from Fgl1 null mice are molecularly distinct from those of the wild type mice. In tumors from Fgl1 null mice there is enhanced activation of Akt and downstream targets of the mammalian target of rapamycin (mTOR). In addition, there is paradoxical up regulation of putative hepatocellular cancer tumor suppressors; tripartite motif-containing protein 35 (Trim35) and tumor necrosis factor super family 10b (Tnfrsf10b). Taken together, these findings suggest that Fgl1 acts as a tumor suppressor in hepatocellular cancer through an Akt dependent mechanism and supports its role as a potential therapeutic target in HCC. - Highlights: • Fgl1 knockout mice (Fgl1KO) are more prone to carcinogen-induced liver cancer compared to wild type (WT) mates. • Tumors from the Fgl1KO are molecularly distinct with enhanced Akt and mTOR activity in comparison with Fgl1WT tumors. • Tumors from the Fgl1KO have enhanced expression of Trim35 and Tnfrsf10b, putative HCC tumor suppressors.

  9. Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure

    PubMed Central

    Nakayama, Hiroyuki; Chen, Xiongwen; Baines, Christopher P.; Klevitsky, Raisa; Zhang, Xiaoying; Zhang, Hongyu; Jaleel, Naser; Chua, Balvin H.L.; Hewett, Timothy E.; Robbins, Jeffrey; Houser, Steven R.; Molkentin, Jeffery D.

    2007-01-01

    Loss of cardiac myocytes in heart failure is thought to occur largely through an apoptotic process. Here we show that heart failure can also be precipitated through myocyte necrosis associated with Ca2+ overload. Inducible transgenic mice with enhanced sarcolemmal L-type Ca2+ channel (LTCC) activity showed progressive myocyte necrosis that led to pump dysfunction and premature death, effects that were dramatically enhanced by acute stimulation of β-adrenergic receptors. Enhanced Ca2+ influx–induced cellular necrosis and cardiomyopathy was prevented with either LTCC blockers or β-adrenergic receptor antagonists, demonstrating a proximal relationship among β-adrenergic receptor function, Ca2+ handling, and heart failure progression through necrotic cell loss. Mechanistically, loss of cyclophilin D, a regulator of the mitochondrial permeability transition pore that underpins necrosis, blocked Ca2+ influx–induced necrosis of myocytes, heart failure, and isoproterenol-induced premature death. In contrast, overexpression of the antiapoptotic factor Bcl-2 was ineffective in mitigating heart failure and death associated with excess Ca2+ influx and acute β-adrenergic receptor stimulation. This paradigm of mitochondrial- and necrosis-dependent heart failure was also observed in other mouse models of disease, which supports the concept that heart failure is a pleiotropic disorder that involves not only apoptosis, but also necrotic loss of myocytes in association with dysregulated Ca2+ handling and β-adrenergic receptor signaling. PMID:17694179

  10. The Oncogenic MicroRNA miR-21 Promotes Regulated Necrosis in Mice

    PubMed Central

    Ma, Xiaodong; Conklin, Daniel J.; Li, Fenge; Dai, Zhongping; Hua, Xiang; Li, Yan; Xu-Monette, Zijun Y.; Young, Ken H.; Xiong, Wei; Wysoczynski, Marcin; Sithu, Srinivas D.; Srivastava, Sanjay; Bhatnagar, Aruni; Li, Yong

    2015-01-01

    MicroRNAs (miRNAs) regulate apoptosis, yet their role in regulated necrosis remains unknown. miR-21 is overexpressed in nearly all human cancer types and its role as an oncogene is suggested to largely depend on its anti-apoptotic action. Here we show that miR-21 is overexpressed in a murine model of acute pancreatitis, a pathologic condition involving RIP3-dependent regulated necrosis (necroptosis). Therefore, we investigate the role of miR-21 in acute pancreatitis injury and necroptosis. miR-21 deficiency protects against caerulein- or L-arginine-induced acute pancreatitis in mice. miR-21 inhibition using locked-nucleic-acid-modified oligonucleotide effectively reduces pancreatitis severity. miR-21 deletion is also protective in tumor necrosis factor-induced systemic inflammatory response syndrome. These data suggest that miRNAs are critical participants in necroptosis, and miR-21 enhances cellular necrosis by negatively regulating tumor suppressor genes associated with the death-receptor-mediated intrinsic apoptosis pathway and could be a therapeutic target for preventing pathologic necrosis. PMID:25990308

  11. A case of spontaneous myocardial necrosis and cerebral ischemic lesions in a laboratory beagle dog.

    PubMed

    Matsushita, Kohei; Kohara, Yukari; Ito, Yuko; Yoshikawa, Tsuyoshi; Sato, Makoto; Kitaura, Keisuke; Matsumoto, Satoshi

    2015-10-01

    A beagle dog treated with saline as a control animal in a preclinical study was euthanized due to sudden systemic deterioration. On histopathological examination, contraction band necrosis of myocardial cells was observed widely in the left ventricular wall, including the papillary muscle and apex, and observed slightly in the ventricular septum and left atrium. In the brain, necrosis was observed in neurons and glia of the cerebral cortex, hippocampal pyramidal cells, glial cells of the rostral commissure and Purkinje cells of the cerebellar vermis. It is highly probable that the marked systemic deterioration was caused by cardiac dysfunction due to the spontaneous contraction band necrosis of the myocardial cells, although the pathogenesis of the myocardial lesions remains unclear. Given the distribution of neuronal necrosis in the brain, it is likely that these lesions resulted from the ischemia responsible for acute cardiac failure.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. Cation dyshomeostasis and cardiomyocyte necrosis: the Fleckenstein hypothesis revisited

    PubMed Central

    Borkowski, Brian J.; Cheema, Yaser; Shahbaz, Atta U.; Bhattacharya, Syamal K.; Weber, Karl T.

    2011-01-01

    An ongoing loss of cardiomyocytes to apoptotic and necrotic cell death pathways contributes to the progressive nature of heart failure. The pathophysiological origins of necrotic cell loss relate to the neurohormonal activation that accompanies acute and chronic stressor states and which includes effector hormones of the adrenergic nervous system. Fifty years ago, Albrecht Fleckenstein and coworkers hypothesized the hyperadrenergic state, which accompanies such stressors, causes cardiomyocyte necrosis based on catecholamine-initiated excessive intracellular Ca2+ accumulation (EICA), and mitochondrial Ca2+ overloading in particular, in which the ensuing dysfunction and structural degeneration of these organelles leads to necrosis. In recent years, two downstream factors have been identified which, together with EICA, constitute a signal–transducer–effector pathway: (i) mitochondria-based induction of oxidative stress, in which the rate of reactive oxygen metabolite generation exceeds their rate of detoxification by endogenous antioxidant defences; and (ii) the opening of the mitochondrial inner membrane permeability transition pore (mPTP) followed by organellar swelling and degeneration. The pathogenesis of stress-related cardiomyopathy syndromes is likely related to this pathway. Other factors which can account for cytotoxicity in stressor states include: hypokalaemia; ionized hypocalcaemia and hypomagnesaemia with resultant elevations in parathyroid hormone serving as a potent mediator of EICA; and hypozincaemia with hyposelenaemia, which compromise antioxidant defences. Herein, we revisit the Fleckenstein hypothesis of EICA in leading to cardiomyocyte necrosis and the central role played by mitochondria. PMID:21398641

  18. Mouse thymic necrosis virus: a novel murine lymphotropic agent.

    PubMed

    Morse, S S

    1987-12-01

    Mouse thymic necrosis virus (TA), one of two naturally occurring herpesviruses in laboratory mice, was first described in 1961. TA has received relatively little attention even though the virus has been isolated independently from various mouse colonies. This neglect is probably due, at least in part, to the lack of suitable cell culture systems. This review summarizes current knowledge concerning thymic necrosis virus, including new results from the author's laboratory. In vivo, TA causes massive thymic necrosis in newborn mice, with temporary ablation of thymocyte precursors for most T lymphocyte classes except T suppressor cells. All strains of laboratory mice appear susceptible. Severe immunosuppression has been demonstrated in acutely infected mice. Most infected animals survive and shed TA chronically from salivary glands and possibly other glandular tissues. In adult mice, primary infection results in persistent salivary gland infection without overt thymic lesions. Infection appears lifelong, with few clinical signs, but possible effects of chronic TA infection on immune function have been studied little. Recent evidence from the author's laboratory suggests that chronic infection may involve T lymphocytes. The name mouse T lymphotropic virus (abbreviation MTLV) is proposed.

  19. Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.

    PubMed

    Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

    2014-02-05

    The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production.

  20. Current concepts in pathophysiology and management of hepatocellular carcinoma.

    PubMed

    Hamza, Amal H; Abdulfattah, Hanaa M; Mahmoud, Rasha H; Khalil, Wagdy K B; Ahmed, Hanaa H

    2015-01-01

    Additional approaches to control malignancies are needed due to the emerging trends in the incidence of cancer of different organ sites. Due to the high frequency of hepatocellular carcinoma (HCC) and its poor prognosis, preventing HCC is an urgent priority. To explore the antioxidant and apoptotic pathways of grape seed extract (GSE) we induce HCC experimentally by diethylnitrosoamine (DEN) and treated the animals with low and high doses of GSE. The results indicate good therapeutic possibilities for GSE use in treatment of HCC., This was evidenced via regression of liver enzymes' function (ALT&AST), the HCC markers; α-fucosidase, α-fetoprotein and carcinoembrionic antigen (CEA) in HCC groups treated with the grape seed extract. Also, tumor necrosis factor (TNF-α) showed a significant decrease using GSE in HCC bearing animals. Regarding the apoptotic pathways of GSE, we found a significant down regulation of apoptosis enhancing nuclease (Aen), Bcl2-associated X protein (Bax), B-cell translocation gene 2(Btg2), Cyclin G1 (Ccng1) and Cyclin-dependent kinase inhibitor 1A (Cdkn1a) gene expression in HCC+GSE groups as compared to HCC bearing group. In the same trend, the necrotic/apoptotic rates were significantly higher in the HCC groups treated with GSE vs. the HCC bearing group. Finally, the 8-OHdG/2-dG generation decreased by 73.8% and 52.9% in HCC+GSE at low and high doses, respectively. Based on these encouraging observations, grape seed extract could be a promising natural remedy for attenuating hepatocellular carcinoma that has a great future in approaches directed towards control of HCC.

  1. Angiogenic Blockade and Radiotherapy in Hepatocellular Carcinoma

    SciTech Connect

    Chi, Kwan-Hwa; Liao, Chao-Sheng; Chang, Chih-Chia; Ko, Hui-Ling; Tsang, Yuk-Wah; Yang, Kuo-Ching; Mehta, Minesh P.

    2010-09-01

    Purpose: We report our preliminary experience of combining sunitinib and helical tomotherapy in patients with advanced HCC. Methods and Materials: Records of patients with advanced hepatocellular carcinoma (HCC) treated with helical tomotherapy and sunitinib after radiation therapy (RT) from March 2007 to August 2008 were retrospectively reviewed. We report acute toxicities, radiologic response, serial {alpha}-fetoprotein (AFP) kinetics, and survival. Results: Of 23 evaluable patients, 60% had {>=}2 hepatic lesions, extrahepatic disease was present in 5 (21.7%), and all received 2 tablets (25 mg) of sunitinib at least 1 week before, during, and 2 weeks after RT. Thirteen patients continued maintenance sunitinib after RT until disease progression. Hypofractionated RT with a median target dose of 52.5 Gy/15 fractions was delivered. An objective response was achieved in 74% of patients. The 1-year survival rate was 70%, with median survival of 16 months. Multivariate analysis showed that maintenance sunitinib was the most significant factor for survival. The time to progression was 10 months in the maintenance group compared with 4 months in the control group. Eighteen out of 21 patients with elevated AFP (85.7%) had {>=}50% decline of AFP within 2 months after RT. There were three episodes of upper gastrointestinal bleeding and one episode of pancreatitis; 10 patients had {>=}Grade 2 elevation of liver enzymes, and 15 had {>=}Grade 2 thrombocytopenia. Conclusions: These preliminary results suggest that sunitinib and helical tomotherapy yield high Response Evaluation Criteria in Solid Tumors (RECIST) and AFP response rates in advanced HCC with an acceptable safety profile. Maintenance sunitinib after RT potentially prolongs survival. A randomized trial is warranted.

  2. [Systemic disorders management in patients with acute pancreatic necrosis].

    PubMed

    Rodoman, G V; Shalaeva, T I; Bargandzhiya, A B

    2016-01-01

    Цель настоящей работы — исследование эффективности сулодексида в коррекции системных нарушений у больных острым панкреатитом. Материал и методы. В исследование были включены 60 пациентов (30 больных в основную и 30  больных в контрольную группу) острым некротическим панкреатитом в возрасте от 27 до 79 лет. Все больные получали стандартную рекомендованную комплексную терапию, всем проводилась профилактика развития ДВС-синдрома и тромботических осложнений. Контрольную группу составили 30 больных, в терапии которых с целью профилактики применялся эноксапарин в профилактических дозах — 4000 МЕ (40 мг) 1 раз в сутки. Продолжительность применения в среднем составила 6±0,9 сут. Основную группу составили 30 больных, в терапии которых использовался сулодексид. Сулодексид назначали пациентам основной группы с 1-х суток пребывания в стационаре по 600 ЛЕ 1 раз в сутки внутривенно в течение 5—10 дней, продолжительность применения определялась динамикой выраженности клинических признаков заболевания и «капиллярной протечки», которую оценивали по уровню потерь сывороточных белков, и в среднем составила 8,8±0,3 сут. Результаты. Сроки госпитализации в основной группе были достоверно ниже, чем в контрольной на 5±2,2 сут (p<0,03), а общая летальность на 10% ниже. В обеих группах все летальные исходы имели место на фоне развития тяжелой ПОН, при сумме баллов по SOFA менее 6 летальных исходов не было. Летальность среди пациентов с тяжелой ПОН была в основной группе в 2,4 раза ниже, чем в контрольной (14% против 33%). Вывод. Применение в комплексной терапии острого некротического панкреатита препарата, оказывающего нормализующее воздействие на микроциркуляцию и перфузию тканей, позволило снизить тяжесть системных проявлений острого деструктивного панкреатита. За счет уменьшения частоты развития, тяжести и продолжительности полиорганной недостаточности и частоты развития осложнений произошло снижение летальности и уменьшение сроков пребывания больных в стационаре.

  3. Therapeutic effect of coenzyme Q10 against experimentally-induced hepatocellular carcinoma in rats.

    PubMed

    Fouad, Amr A; Al-Mulhim, Abdulruhman S; Jresat, Iyad

    2013-01-01

    The therapeutic potential of coenzyme Q10 was investigated in rats with hepatocellular carcinoma induced by trichloroacetic acid (0.5g/kg/day, p.o., for five days). Coenzyme Q10 treatment (0.4mg/kg/day, i.p.) was applied for four weeks following trichloroacetic acid administration. Coenzyme Q10 significantly suppressed lipid peroxidation, prevented the depletion of reduced glutathione and superoxide dismutase activity, and decreased the elevations of tumor necrosis factor-α and nitric oxide in liver tissue of rats with hepatocellular carcinoma. Also, the histopathological dysplastic changes induced by trichloroacetic acid in liver tissue were ameliorated by coenzyme Q10. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the expression of hepPar-1, alpha-fetoprotein, inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor-κB in liver tissue of rats with hepatocellular carcinoma. It was concluded that coenzyme Q10 may represent a potential therapeutic option for liver carcinogenesis.

  4. 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.

  5. Thermal inactivation of infectious hematopoietic necrosis and infectious pancreatic necrosis virus

    USGS Publications Warehouse

    Gosting, L.; Gould, R.W.

    1981-01-01

    A plaque assay was used to follow the inactivation kinetics of infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus in cell culture media at various temperatures. Inactivation of infectious hematopoietic necrosis virus in a visceral organ slurry was compared with that in culture media.

  6. A population-based study of hepatitis D virus as potential risk factor for hepatocellular carcinoma.

    PubMed

    Ji, Jianguang; Sundquist, Kristina; Sundquist, Jan

    2012-05-16

    Hepatitis D virus (HDV) is dependent on the presence of hepatitis B virus (HBV) for transmission and replication because of its inability to produce its own coat. It remains unclear whether HDV infection increases the risk of hepatocellular carcinoma. Using the Swedish Hospital Discharge Register and Outpatient Registry, we identified 9160 patients with chronic HBV infection between 1997 and 2008, of whom 327 had chronic HDV infection and 323 had acute HDV infection. Standardized incidence ratios (SIRs) were calculated for these patients compared with the general population. The risk of hepatocellular carcinoma was greatly increased in patients with HBV and HDV (SIR = 137.17, 95% confidence interval [CI] = 62.19 to 261.51). The risk of hepatocellular carcinoma among patients with HBV and HDV was increased (SIR = 6.11, 95% CI = 2.77 to 11.65) when patients with chronic HBV infection alone were used as the reference population. Similar results were observed for patients with chronic HDV infection (SIR = 99.26, 95% CI = 42.39 to 196.55). Our findings indicate that HDV is a strong risk factor for hepatocellular carcinoma.

  7. 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

  8. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

    ClinicalTrials.gov

    2017-04-05

    B Acute Lymphoblastic Leukemia; Bone Necrosis; Central Nervous System Leukemia; Cognitive Side Effects of Cancer Therapy; Neurotoxicity Syndrome; Pain; Testicular Leukemia; Therapy-Related Toxicity; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  9. Diagnosis of Hepatocellular Carcinoma Complicating Liver Cirrhosis: Utility of Repeat Ultrasound-Guided Biopsy after Unsuccessful First Sampling

    SciTech Connect

    Caturelli, Eugenio; Biasini, Elisabetta; Bartolucci, Francesca; Facciorusso, Domenico; Decembrino, Francesco; Attino, Vito; Bisceglia, Michele

    2002-08-15

    Purpose: To evaluate the utility of a second ultrasound-guided fine-needle biopsy of liver nodules thought to be hepatocellular carcinoma when the original biopsy has failed to provide a reliable diagnosis. Methods: Thirty-seven cirrhotic patients underwent ultrasound-guided fine-needle biopsy of liver nodules that were subsequently diagnosed as hepatocellular carcinoma. Each biopsy involved a single puncture with a 20 G cutting needle, which yielded pathologic material used both for cytologic and histologic studies. In 23 cases (mean diameter of nodules 48 mm) the biopsy furnished exclusively necrotic material (non-diagnostic subgroup); in the other 14 cases (mean diameter 26 mm) the biopsy yielded no neoplastic elements (false-negative subgroup). All 37 nodules were subjected to repeat biopsies performed in the same manner. Results: The repeat biopsies provided a diagnosis of hepatocellular carcinoma in six of the 23 patients from the non-diagnostic subgroup and in seven of the 14 in the false-negative subgroup. Overall, repeat biopsy produced a diagnostic gain of 35.1%. Conclusion: The chance of success with repeat biopsy of hepatocellular carcinoma is limited and may depend to some extent on the characteristics of the lesions (i.e., areas of necrosis in large nodules, well-differentiated cellular populations in small ones)

  10. 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

  11. 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

  12. Hepatocellular carcinoma: A comprehensive review

    PubMed Central

    Waller, Lisa P; Deshpande, Vrushak; Pyrsopoulos, Nikolaos

    2015-01-01

    Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals with chronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival. PMID:26609342

  13. 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.

  14. 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

  15. 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

  16. Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells

    NASA Technical Reports Server (NTRS)

    Plymale, D. R.; Tang, D. S.; Comardelle, A. M.; Fermin, C. D.; Lewis, D. E.; Garry, R. F.

    1999-01-01

    BACKGROUND: Data currently available on HIV-1-induced cytopathology is unclear regarding the mechanism of cell killing. OBJECTIVE: To clarify the extent to which apoptosis or necrosis is involved in HIV-1-induced cell death in view of conflicting existing data. METHODS: T lymphoblastoid cells or peripheral blood mononuclear cells were infected by various strains of HIV-1 and the numbers of apoptotic or necrotic cells were quantified at various times after infection using video-image analysis techniques; the results were compared with the amount of fragmented DNA using a quantitative method. Measurement of mitochondrial transmembrane potential (deltapsi(m)) and intracellular calcium concentrations [Ca2+]i was performed with fluorescent probes and fluorescence concentration analysis (FCA). RESULTS: Although lymphoblastoid and monocytoid cells acutely infected by HIV-1 had increased levels of fragmented DNA, a marker of apoptotic cell death, few (<12%) had condensed chromatin and fragmented nuclei, the morphological features of apoptosis. The predominant alterations in acutely infected cells were distended endoplasmic reticulum and abnormal mitochondria; these ultrastructural changes are consistent with necrosis, although some infected cells simultaneously displayed features of both necrosis and apoptosis. Viability of cells persistently infected by HIV-1 was only minimally reduced from that of uninfected cells. This reduction was accounted for by an increased propensity of the persistently infected cells to die by apoptosis. Alterations in [Ca2+]i and deltapsi(m) occurred in both acutely and persistently infected cells. CONCLUSION: Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells.

  17. Somatostatin therapy of acute experimental pancreatitis.

    PubMed Central

    Lankisch, P G; Koop, H; Winckler, K; Fölsch, U R; Creutzfeldt, W

    1977-01-01

    Because somatostatin (SRIF) reduces exocrine pancreatic secretion, its effect on acute pancreatitis was investigated in rats. Linear SRIF reduced serum amylase and lipase but had no effect on pancreatic necrosis, oedema, leucocyte infiltration, and enzyme content. The mortality rate was not reduced. These results do not recommend the use of SRIF in the treatment of acute pancreatitis. PMID:604191

  18. Pulmonary complications of transcatheter arterial chemoembolization for hepatocellular carcinoma

    PubMed Central

    Nhu, Quan M; Knowles, Harry; Pockros, Paul J; Frenette, Catherine T

    2016-01-01

    Transarterial chemoembolization (TACE) is an effective palliative intervention that is widely accepted for the management of hepatocellular carcinoma (HCC). Post-TACE pulmonary complications resulting in acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are rare events. Pulmonary complications after TACE are thought to be related to chemical injury subsequent to the migration of the infused ethiodized oil or chemotherapeutic agent to the lung vasculature, facilitated by arteriovenous (AV) shunts within the hyper-vascular HCC. We review herein the literature on pulmonary complications related to TACE for HCC. Post-TACE pulmonary complications have included pulmonary oil embolism, interstitial pneumonitis, chemical pneumonitis, ALI, ARDS, lipoid pneumonia, acute eosinophilic and neutrophilic pneumonia, bilious pleuritis, pulmonary abscess, pulmonary tumor embolism, and possibly pulmonary metastasis with HCC. The risk factors associated with post-TACE pulmonary complications identified in the literature include large hyper-vascular HCC with AV shunts, large-volume Lipiodol infusion, and embolization via the right inferior phrenic artery. However, the absence of known risk factors is not a guarantee against serious complications. An astute awareness of the potential post-TACE pulmonary complications should expedite appropriate therapeutic interventions and increase potential for early recovery. PMID:27904836

  19. Local ablative treatments for hepatocellular carcinoma: An updated review

    PubMed Central

    Facciorusso, Antonio; Serviddio, Gaetano; Muscatiello, Nicola

    2016-01-01

    Ablative treatments currently represent the first-line option for the treatment of early stage unresectable hepatocellular carcinoma (HCC). Furthermore, they are effective as bridging/downstaging therapies before orthotopic liver transplantation. Contraindications based on size, number, and location of nodules are quite variable in literature and strictly dependent on local expertise. Among ablative therapies, radiofrequency ablation (RFA) has gained a pivotal role due to its efficacy, with a reported 5-year survival rate of 40%-70%, and safety. Although survival outcomes are similar to percutaneous ethanol injection, the lower local recurrence rate stands for a wider application of RFA in hepato-oncology. Moreover, RFA seems to be even more cost-effective than liver resection for very early HCC (single nodule ≤ 2 cm) and in the presence of two or three nodules ≤ 3 cm. There is increasing evidence that combining RFA to transarterial chemoembolization may increase the therapeutic benefit in larger HCCs without increasing the major complication rate, but more robust prospective data is still needed to validate these pivotal findings. Among other thermal treatments, microwave ablation (MWA) uses high frequency electromagnetic energy to induce tissue death via coagulation necrosis. In comparison to RFA, MWA has several theoretical advantages such as a broader zone of active heating, higher temperatures within the targeted area in a shorter treatment time and the lack of heat-sink effect. The safety concerns raised on the risks of this procedure, due to the broader and less predictable necrosis areas, have been recently overcome. However, whether MWA ability to generate a larger ablation zone will translate into a survival gain remains unknown. Other treatments, such as high-intensity focused ultrasound ablation, laser ablation, and cryoablation, are less investigated but showed promising results in early HCC patients and could be a valuable therapeutic option in

  20. Experimental Papillary Necrosis of the Kidney

    PubMed Central

    Solez, K.; Miller, M.; Quarles, P. A.; Finer, P. M.; Heptinstall, R. H.

    1974-01-01

    To test the thesis that vasoconstriction plays a significant role in the pathogenesis of papillary necrosis caused by bromoethylamine hydrobromide (BEA), medullary plasma flow was determined in rats treated with BEA. Medullary blood flow was normal ½ to 1 hour after BEA treatment, and was actually elevated 6 hours after BEA. There was no increase in plasma levels of prostaglandins A and E, which would have been expected if there had been medullary ischemia. Pretreatment with reserpine, which inhibited the development of papillary necrosis, had little effect on medullary plasma flow. These observations do not support the notion that vasoconstriction is the mechanism by which BEA causes papillary necrosis. PMID:4472110

  1. Gold Nanoparticles and Radiofrequency in Experimental Models for Hepatocellular Carcinoma

    PubMed Central

    Raoof, Mustafa; Corr, Stuart J.; Zhu, Cihui; Cisneros, Brandon T.; Kaluarachchi, Warna D; Phounsavath, Sophia; Wilson, Lon J.; Curley, Steven A.

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most lethal and chemo-refractory cancers, clearly, alternative treatment strategies are needed. We utilized 10nm gold nanoparticles as a scaffold to synthesize nanoconjugates bearing a targeting antibody (cetuximab, C225) and gemcitabine. Loading efficiency of gemcitabine on the gold nanoconjugates was 30%. Targeted gold nanoconjugates in combination with RF were selectively cytotoxic to EGFR expressing Hep3B and SNU449 cells when compared to isotype particles with/without RF (p<0.05). In animal experiments, targeted gold nanoconjugates halted the growth of subcutaneous Hep3B xenografts in combination with RF exposure (p<0.05). These xenografts also demonstrated increased apoptosis, necrosis and decreased proliferation compared to controls. Normal tissues were unharmed. We have demonstrated that non-invasive RF-induced hyperthermia when combined with targeted delivery of gemcitabine is more effective and safe at dosages ~275-fold lower than the current clinically-delivered systemic dose of gemcitabine. PMID:24650884

  2. HCV-related hepatocellular carcinoma: From chronic inflammation to cancer.

    PubMed

    Castello, Giuseppe; Scala, Stefania; Palmieri, Giuseppe; Curley, Steven A; Izzo, Francesco

    2010-03-01

    Hepatitis C virus (HCV) infection is a worldwide health problem because of its incidence and pathogenicity. It might evolve into chronic disease, cirrhosis, and/or hepatocellular carcinoma (HCC) and the outcome is mainly determined by the host immune response. For viral clearance, combined innate and adaptive immune responses are required; resolution requires a vigorous, durable, polyclonal CD4(+) and CD8(+) T-cell response, with an increase in virus-specific CD8(+) T cells or cytotoxic T lymphocytes. Failure of efficient immune response can lead to chronic inflammation, tissue remodeling through cell growth, apoptosis and/or necrosis and induction of oxidative stress. Development of fibrosis and/or cirrhosis plus a microenvironment conducive to genomic instability mutations will promote neoplastic transformation. System governance derives from cellular (regulatory cells) and humoral (cytokines and chemokines) immune networks. Therefore, HCC pathogenesis may be a model to study the disease progression from chronic inflammation to cancer allowing design of new strategies targeting the immune response, thereby modifying disease outcome.

  3. Hepatocellular carcinoma with characteristic mucin production: a case report

    PubMed Central

    Lee, Kyung Hwa; Kim, Young Bog; Cho, Sung Bum; Lee, Min Cheol; Park, Chang Soo

    2009-01-01

    We present a unique case of hepatocellular carcinoma with mucin-producing gland formation. A 53-year-old man with hepatitis B infection presented with weight loss for the past month. Computed tomography demonstrated a 10 × 9.8 cm mass in the right hepatic lobe accompanied by cirrhotic changes in the hepatic parenchyma. Right hepatectomy was performed, and the tumor cut surface showed a poorly-circumscribed, white to pink tumor with numerous nodules and extensive necrosis. Microscopically, the tumor was composed of thick trabeculae and large, irregularly-shaped islands, both of which were filled with pleomorphic eosinophilic hepatoid cells or gland-forming columnar cells with mucin production. Those cells were immunoreactive for cytokeratin 19 in both the trabeculae and the glands. In some tumor cells, limited immunoreactivity for cytokeratin 7, epithelial membrane antigen and carcinoembryonic antigen was noted. The cells forming thick trabeculae were focally positive for hepatocyte paraffin 1 and alpha-fetoprotein. We suggest that this tumor shows bidirectional differentiation into hepatocytes and cholangiocytes, supporting the concepts that human hepatocarcinogenesis can be based on transformation of progenitor cells which can imply divergent differentiation. PMID:19918544

  4. Therapeutic inhibition of phospholipase D1 suppresses hepatocellular carcinoma.

    PubMed

    Xiao, Junjie; Sun, Qi; Bei, Yihua; Zhang, Ling; Dimitrova-Shumkovska, Jasmina; Lv, Dongchao; Yang, Yuefeng; Cao, Yan; Zhao, Yingying; Song, Meiyi; Song, Yang; Wang, Fei; Yang, Changqing

    2016-07-01

    Hepatocellular carcinoma (HCC) represents a leading cause of deaths worldwide. Novel therapeutic targets for HCC are needed. Phospholipase D (PD) is involved in cell proliferation and migration, but its role in HCC remains unclear. In the present study, we show that PLD1, but not PLD2, was overexpressed in HCC cell lines (HepG2, Bel-7402 and Bel-7404) compared with the normal human L-02 hepatocytes. PLD1 was required for the proliferation, migration and invasion of HCC cells without affecting apoptosis and necrosis, and PLD1 overexpression was sufficient to promote those effects. By using HCC xenograft models, we demonstrated that therapeutic inhibition of PLD1 attenuated tumour growth and epithelial-mesenchymal transition (EMT) in HCC mice. Moreover, PLD1 was found to be highly expressed in tumour tissues of HCC patients. Finally, mTOR (mechanistic target of rapamycin) and Akt (protein kinase B) were identified as critical pathways responsible for the role of PLD1 in HCC cells. Taken together, the present study indicates that PLD1 activation contributes to HCC development via regulation of the proliferation, migration and invasion of HCC cells, as well as promoting the EMT process. These observations suggest that inhibition of PLD1 represents an attractive and novel therapeutic modality for HCC.

  5. Intracellular serpins, firewalls and tissue necrosis.

    PubMed

    Marciniak, Stefan J; Lomas, David A

    2008-02-01

    Luke and colleagues have recently attributed a new role to a member of the serpin superfamily of serine proteinase inhibitors. They have used Caenorhabditis elegans to show that an intracellular serpin is crucial for maintaining lysosomal integrity. We examine the role of this firewall in preventing necrosis and attempt to integrate this with current theories of stress-induced protein degradation. We discuss how mutant serpins cause disease either through polymerization or now, perhaps, by unleashing necrosis.

  6. Muscle necrosis in the extremities: evaluation with Tc-99m pyrophosphate scanning--a retrospective review

    SciTech Connect

    Timmons, J.H.; Hartshorne, M.F.; Peters, V.J.; Cawthon, M.A.; Bauman, J.M.

    1988-04-01

    A retrospective review was done of 34 extremities studied between 1981 and 1985 with technetium-99m pyrophosphate scanning; 22 were subsequently amputated. Results of detailed pathologic examination or immediate postoperative examination of the resected extremity were available in 16 cases. In these cases, scanning had allowed correct prediction of the level of amputation and of the specific areas of muscle infarction in 13 cases. In the one case in which amputation was performed for infection rather than muscle necrosis, the lack of necrosis was correctly predicted with the scan. The limited results of this study indicate that the Tc-99m pyrophosphate scan allows the location of necrotic muscle to be predicted accurately and may therefore be a useful adjunct in determining the best level for ultimate amputation. Special caution is required in those cases in which muscle necrosis is due to acute causes (e.g., traumatic thrombosis) rather than chronic vascular disease.

  7. Tumor Necrosis Factor-α T-857C (rs1799724) Polymorphism and Risk of Cancers: A Meta-Analysis

    PubMed Central

    Wang, June

    2016-01-01

    Objectives. To investigate the potential association of tumor necrosis factor-α T-857C polymorphism with susceptibility to the five common malignant tumors. Materials and Methods. A comprehensive search of PubMed/Medline, Embase, and Web of Science databases was performed up to November 2015. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis, heterogeneity analyses, and publication bias were also texted in the meta-analysis. Results. A total of twenty-two publications involving 5215 cases and 6755 controls were recruited. Overall, the meta-analysis revealed an increased risk between the TNF-α T-857C polymorphism and gastric cancer susceptibility in T versus C model, heterozygote genetic model, and dominant genetic model. An increased risk between the TNF-α T-857C polymorphism and hepatocellular cancer susceptibility in homozygote genetic model and recessive genetic model was also found. No significant association was found between the TNF-α T-857C polymorphism and colorectal cancer, cervical cancer, and prostate cancer. Conclusions. Our meta-analyses suggest that TNF-α T-857C polymorphism may be associated with increased risk of gastric cancer and hepatocellular cancer development. Therefore, the TNF-α T-857C polymorphism could be considered as one possible risk factor of gastric cancer and hepatocellular cancer according to our study. PMID:28115787

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Blood pressure and hepatocellular effects of the cyclic heptapeptide toxin produced by the freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa strain PCC-7820.

    PubMed

    Theiss, W C; Carmichael, W W; Wyman, J; Bruner, R

    1988-01-01

    Laboratory rats and mice were used to investigate the hepatotoxicity caused by the cyclic heptapeptide (mol. wt 994) termed microcystin-LR. Microcystin-LR (also known as cyanoginosin-LR) is produced by the freshwater cyanobacterium (blue-green alga) M. aeruginosa strain PCC-7820. In time course histopathology studies with mice significant liver damage, with an absence of pulmonary emboli, were observed after 15 min. Pulmonary emboli did not appear until 1 hr. In rats, significant liver damage and the presence of occasional emboli were observed at 20 min. Pulmonary emboli did not contain fibrin nor appear life-threatening in any case and resembled the globular eosinophilic debris found in the liver sinusoids and central veins. Measurements of rat femoral arterial, jugular venous and hepatic portal venous blood pressures during the course of toxicity revealed a slowly declining arterial pressure and stable, normal venous pressures. Blood lactic acid levels rose in parallel with the fall in arterial pressure, a pattern typical of hemorrhagic shock. There was no indication of venous congestion that would accompany right heart failure. Isolated, perfused rat livers dosed with toxin showed rapid changes in the liver, including cessation of bile flow within 10 min and complete obliteration of normal lobular architecture within 60 min. No effect of the toxin was observed in isolated perfused rat heart. We conclude that in the mouse and rat, microcystin-LR is a potent, rapid-acting, direct hepatotoxin, with the immediate cause of death in acute toxicities being hemorrhagic shock secondary to massive hepatocellular necrosis and collapse of hepatic parenchyma.

  13. Extensive bone marrow necrosis associated with antiphospholipid antibodies.

    PubMed

    Bulvik, S; Aronson, I; Ress, S; Jacobs, P

    1995-06-01

    Bone marrow necrosis (BMN), defined morphologically by destruction of hematopoietic tissue, including the stroma, with preservation of the bone, is a rare syndrome. The conditions in which it is seen include sickle cell disease, acute leukemia, metastatic neoplasia, and bacterial infection, particularly when hypovolemia and septic shock are present. BMN is also associated with disseminated intravascular coagulation (DIC) following irradiation and antineoplastic therapy. The antiphospolipid syndrome (APS) is characterized by antibodies directed against the antiphospolipid substrate. Because this substrate is prominently involved in the coagulation cascade and widely distributed on cell walls, patients present with venous or arterial thromboses, recurrent abortion, thrombocytopenia, and Coombs' positive hemolytic anemia, typically with raised anticardiolipin antibodies or a diagnostic lupus anticoagulant test. BMN does not appear to have been previously recognized in this context. We report what we believe to be the first such case and suggest that the high titers of antibodies present may have played a central role in its pathogenesis.

  14. 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.

  15. 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

  16. 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.

  17. Renal Papillary Necrosis: Role of Radiology

    PubMed Central

    Pandya, Vaidehi K.

    2016-01-01

    Renal Papillary Necrosis (RPN) is idefined as Ischemic necrobiosis of the papilla in the medulla of the kidneys. Variety of etiological factors are recognized which cause papillary necrosis, such as analgesic nephropathy, diabetes mellitus, urinary obstruction and sickle cell haemoglobinopathy. The early diagnosis of RPN is important to improve prognosis and reduce morbidity. Radiological Imaging offers early diagnosis and can guide prompt treatment of papillary necrosis and can minimize a decline in renal function. Here we report three cases of RPN with typical imaging findings. One of them was diabetic and hypertensive female with recurrent Urinary tract Infections and other was a male with no known co-morbidity. Both of them were diagnosed to have renal papillary necrosis on CT scan and were managed operatively and conservatively, respectively. Third case was a healthy female being investigated to be renal donor for her son. Here RPN was an incidental finding and was treated conservatively. Thus CT scan could detect it pre-operatively and complications due to transplantation of a kidney with papillary necrosis were avoided. So, we want to emphasize the importance of Radiology, particularly CT scanning in detection of RPN and to guide early and prompt treatment. PMID:26894147

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. Bilateral pallidostriatal necrosis caused by a wasp sting: a clinical and pathological study.

    PubMed

    Gállego, J; Tuñón, T; Soriano, G; Delgado, G; Lacruz, F; Villanueva, J A

    1995-04-01

    A previously healthy man developed an acute encephalopathy with coma after a single wasp sting on his chin. Brain CT showed bilateral pallidostriatal radio-lucencies. He died 72 hours after the sting with no evidence of primary cardiorespiratory failure or allergic reaction. Pathological findings were bilateral pallidostriatal necrosis and diffuse neuronal damage in the frontal, temporal, and parietal cortex. The neurotoxic effect of the poison, together with a hypersensitivity are the most likely explanations for this unusual encephalopathy.

  4. Monocyte Tumor Necrosis Factor-α–Converting Enzyme Catalytic Activity and Substrate Shedding in Sepsis and Noninfectious Systemic Inflammation*

    PubMed Central

    O’Callaghan, David J. P.; O’Dea, Kieran P.; Scott, Alasdair J.; Takata, Masao

    2015-01-01

    Objectives: To determine the effect of severe sepsis on monocyte tumor necrosis factor-α–converting enzyme baseline and inducible activity profiles. Design: Observational clinical study. Setting: Mixed surgical/medical teaching hospital ICU. Patients: Sixteen patients with severe sepsis, 15 healthy volunteers, and eight critically ill patients with noninfectious systemic inflammatory response syndrome. Interventions: None. Measurements and Main Results: Monocyte expression of human leukocyte antigen-D-related peptide, sol-tumor necrosis factor production, tumor necrosis factor-α–converting enzyme expression and catalytic activity, tumor necrosis factor receptor 1 and 2 expression, and shedding at 48-hour intervals from day 0 to day 4, as well as p38-mitogen activated protein kinase expression. Compared with healthy volunteers, both sepsis and systemic inflammatory response syndrome patients’ monocytes expressed reduced levels of human leukocyte antigen-D-related peptide and released less sol-tumor necrosis factor on in vitro lipopolysaccharide stimulation, consistent with the term monocyte deactivation. However, patients with sepsis had substantially elevated levels of basal tumor necrosis factor-α–converting enzyme activity that were refractory to lipopolysaccharide stimulation and this was accompanied by similar changes in p38-mitogen activated protein kinase signaling. In patients with systemic inflammatory response syndrome, monocyte basal tumor necrosis factor-α–converting enzyme, and its induction by lipopolysaccharide, appeared similar to healthy controls. Changes in basal tumor necrosis factor-α–converting enzyme activity at day 0 for sepsis patients correlated with Acute Physiology and Chronic Health Evaluation II score and the attenuated tumor necrosis factor-α–converting enzyme response to lipopolysaccharide was associated with increased mortality. Similar changes in monocyte tumor necrosis factor-α–converting enzyme activity could

  5. 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

  6. 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

  7. 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

  8. Hepatocellular carcinoma associated with precocious puberty and oral contraceptives. A case report.

    PubMed

    Mansvelt, B; Etienne, P Y; Bertrand, C; Henrion, J; Gerard, R

    2003-08-01

    A 36-year-old woman presented with sudden abdominal pain and vomiting. Computed tomography showed a tumour of the right hepatic lobe with possible signs of acute haemorrhage. Her medical history revealed precocious puberty when she was a 5-year-old and the use of oral contraceptives for 18 years. Bisegmentectomy was performed and histological examination revealed hepatocellular carcinoma. The role of male and female sex hormones in the development of hepatic tumours has been well documented but, to our knowledge, association with precocious puberty has not yet been described.

  9. 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

  10. Green Tea Extract-induced Acute Hepatotoxicity in Rats.

    PubMed

    Emoto, Yuko; Yoshizawa, Katsuhiko; Kinoshita, Yuichi; Yuki, Michiko; Yuri, Takashi; Yoshikawa, Yutaka; Sayama, Kazutoshi; Tsubura, Airo

    2014-10-01

    Although green tea is considered to be a healthy beverage, hepatotoxicity associated with the consumption of green tea extract has been reported. In the present study, we characterized the hepatotoxicity of green tea extract in rats and explored the responsible mechanism. Six-week-old IGS rats received a single intraperitoneal (ip) injection of 200 mg/kg green tea extract (THEA-FLAN 90S). At 8, 24, 48 and 72 hrs and 1 and 3 months after exposure, liver damage was assessed by using blood-chemistry, histopathology, and immunohistochemistry to detect cell death (TUNEL and caspase-3) and proliferative activity (PCNA). Analyses of malondialdehyde (MDA) in serum and the liver and of MDA and thymidine glycol (TG) by immunohistochemistry, as oxidative stress markers, were performed. Placental glutathione S-transferase (GST-P), which is a marker of hepatocarcinogenesis, was also immunohistochemically stained. To examine toxicity at older ages, 200 mg/kg green tea extract was administered to 18-wk-old female rats. In 6-wk-old rats, 12% of males and 50% of females died within 72 hrs. In 18-wk-old rats, 88% died within 72 hrs. The serum levels of aspartate aminotransferase, alanine aminotransferase and/or total bilirubin increased in both males and females. Single-cell necrosis with positive signs of TUNEL and caspase-3 was seen in perilobular hepatocytes from 8 hrs onward in all lobular areas. PCNA-positive hepatocytes increased at 48 hrs. MDA levels in the serum and liver tended to increase, and MDA- and TG-positive hepatocytes were seen immunohistochemically. GST-P-positive hepatocellular altered foci were detected in one female rat at the 3-month time point. In conclusion, a single injection of green tea extract induced acute and severe hepatotoxicity, which might be associated with lipid peroxidation and DNA oxidative stress in hepatocytes.

  11. Pathophysiology of acute pancreatitis.

    PubMed

    Bhatia, Madhav; Wong, Fei Ling; Cao, Yang; Lau, Hon Yen; Huang, Jiali; Puneet, Padmam; Chevali, Lakshmi

    2005-01-01

    Acute pancreatitis is a common clinical condition. It is a disease of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction. If this inflammatory reaction is marked, it leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and the resultant MODS. At the same time, recent research has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In this review, we will discuss about our current understanding of the pathophysiology of acute pancreatitis.

  12. Hepatocellular carcinoma in captive slender tailed meerkats (Suricata suricatta): 5 cases.

    PubMed

    Marrow, Judilee C; Basu, Puja; Walsh, Timothy F; Siegal-Willott, Jessica L

    2014-03-01

    Hepatocellular carcinoma was diagnosed in five slender tailed meerkats (Suricata suricatta) housed at the Smithsonian Institution's National Zoological Park between 1980 and 2013. Animals included four females and one male, ranging from 7 to 15 yr of age. Common clinical signs included weight loss and lethargy. Three of the neoplasms originated from the right medial liver lobe and were located adjacent to or partially incorporated in the gall bladder. Three animals had solitary masses, and two animals had multiple hepatic masses; all were characterized by polygonal to round neoplastic hepatocytes arranged in a trabecular pattern with smaller regions of varied solid, adenoid, and rarely peliod cell patterns. Hemorrhage and necrosis often with cystic degeneration was noted in all five cases. There was no evidence of metastatic disease in any of the cases examined.

  13. Risk of hepatocellular carcinoma and cancers at other sites among patients diagnosed with chronic hepatitis B virus infection in Sweden.

    PubMed

    Sundquist, Kristina; Sundquist, Jan; Ji, Jianguang

    2014-01-01

    Hepatitis B virus (HBV) infection is one of most common viral infections worldwide. While chronic HBV infection has been shown consistently to be associated with hepatocellular carcinoma, data on associations with cancers at other sites are limited. In this study a total of 10,197 patients were diagnosed with chronic HBV infection in Sweden, and they were retrieved from the nationwide Swedish Hospital Discharge Register and Outpatient Register and linked to Cancer Registry data. Standardized incidence ratios (SIRs) for cancers were calculated for these patients in comparison with the population without HBV infection. Five hundred sixty-seven of whom developed cancer (SIR 1.82 (95% confidence interval (CI) 1.67-1.97)) during the study period. The SIR for hepatocellular carcinoma in patients with HBV infection was 40.58 (95% CI 30.50-50.07). In addition, a total of seven other cancer sites/types showed increased SIRs: cancers of the upper aerodigestive tract, lung, kidney, skin (squamous cell carcinoma), and thyroid gland, and lymphoma and leukemia. The risks of non-Hodgkin lymphoma and acute myeloid leukemia were increased in both Swedish- and foreign-born patients with HBV infection. In summary, chronic HBV infection is a strong risk factor for hepatocellular carcinoma and also increases the risk of seven other cancers. These findings illustrate the need for surveillance for cancers other than hepatocellular carcinoma in patients with HBV infection.

  14. Infectious pancreatic necrosis: its detection and identification

    USGS Publications Warehouse

    Wolf, K.

    1965-01-01

    Ultimate control of infectious pancreatic necrosis (IPN) in hatcheries depends largely upon learning where the virus occurs. To detect the presence of virus either susceptible fish or susceptible fish cell cultures may be used as test systems. In modern virology, it is generally agreed that cell cultures are more convenient, are usually a much more sensitive test system, and allow more rapid determinations.

  15. [Acral necrosis as a complication of urosepsis].

    PubMed

    Blarer, J; Pfister, D; Jandali, A R; Gutzeit, A; John, H; Horstmann, M

    2014-06-01

    Sepsis is the third most common cause of death in Germany. Every fourth patient with sepsis has urosepsis. Even if substantial therapeutic progress has been made, sepsis remains a severe condition with high morbidity and mortality that requires rapid interdisciplinary measures. Besides life-threatening complications, acral necrosis as presented here can occur as a result of disseminated intravascular coagulation and severe microcirculatory disorders.

  16. Excitotoxins in neuronal apoptosis and necrosis.

    PubMed

    Nicotera, P; Lipton, S A

    1999-06-01

    Neuronal loss is common to many neurodegenerative diseases. Although necrosis is a common histopathologic feature observed in neuropathologic conditions, evidence is increasing that apoptosis can significantly contribute to neuronal demise. The prevalence of either type of cell death, apoptosis or necrosis, and the relevance for the progression of disease is still unclear. The debate on the occurrence and prevalence of one or the other type of death in pathologic conditions such as stroke or neurotoxic injury may in part be resolved by the proposal that different types of cell death within a tissue reflect either partial or complete execution of a common death program. Apoptosis is an active process of cell destruction, characterized morphologically by cell shrinkage, chromatin aggregation with extensive genomic fragmentation, and nuclear pyknosis. In contrast, necrosis is characterized by cell swelling, linked to rapid energy loss, and generalized disruption of ionic and internal homeostasis. This swiftly leads to membrane lysis, release of intracellular constituents that evoke a local inflammatory reaction, edema, and injury to the surrounding tissue. During the past few years, our laboratories have studied the signals and mechanisms responsible for induction or prevention of apoptosis/necrosis in neuronal injury and this is the subject of this review.

  17. Snapshot in surgery: intraperitoneal encapsulated fat necrosis

    PubMed Central

    Oh, Han Boon; Arab, Nahlah; Teo, Lynette; Lieske, Bettina

    2015-01-01

    Key Clinical Message A 66-year-old man with rectal cancer was found to have an incidental ring-like lesion in the left rectovesical pouch. Histology revealed an encapsulated fat necrosis. Intraperitoneal encapsulated fat necroses are postulated to be a result of infarcted epiploic appendages resulting in a free-floating lesion. PMID:25767714

  18. A fifteen year experience with open drainage for infected pancreatic necrosis.

    PubMed

    Bradley, E L

    1993-09-01

    Advances in the understanding of the pathophysiologic factors of acute pancreatitis, combined with several recent technologic breakthroughs, have led to the establishment of infected pancreatic necrosis as the most common, the most severe and the most lethal of the infectious complications of acute pancreatitis. In this report, a single institutional experience in the surgical management of infected pancreatic necrosis during a 15 year period is chronicled. Using open drainage with scheduled abdominal re-explorations, the overall mortality rate was 15 percent in 71 consecutive patients with infected pancreatic necrosis. In the most recent 25 instances, sequential re-explorations were performed until retroperitoneal granulation occurred, at which time the abdomen was closed over lesser sac lavage catheters. Compared with the original 46 patients permitted to heal entirely by secondary intention, patients undergoing delayed secondary closure and lavage had a significant decrease during the hospitalization period (48.8 versus 30.1 days; p < 0.05), without a significant change in the mortality rate. In the most recent patients, dynamic pancreatography and fine needle aspiration bacteriologic factors were accurate in the preoperative prediction of pancreatic necrosis and microbial infection in 95 and 97 percent of the patients, respectively. Preoperative endoscopic retrograde cholangiopancreatography demonstrated leakage of contrast material from necrotic pancreatic ducts in seven of eight patients, while postoperative pancreatograms revealed abrupt truncation or other abnormalities in 11 of 13 patients. These observations establish that necrotizing pancreatitis involves pancreatic parenchyma as well as peripancreatic adipose tissue. Open drainage with contingent secondary closure and high volume lavage deserves a place in the management of patients with extensive infected pancreatic necrosis.

  19. Chemoembolization for Hepatocellular Carcinoma Supplied by a Lumbar Artery

    SciTech Connect

    Kim, Han Myun; Kim, Hyo-Cheol Woo, Sungmin; Son, Kyu Ri; Cho, Seong Whi; Chung, Jin Wook

    2015-02-15

    PurposeTo describe the radiologic findings and imaging response of hepatocellular carcinoma (HCC) supplied by the lumbar artery.MethodsBetween April 2004 and December 2012, we encountered HCC supplied by a lumbar artery in 21 patients. Two investigators retrospectively reviewed clinical and radiological findings of HCC supplied by the lumbar artery using computed tomography (CT) scans and digital subtraction angiograms.ResultsPatients had received 1–27 sessions of previous chemoembolization procedures (mean 7.7 sessions, median 4 sessions). Mean tumor size was 5.3 cm. The locations of HCC supplied by lumbar artery were the bare area (n = 14, 67 %) and segment VI (n = 7, 33 %). Tumor-feeding arteries arose from the main lumbar artery (n = 7), proximal anterior division (n = 4), and distal anterior division (n = 14). In 20 patients, selective chemoembolization through the tumor-feeding arteries of the lumbar artery was achieved. In 1 patient, nonselective embolization at the main lumbar artery was performed. There was no complication such as skin necrosis or paralysis. On the first follow-up enhanced CT scan, target tumors fed by the lumbar artery showed complete response (n = 6), partial response (n = 4), stable disease (n = 3), and progressive disease (n = 8), but overall tumor response was partial response (n = 1) and progressive disease (n = 20).ConclusionWhen HCC is located in the inferior tip or bare area of the liver, a lumbar artery may supply the tumor. Although selective chemoembolization via the tumor-feeding vessel of the lumbar artery can be achieved in most cases, overall tumor response is commonly unfavorable.

  20. Increased FNDC5/Irisin expression in human hepatocellular carcinoma.

    PubMed

    Gaggini, Melania; Cabiati, Manuela; Del Turco, Serena; Navarra, Teresa; De Simone, Paolo; Filipponi, Franco; Del Ry, Silvia; Gastaldelli, Amalia; Basta, Giuseppina

    2017-02-01

    The fibronectin type III domain containing 5 (FNDC5)/Irisin, a novel energy-regulating hormone, is associated with lipid and carbohydrate metabolism. It is produced in low amounts by normal hepatic tissue, while in human hepatocellular carcinoma (HCC), in which aberrant de novo lipogenesis (DNL) occurs, the hepatic expression of FNDC5/Irisin is still unknown. The gene expression of FNDC5/Irisin, associated to key regulators of DNL, inflammation and cancer progression was evaluated in liver tissue of 18 patients with HCC undergoing liver transplantation and of 18 deceased donors. Hepatic mRNA expression of FNDC5/Irisin and stearoyl-CoA desaturase (SCD-1), main enzymatic regulator of DNL, were significantly higher in HCC patients than in donors (p<0.0001 and p=0.015, respectively). The hepatic mRNA expression of the neurogenic locus notch homolog protein 1 (NOTCH1) tended to be higher in HCC patients than in donors (p=0.06). Only in HCC patients, hepatic FNDC5/Irisin strongly correlated with the transcription factor sterol regulatory element-binding factor 1, SCD-1, NOTCH1, tumor necrosis factor-α and Interleukin-6 mRNA expression. Further, in HCC patients, FNDC5/Irisin mRNA tended to correlate to plasma lipid profile namely triglycerides, palmitic/linoleic acid and polyunsaturated fatty acid/saturated fatty acid ratios. In conclusion, HCC-liver tissue over-expressed FNDC5/Irisin in association with gene expression of mediators involved in lipogenesis, inflammation and cancer, suggesting a possible protective role of the hormone from the liver damage.

  1. 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

  2. Enterolobium contortisiliquum is a cause of acute ruminal acidosis in sheep.

    PubMed

    Pupin, Rayane C; Leal, Paula V; Lima, Stephanie C; Melo, Gleice Kelli A; Pott, Arnildo; Araújo, Marcelo A; Barros, Claudio S L; Lemos, Ricardo A A

    2017-02-01

    The ingestion of pods of Enterolobium contortisiliquum is associated with digestive disturbances, photosensitivity and abortion in domestic ruminants. This experiment was designed to test the hypothesis that digestive disturbances in this toxicosis are really caused by acute ruminal acidosis. Three sheep fed large doses (10-15 g/kg/body weight [bw]) of E. contortisiliquum pods developed ruminal acidosis and were treated with sodium bicarbonate to try to control this metabolic disturbance, thus providing additional evidence of the involvement of ruminal acidosis in the pathogenesis of toxicosis. Two of the sheep died, and one recovered after treatment. In the two sheep that developed severe signs of ruminal acidosis, the values of blood lactate were 18 mg/dL and 196.88 mg/dL, indicating metabolic acidosis as the cause of death. Additionally, four sheep developed elevated serum levels of aspartate aminotransferase and gamma glutamyl transferase, indicating that the pods had hepatotoxic effects. Necropsy findings included the accentuation of the hepatic lobular pattern and multiple focally extensive red areas in the rumen mucosa and on the surface of the liver. Repeated ingestion of small doses induced tolerance but did not induce cumulative effects. Histopathologically, the epithelial mucosa of the rumen and reticulum exhibited swollen and vacuolated epithelia with intraepithelial pustules. Focal ulceration of the mucosa was also observed. Multifocal vacuolar degeneration of hepatocytes and scattered individual hepatocellular necrosis were evident in the liver. We concluded that the main clinical manifestation of intoxication by E. contortisiliquum pods in sheep was acute ruminal lactic acidosis and metabolic acidosis. Ingestion of repeated sublethal doses could stimulate proliferation of the ruminal fauna that degrades the sugar present in the pods, and thereby prevent the occurrence of ruminal acidosis. The plant is also hepatotoxic, and no abortions were

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Ethanol, ethyl and sodium pyruvate decrease the inflammatory responses of human lung epithelial cells via Akt and NF-κB in vitro but have a low impact on hepatocellular cells.

    PubMed

    Relja, B; Omid, N; Wagner, N; Mörs, K; Werner, I; Juengel, E; Perl, M; Marzi, I

    2016-02-01

    Increases in pro-inflammatory cytokine levels and tissue-infiltrating leukocytes have been closely linked to increased systemic and local inflammation, which result in organ injury. Previously, we demonstrated the beneficial and hepatoprotective anti-inflammatory effects of acute ethanol (EtOH) ingestion in an in vivo model of acute inflammation. Due to its undesirable side-effects, however, EtOH does not represent a therapeutic option for treatment of acute inflammation. Therefore, in this study, we compared the effects of acute EtOH exposure with ethyl pyruvate (EtP) as an alternative anti-inflammatory drug in an in vitro model of hepatic and pulmonary inflammation. Human hepatocellular carcinoma cells Huh7 and alveolar epithelial cells A549 were stimulated with either interleukin (IL) IL-1β (1 ng/ml, 24 h) or tumor necrosis factor (TNF) (10 ng/ml, 4 h), and then treated with EtP (2.5-10 mM), sodium pyruvate (NaP, 10 mM) or EtOH (85-170 mM) for 1 h. IL-6 or IL-8 release from Huh7 or A549 cells, respectively, was measured by an enzyme‑linked immunosorbent assay. Neutrophil adhesion to cell monolayers and CD54 expression were also analyzed. Bcl-2 and Bax gene expression was determined by RT-qPCR, and western blot analysis was performed to determine the mechanisms involved. Treating A549 cells with either EtOH or EtP significantly reduced the IL-1β- or TNF‑induced IL-8 release, whereas treating Huh7 cells did not significantly alter IL-6 release. Similarly, neutrophil adhesion to stimulated A549 cells was significantly reduced by EtOH or EtP, whereas for Huh7 cells the tendency for reduced neutrophil adhesion rates by EtOH or EtP was not significant. CD54 expression was noticeably reduced in A549 cells, but this was not the case in Huh7 cells after treatment. The Bax/Bcl-2 ratio was dose‑dependently decreased by EtOH and by high-dose EtP in A549 cells, indicating a reduction in apoptosis, whereas this effect was not observed in Huh7 cells. The underlying

  9. 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

  10. Warfarin-Induced Skin Necrosis in Patients With Low Protein C Levels.

    PubMed

    Marčić, Marino; Marčić, Ljiljana; Titlić, Marina

    2016-08-01

    Warfarin-induced skin necrosis (WISN) is a rare complication of anticoagulant therapy associated with a high incidence of  morbidity and mortality requiring immediate drug cessation. At particular risk are those with various thrombophilic abnormalities, especially when warfarinisation is undertaken rapidly with large loading doses of warfarin. Cutaneous findings include petechiae that progress to ecchymosis and hemorrhagic bullae. With the increasing number of patients anticoagulated as out-patients for thromboprophylaxis, we are concerned that the incidence of skin necrosis may increase. We present a case of WISN with low protein C level. He was a 50-year-old male who came to our department because of acute infarction in irrigation area of the superior cerebellar artery. He had intermittent atrial fibrillation and was started on anticoagulant therapy.  After few day of therapy, he developed skin necrosis, and his level of protein C was low. Warfarin-induced skin necrosis is a rare but serious complication that can be prevented by routine screening for protein C, protein S or antithrombin deficiencies or for the presence of antiphospholipid antibodies before beginning warfarin therapy.

  11. Giant cell arteritis presenting as scalp necrosis.

    PubMed

    Maidana, Daniel E; Muñoz, Silvia; Acebes, Xènia; Llatjós, Roger; Jucglà, Anna; Alvarez, Alba

    2011-07-07

    The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness.

  12. 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.

  13. Role of innate immunity in the development of hepatocellular carcinoma

    PubMed Central

    Aravalli, Rajagopal N

    2013-01-01

    Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide. It is caused by a variety of risk factors, most common ones being infection with hepatitis viruses, alcohol, and obesity. HCC often develops in the background of underlying cirrhosis, and even though a number of interventional treatment methods are currently in use, recurrence is fairly common among patients who have had a resection. Therefore, whole liver transplantation remains the most practical treatment option for HCC. Due to the growing incidence of HCC, intense research efforts are being made to understand cellular and molecular mechanisms of the disease so that novel therapeutic strategies can be developed to combat liver cancer. In recent years, it has become clear that innate immunity plays a critical role in the development of a number of liver diseases, including HCC. In particular, the activation of Toll-like receptor signaling results in the generation of immune responses that often results in the production of pro-inflammatory cytokines and chemokines, and could cause acute inflammation in the liver. In this review, the current knowledge on the role of innate immune responses in the development and progression of HCC is examined, and emerging therapeutic strategies based on molecular mechanisms of HCC are discussed. PMID:24282342

  14. Peripheral fat necrosis after penetrating pancreatic trauma: a case report.

    PubMed

    Adams, D B

    1993-11-01

    Peripheral fat necrosis (PFN), a rare complication of pancreatitis, has been reported previously in association with blunt pancreatic trauma. A patient who developed peripheral fat necrosis after penetrating pancreatic trauma and needed bilateral above-the-knee amputations to treat complications of lower extremity fat necrosis is reported.

  15. Alveolar bone necrosis and spontaneous tooth exfoliation in an HIV-seropositive subject with herpes zoster.

    PubMed

    Feller, L; Wood, N H; Raubenheimer, E J; Meyerov, R; Lemmer, J

    2008-03-01

    Herpes zoster in the distribution of the maxillary and mandibular divisions of the trigeminal nerve is characterized by painful vesicular eruptions of the skin and oral mucosa in the distribution of the affected nerves. Oral complications may occur, including post-herpetic neuralgia, devitalization of teeth, abnormal development of permanent teeth, root resorption and periapical lesions. In cases where necrosis of the alveolar bony process occur it may be preceded or accompanied by spontaneous exfoliation of teeth. This usually follows the resolution of the acute phase of HZ and is more prevalent in HIV-seropositive than in HIV-seronegative subjects. A case of HZ of the trigeminal nerve in an HIV-seropositive subject, with complications of necrosis of alveolar bony process, external root resorption and tooth exfoliation is presented and the literature of HIV-associated HZ is reviewed.

  16. Stereotactic Hypofractionated Radiation Therapy as a Bridge to Transplantation for Hepatocellular Carcinoma: Clinical Outcome and Pathologic Correlation

    SciTech Connect

    Katz, Alan W.; Chawla, Sheema; Qu, Zhenhong; Kashyap, Randeep; Milano, Michael T.; Hezel, Aram F.

    2012-07-01

    Purpose: We sought to determine efficacy, safety, and outcome of stereotactic hypofractionated radiation therapy (SHORT) as a suitable bridging therapy for patients awaiting liver transplantation (LT) for hepatocellular carcinoma (HCC). We also examined histological response to radiation in the resected or explanted livers. Methods and Materials: Between August 2007 and January 2009, 18 patients with 21 lesions received SHORT. A median total dose of 50 Gy was delivered in 10 fractions. Three patients underwent either chemoembolization (n = 1) or radiofrequency ablation (n = 2) prior to SHORT. Radiographic response was based on computed tomography evaluation at 3 months after SHORT. Histological response as a percentage of tumor necrosis was assessed by a quantitative morphometric method. Results: Six of 18 patients were delisted because of progression (n = 3) or other causes (n = 3). Twelve patients successfully underwent major hepatic resection (n = 1) or LT (n = 11) at a median follow-up of 6.3 months (range, 0.6-11.6 months) after completion of SHORT. No patient developed gastrointestinal toxicity Grade {>=}3 or radiation-induced liver disease. Ten patients with 11 lesions were evaluable for pathological response. Two lesions had 100% necrosis, three lesions had {>=}50% necrosis, four lesions had {<=}50% necrosis, and two lesions had no necrosis. All patients were alive after LT and/or major hepatic resection at a median follow-up of 19.6 months. Conclusions: SHORT is an effective bridging therapy for patients awaiting LT for HCC. It provides excellent in-field control with minimal side effects, helps to downsize or stabilize tumors prior to LT, and achieves good pathological response.

  17. [A case of double cancer of gastric and hepatocellular carcinoma associated with cirrhosis treated by hepatic resection after intra-hepatic arterial infusion chemotherapy].

    PubMed

    Une, Y; Nagabuchi, E; Ogasawara, K; Kamiyama, T; Sato, Y; Kawamukai, Y; Sato, N; Nakajima, Y; Uchino, J

    1990-08-01

    A case of double cancer, early gastric cancer and hepatocellular carcinoma, was reported. The patient was diabetic and had liver cirrhosis. After gastrectomy for gastric cancer which was hemorrhagic, he was treated by intra-hepatic arterial infusion chemotherapy followed by hepatic resection. Histopathologically, about half of the main tumor showed necrosis, but very viable new cancer cell nests were seen around the main nodule. The patient is in good condition without recurrence of hepatic lesion 1 year after resection. The usefulness of arterial infusion chemotherapy was demonstrated in the case of double cancer, in which it is difficult to resect both cancers simultaneously.

  18. 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.

  19. 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

  20. Utility of diffusion-weighted imaging to assess hepatocellular carcinoma viability following transarterial chemoembolization.

    PubMed

    Yuan, Zheng; Li, Wen-Tao; Ye, Xiao-Dan; Peng, Wei-Jun; Xiao, Xiang-Sheng

    2014-08-01

    The purpose of the present study was to evaluate whether diffusion-weighted imaging (DWI) can be used to assess hepatocellular carcinoma (HCC) viability following transarterial chemoembolization (TACE). A total of 41 consecutive patients were treated according to chemoembolization protocols. The follow-up was performed between six and eight weeks post-chemoembolization by multidetector computed tomography [or enhanced magnetic resonance imaging (MRI)] and DW-MRI on the same day. The presence of any residual tumor and the extent of tumor necrosis were evaluated according to the European Association for the Study of the Liver. The apparent diffusion coefficient (ADC) values of the entire area of the treated mass and the vital and necrotic tumor tissues were recorded. Correlation coefficients were also calculated to compare the percentage of necrosis with ADC values. The mean ADC values of the necrotic and vital tumor tissues were 2.22±0.31×10(-3) mm(2)/sec and 1.42±0.25×10(-3) mm(2)/sec, respectively (Mann-Whitney U test, P<0.001). The results from the receiver operating characteristic analysis showed that the threshold ADC value was 1.84×10(-3) mm(2)/sec with 92.3% sensitivity and 100% specificity for identifying the necrotic tumor tissues. A significant linear regression correlation was identified between the ADC value of the entire area of the treated mass and the extent of tumor necrosis (r=0.58; P<0.001). In conclusion, DWI can be used to assess HCC viability following TACE.

  1. Treating and Downstaging Hepatocellular Carcinoma in the Caudate Lobe with Yttrium-90 Radioembolization

    SciTech Connect

    Ibrahim, Saad M.; Kulik, Laura; Baker, Talia; Ryu, Robert K.; Mulcahy, Mary F.; Abecassis, Michael; Salem, Riad; Lewandowski, Robert J.

    2012-10-15

    Purpose: This study was designed to determine the technical feasibility, safety, efficacy, and potential to downstage patients to within transplantation criteria when treating patients with hepatocellular carcinoma (HCC) of the caudate lobe using Y90 radioembolization. Methods: During a 4-year period, 8 of 291 patients treated with radioembolization for unresectable HCC had disease involving the caudate lobe. All patients were followed for treatment-related clinical/biochemical toxicities, serum tumor marker response, and treatment response. Imaging response was assessed with the World Health Organization (WHO) and European Association for the Study of the Liver (EASL) classification schemes. Pathologic response was reported as percent necrosis at explantation. Results: Caudate lobe radioembolization was successfully performed in all eight patients. All patients presented with both cirrhosis and portal hypertension. Half were United Network for Organ Sharing (UNOS) stage T3 (n = 4, 50%). Fatigue was reported in half of the patients (n = 4, 50%). One (13%) grade 3/4 bilirubin toxicity was reported. One patient (13%) showed complete tumor response by WHO criteria, and three patients (38%) showed complete response using EASL guidelines. Serum AFP decreased by more than 50% in most patients (n = 6, 75%). Four patients (50%) were UNOS downstaged from T3 to T2, three of who underwent transplantation. One specimen showed histopathologic evidence of 100% complete necrosis, and two specimens demonstrated greater than 50% necrosis. Conclusions: Radioembolization with yttrium-90 appears to be a feasible, safe, and effective treatment option for patients with unresectable caudate lobe HCC. It has the potential to downstage patients to transplantation.

  2. Segmental Transarterial Embolization in a Translational Rat Model of Hepatocellular Carcinoma

    PubMed Central

    Gade, Terence P.F.; Hunt, Stephen J.; Harrison, Neil; Nadolski, Gregory J.; Weber, Charles; Pickup, Stephen; Furth, Emma E.; Schnall, Mitchell D.; Soulen, Michael C.; Simon, M. Celeste

    2016-01-01

    Purpose To develop a clinically relevant, minimally invasive technique for transarterial embolization in a translational rat model of hepatocellular carcinoma (HCC). Materials and Methods Oral diethylnitrosamine was administered to 53 male Wistar rats ad libitum for 12 weeks. Tumor induction was monitored using magnetic resonance imaging. Minimally invasive lobar or segmental transarterial embolization was performed through a left common carotid artery approach. Necropsy was performed to evaluate periprocedural mortality. Histologic analysis of tumors that received embolization was performed to assess percent tumor necrosis. Results Severe cirrhosis and autochthonous HCCs were characterized in a cohort of rats composed of two groups of rats identically treated with diethylnitrosamine with median survival times of 101 days and 105 days (n = 10/group). A second cohort was used to develop minimally invasive transarterial embolization of HCCs (n = 10). In a third cohort, lobar embolization was successfully performed in 9 of 10 rats and demonstrated a high rate of periprocedural mortality (n = 5). Necropsy performed for periprocedural mortality after lobar embolization demonstrated extensive tissue necrosis within the liver (n = 3) and lungs (n = 2), indicating nontarget embolization as the likely cause of mortality. In a fourth cohort of rats, a segmental embolization technique was successfully applied in 10 of 13 rats. Segmental embolization resulted in a reduction in periprocedural mortality (P = .06) relative to selective embolization and a 19% increase in average tumor necrosis (P = .04). Conclusions Minimally invasive, segmental embolization mimicking the currently applied clinical approach is feasible in a translational rat model of HCC and offers the critical advantage of reduced nontarget embolization relative to lobar embolization. PMID:25863596

  3. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  4. Cystic avascular necrosis of the triquetrum.

    PubMed

    Albtoush, Omar M; Esmadi, Mohammad; Al-Omari, Mamoon H

    2013-01-01

    Carpal bones are rarely affected by avascular necrosis (AVN) in the absence of fractures. The lunate is the most frequently affected carpal bone, followed by the scaphoid and the capitate. The triquetrum is rarely affected by AVN. We report a case of multiple cystic changes in the triquetrum in a patient with a history of trauma. He was treated by below elbow Colles plaster cast for 3 months, with no improvement. Cystic changes resulted from irreversible AVN of the triquetrum. This is the first case to be reported in the literature with cystic AVN changes in the triquetrum.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. Mastectomy skin flap necrosis: challenges and solutions

    PubMed Central

    Robertson, Stuart A; Jeevaratnam, Johann A; Agrawal, Avi; Cutress, Ramsey I

    2017-01-01

    Introduction Mastectomy skin flap necrosis (MSFN) has a reported incidence of 5%–30% in the literature. It is often a significant and underappreciated problem. The aim of this article was to review the associated challenges and possible solutions. Methods A MEDLINE search was performed using the search term “mastectomy skin flap necrosis”. Titles and abstracts from peer-reviewed publications were screened for relevance. Results MSFN is a common complication and may present as partial- or full-thickness necrosis. Predictive patient risk factors include smoking, diabetes, obesity, radiotherapy, previous scars and severe medical comorbidity. MSFN leads to a number of challenges, including wound management problems, delays to adjuvant therapy, esthetic compromise, implant extrusion, patient distress and financial loss. Careful preoperative planning and meticulous surgical technique may reduce the incidence of MSFN. A number of intraoperative techniques are available to try and predict skin flaps at risk of MSFN. MSFN may be managed operatively or nonoperatively. Early intervention may reduce the morbidity of MSFN in selected cases. Topical nitroglycerin ointment may be beneficial in reducing MSFN following immediate reconstruction, but the evidence base is still limited. Conclusion MSFN can result in considerable challenges for the patient and the health care service. This review discusses the management options for this problem. PMID:28331365

  14. Raised serum levels of cachectin/tumor necrosis factor alpha in renal allograft rejection

    PubMed Central

    1987-01-01

    A sensitive radioimmunoassay was used for monitoring serum levels of endogenous cachectin/tumor necrosis factor alpha (TNF) in 10 renal transplant recipients. Acute allograft rejections were associated with marked elevations of circulating TNF. The peak levels of TNF (median 140 pg/ml) were in the same concentration range as previously reported in parasitic infections. The results show that the release of TNF into circulation is an early event in renal allograft rejection and that raised levels of TNF in man can also be induced by noninfectious stimuli. PMID:3309124

  15. A steroid-induced bilateral avascular necrosis of the femoral head in an underage patient affected by multiple sclerosis

    PubMed Central

    Carulli, Christian; Nistri, Lorenzo; Bracco, Laura; Giannini, Marta; Amato, Maria Pia

    2015-01-01

    Summary Patients affected by Multiple Sclerosis are often treated by pulsed intravenous corticosteroids to manage acute relapses with positive outcomes. The intravenous administration is frequently associated to avascular necrosis of several bones, particularly the femur. The present report regards a case of an underage MS patient with a bilateral ANFH secondary to pulsed administrations of steroids, managed by a conservative approach on a hip, and by a novel surgical technique on the contralateral side. PMID:26811707

  16. 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.

  17. 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.

  18. Avascular necrosis of bone complicating corticosteroid replacement therapy.

    PubMed Central

    Williams, P L; Corbett, M

    1983-01-01

    Two patients who developed widespread severe avascular necrosis of bone while on steroid replacement therapy are described. One, a diabetic, underwent yttrium-90 pituitary ablation for retinopathy and developed avascular necrosis within 18 months of starting prednisolone. The other, who had Addison's disease, developed avascular necrosis within 14 months of starting cortisol replacement therapy. Both cases came to bilateral total hip replacement. Images PMID:6859959

  19. The role of tumour necrosis factor in hepatitis B infection: Jekyll and Hyde

    PubMed Central

    Valaydon, Zina; Pellegrini, Marc; Thompson, Alexander; Desmond, Paul; Revill, Peter; Ebert, Gregor

    2016-01-01

    Chronic hepatitis B (CHB) is a major health problem worldwide and is associated with significant long-term morbidity and mortality. The hepatitis B virus (HBV) is a hepatotropic virus that is capable of integrating in the host nucleus permanently resulting in lifelong infection. To date, there is no definitive cure for HBV, as our current treatments cannot eradicate the viral reservoir that has integrated in the liver. Elucidating the immunopathogenesis is key to finding a therapeutic target for HBV as the virus is not in itself cytopathic but the immune response to the virus causes the majority of the cellular injury. In most cases, the virus reaches a state of equilibrium with low viral replication constrained by host immunity. Multiple cytokines have been implicated in the pathogenesis of CHB. Tumor necrosis factor (TNF) has emerged as a key player; on one hand it can facilitate immune-mediated virological control but on the other hand it can cause collateral hepatocyte damage, cirrhosis and possibly promote hepatocellular carcinoma. In this review, we discuss the current understanding of the immunopathogenesis of HBV, focusing on TNF and whether it can be harnessed in therapeutic strategies to cure HBV infection. PMID:28090316

  20. Concomitant avascular necrosis of the scaphoid and lunate.

    PubMed

    Bhardwaj, Praveen; Sharma, Chetna; Sabapathy, S Raja

    2012-01-01

    Simultaneous avascular necrosis of multiple carpal bones is rare. Concomitant avascular necrosis of scaphoid and lunate has been reported only once. We report one more case of this rare condition which can be a cause of wrist pain. Steroid intake is a known risk factor for avascular necrosis but in our case the patient had been taking herbal medicines for joint pain the composition of which was not known. Probably the presence of steroid in these medicines was the cause of avascular necrosis in this case.

  1. Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

    PubMed Central

    Jakubowska, Monika A.; Gerasimenko, Julia V.; Gerasimenko, Oleg V.; Petersen, Ole H.

    2016-01-01

    Key points Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas.Bile acids are known to induce Ca2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored.Here we show that cholate and taurocholate elicit more dramatic Ca2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3‐sulfate primarily affects acinar cells.Ca2+ signals and necrosis are strongly dependent on extracellular Ca2+ as well as Na+; and Na+‐dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells.Bile acid‐mediated pancreatic damage can be further escalated by bradykinin‐induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Abstract Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca2+ signals and necrosis in acinar cells. However, bile acid‐elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3‐sulfate (TLC‐S), known to induce Ca2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca2+ signals on extracellular Na+ and the presence of sodium–taurocholate cotransporting polypeptide (NTCP) indicate a Na

  2. Stereotactic Body Radiation Therapy in Recurrent Hepatocellular Carcinoma

    SciTech Connect

    Huang, Wen-Yen; Jen, Yee-Min; Lee, Meei-Shyuan; Chang, Li-Ping; Chen, Chang-Ming; Ko, Kai-Hsiung; Lin, Kuen-Tze; Lin, Jang-Chun; Chao, Hsing-Lung; Lin, Chun-Shu; Su, Yu-Fu; Fan, Chao-Yueh; Chang, Yao-Wen

    2012-10-01

    Purpose: To examine the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients of recurrent hepatocellular carcinoma (HCC). Methods and Materials: This was a matched-pair study. From January 2008 to December 2009, 36 patients with 42 lesions of unresectable recurrent HCC were treated with SBRT. The median prescribed dose was 37 Gy (range, 25 to 48 Gy) in 4-5 fractions over 4-5 consecutive working days. Another 138 patients in the historical control group given other or no treatments were selected for matched analyses. Results: The median follow-up time was 14 months for all patients and 20 months for those alive. The 1- and 2-year in-field failure-free rates were 87.6% and 75.1%, respectively. Out-field intrahepatic recurrence was the main cause of failure. The 2-year overall survival (OS) rate was 64.0%, and median time to progression was 8.0 months. In the multivariable analysis of all 174 patients, SBRT (yes vs. no), tumor size ({<=}4 cm vs. >4 cm), recurrent stage (stage IIIB/IV vs. I) and Child-Pugh classification (A vs. B/C) were independent prognostic factors for OS. Matched-pair analysis revealed that patients undergoing SBRT had better OS (2-year OS of 72.6% vs. 42.1%, respectively, p = 0.013). Acute toxicities were mild and tolerable. Conclusion: SBRT is a safe and efficacious modality and appears to be well-tolerated at the dose fractionation we have used, and its use correlates with improved survival in this cohort of patients with recurrent unresectable HCC. Out-field recurrence is the major cause of failure. Further studies of combinations of SBRT and systemic therapies may be reasonable.

  3. Nuclear medicine in acute and chronic renal failure

    SciTech Connect

    Sherman, R.A.; Byun, K.J.

    1982-07-01

    The diagnostic value of renal scintiscans in patients with acute or chronic renal failure has not been emphasized other than for the estimation of renal size. /sup 131/I OIH, /sup 67/gallium, /sup 99m/TcDTPA, glucoheptonate and DMSA all may be valuable in a variety of specific settings. Acute renal failure due to acute tubular necrosis, hepatorenal syndrome, acute interstitial nephritis, cortical necrosis, renal artery embolism, or acute pyelonephritis may be recognized. Data useful in the diagnosis and management of the patient with obstructive or reflux nephropathy may be obtained. Radionuclide studies in patients with chronic renal failure may help make apparent such causes as renal artery stenosis, chronic pyelonephritis or lymphomatous kidney infiltration. Future correlation of scanning results with renal pathology promises to further expand nuclear medicine's utility in the noninvasive diagnosis of renal disease.

  4. Definition of bone necrosis by the pathologist

    PubMed Central

    Fondi, Cristina; Franchi, Alessandro

    2007-01-01

    Osteonecrosis is a common disorder that may go clinically unrecognized or may result in the collapse of the architecture of bone, determining severe anatomic alterations of the involved site. Osteonecrosis is not a specific disease entity, but rather the result of a number of conditions ultimately leading to an impairment of blood supply to the bone tissue, although there is evidence that modifications of bone remodelling activity and weakening of bone structure with formation of microfractures are implicated as well. According to the site involved and to the factors promoting its development, the morbid anatomy and histopathology of osteonecrosis show a different appearance. This review discusses the main skeletal manifestations of osteonecrosis, including subarticular avascular necrosis of the femoral head and of the knee, as well as osteonecrosis of the jaw. PMID:22460748

  5. Cortical bone allografting in femoral head necrosis.

    PubMed

    Delloye, C; Cornu, O

    1999-01-01

    Ten femoral heads (six patients) with avascular necrosis were operated on using a fibular allograft. The procedure included core decompression followed by insertion of a cortical bone graft in order to relieve mechanical stresses from the overlying subchondral bone. The presence of the supporting graft should avoid an expected collapse or prevent its worsening if already present. A freeze-dried and processed cortical bone allograft was preferred to an autograft. Weightbearing was normally and fully resumed at the second postoperative month. There were three failures within the first year, four satisfactory results, in which the hip was replaced after 4 years while there are still 3 hips that have been preserved from arthroplasty in young patients after 5 years. The technique is easy and able to substantially delay an arthroplasty in an active patient.

  6. Churg-Strauss syndrome (CSS) manifested as necrosis of fingers and toes and liver infarction.

    PubMed

    Otani, Yuichiro; Anzai, Saburo; Shibuya, Hiromi; Fujiwara, Sakuhei; Takayasu, Susumu; Asada, Yuji; Terashi, Hiroto; Takuma, Masahisa; Yokoyama, Shigeo

    2003-11-01

    We report a case of Churg-Strauss syndrome (CSS) with necrosis of the fingers and toes and liver infarction. A 59-year-old man with asthma suddenly noticed that his fingers and toes felt unusually cold. This condition worsened progressively, and some digits became necrotic within several weeks. Laboratory studies revealed hypereosinophilia and an extremely elevated serum level of IgE. Digital subtraction angiography of the extremities revealed extensive irregular narrowing of small and medium-sized arteries in the extremities. Abdominal computed tomography (CT) revealed an area of low density at the periphery of the right lobe of the liver. Angiography revealed irregular narrowing of small arteries that corresponded to the ischemic area. A nerve conduction study suggested sensory nerve neuropathy. The preceding asthma, acute onset of digital necrosis, liver infarction, neuropathy, and hypereosinophilia strongly suggested a diagnosis of CSS. The patient was treated with 40 mg of prednisolone and 120 micro g of intravenous prostaglandin E1 daily, and all the digits that had turned black and necrotic were amputated. After the amputation, the dose of prednisolone was gradually reduced, and no new lesions appeared on the skin or in the liver. The rare possible complications of CSS, including necrosis of digits and liver infarction, should not be ignored.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. [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.

  1. Avascular necrosis of multiple carpal bones. A case report.

    PubMed

    De Smet, L

    1999-01-01

    A case of a 66-year-old female patient with hyperlipaemia, corticosteroid osteoporosis and chronic obstructive lung disease with avascular necrosis of the proximal row of the carpus and hamate is described. No other sites of avascular bone necrosis were found. A proximal row carpectomy was performed with an excellent outcome.

  2. [Myocellular necrosis by cathecolamines in pheochromocytoma (author's transl)].

    PubMed

    Thiene, G; Valente, M; Cecchetto, A; Giordano, R; Pennelli, N

    1975-01-01

    A case of myocellular necrosis by cathecholamines in a patient presenting pheocromocytoma is reported. Death was due to cerbral apoplexy. The histological findings are quite specific and show myofibrillar degeneration with substitution of the normal striation by coarse sarcomeric transversal bands. The possible role of necrosis by catecholamines in sudden deaths and non-coronary myocardiosclerosis is emphasized.

  3. Pseudotumoral encapsulated fat necrosis with diffuse pseudomembranous degeneration.

    PubMed

    Felipo, F; Vaquero, M; del Agua, C

    2004-09-01

    An extraordinary case of encapsulated fat necrosis characterized by its large size, diffuse formation of pseudomembranes, and tendency to recur after excision is reported. A 67-year-old Caucasian woman suffering from morbid obesity was admitted for diagnosis and surgical treatment of a soft tissue mass showing a longest diameter of 14 cm and lying adjacently to the scar from previous appendicectomy. Histopathologic features were consistent with a nodular-cystic encapsulated fat necrosis with diffuse pseudomembranous transformation. Eight months after surgery, a new larger mass (longest diameter of 18 cm) sharing identical histopathologic features appeared in the same location. Encapsulated fat necrosis is a well-defined entity even though several names have been proposed for this condition, including mobile encapsulated lipoma, encapsulated necrosis, or nodular-cystic fat necrosis. Its pathogenesis seems to be related to ischemic changes secondary to previous trauma. It may occasionally show degenerative changes, including dystrophic calcifications and presence of pseudomembranes. To our knowledge, these are the first reported cases of encapsulated fat necrosis presenting as lesions of such size and showing diffuse formation of pseudomembranes; these particular features made diagnosis difficult and led to consideration of a wide range of potential diagnostic possibilities. This case expands the clinico-pathologic spectrum of membranocystic fat necrosis, including the potential ability of this subcutaneous fatty tissue abnormality to recur after surgical excision. Felipo F, Vaquero M, del Agua C. Pseudotumoral encapsulated fat necrosis with diffuse pseudomembranous degeneration.

  4. Delayed Pneumoperitoneum and Acute Pulmonary Edema Secondary to Acute Gastric Dilatation

    PubMed Central

    Ahn, Jae Yun; Kim, Jong Kun

    2015-01-01

    Pneumoperitoneum caused by acute gastric dilatation (AGD) is a very rare complication. We report a case of pneumoperitoneum and acute pulmonary edema caused by AGD in a patient with Parkinson’s disease. A 78-year-old woman presented with pneumonia and AGD. We inserted a nasogastric tube and administered empirical antibiotics. We performed an endoscopy, and perforation or necrosis of the stomach and pyloric stenosis were not observed. Thirty-six hours after admission, the patient suddenly developed dyspnea and shock, and eventually died. We suspected the cause of death was pneumoperitoneum and acute pulmonary edema caused by AGD during the conservative treatment period. Immunocompromised patients with chronic illness require close observation even if they do not show any symptoms suggestive of complications. Even if the initial endoscopic or abdominal radiologic findings do not show gastric necrosis or perforation, follow-up with endoscopy is essential to recognize complications of AGD early. PMID:26668807

  5. Pathophysiology, diagnosis, and treatment of radiation necrosis in the brain.

    PubMed

    Miyatake, Shin-Ichi; Nonoguchi, Noasuke; Furuse, Motomasa; Yoritsune, Erina; Miyata, Tomo; Kawabata, Shinji; Kuroiwa, Toshihiko

    2015-01-01

    New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient's quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain.

  6. Pathophysiology, Diagnosis, and Treatment of Radiation Necrosis in the Brain.

    PubMed

    Miyatake, Shin-Ichi; Nonoguchi, Noasuke; Furuse, Motomasa; Yoritsune, Erina; Miyata, Tomo; Kawabata, Shinji; Kuroiwa, Toshihiko

    2015-01-01

    New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient’s quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain.

  7. Acute Bronchitis

    MedlinePlus

    ... can also cause acute bronchitis. To diagnose acute bronchitis, your health care provider will ask about your symptoms and listen to your breathing. You may also have other tests. Treatments include rest, fluids, and aspirin (for adults) or ...

  8. Regulation of necrotic cell death: p53, PARP1 and cyclophilin D-overlapping pathways of regulated necrosis?

    PubMed

    Ying, Yuan; Padanilam, Babu J

    2016-06-01

    In contrast to apoptosis and autophagy, necrotic cell death was considered to be a random, passive cell death without definable mediators. However, this dogma has been challenged by recent developments suggesting that necrotic cell death can also be a regulated process. Regulated necrosis includes multiple cell death modalities such as necroptosis, parthanatos, ferroptosis, pyroptosis, and mitochondrial permeability transition pore (MPTP)-mediated necrosis. Several distinctive executive molecules, particularly residing on the mitochondrial inner and outer membrane, amalgamating to form the MPTP have been defined. The c-subunit of the F1F0ATP synthase on the inner membrane and Bax/Bak on the outer membrane are considered to be the long sought components that form the MPTP. Opening of the MPTP results in loss of mitochondrial inner membrane potential, disruption of ATP production, increased ROS production, organelle swelling, mitochondrial dysfunction and consequent necrosis. Cyclophilin D, along with adenine nucleotide translocator and the phosphate carrier are considered to be important regulators involved in the opening of MPTP. Increased production of ROS can further trigger other necrotic pathways mediated through molecules such as PARP1, leading to irreversible cell damage. This review examines the roles of PARP1 and cyclophilin D in necrotic cell death. The hierarchical role of p53 in regulation and integration of key components of signaling pathway to elicit MPTP-mediated necrosis and ferroptosis is explored. In the context of recent insights, the indistinct role of necroptosis signaling in tubular necrosis after ischemic kidney injury is scrutinized. We conclude by discussing the participation of p53, PARP1 and cyclophilin D and their overlapping pathways to elicit MPTP-mediated necrosis and ferroptosis in acute kidney injury.

  9. Immunization with viral antigens: Infectious haematopoietic necrosis

    USGS Publications Warehouse

    Winton, J.R.

    1997-01-01

    Infectious haematopoietic necrosis (IHN) is one of the most important viral diseases of salmonids, especially among juvenile fish where losses can be high. For over 20 years, researchers have tested a variety of preparations for control of IHN. Early vaccines consisted of killed virus and were effective when delivered by injection, but too costly to be practical on a large scale. Attenuated vaccines were developed by serial passage in cell culture and by monoclonal antibody selection. These offered excellent protection and were cost-effective, but residual virulence and uncertainty about their effects on other aquatic species made them poor candidates for licensing. Subunit vaccines using part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated strain of A. salmonicida have been tested, appeared safe and were inexpensive. These vaccines were reported to provide some protection when delivered by immersion. Information on the location of antigenic sites on the glycoprotein led to trials using synthetic peptides, but these did not seem to be economically viable. Recently, plasmid vectors encoding the glycoprotein gene under control of a cytomegalovirus promoter were developed for genetic immunization. The constructs were highly protective when delivered by injection, but a more practical delivery system is needed. Thus, while several vaccine strategies have been tried in order to stimulate specific immunity against IHN, more research is needed to develop a commercially viable product for control of this important disease.

  10. Stimulation of neutrophils by tumor necrosis factor

    SciTech Connect

    Klebanoff, S.J.; Vadas, M.A.; Harlan, J.M.; Sparks, L.H.; Gamble, J.R.; Agosti, J.M.; Waltersdorph, A.M.

    1986-06-01

    Human recombinant tumor necrosis factor (TNF) was shown to be a weak direct stimulus of the neutrophil respiratory burst and degranulation. The stimulation, as measured by iodination, H/sub 2/O/sub 2/ production, and lysozyme release, was considerably increased by the presence of unopsonized zymosan in the reaction mixture, an effect which was associated with the increased ingestion of the zymosan. TNF does not act as an opsonin but, rather, reacts with the neutrophil to increase its phagocytic activity. TNF-dependent phagocytosis, as measured indirectly by iodination, is inhibited by monoclonal antibodies (Mab) 60.1 and 60.3, which recognize different epitopes on the C3bi receptor/adherence-promoting surface glycoprotein of neutrophils. Other neutrophil stimulants, namely N-formyl-methionyl-leucyl-phenylalanine, the Ca2+ ionophore A23187, and phorbol myristic acetate, also increase iodination in the presence of zymosan; as with TNF, the effect of these stimulants is inhibited by Mab 60.1 and 60.3, whereas, in contrast to that of TNF, their stimulation of iodination is unaffected by an Mab directed against TNF. TNF may be a natural stimulant of neutrophils which promotes adherence to endothelial cells and to particles, leading to increased phagocytosis, respiratory burst activity, and degranulation.

  11. Immunization with viral antigens: infectious haematopoietic necrosis.

    PubMed

    Winton, J R

    1997-01-01

    Infectious haematopoietic necrosis (IHN) is one of the most important viral diseases of salmonids, especially among juvenile fish where losses can be high. For over 20 years, researchers have tested a variety of preparations for control of IHN. Early vaccines consisted of killed virus and were effective when delivered by injection, but too costly to be practical on a large scale. Attenuated vaccines were developed by serial passage in cell culture and by monoclonal antibody selection. These offered excellent protection and were cost-effective, but residual virulence and uncertainty about their effects on other aquatic species made them poor candidates for licensing. Subunit vaccines using part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated strain of A. salmonicida have been tested, appeared safe and were inexpensive. These vaccines were reported to provide some protection when delivered by immersion. Information on the location of antigenic sites on the glycoprotein led to trials using synthetic peptides, but these did not seem to be economically viable. Recently, plasmid vectors encoding the glycoprotein gene under control of a cytomegalovirus promoter were developed for genetic immunization. The constructs were highly protective when delivered by injection, but a more practical delivery system is needed. Thus, while several vaccine strategies have been tried in order to stimulate specific immunity against IHN, more research is needed to develop a commercially viable product for control of this important disease.

  12. Inactivated infectious haematopoietic necrosis virus (IHNV) vaccines.

    PubMed

    Anderson, E; Clouthier, S; Shewmaker, W; Weighall, A; LaPatra, S

    2008-10-01

    The inactivation dynamics of infectious haematopoietic necrosis virus (IHNV) by b-propiolactone (BPL), binary ethylenimine (BEI), formaldehyde or heat and the antigenic and immunogenic properties of the inactivated vaccines were evaluated. Chemical treatment of IHNV with 2.7 mm BPL, 1.5 mm BEI or 50 mm formaldehyde abolished virus infectivity within 48 h whereas heat treatment at 50 or 100 degrees C rendered the virus innocuous within 30 min. The inactivated IHNV vaccines were recognized by rainbow trout, Oncorhynchus mykiss, IHNV-specific antibodies and were differentially recognized by antigenic site I or antigenic site II IHNV glycoprotein-specific neutralizing monoclonal antibodies. The BPL inactivated whole virus vaccine was highly efficacious in vaccinated rainbow trout challenged by waterborne exposure to IHNV 7, 28, 42 or 56 days (15 degrees C) after immunization. The formaldehyde inactivated whole virus vaccine was efficacious 7 or 11 days after vaccination of rainbow trout but performed inconsistently when tested at later time points. The other vaccines tested were not efficacious.

  13. Influence of P53 on the radiotherapy response of hepatocellular carcinoma

    PubMed Central

    Gomes, Ana R.; Abrantes, Ana M.; Brito, Ana F.; Laranjo, Mafalda; Casalta-Lopes, João E.; Gonçalves, Ana C.; Sarmento-Ribeiro, Ana B.; Tralhão, José G.

    2015-01-01

    Background/Aims Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines. Methods Western blotting was used to measure P53 expression. The effects of radiotherapy with iodine-131 were assessed by using the clonogenic assay to evaluate cell survival. Flow cytometry was carried out to examine the effects of iodine-131 on cell death, oxidative stress, reduced intracellular glutathione expression, the mitochondrial membrane potential, and the cell cycle. Results The P53 protein was not expressed in Hep3B2.1-7 cells, was expressed at normal levels in HepG2 cells, and was overexpressed in HuH7 cells. P53 expression in the HuH7 and HepG2 cell lines increased after internal and external irradiation with iodine-131. Irradiation induced a decrease in cell survival and led to a decrease in cell viability in all of the cell lines studied, accompanied by cell death via late apoptosis/necrosis and necrosis. Irradiation with 131-iodine induced mostly cell-cycle arrest in the G0/G1 phase. Conclusions These results suggest that P53 plays a key role in the radiotherapy response of HCC. PMID:26527121

  14. Emerging role of autophagy during ischemia-hypoxia and reperfusion in hepatocellular carcinoma.

    PubMed

    Du, Hailei; Yang, Weiping; Chen, Lin; Shen, Baiyong; Peng, Chenghong; Li, Hongwei; Ann, David K; Yen, Yun; Qiu, Weihua

    2012-06-01

    Hepatocellular carcinoma (HCC) is the most common primary malignancy found in the liver. Autophagy is the intracellular bulk degradation process for long-lived proteins and dysfunctional organelles. In this study, we report that autophagy plays a role in HCC cell proliferation in response to ischemia-hypoxia (I/H) and reperfusion and discuss its potential therapeutic implications. By establishing a simulated model in cultured HepG2 (p53 wild-type) and Hep3B (p53 null) hepatoma cells in vitro, we found that exposure to I/H induced a significant increase in microtubule-associated protein 1 light chain 3 (LC3) lipidation and subsequent LC3 puncta formation. While the proliferation of HCC cells was stimulated upon acute I/H exposure compared to that of control, inhibition of autophagy by autophagy-related protein 7 interference abolished it. In addition, the steady-state levels of sequestosome 1 (p62) in both HepG2 and Hep3B cells were reduced following I/H exposure, supporting the notion that acute I/H induces autophagy. Intriguingly, the p62 level further decreased during reperfusion following I/H, accompanied by increased LC3 lipidation. The intracellular reactive oxygen species (ROS) accumulated during acute I/H exposure and persisted through reperfusion in both HepG2 and Hep3B cells and the ROS levels increased at a much faster rate during reperfusion than during I/H periods in both cells. Autophagy functions as a promoter for HCC cell survival during acute I/H and reperfusion and this also points to potential therapy for hepatoma by perturbing the acute I/H-reperfusion-autophagy axis.

  15. 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.

  16. Great Toe Necrosis Predicts an Unfavorable Limb Salvage Prognosis

    PubMed Central

    Ichioka, Shigeru

    2014-01-01

    Summary: The initial location of necrosis may affect the limb salvage rate. This study of 130 patients with chronic toe ulcers or gangrene was performed to assess whether the location of initial necrosis in the toes affected limb salvage prognosis. The patients were divided into 2 groups according to whether the initial necrosis was in the great toe or in other toes. Limb salvage prognosis was determined retrospectively. In the great toe group, the rates of total toe loss and major amputation were 50.0% and 24.4%, respectively. When the initial necrosis was in other toes, these rates were 27.3% and 9.3%, respectively. Great toe necrosis is associated with significantly higher rates of total toe loss (odds ratio = 3.10; P = 0.003; 95% confidence interval, 1.43−6.68) and major amputation (odds ratio = 3.66; P = 0.007; 95% confidence interval, 1.37−9.79). The great toe is supplied by 3 source arteries, whereas the lesser toes are fed by 1 or 2 arteries. Therefore, necrosis initiating from the great toe may reflect the presence of severe vascular disorders. The great toe is also anatomically connected to much of the foot via the tendons. Infection is more likely to spread along these tendons, which may reduce limb prognosis. Thus, the initial location of necrosis may be predictive of limb prognosis. PMID:25426399

  17. [Torsion and necrosis of epiploic appendices of the large bowel].

    PubMed

    Timofeev, M E; Fedorov, E D; Krechetova, A P; Shapoval'iants, S G

    2014-01-01

    The features of the clinical symptoms was studied, the possibility of laparoscopy in modern diagnosis and treatment of epiploic appendices torsion and necrosis of the large bowel was assessed in the article. It was done the retrospective analysis of the medical records of 87 patients with a diagnosis of epiploic appendices torsion and necrosis of the large bowel. The patients had laparoscopic operations in our hospital in the period from January 1995 to December 2012. The clinical picture, laboratory and instrumental datas in cases of epiploic appendices torsion and necrosis were scarce and nonspecific. An abdominal pain preferentially localized in the lower divisions was the main symptom (97.7%). The instrumental methods did not allow to diagnose the torsion and necrosis of epiploic appendices in the majority of cases and all these techniques were used for the differential diagnosis with other diseases. The assumption of the presence of appendices torsion and necrosis occured just in 34.5% of cases before the operation. Diagnosis of epiploic appendices torsion and necrosis present significant difficulties on prehospital and preoperative stages. The diagnostic laparoscopy is the method of choice in unclear situations and it allows to diagnose the torsion and necrosis of epiploic appendices in 96.6% of cases. Successful surgical treatment by using laparoscopic approach is possible in 90.8% of cases.

  18. Testicular hemorrhage, necrosis, and vasculopathy: likely manifestations of intermittent torsion that clinically mimic a neoplasm.

    PubMed

    Kao, Chia-Sui; Zhang, Chen; Ulbright, Thomas M

    2014-01-01

    parenchyma in all 30 cases. Clinical follow-up in 20 patients (4 to 131 mo, mean 38 mo) showed no evidence of recurrence in the contralateral testis or later development of systemic vasculitis. The histologic findings were compared with those in 11 orchiectomies resected for clinical acute torsion. All clinical acute torsion cases showed both parenchymal and fibrinoid vascular necrosis, and 10 had hemorrhage/hematoma; they lacked vasculitis, interstitial inflammation, and chronic vascular changes. Testicular vasculopathy, characterized by acute and chronic vascular injury, commonly occurs in testes with parenchymal hemorrhage and necrosis that clinically mimic a tumor. It shares the acute features of recent torsion but also has findings indicative of chronic injury. Testicular vasculopathy is most likely a result of chronic intermittent torsion that leads to localized hemorrhage/necrosis and should be distinguished from cases of systemic vasculitis given the significantly different clinical implications.

  19. Sodium hypochlorite-induced acute kidney injury.

    PubMed

    Peck, Brandon W; Workeneh, Biruh; Kadikoy, Huseyin; Abdellatif, Abdul

    2014-03-01

    Sodium hypochlorite (bleach) is commonly used as an irrigant during dental procedures as well as a topical antiseptic agent. Although it is generally safe when applied topically, reports of accidental injection of sodium hypochlorite into tissue have been reported. Local necrosis, pain and nerve damage have been described as a result of exposure, but sodium hypo-chlorite has never been implicated as a cause of an acute kidney injury (AKI). In this report, we describe the first case of accidental sodium hypochlorite injection into the infraorbital tissue during a dental procedure that precipitated the AKI. We speculate that oxidative species induced by sodium hypochlorite caused AKI secondary to the renal tubular injury, causing mild acute tubular necrosis.

  20. Tumor necrosis factor interaction with gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Tsai, De-Hao; Elzey, Sherrie; Delrio, Frank W.; Keene, Athena M.; Tyner, Katherine M.; Clogston, Jeffrey D.; Maccuspie, Robert I.; Guha, Suvajyoti; Zachariah, Michael R.; Hackley, Vincent A.

    2012-05-01

    We report on a systematic investigation of molecular conjugation of tumor necrosis factor-α (TNF) protein onto gold nanoparticles (AuNPs) and the subsequent binding behavior to its antibody (anti-TNF). We employ a combination of physical and spectroscopic characterization methods, including electrospray-differential mobility analysis, dynamic light scattering, polyacrylamide gel electrophoresis, attenuated total reflectance-Fourier transform infrared spectroscopy, fluorescence assay, and enzyme-linked immunosorbent assay. The native TNF used in this study exists in the active homotrimer configuration prior to conjugation. After binding to AuNPs, the maximum surface density of TNF is (0.09 +/- 0.02) nm-2 with a binding constant of 3 × 106 (mol L-1)-1. Dodecyl sulfate ions induce desorption of monomeric TNF from the AuNP surface, indicating a relatively weak intermolecular binding within the AuNP-bound TNF trimers. Anti-TNF binds to both TNF-conjugated and citrate-stabilized AuNPs, showing that non-specific binding is significant. Based on the number of anti-TNF molecules adsorbed, a substantially higher binding affinity was observed for the TNF-conjugated surface. The inclusion of thiolated polyethylene glycol (SH-PEG) on the AuNPs inhibits the binding of anti-TNF, and the amount of inhibition is related to the number ratio of surface bound SH-PEG to TNF and the way in which the ligands are introduced. This study highlights the challenges in quantitatively characterizing complex hybrid nanoscale conjugates, and provides insight on TNF-AuNP formation and activity.We report on a systematic investigation of molecular conjugation of tumor necrosis factor-α (TNF) protein onto gold nanoparticles (AuNPs) and the subsequent binding behavior to its antibody (anti-TNF). We employ a combination of physical and spectroscopic characterization methods, including electrospray-differential mobility analysis, dynamic light scattering, polyacrylamide gel electrophoresis

  1. Plaquing procedure for infectious hematopoietic necrosis virus

    USGS Publications Warehouse

    Burke, J.A.; Mulcahy, D.

    1980-01-01

    A single overlay plaque assay was designed and evaluated for infectious hematopoietic necrosis virus. Epithelioma papillosum carpio cells were grown in normal atmosphere with tris(hydroxymethyl)aminomethane- or HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered media. Plaques were larger and formed more quickly on 1- to 3-day-old cell monolayers than on older monolayers. Cell culture medium with a 10% addition of fetal calf serum (MEM 10) or without serum (MEM 0) were the most efficient virus diluents. Dilution with phosphate-buffered saline, saline, normal broth, or deionized water reduced plaque numbers. Variations in the pH (7.0 to 8.0) of a MEM 0 diluent did not affect plaque numbers. Increasing the volume of viral inoculum above 0.15 ml (15- by 60-mm plate) decreased plaquing efficiency. Significantly more plaques occurred under gum tragacanth and methylcellulose than under agar or agarose overlays. Varying the pH (6.8 to 7.4) of methylcellulose overlays did not significantly change plaque numbers. More plaques formed under the thicker overlays of both methylcellulose and gum tragacanth. Tris(hydroxymethyl)aminomethane and HEPES performed equally well, buffering either medium or overlay. Plaque numbers were reduced when cells were rinsed after virus adsorption or less than 1 h was allowed for adsorption. Variation in adsorption time between 60 and 180 min did not change plaque numbers. The mean plaque formation time was 7 days at 16 degrees C. The viral dose response was linear when the standardized assay was used.

  2. 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.

  3. 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

  4. Coenzyme Q10 and Oxidative Stress: Inflammation Status in Hepatocellular Carcinoma Patients after Surgery.

    PubMed

    Liu, Hsiao-Tien; Cheng, Shao-Bin; Huang, Yi-Chia; Huang, Yin-Tzu; Lin, Ping-Ting

    2017-01-04

    (1) Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths worldwide, and surgical resection is the main treatment for HCC. To date, no published study has examined the status of coenzyme Q10 in patients with HCC after surgery. Thus, the purpose of this study was to investigate the correlations between the level of coenzyme Q10, oxidative stress, and inflammation in patients with HCC after surgery; (2) Methods: 71 primary HCC patients were recruited. Levels of coenzyme Q10, vitamin E, oxidative stress (malondialdehyde), antioxidant enzymes activity (superoxidase dismutase, catalase, and glutathione peroxidase), and inflammatory markers (high sensitivity C-reactive protein; tumor necrosis factor-α; and interleukin-6) were measured; (3) Results: Patients with HCC had a significantly lower levels of coenzyme Q10 (p = 0.01) and oxidative stress (p < 0.01), and significantly higher levels of antioxidant enzymes activities and inflammation after surgery (p < 0.05). The level of coenzyme Q10 was significantly positively correlated with antioxidant capacity (vitamin E and glutathione peroxidase activity) and negatively correlated with inflammation markers after surgery; (4) Conclusion: Hepatocarcinogenesis is associated with oxidative stress, and coenzyme Q10 may be considered an antioxidant therapy for patients with HCC, particularly those with higher inflammation after surgery.

  5. Coenzyme Q10 and Oxidative Stress: Inflammation Status in Hepatocellular Carcinoma Patients after Surgery

    PubMed Central

    Liu, Hsiao-Tien; Cheng, Shao-Bin; Huang, Yi-Chia; Huang, Yin-Tzu; Lin, Ping-Ting

    2017-01-01

    (1) Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths worldwide, and surgical resection is the main treatment for HCC. To date, no published study has examined the status of coenzyme Q10 in patients with HCC after surgery. Thus, the purpose of this study was to investigate the correlations between the level of coenzyme Q10, oxidative stress, and inflammation in patients with HCC after surgery; (2) Methods: 71 primary HCC patients were recruited. Levels of coenzyme Q10, vitamin E, oxidative stress (malondialdehyde), antioxidant enzymes activity (superoxidase dismutase, catalase, and glutathione peroxidase), and inflammatory markers (high sensitivity C-reactive protein; tumor necrosis factor-α; and interleukin-6) were measured; (3) Results: Patients with HCC had a significantly lower levels of coenzyme Q10 (p = 0.01) and oxidative stress (p < 0.01), and significantly higher levels of antioxidant enzymes activities and inflammation after surgery (p < 0.05). The level of coenzyme Q10 was significantly positively correlated with antioxidant capacity (vitamin E and glutathione peroxidase activity) and negatively correlated with inflammation markers after surgery; (4) Conclusion: Hepatocarcinogenesis is associated with oxidative stress, and coenzyme Q10 may be considered an antioxidant therapy for patients with HCC, particularly those with higher inflammation after surgery. PMID:28054958

  6. Therapeutic Effect of Astragalus Polysaccharides on Hepatocellular Carcinoma H22-Bearing Mice

    PubMed Central

    Lai, Xiaoyu; Xia, Weibiao; Wei, Jing

    2017-01-01

    The purpose of this study was to investigate the effect of astragalus polysaccharides (APSs), active constituents of astragalus, in the treatment of hepatocellular carcinoma (HCC) and their potential as a promising candidate for future anticancer drug development. Astragalus polysaccharide was administered at different doses to HCC H22-bearing mice to investigate their antitumor effects. Results revealed that APS inhibited the growth of H22 cells with a tumor inhibition rate in the APS 400 mg·kg−1 group of 59.01%. Astragalus polysaccharides significantly increased the spleen and thymus indexes, and also the interleukin (IL) 2, IL-6, and tumor necrosis factor α cytokine concentration in serum, indicating that APS influences immune-regulating properties involved in antitumor activity. In addition, APS increased Bax protein expression and decreased Bcl-2 protein expression; these proteins are apoptosis-regulating factors responsible for cell death or survival. Further development and exploration of APS may enable it to become an effective clinical agent for liver cancer therapy. PMID:28210201

  7. Hepatocellular carcinoma detection by gallium scan and subsequent treatment by gallium maltolate: rationale and case study.

    PubMed

    Bernstein, Lawrence R; van der Hoeven, Jacobus J M; Boer, Robbert O

    2011-07-01

    Gallium is antiproliferative to many types of cancer, due primarily to its ability to act as a non-functional mimic of ferric iron (Fe(3+)). Because Fe(3+) is needed for ribonucleotide reductase activity--and thus DNA synthesis--gallium can inhibit DNA production and cell division. Diagnostic gallium scans have shown that hepatocellular carcinoma (HCC) is commonly avid for gallium. Furthermore, in vitro studies have found that gallium nitrate, and particularly gallium maltolate (GaM), have dose-dependent antiproliferative activity against HCC cell lines. Rationale thus exists to use GaM, an orally active compound that has been well tolerated in Phase I clinical trials, to treat patients whose HCC is gallium-avid in a gallium scan. Because gallium absorbed from orally administered GaM is bound predominately to serum transferrin, which travels to all tissues in the body, GaM has the potential to treat even distant metastases. A patient with advanced HCC (20 × 10 cm primary tumor, ascites around liver and spleen, resistant to Nexavar(®) (sorafenib)), whose cancer was highly gallium-avid in a (67)Ga-scan, was treated with oral gallium maltolate at 1500 mg/day q.d. After four weeks of treatment, the patient had a large reduction in pain, with greatly increased mobility and quality of life, and significantly lowered serum bilirubin and inflammation-related liver enzymes. At eight weeks, CT scans showed apparent necrosis of the tumor.

  8. Selenium-substituted hydroxyapatite nanoparticles and their in vivo antitumor effect on hepatocellular carcinoma.

    PubMed

    Yanhua, Wang; Hao, Hang; Li, Yan; Zhang, Shengmin

    2016-04-01

    Absence of curative treatment creates urgent need for new strategies for unresectable hepatoma. Novel selenium-substituted hydroxyapatite nanoparticles (SeHAN) were designed to serve as anticancer agent. The authors examined the nanoparticles by physicochemical techniques. The in vivo efficacy and toxicity of these nanoparticles were also investigated on a nude mice model of human hepatocellular carcinoma. The results showed that the selenite ions can be incorporated into the hydroxyapatite lattice facilely. They exhibited bundles of needles shape with a size of 160-200 nm. In the in vivo study, they showed better survival advantage. The overall survival rate of nude mice in the control, pure hydroxyapatite and SeHAN group were 50.00%, 76.92%, and 100.00% respectively. Blood biochemical studies showed that SeHAN group had significantly lower toxicities on the liver and kidney functions. Histopathological studies confirmed that massive tumor necrosis and calcium deposition were evident after SeHAN treatment. Moreover, immunohistochemistry and Western blot assay showed significantly reduced expression of the Ki-67, VEGF and MMP-9 protein in the SeHAN group. Taken together, these results suggest that the selenium-substituted hydroxyapatite nanoparticles could be a new type of promising anticancer agent to provide both survival advantage and lower toxicity.

  9. Antitumor effects of hyaluronic acid inhibitor 4-methylumbelliferone in an orthotopic hepatocellular carcinoma model in mice.

    PubMed

    Piccioni, Flavia; Malvicini, Mariana; Garcia, Mariana G; Rodriguez, Andrés; Atorrasagasti, Catalina; Kippes, Nestor; Piedra Buena, Ignacio T; Rizzo, Manglio M; Bayo, Juan; Aquino, Jorge; Viola, Manuela; Passi, Alberto; Alaniz, Laura; Mazzolini, Guillermo

    2012-03-01

    Liver cirrhosis is characterized by an excessive accumulation of extracellular matrix components, including hyaluronan (HA). In addition, cirrhosis is considered a pre-neoplastic disease for hepatocellular carcinoma (HCC). Altered HA biosynthesis is associated with cancer progression but its role in HCC is unknown. 4-Methylumbelliferone (4-MU), an orally available agent, is an HA synthesis inhibitor with anticancer properties. In this work, we used an orthotopic Hepa129 HCC model established in fibrotic livers induced by thioacetamide. We evaluated 4-MU effects on HCC cells and hepatic stellate cells (HSCs) in vitro by proliferation, apoptosis and cytotoxicity assays; tumor growth and fibrogenesis were also analyzed in vivo. Our results showed that treatment of HCC cells with 4-MU significantly reduced tumor cell proliferation and induced apoptosis, while primary cultured hepatocytes remained unaffected. 4-MU therapy reduced hepatic and systemic levels of HA. Tumors systemically treated with 4-MU showed the extensive areas of necrosis, inflammatory infiltrate and 2-3-fold reduced number of tumor satellites. No signs of toxicity were observed after 4-MU therapy. Animals treated with 4-MU developed a reduced fibrosis degree compared with controls (F1-2 vs F2-3, respectively). Importantly, 4-MU induced the apoptosis of HSCs in vitro and decreased the amount of activated HSCs in vivo. In conclusion, our results suggest a role for 4-MU as an anticancer agent for HCC associated with advanced fibrosis.

  10. Hepatocellular Carcinoma Post Embolotherapy: Imaging Appearances and Pitfalls on Computed Tomography and Magnetic Resonance Imaging.

    PubMed

    Chiu, Rita Y W; Yap, Wan W; Patel, Roshni; Liu, David; Klass, Darren; Harris, Alison C

    2016-05-01

    Embolotherapies used in the treatment of hepatocellular carcinoma (HCC) include bland embolization, conventional transarterial chemoembolization (cTACE) using ethiodol as a carrier, TACE with drug-eluting beads and super absorbent polymer microspheres (DEB-TACE), and selective internal radiation therapy (SIRT). Successfully treated HCC lesions undergo coagulation necrosis, and appear as nonenhancing hypoattenuating or hypointense lesions in the embolized region on computed tomography (CT) and magnetic resonance. Residual or recurrent tumours demonstrate arterial enhancement with portal venous phase wash-out of contrast, features characteristic of HCC, in and/or around the embolized area. Certain imaging features that result from the procedure itself may limit assessment of response. In conventional TACE, the high-attenuating retained ethiodized oil may obscure arterially-enhancing tumours and limit detection of residual tumours; thus a noncontrast CT on follow-up imaging is important post-cTACE. Hyperenhancement within or around the treated zone can be seen after cTACE, DEB-TACE, or SIRT due to physiologic inflammatory response and may mimic residual tumour. Recognition of these pitfalls is important in the evaluation embolotherapy response.

  11. Current role of microwave ablation in the treatment of small hepatocellular carcinomas

    PubMed Central

    Lucchina, Natalie; Tsetis, Dimitrios; Ierardi, Anna Maria; Giorlando, Francesca; Macchi, Edoardo; Kehagias, Elias; Duka, Ejona; Fontana, Federico; Livraghi, Lorenzo; Carrafiello, Gianpaolo

    2016-01-01

    Percutaneous radiofrequency ablation (RFA) can be as effective as surgical resection in terms of overall survival and recurrence-free survival rates in patients with small hepatocellular carcinoma (HCC). Effectiveness of RFA is adversely influenced by heat-sink effect. Other ablative therapies could be considered for larger tumors or for tumors located near the vessels. In this regard, recent improvements in microwave energy delivery systems seem to open interesting perspectives to percutaneous ablation, which could become the ablation technique of choice in the near future. Microwave ablation (MWA) has the advantages of possessing a higher thermal efficiency. It has high efficacy in coagulating blood vessels and is a relatively fast procedure. The time required for ablation is short and the shape of necrosis is elliptical with the older systems and spherical with the new one. There is no heat-sink effect and it can be used to ablate tumors adjacent to major vessels. These factors yield a large ablation volume, and result in good local control and fewer complications. This review highlights the most relevant updates on MWA in the treatment of small (<3 cm) HCC. Furthermore, we discuss the possibility of MWA as the first ablative choice, at least in selected cases. PMID:27708511

  12. Duodenal perforation and esophageal ischemia following transarterial chemoembolization for hepatocellular carcinoma

    PubMed Central

    Kim, Shin Il; Jin, Young-Joo; Cho, Soon Gu; Shin, Woo Young; Kim, Joon Mee; Lee, Jin-Woo

    2016-01-01

    Abstract Transarterial chemoembolization (TACE) is frequently used for treatment of unresectable hepatocellular carcinoma (HCC) and can also be used for case of liver metastases from rectal cancer. Although it is recognized as safe and effective treatment, various complications have been reported. However, post-TACE duodenal perforation with duodenal and esophageal ischemia has not been reported in the literature. A 43-year-old male had experienced duodenal perforation combined with duodenal and lower esophageal ischemia after 8 times of repeated TACE for recurrent and unresectable HCCs, that was confirmed on esophagogastroduodenoscopy and abdominal computed tomography. Interestingly, operative findings showed complete recovery of duodenal ischemia except perforation, and he recovered with just the segmental duodenectomy and gastrojejunostomy. We report a case of duodenal perforation with necrosis and esophageal ischemia after 8th TACE for unresectable HCC. Although this complication is rare and unexpected, it may result in severe sequelae requiring surgical repair. The careful procedure during TACE followed by post-TACE careful monitoring is required in patients with posthepatectomy or repeated TACE, especially in the case with unusual clinical manifestations. PMID:27399074

  13. The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells.

    PubMed

    Louandre, Christophe; Marcq, Ingrid; Bouhlal, Hicham; Lachaier, Emma; Godin, Corinne; Saidak, Zuzana; François, Catherine; Chatelain, Denis; Debuysscher, Véronique; Barbare, Jean-Claude; Chauffert, Bruno; Galmiche, Antoine

    2015-01-28

    Sorafenib is the treatment of reference for advanced hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour. The loss of function of the retinoblastoma (Rb) protein is an important event during liver carcinogenesis, but it is unclear whether the Rb status modulates the response of HCC cells to sorafenib. Here, we examined this question in HCC cells with reduced levels of Rb achieved through stable RNA interference. We show that HCC cells with reduced levels of Rb exhibit a two- to threefold increase in cell death induction upon exposure to sorafenib compared with controls. Sorafenib treatment of Balb/c nude mice that received tumour xenografts derived from HCC cells with reduced Rb levels resulted in complete tumour regression in 50% of the animals treated, compared with tumour stabilization in mice that received control cells. We show that, upon exposure to sorafenib, the Rb-negative status of HCC cells promotes the occurrence of ferroptosis, a form of oxidative necrosis. The findings highlight the role of Rb in the response of HCC cells to sorafenib and the regulation of ferroptosis.

  14. Cancer-Associated Fibroblasts from Hepatocellular Carcinoma Promote Malignant Cell Proliferation by HGF Secretion

    PubMed Central

    Fu, Bin-Sheng; Hua, XueFeng; Wang, Guo-Ying; Li, Tuan-Jie; Li, Xing; Wu, Xiang-Yuan; Tai, Yan; Zhou, Jie; Chen, Gui-Hua; Zhang, Qi

    2013-01-01

    Cancer-associated fibroblasts (CAFs) are reported to support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion in most solid tumors. However, the roles of CAFs in the liver cancer microenvironment have not been thoroughly studied. In our previous study, we successfully isolated CAFs from hepatocellular carcinoma (HCC) (H-CAFs) and proved that H-CAFs suppressed the activation of NK cells and thereby created favorable conditions for HCC progression. In our present study, we found that the proliferation of MHCC97L and Hep3B cells was significantly promoted by treatment with conditioned medium from H-CAFs. Pathological analysis also revealed that H-CAFs increased the proportion of Ki-67 (+) malignant cells and prevented them from undergoing necrosis. Moreover, the concentration of hepatocyte growth factor (HGF) cytokine in the conditioned medium of H-CAFs was higher than conditioned medium from normal skin fibroblasts (NSFs). Anti-HGF significantly reduced the proliferation-promoting capability of H-CAFs. In addition, we found that the abundance of H-CAFs correlated positively with tumor size. These results indicate that H-CAFs are an important factor for promoting the growth of HCC in vitro and in vivo, and that HGF plays a key role in HCC proliferation induced by H-CAFs. PMID:23667593

  15. TIPE1 induces apoptosis by negatively regulating Rac1 activation in hepatocellular carcinoma cells.

    PubMed

    Zhang, Z; Liang, X; Gao, L; Ma, H; Liu, X; Pan, Y; Yan, W; Shan, H; Wang, Z; Chen, Y H; Ma, C

    2015-05-14

    TIPE1 (tumor necrosis factor-α-induced protein 8-like 1 or TNFAIP8L1) is a newly identified member of the TIPE (TNFAIP8) family, which play roles in regulating cell death. However, the biologic functions of TIPE1 in physiologic and pathologic conditions are largely unknown. Here, we report the roles of TIPE1 in hepatocellular carcinoma (HCC). Evaluated by immunohistochemical staining, HCC tissues showed significantly downregulated TIPE1 expression compared with adjacent non-tumor tissues, which positively correlated with tumor pathologic grades and patient survival. Using a homograft tumor model in Balb/c mice, we discovered that TIPE1 significantly diminished the growth and tumor weight of murine liver cancer homografts. Consistently, TIPE1 inhibited both cell growth and colony formation ability of cultured HCC cell lines, which was further identified to be due to TIPE1-inducing apoptosis in a caspase-independent, necrostatin-1 (Nec-1)-insensitive manner. Furthermore, mechanistic investigations revealed that TIPE1 interacted with Rac1, and inhibited the activation of Rac1 and its downstream p65 and c-Jun N-terminal kinase pathway. Moreover, overexpression of constitutively active Rac1 partially rescued the apoptosis induced by TIPE1, and Rac1 knockdown significantly restored the deregulated cell growth induced by TIPE1 small interfering RNA. Our findings revealed that TIPE1 induced apoptosis in HCC cells by negatively regulating Rac1 pathway, and loss of TIPE1 might be a new prognostic indicator for HCC patients.

  16. Challenges With the Diagnosis and Treatment of Cerebral Radiation Necrosis

    SciTech Connect

    Chao, Samuel T.; Ahluwalia, Manmeet S.; Barnett, Gene H.; Stevens, Glen H.J.; Murphy, Erin S.; Stockham, Abigail L.; Shiue, Kevin; Suh, John H.

    2013-11-01

    The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis.

  17. Mandibular bone necrosis after use of paraformaldehyde-containing paste

    PubMed Central

    Lee, Chi-hwan; Choi, Yoorina

    2016-01-01

    Paraformaldehyde has been used in the past as a pulpotomy agent. However, it has a severe cytotoxic effect and may cause alveolar bone necrosis. Depulpin, a devitalizing agent containing 49% paraformaldehyde, is no longer used frequently due to its severe side effects. In the two cases described in the present study, Depulpin was used as a devitalizing agent during root canal treatment. It caused a gradual loss of sensibility in adjacent teeth, gingival necrosis, and osteomyelitis. This case report demonstrates the serious side effects of using a paraformaldehyde-containing paste as a devitalizing agent for pulp, particularly mandibular bone necrosis. PMID:27847756

  18. Breast lipoma with central fat necrosis: case report

    PubMed Central

    Bouroumane, Mohamed Reda; Khalil, Reda; Khalil, Hind; Jalal, Hicham

    2016-01-01

    Fat necrosis of the breast is a benign non-suppurative inflammatory process of adipose tissue that most commonly occurs as the result of minor breast trauma. We present a case of a 40-years-old female with fat necrosis in a breast lipoma. She presented with an overlapping mass on the lateral quadrants. Mammography showed Well delineated radiolucent mass with peripheral “egg-shell” calcifications, that appeared an hypoechoic mass with posterior shadowing on ultrasonography. A history of accidental trauma raises the suspicion of fat necrosis. Pathology is necessary when radiological findings simulate malignancy.

  19. 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.

  20. 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

  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 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. Potentiality of immunotherapy against hepatocellular carcinoma.

    PubMed

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

    2015-09-28

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

  12. 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

  13. 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.

  14. Hepatocellular carcinoma: clinical frontiers and perspectives

    PubMed Central

    Bruix, Jordi; Gores, Gregory J; Mazzaferro, Vincenzo

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death and is currently the main event leading to death in patients with cirrhosis. Evolving information suggests that the metabolic syndrome with non-alcoholic liver disease may be an important cause of HCC in addition to viral hepatitis and alcohol-induced liver disease. The molecular pathogenesis is extremely complex and heterogeneous. To date the molecular information has not impacted on treatment decisions. Periodic surveillance imaging of patients with cirrhosis is widely practiced, especially because diagnostic, radiographic criteria for early-stage HCC have been defined (including nodules between 1 and 2 cm) and effective treatment is available for tumours detected at an early stage. Worldwide the approach to resection versus transplantation varies depending upon local resources, expertise and donor availability. The criteria for transplantation are discussed, and the controversial areas highlighted with evidence-based recommendations provided. Several approaches are available for intermediate stage disease, including radiofrequency ablation, transarterial chemoembolisation and radioembolisation; the rationale for these therapies is buttressed by appropriate outcome-based studies. For advanced disease, systemic therapy with sorafenib remains the option best supported by current data. Thus, while several trials have failed to improve the benefits of established therapies, studies assessing the sequential or combined application of those already known to be beneficial are needed. Also, new concepts are provided in regards to selecting and stratifying patients for second-line studies, which may help explain the failure of prior studies. PMID:24531850

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. [Subcutaneous fat necrosis and persistent hypercalcaemia in a newborn treated with therapeutic neonatal hypothermia. A case report].

    PubMed

    Martínez de Zabarte Fernández, José M; Laliena Aznar, Sara; Corella Aznar, Elena; Cuadrado Piqueras, Laura; Oliván del Cacho, María J; Pinillos Pisón, Raquel

    2016-02-01

    Therapeutic hypothermia is the current standard treatment in newborns with moderate to severe hypoxic-ischemic encephalopathy, changing the outcome of these children. It is considered a safe technique with almost no side effects. A possible adverse side event is subcutaneous fat necrosis, which is an acute self-limiting panniculitis that develops during the first weeks of life. We report a case of a newborn at term suffering hypoxic-ischemic encephalopathy with a generalized multiform erythematous rash and firm and indurated plaques over the back, buttocks and extremities on his 12th day of life after being treated with therapeutic hypothermia. Histopathological study after skin punchbiopsy confirmed the suspicion of subcutaneous fat necrosis. The infant developed asymptomatic moderate hypercalcaemia within the first month of life, which was treated with intravenous fluids and diuretics. Serum calcium levels decreased and normalized in 3 months, with progressive disappearance of skin lesions.

  9. Toe Necrosis, Etiologies and Management, a Case Series

    PubMed Central

    Issa, Abdelfatah Abou; Newman, Mackenzie; Simman, Richard

    2014-01-01

    Toe necrosis may have vast different etiologies. These include ischemia, embolus, and others. (1) The most common etiology is ischemia. It is a reduction in blood supply to a viable tissue that can lead to susceptibility to infection and tissue death. Peripheral ischemia, which is rooted in the lower limbs, is a major risk factor for toe necrosis because the basal metabolic requirements of tissue are not being sufficiently met. As a result, pain, ulcers, and gangrene commonly occur. (2) Other causes of direct and indirect toe necrosis and related lower limb gangrene include mechanical trauma, infectious, pharmacological sensitivity, cancer, blue toe syndrome, and other granulomatous diseases, such as Churg-Strauss syndrome. We present a case series of toes necrosis which resulted from different etiologies and their management. PMID:26199887

  10. Cerebral radiation necrosis: diagnostic challenge and clinical management.

    PubMed

    Eisele, S C; Dietrich, J

    2015-09-01

    Cerebral radiation is an indispensable cornerstone in the treatment of many primary and metastatic brain tumors. However, besides its desired therapeutic effect on tumor cells, a significant proportion of patients will experience neurotoxic side effects as the consequence of radiotherapy. Radiation necrosis can result in progressive neurological symptoms and radiographic changes. To differentiate radiation necrosis from progressive tumor based on imaging can pose a diagnostic challenge because the MRI characteristics may be similar in both situations. Therefore, surgical biopsy and pathological confirmation is sometimes necessary to guide further management. Effective treatment options for cerebral radiation necrosis exist and should be offered to symptomatic patients. A better understanding of the cellular and molecular processes underlying the development of radiation necrosis is necessary to prevent and minimize radiation-associated morbidity and to improve treatment strategies.

  11. Renal papillary necrosis and pyelonephritis accompanying fenoprofen therapy.

    PubMed

    Husserl, F E; Lange, R K; Kantrow, C M

    1979-10-26

    Renal papillary necrosis occurred after fenoprofen calcium administration in a patient with systemic lupus erythematosus and urinary tract infection. Possible mechanisms of renal damage may be hypersensitivity, decreased blood flow, and decreased production of a prostaglandin E-like substance.

  12. Recommendations from the INHAND Apoptosis/Necrosis Working Group.

    PubMed

    Elmore, Susan A; Dixon, Darlene; Hailey, James R; Harada, Takanori; Herbert, Ronald A; Maronpot, Robert R; Nolte, Thomas; Rehg, Jerold E; Rittinghausen, Susanne; Rosol, Thomas J; Satoh, Hiroshi; Vidal, Justin D; Willard-Mack, Cynthia L; Creasy, Dianne M

    2016-02-01

    Historically, there has been confusion relating to the diagnostic nomenclature for individual cell death. Toxicologic pathologists have generally used the terms "single cell necrosis" and "apoptosis" interchangeably. Increased research on the mechanisms of cell death in recent years has led to the understanding that apoptosis and necrosis involve different cellular pathways and that these differences can have important implications when considering overall mechanisms of toxicity, and, for these reasons, the separate terms of apoptosis and necrosis should be used whenever differentiation is possible. However, it is also recognized that differentiation of the precise pathway of cell death may not be important, necessary, or possible in routine toxicity studies and so a more general term to indicate cell death is warranted in these situations. Morphological distinction between these two forms of cell death can sometimes be straightforward but can also be challenging. This article provides a brief discussion of the cellular mechanisms and morphological features of apoptosis and necrosis as well as guidance on when the pathologist should use these terms. It provides recommended nomenclature along with diagnostic criteria (in hematoxylin and eosin [H&E]-stained sections) for the most common forms of cell death (apoptosis and necrosis). This document is intended to serve as current guidance for the nomenclature of cell death for the International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups and the toxicologic pathology community at large. The specific recommendations are:Use necrosis and apoptosis as separate diagnostic terms.Use modifiers to denote the distribution of necrosis (e.g., necrosis, single cell; necrosis, focal; necrosis, diffuse; etc.).Use the combined term apoptosis/single cell necrosis whenThere is no requirement or need to split the processes, orWhen the nature of cell death cannot be determined with certainty, orWhen both

  13. Coexisting avascular necrosis of the scaphoid and lunate.

    PubMed

    Park, Il-Jung; Lee, Sang-Uk; Kim, Hyoung-Min

    2010-11-01

    Reports of coexisting avascular necrosis of more than one carpal bone are rare. We report coexisting avascular necrosis of the scaphoid and lunate in a 56-year-old woman with no history of using steroids or injury. We treated her with a radioscapholunate fusion with two angled 2.4 mm distal radius plates to stabilise the locking plate. At her 12-month follow up there was no evidence of non-union.

  14. [The asterisk sign and adult ischemic femur head necrosis].

    PubMed

    Dihlmann, W; Heller, M

    1985-04-01

    The asterisk sign is a stellate density, which is seen normally in the femoral head on computed tomography. It is due to the demonstration of the trabeculae in the femoral head. In adult ischaemic necrosis of the femoral head, there are characteristic changes in the asterisk sign at an early stage, even before there is collapse of the head. The changes are described and the indications for performing CT of the hip for diagnosing adult ischaemic necrosis are discussed.

  15. Relationship between dental disease and radiation necrosis of the mandible

    SciTech Connect

    Murray, C.G.; Daly, T.E.; Zimmerman, S.O.

    1980-02-01

    Preirradiation panoramic radiographs of forty-six dentate patients were examined for the presence of significant dental disease. Evidence of a positive association between dental disease present before radiation therapy and subsequent necrosis of the mandible was found leading to a recommendation that significant disease be eradicated before irradiation of oral tissues. Considerable suffering results from bone necrosis, which can be reduced by careful and rational dental diagnosis and treatment.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. Intestinal Necrosis due to Sodium Polystyrene Sulfonate (Kayexalate) in Sorbitol

    PubMed Central

    McGowan, C. E.; Saha, S.; Chu, G.; Resnick, M. B.; Moss, S. F.

    2013-01-01

    Background Sodium polystyrene sulfonate (SPS, Kayexalate) has been implicated in the development of intestinal necrosis. Sorbitol, added as a cathartic agent, may be primarily responsible. Previous studies have documented bowel necrosis primarily in postoperative, dialysis, and transplant patients. We sought to identify additional clinical characteristics among patients with probable SPS-induced intestinal necrosis. Methods Rhode Island Hospital surgical pathology records were reviewed to identify all gastrointestinal specimens reported as containing SPS crystals from December 1998 to June 2007. Patient demographics, medical comorbidities, and hospital courses of histologically verified cases of intestinal necrosis were extracted from the medical records. Results Twenty-nine patients with reports of SPS crystals were identified. Nine cases were excluded as incidental findings with normal mucosa. Nine patients were excluded as their symptoms began before SPS administration or because an alternate etiology for bowel ischemia was identified. Eleven patients had confirmed intestinal necrosis and a temporal relationship with SPS administration suggestive of SPS-induced necrosis. Only 2 patients were postoperative, and only 4 had end-stage renal disease (ESRD). All patients had documented hyperkalemia, received oral SPS, and developed symptoms of intestinal injury between 3 hours and 11 days after SPS administration. Four patients died. Conclusion Intestinal ischemia is a recognized risk of SPS in sorbitol. Our series highlights that patients may be susceptible even in the absence of ESRD, surgical intervention, or significant comorbidity. PMID:19373153

  2. Serum transaminase levels after experimental paracetamol-induced hepatic necrosis.

    PubMed Central

    Dixon, M F; Fulker, M J; Walker, B E; Kelleher, J; Losowsky, M S

    1975-01-01

    The relationship between serum transaminase levels and the extent of paracetamol-induced liver necrosis has been investigated in the rat. Three methods of histological quantitation were used to assess of necrosis--arbitrary grading, point counting, and the image-analysis computer. Highly significant correlations were obtained between the three methods and all were found to be reproducible. A close correlation was found between the extent of hepatic necrosis and the serum ASAT and ALAT 24 hours after a large dose (4 g/kg) of paracetamol. Likewise, the mean grade of necrosis correlated reasonably well with the serum enzyme levels in the recovery phase at 36 and 72 hours, although the transaminase level for a given degree of necrosis was considerably lower at 72 hours than at 24 hours. These findings suggest that serum transaminase levels gives a reliable indication of the severity of hepatic necrosis if the time of ingestion of the paracetamol is known and taken into account. Images Fig 1 Fig 2 PMID:1205274

  3. Inguinoscrotal region as an unusual site of extra-pancreatic collections in infected pancreatic necrosis

    PubMed Central

    Kalia, Saurabh; Gupta, Rahul; Shenvi, Sunil D.; Kumar, Hemanth; Gupta, Rajesh; Kang, Mandeep; Rana, Surinder Singh; Bhasin, Deepak Kumar; Singh, Rajinder

    2016-01-01

    Severe acute pancreatitis often leads to pancreatic and peripancreatic collections but, rarely, it can lead to collections at sites remote from the pancreas. Three male patients presented with abdominal pain and inguinoscrotal swelling. They were initially misdiagnosed with obstructed inguinal hernia, epididymo-orchitis and hydrocele, respectively. Later, their diagnosis of acute pancreatitis was revealed on laparotomy in one patient and on computed tomography (CT) in the remaining two patients. All these cases had extensive peripancreatic necrosis and paracolic collections tracking along the psoas muscle, downwards towards the pelvis. These collections were initially managed by percutaneous drainage and saline irrigation as a part of the ‘step-up’ approach. Two of these patients required open necrosectomy, while all required incision and drainage of inguinoscrotal collections. All the patients were discharged in satisfactory condition. Inguinoscrotal swelling is unusual as a first presentation of acute pancreatitis. A high index of suspicion, with careful study of patient's history and examination along with CT, may provide an accurate diagnosis. Local drainage may be required to control sepsis and also provide an egress route for intra-abdominal collections. PMID:25649933

  4. Inguinoscrotal region as an unusual site of extra-pancreatic collections in infected pancreatic necrosis.

    PubMed

    Kalia, Saurabh; Gupta, Rahul; Shenvi, Sunil D; Kumar, Hemanth; Gupta, Rajesh; Kang, Mandeep; Rana, Surinder Singh; Bhasin, Deepak Kumar; Singh, Rajinder

    2016-08-01

    Severe acute pancreatitis often leads to pancreatic and peripancreatic collections but, rarely, it can lead to collections at sites remote from the pancreas. Three male patients presented with abdominal pain and inguinoscrotal swelling. They were initially misdiagnosed with obstructed inguinal hernia, epididymo-orchitis and hydrocele, respectively. Later, their diagnosis of acute pancreatitis was revealed on laparotomy in one patient and on computed tomography (CT) in the remaining two patients. All these cases had extensive peripancreatic necrosis and paracolic collections tracking along the psoas muscle, downwards towards the pelvis. These collections were initially managed by percutaneous drainage and saline irrigation as a part of the 'step-up' approach. Two of these patients required open necrosectomy, while all required incision and drainage of inguinoscrotal collections. All the patients were discharged in satisfactory condition. Inguinoscrotal swelling is unusual as a first presentation of acute pancreatitis. A high index of suspicion, with careful study of patient's history and examination along with CT, may provide an accurate diagnosis. Local drainage may be required to control sepsis and also provide an egress route for intra-abdominal collections.

  5. Treatment Planning and Volumetric Response Assessment for Yttrium-90 Radioembolization: Semiautomated Determination of Liver Volume and Volume of Tumor Necrosis in Patients with Hepatic Malignancy

    SciTech Connect

    Monsky, Wayne L.; Garza, Armando S.; Kim, Isaac; Loh, Shaun; Lin, Tzu-Chun; Li Chinshang; Fisher, Jerron; Sandhu, Parmbir; Sidhar, Vishal; Chaudhari, Abhijit J.; Lin, Frank; Deutsch, Larry-Stuart; Badawi, Ramsey D.

    2011-04-15

    Purpose: The primary purpose of this study was to demonstrate intraobserver/interobserver reproducibility for novel semiautomated measurements of hepatic volume used for Yttrium-90 dose calculations as well as whole-liver and necrotic-liver (hypodense/nonenhancing) tumor volume after radioembolization. The secondary aim was to provide initial comparisons of tumor volumetric measurements with linear measurements, as defined by Response Evaluation Criteria in Solid Tumors criteria, and survival outcomes. Methods: Between 2006 and 2009, 23 consecutive radioembolization procedures were performed for 14 cases of hepatocellular carcinoma and 9 cases of hepatic metastases. Baseline and follow-up computed tomography obtained 1 month after treatment were retrospectively analyzed. Three observers measured liver, whole-tumor, and tumor-necrosis volumes twice using semiautomated software. Results: Good intraobserver/interobserver reproducibility was demonstrated (intraclass correlation [ICC] > 0.9) for tumor and liver volumes. Semiautomated measurements of liver volumes were statistically similar to those obtained with manual tracing (ICC = 0.868), but they required significantly less time to perform (p < 0.0001, ICC = 0.088). There was a positive association between change in linear tumor measurements and whole-tumor volume (p < 0.0001). However, linear measurements did not correlate with volume of necrosis (p > 0.05). Dose, change in tumor diameters, tumor volume, and necrotic volume did not correlate with survival (p > 0.05 in all instances). However, Kaplan-Meier curves suggest that a >10% increase in necrotic volume correlated with survival (p = 0.0472). Conclusion: Semiautomated volumetric analysis of liver, whole-tumor, and tumor-necrosis volume can be performed with good intraobserver/interobserver reproducibility. In this small retrospective study, measurements of tumor necrosis were suggested to correlate with survival.

  6. Interactive toxicity of inorganic mercury and trichloroethylene in rat and human proximal tubules: Effects on apoptosis, necrosis, and glutathione status

    SciTech Connect

    Lash, Lawrence H. . E-mail: l.h.lash@wayne.edu; Putt, David A.; Hueni, Sarah E.; Payton, Scott G.; Zwickl, Joshua

    2007-06-15

    Simultaneous or prior exposure to one chemical may alter the concurrent or subsequent response to another chemical, often in unexpected ways. This is particularly true when the two chemicals share common mechanisms of action. The present study uses the paradigm of prior exposure to study the interactive toxicity between inorganic mercury (Hg{sup 2+}) and trichloroethylene (TRI) or its metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) in rat and human proximal tubule. Pretreatment of rats with a subtoxic dose of Hg{sup 2+} increased expression of glutathione S-transferase-{alpha}1 (GST{alpha}1) but decreased expression of GST{alpha}2, increased activities of several GSH-dependent enzymes, and increased GSH conjugation of TRI. Primary cultures of rat proximal tubular (rPT) cells exhibited both necrosis and apoptosis after incubation with Hg{sup 2+}. Pretreatment of human proximal tubular (hPT) cells with Hg{sup 2+} caused little or no changes in GST expression or activities of GSH-dependent enzymes, decreased apoptosis induced by TRI or DCVC, but increased necrosis induced by DCVC. In contrast, pretreatment of hPT cells with TRI or DCVC protected from Hg{sup 2+} by decreasing necrosis and increasing apoptosis. Thus, whereas pretreatment of hPT cells with Hg{sup 2+} exacerbated cellular injury due to TRI or DCVC by shifting the response from apoptosis to necrosis, pretreatment of hPT cells with either TRI or DCVC protected from Hg{sup 2+}-induced cytotoxicity by shifting the response from necrosis to apoptosis. These results demonstrate that by altering processes related to GSH status, susceptibilities of rPT and hPT cells to acute injury from Hg{sup 2+}, TRI, or DCVC are markedly altered by prior exposures.

  7. 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

  8. 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.

  9. [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.

  10. [Latest advances in acute pancreatitis].

    PubMed

    de-Madaria, Enrique

    2013-10-01

    The present article analyzes the main presentations on acute pancreatitis (AP) in Digestive Disease Week 2013. Perfusion computed tomography allows early diagnosis of pancreatic necrosis. Neutrophil gelatinase-associated lipocalin predicts the development of acute renal failure, severe AP and death. Factors associated with greater fluid sequestration in AP are alcoholic etiology, an elevated hematocrit, and the presence of criteria of systemic inflammatory response syndrome; fluid sequestration is associated with a worse outcome. True pseudocysts (fluid collections without necrosis for more than 4 weeks) are a highly infrequent complication in AP. Patients with necrotic collections have a poor prognosis, especially if associated with infection. A meta-analysis on fluid therapy suggests that early aggressive fluid administration is associated with higher mortality and more frequent respiratory complications. According to a meta-analysis, enteral nutrition initiated within 24 hours of admission improves the outcome of AP compared with later initiation of enteral nutrition. Pentoxifylline could be a promising alternative in AP; a double-blind randomized study showed that this drug reduced the length of hospital and intensive care unit stay, as well as the need for intensive care unit admission. The association of octreotide and celecoxib seems to reduce the frequency of organ damage compared with octreotide alone. Mild AP can be managed in the ambulatory setting through hospital-at-home units after a short, 24-hour admission.

  11. 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.

  12. 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

  13. Evaluation of liver cirrhosis and hepatocellular carcinoma using Protein-Protein Interaction Networks

    PubMed Central

    Ehsani Ardakani, Mohammad Javad; Safaei, Akram; Arefi Oskouie, Afsaneh; Haghparast, Hesam; Haghazali, Mehrdad; Mohaghegh Shalmani, Hamid; Peyvandi, Hassan; Naderi, Nosratollah; Zali, Mohammad Reza

    2016-01-01

    Aim: In the current study, we analysised only the articles that investigate serum proteome profile of cirrhosis patients or HCC patients versus healthy controls. Background: Increased understanding of cancer biology has enabled identification of molecular events that lead to the discovery of numerous potential biomarkers in diseases. Protein-protein interaction networks is one of aspect that could elevate the understanding level of molecular events and protein connections that lead to the identification of genes and proteins associated with diseases. Methods: Gene expression data, including 63 gene or protein names for hepatocellular carcinoma and 29 gene or protein names for cirrhosis, were extracted from a number of previous investigations. The networks of related differentially expressed genes were explored using Cytoscape and the PPI analysis methods such as MCODE and ClueGO. Centrality and cluster screening identified hub genes, including APOE, TTR, CLU, and APOA1 in cirrhosis. Results: CLU and APOE belong to the regulation of positive regulation of neurofibrillary tangle assembly. HP and APOE involved in cellular oxidant detoxification. C4B and C4BP belong to the complement activation, classical pathway and acute inflammation response pathway. Also, it was reported TTR, TFRC, VWF, CLU, A2M, APOA1, CKAP5, ZNF648, CASP8, and HSP27 as hubs in HCC. In HCC, these include A2M that are corresponding to platelet degranulation, humoral immune response, and negative regulation of immune effector process. CLU belong to the reverse cholesterol transport, platelet degranulation and human immune response. APOA1 corresponds to the reverse cholesterol transport, platelet degranulation and humoral immune response, as well as negative regulation of immune effector process pathway. Conclusion: In conclusion, this study suggests that there is a common molecular relationship between cirrhosis and hepatocellular cancer that may help with identification of target molecules for

  14. [Pyelonephritis with massive renal tissue necrosis in child with urinary tract malformation--a case report].

    PubMed

    Pawlak-Bratkowska, Monika; Finke, Daria; Olejniczak, Dariusz; Midel, Anna; Tkaczyk, Marcin

    2009-04-01

    The aim of the case report is presentation of unusual and heavy clinical course of pyelonephritis with renal tissue necrosis in a child with urinary tract malformation. Nine month old girl was admitted to hospital in heavy clinical status due to pyelonephritis--urosepsis. It was complicated by acute renal insufficiency. Patient was treated by broad-spectrum antibiotics and parenteral nutrition. She was feverish for 14 days. Computed tomography done in order to exclude abdominal abscess showed massive renal tissue necrosis of on both sides. Antibiotic treatment was successful after 6 weeks. Urological evaluation revealed bilateral vesico-ureteral refluxes grade IV. Scintigraphy showed multiple scars. Patient was treated Deflux injections (twice). We noted 5 urinary tract recurrences despite antibiotic profilaxis. GFR of 75 ml/min/1.73 m2 was estimated at age of 16 m. Immunodeficiency or malignancy as background of clinical course were excluded. The case we describe presents severe clinical course of pyelonephritis due to complex urinary tract malformation that is to be considered despite based on modern publications "sparing" strategies of diagnosis and profilaxis in urinary tract malformations.

  15. Progressive outer retinal necrosis syndrome in the course of systemic lupus erythematosus.

    PubMed

    Turno-Kręcicka, A; Tomczyk-Socha, M; Zimny, A

    2016-12-01

    Progressive outer retinal necrosis syndrome (PORN) is a severe clinical variant of necrotizing herpetic chorioretinitis, which occurs almost exclusively in patients with advanced acquired immunodeficiency syndrome (AIDS). To date, only a few cases of PORN have been reported in patients, mostly among those who were immunocompromised. To our knowledge, only one case of PORN in a patient with systemic lupus erythematosus (SLE) has been described. We report the case of a 44-year old HIV-negative patient with lupus nephritis, whom was being treated by mycophenolate mophetil (MMF), arechin and prednisone. After 14 months of MMF therapy, the patient revealed PORN symptoms; and several months later, the patient developed Type B primary central nervous system lymphoma (PCNSL). PORN is usually compared to acute retinal necrosis (ARN) syndrome, because of having the same causative agent: varicella zoster virus (VZV). There are also some similarities in clinical findings. Our observation supports the hypothesis that PORN symptoms in HIV-negative patients can be an intermediate form between ARN and PORN, and can vary according to the patient's immune status.

  16. 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

  17. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    PubMed

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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 of the new molecular entities have not yet resulted in significant prolongation of progression-free or overall survival. Nevertheless, there are a number of promising agents currently under investigation. Given the unique tumor biology and heterogeneous clinical manifestations of HCC, the application of molecular and cellular markers could also benefit patient selection, disease prognosis and trial design. Summary This paper provides an overview of the current therapeutic strategies for HCC in the curative and palliative settings. Furthermore, we introduce some of the promising small molecules and antibodies that may find their way into clinical practice, with a focus on substances that are currently in phase III testing. Finally, we summarize the role of promising biomarkers, such as circulating tumor or cancer stem cells. Key Message Despite the rising prevalence of HCC and active clinical research, few therapeutic options besides sorafenib have been established. This review discusses the new therapeutic agents in the pipeline. Practical Implications Although many promising preclinical studies have resulted in phase I-II trials on HCC, so far only the tyrosine and Raf kinase inhibitor sorafenib has made its way into the hands of physicians. This multikinase inhibitor is the only approved option for systemic treatment of advanced HCC. Currently, the development of promising approaches for disease management is guided by biomarkers such as molecular markers or cellular characteristics. The use of biomarkers may facilitate early diagnosis in high-risk groups and therefore enhance outcomes by detecting patients whose disease is still curable. PMID:26676221

  9. 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.

  10. Redox signaling in acute pancreatitis

    PubMed Central

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-01-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis. PMID:25778551

  11. Redox signaling in acute pancreatitis.

    PubMed

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-08-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF-VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

  12. Atypical Hepatocellular Neoplasm With Peliosis in Cirrhotic Liver Versus Hepatocellular Carcinoma

    PubMed Central

    Gurzu, Simona; Jung, Ioan; Contac, Anca Otilia; Turcu, Mihai; Tudor, Adrian

    2015-01-01

    Abstract Atypical hepatocellular neoplasm (AHN) is an adenoma-like hepatic tumor that even occurs in noncirrhotic liver of males (any age) or females ≥50 years old, or associates focal atypical features. In this article, 2 unusual cases diagnosed in elderly cirrhotic patients, unrelated to steroids, are presented. The first case was incidentally diagnosed in an 83-year-old female. During laparoscopic surgery for cholecystectomy, hemoperitoneum was installed and laparotomy was necessary to remove a 70-mm nodular encapsulated hepatic tumor that was microscopically composed by hepatocyte-like cells with clear cytoplasm, arranged in 1- to 2-cell-thick plates and intermingled with areas of peliosis, negative for alpha fetoprotein (αFP), p53, and keratin 7, with low Ki67 index and intact reticulin framework. The second case was incidentally diagnosed at ultrasound examination in a 66-year-old male. The surgical specimen was a 50-mm solid multinodular tumor that microscopically consisted of 3-cell-thick plates of hepatocyte-like cells with acinar, pseudoglandular, and trabecular architecture, intermingled with peliotic areas, without nuclear atypia and disintegrated reticulin framework. Both of the cases occurred in cirrhotic liver. The tumor cells were marked by AE1/AE3 keratin, displayed a Ki67 index < 5% and were negative for αFP, p53, and keratin 7. No recurrences or any other disorder occurred 6 months after surgery. In cirrhotic liver, adenomas with peliosis that do not satisfy all the diagnosis criteria synthesized in the article should be considered AHNs and differential diagnosis includes hepatocellular carcinoma but also focal nodular hyperplasia, regenerative nodules, and dysplastic nodules. This histological entity is not yet included in the WHO Classification list. PMID:26200629

  13. Amiodarone exposure during modest inflammation induces idiosyncrasy-like liver injury in rats: role of tumor necrosis factor-alpha.

    PubMed

    Lu, Jingtao; Jones, A Daniel; Harkema, Jack R; Roth, Robert A; Ganey, Patricia E

    2012-01-01

    Amiodarone [2-butyl-3-(3',5'-diiodo-4'α-diethylaminoethoxybenzoyl)-benzofuran] (AMD), a class III antiarrhythmic drug, is known to cause idiosyncratic hepatotoxic reactions in human patients. One hypothesis for the etiology of idiosyncratic adverse drug reactions is that a concurrent inflammatory stress results in decreased threshold for drug toxicity. To explore this hypothesis in an animal model, male Sprague-Dawley rats were treated with nonhepatotoxic doses of AMD or its vehicle and with saline vehicle or lipopolysaccharide (LPS) to induce low-level inflammation. Elevated alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase activities as well as increased total bile acid concentrations in serum and midzonal hepatocellular necrosis were observed only in AMD/LPS-cotreated rats. The time interval between AMD and LPS administration was critical: AMD injected 16 h before LPS led to liver injury, whereas AMD injected 2-12 h before LPS failed to cause this response. The increase in ALT activity in AMD/LPS cotreatment showed a clear dose-response relationship with AMD as well as LPS. The metabolism and hepatic accumulation of AMD were not affected by LPS coexposure. Serum concentration of tumor necrosis factor-alpha (TNF) was significantly increased by LPS and was slightly prolonged by AMD. In Hepac1c7 cells, addition of TNF potentiated the cytotoxicity of both AMD and its primary metabolite, mono-N-desethylamiodarone. In vivo inhibition of TNF signaling by etanercept attenuated the AMD/LPS-induced liver injury in rats. In summary, AMD treatment during modest inflammation induced severe hepatotoxicity in rats, and TNF contributed to the induction of liver injury in this animal model of idiosyncratic AMD-induced liver injury.

  14. Tissue Biomarkers in Hepatocellular Tumors: Which, When, and How.

    PubMed

    Di Tommaso, Luca; Roncalli, Massimo

    2017-01-01

    Few tissue markers are currently available to pathologists in the study of hepatocellular tumors. These markers should be used carefully taking into consideration not only morphology but also, and sometimes even more important, the clinical setting where the lesion to be diagnosed had developed. Glypican-3, heat shock protein 70, and glutamine synthetase (GS) are markers currently used, as a single panel, to discriminate the nature of a <2 cm hepatocellular lesion lacking radiological features of hepatocellular carcinoma (HCC) detected in a cirrhotic patient under surveillance. Their use, which can be improved by clathrin heavy chain, is mostly requested on liver biopsy. Hepatocyte paraffin 1, arginase-1, polyclonal carcinoembryonic antigen, CD10, and bile salt export pump are tissue markers used to confirm, at histology, the diagnosis of HCC made by imaging before enrollment for phase III studies on novel anti-HCC drugs. In this setting, pathologists are usually requested a conclusive diagnosis on a liver biopsy of a poorly differentiated, necrotic, enriched in stem-phenotype, carcinoma. Liver fatty acid-binding protein, serum amyloid A, C-reactive protein, prostaglandin D2 synthetase, GS, and β-catenin can be used either on biopsy or surgical specimen to classify hepatocellular adenoma into hepatocyte nuclear factor (HNF-1α) inactivated (steatotic), inflammatory, with dysregulation of sonic hedgehog and prostaglandin pathways, β-catenin mutated, and unclassified.

  15. [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.

  16. Tissue Biomarkers in Hepatocellular Tumors: Which, When, and How

    PubMed Central

    Di Tommaso, Luca; Roncalli, Massimo

    2017-01-01

    Few tissue markers are currently available to pathologists in the study of hepatocellular tumors. These markers should be used carefully taking into consideration not only morphology but also, and sometimes even more important, the clinical setting where the lesion to be diagnosed had developed. Glypican-3, heat shock protein 70, and glutamine synthetase (GS) are markers currently used, as a single panel, to discriminate the nature of a <2 cm hepatocellular lesion lacking radiological features of hepatocellular carcinoma (HCC) detected in a cirrhotic patient under surveillance. Their use, which can be improved by clathrin heavy chain, is mostly requested on liver biopsy. Hepatocyte paraffin 1, arginase-1, polyclonal carcinoembryonic antigen, CD10, and bile salt export pump are tissue markers used to confirm, at histology, the diagnosis of HCC made by imaging before enrollment for phase III studies on novel anti-HCC drugs. In this setting, pathologists are usually requested a conclusive diagnosis on a liver biopsy of a poorly differentiated, necrotic, enriched in stem-phenotype, carcinoma. Liver fatty acid-binding protein, serum amyloid A, C-reactive protein, prostaglandin D2 synthetase, GS, and β-catenin can be used either on biopsy or surgical specimen to classify hepatocellular adenoma into hepatocyte nuclear factor (HNF-1α) inactivated (steatotic), inflammatory, with dysregulation of sonic hedgehog and prostaglandin pathways, β-catenin mutated, and unclassified. PMID:28280721

  17. Downstaging Hepatocellular Carcinoma with Yttrium-90 radioembolization: resection or transplantation?

    PubMed

    Ettorre, G M; Laurenzi, A; Vennarecci, G

    2014-06-01

    Trans Arterial Radio Embolization with Yttrium 90 in the treatment of Hepatocellular Carcinoma is becoming a new interesting tool in the treatment of patients that are considered non resectable and non transplantable. A successful downstaging could improve the number of patients that could benefit from a resection or a liver transplantation, but some points still need to be addressed.

  18. The Extracellular Matrix Regulates Granuloma Necrosis in Tuberculosis.

    PubMed

    Al Shammari, Basim; Shiomi, Takayuki; Tezera, Liku; Bielecka, Magdalena K; Workman, Victoria; Sathyamoorthy, Tarangini; Mauri, Francesco; Jayasinghe, Suwan N; Robertson, Brian D; D'Armiento, Jeanine; Friedland, Jon S; Elkington, Paul T

    2015-08-01

    A central tenet of tuberculosis pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. We reconsider the underlying mechanism of tuberculosis pathology and demonstrate that collagen destruction may be a critical initial event, causing caseous necrosis as opposed to resulting from it. In human tuberculosis granulomas, regions of extracellular matrix destruction map to areas of caseous necrosis. In mice, transgenic expression of human matrix metalloproteinase 1 causes caseous necrosis, the pathological hallmark of human tuberculosis. Collagen destruction is the principal pathological difference between humanised mice and wild-type mice with tuberculosis, whereas the release of proinflammatory cytokines does not differ, demonstrating that collagen breakdown may lead to cell death and caseation. To investigate this hypothesis, we developed a 3-dimensional cell culture model of tuberculosis granuloma formation, using bioelectrospray technology. Collagen improved survival of Mycobacterium tuberculosis-infected cells analyzed on the basis of a lactate dehydrogenase release assay, propidium iodide staining, and measurement of the total number of viable cells. Taken together, these findings suggest that collagen destruction is an initial event in tuberculosis immunopathology, leading to caseous necrosis and compromising the immune response, revealing a previously unappreciated role for the extracellular matrix in regulating the host-pathogen interaction.

  19. Apoptosis, oncosis, and necrosis. An overview of cell death.

    PubMed Central

    Majno, G.; Joris, I.

    1995-01-01

    The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from ónkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7856735

  20. Effect of bevacizumab on radiation necrosis of the brain

    SciTech Connect

    Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.; Levin, Victor A. . E-mail: vlevin@mdanderson.org

    2007-02-01

    Purpose: Because blocking vascular endothelial growth factor (VEGF) from reaching leaky capillaries is a logical strategy for the treatment of radiation necrosis, we reasoned that bevacizumab might be an effective treatment of radiation necrosis. Patients and Methods: Fifteen patients with malignant brain tumors were treated with bevacizumab or bevacizumab combination for their tumor on either a 5 mg/kg/2-week or 7.5 mg/kg/3-week schedule. Radiation necrosis was diagnosed in 8 of these patients on the basis of magnetic resonance imaging (MRI) and biopsy. MRI studies were obtained before treatment and at 6-week to 8-week intervals. Results: Of the 8 patients with radiation necrosis, posttreatment MRI performed an average of 8.1 weeks after the start of bevacizumab therapy showed a reduction in all 8 patients in both the MRI fluid-attenuated inversion-recovery (FLAIR) abnormalities and T1-weighted post-Gd-contrast abnormalities. The average area change in the T1-weighted post-Gd-contrast abnormalities was 48% ({+-}22 SD), and the average change in the FLAIR images was 60% ({+-}18 SD). The average reduction in daily dexamethasone requirements was 8.6 mg ({+-}3.6). Conclusion: Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis by decreasing capillary leakage and the associated brain edema. Our findings will need to be confirmed in a randomized trial to determine the optimal duration of treatment.

  1. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  2. Hyponatremia and hypoglycemia in acute Sheehan's syndrome.

    PubMed

    Bunch, T J; Dunn, W F; Basu, A; Gosman, R I

    2002-10-01

    We report the case of a 23-year-old Saudi Arabian woman who presented to the medical intensive care unit with severe hyponatremia and hypoglycemia following a Cesarean section delivery complicated by hemorrhage due to disseminated intravascular coagulopathy. She was treated successfully for adrenal insufficiency acutely, and was later discharged on hormone replacement therapy. To our knowledge, this is the first case report of acute Sheehan's syndrome presenting with both hyponatremia and suggestive hypoglycemia. Pituitary necrosis is an uncommon complication of peripartum hemorrhagic shock. Since the initial description by Sheehan in 1937, the incidence of the syndrome has gradually declined through improved management of hemodynamic complications leading to the infarction of the gland. There are many studies describing complications of late Sheehan's syndrome; however, relatively few contain descriptions of the acute phase. In addition, the diagnosis of this syndrome is often determined after resolution of the acute process with resultant lack of data regarding immediate endocrine and imaging abnormalities. In this report, we describe the complete endocrine and imaging assessment of a patient presenting in critical condition due to necrosis of the pituitary gland in the immediate postpartum period.

  3. Acute kidney injury in the pregnant patient.

    PubMed

    Nwoko, Rosemary; Plecas, Darko; Garovic, Vesna D

    2012-12-01

    Acute kidney injury (AKI) is costly and is associated with increased mortality and morbidity. An understanding of the renal physiologic changes that occur during pregnancy is essential for proper evaluation, diagnosis, and management of AKI. As in the general population, AKI can occur from prerenal, intrinsic, and post-renal causes. Major causes of pre-renal azotemia include hyperemesis gravidarum and uterine hemorrhage in the setting of placental abruption. Intrinsic etiologies include infections from acute pyelonephritis and septic abortion, bilateral cortical necrosis, and acute tubular necrosis. Particular attention should be paid to specific conditions that lead to AKI during the second and third trimesters, such as preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, and TTP-HUS. For each of these disorders, delivery of the fetus is the recommended therapeutic option, with additional therapies indicated for each specific disease entity. An understanding of the various etiologies of AKI in the pregnant patient is key to the appropriate clinical management, prevention of adverse maternal outcomes, and safe delivery of the fetus. In pregnant women with pre-existing kidney disease, the degree of renal dysfunction is the major determining factor of pregnancy outcomes, which may further be complicated by a prior history of hypertension.

  4. Acute mesenteric ischemia in young adults.

    PubMed

    Ozturk, Gurkan; Aydinli, Bulent; Atamanalp, S Selcuk; Yildirgan, M Ilhan; Ozoğul, Bünyami; Kısaoğlu, Abdullah

    2012-08-01

    Acute mesenteric ischemia is commonly seen in old patients. This study was undertaken to show that mesenteric ischemia might be seen in individuals under 40 years of age and that its diagnosis is challenging. Twenty-six patients with acute mesenteric ischemia under the age of 40 were studied. The main symptom on admission was abdominal pain. Symptom duration varied between 12 h and 5 days. The medical history of the patients revealed that 9 had no previous diseases. Other 17 had predisposing factors in the first evaluation. None of the patients had any history of narcotic or drug abuse. Ten patients presented with signs and symptoms of sepsis and septic shock. Preoperative diagnosis was acute intestinal ischemia only in 6 patients. Preoperatively, all the patients had intestinal or colonic ischemia and necrosis; one had additional ischemia of the liver, stomach, duodenum, and pancreas. Six patients had massive intestinal necrosis. The overall postoperative complication and overall mortality rates were 61.5 and 26.9 %, respectively. Complications and mortality were determined to be associated with previous pulmonary disease, acidosis, presence of septic shock, acute renal failure, extent of the ischemia and extent of resection, second look operations, previous cardiac events, and the kind of affected bowel (colon involvement).

  5. Acute renal failure caused by Klebsiella pneumoniae pyelonephritis.

    PubMed

    Creyghton, W M; Lobatto, S; Weening, J J

    2001-11-01

    We report a 34-year-old male patient without prior medical history who presented with acute renal failure due to acute bacterial pyelonephritis. Both blood and urine cultures grew Klebsiella pneumoniae. Although a kidney biopsy revealed extensive necrosis and no viable glomeruli, renal function recovered to near normal after intermittent hemodialysis and antibiotic therapy. We believe that it is important to include this entity in the differential diagnosis of acute renal failure since proper diagnosis and treatment is essential for recovery of renal function. Furthermore, we would like to draw attention to Klebsiella pneumoniae as an important potential pathogen in such cases, in addition to Escherichia coli.

  6. Acute renal failure: A rare presentation of Sheehan's syndrome.

    PubMed

    Bhat, Manzoor A; Laway, Bashir A; Allaqaband, Faheem A; Kotwal, Suman K; Wani, Imtiyaz A; Banday, Khursheed A

    2012-03-01

    Sheehan's syndrome occurs as a result of ischemic pituitary necrosis secondary to severe postpartum bleeding. It is one of the most common causes of hypopituitarism, characterized by variable clinical presentation. Acute kidney injury occurs rarely in Sheehan's syndrome and most of the cases have been found to be precipitated by rhabdomyolysis. We here present a case of Sheehan's syndrome with acute kidney injury where theprecipitating cause was chronic hypocortisolemia. We believe this is the first reported case of Sheehan's syndrome in which acute kidney injury was precipitated by adrenal insufficiency.

  7. [Cell death in inflammatory heart muscle diseases--apoptosis or necrosis?].

    PubMed

    Pankuweit, S; Jobmann, M; Crombach, M; Portig, I; Alter, P; Kruse, T; Hufnagel, G; Maisch, B

    1999-05-01

    Cell death can be induced by 2 different mechanisms: necrosis and apoptosis. Necrosis, on the one hand, is usually caused by unphysiological stress factors such as hyperthermia or hypoxia, apoptosis, on the other hand, is part of the normal organ development and controls for example immune responses. Morphologically, necrosis is characterized by swelling of cells and their organelles leading to the disruption of the cell membrane, which in turn causes an inflammatory reaction in the surrounding tissue. Morphological and biochemical criteria (Figure 1, Table 1) of apoptosis are the condensation of chromatin leading to the development of apoptotic bodies or membrane-enclosed vesicles containing oligonucleosomal DNA fragments. Important diagnostic tools of cell death (Table 2), such as the TUNEL test (Figure 2) or gel electrophoresis of extracted DNA (Figure 3) are based on the above mentioned biochemical characteristics, but a reliable differentiation of apoptotic versus necrotic processes is not always possible. Experimental studies in animals and studies in various diseases of the cardiovascular system were able to show that apoptosis in myocytes can be induced, an issue that has long been discussed controversially. Ischemia, reperfusion, and myocardial infarction were also shown to lead to apoptosis in cardiomyocytes, whereas cell destruction was caused mainly by necrosis. Several authors (Table 3) demonstrated apoptotic indices in cardiomyocytes of patients with dilatated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and patients with acute infarction from 0.25 to 35% by the use of the TUNEL test. Others were able to demonstrate an elevated expression of Fas-receptor in cells of atheroslerotic plaques in patients with atherosclerosis and high indices of apoptotic cardiomyocytes in patients with chronic heart failure. We investigated endomyocardial biopsies of patients with inflammatory cardiomyopathy, DCM without inflammatory reaction but the

  8. Liver Necrosis and Lipid Peroxidation in the Rat as the Result of Paraquat and Diquat Administration

    PubMed Central

    Burk, Raymond F.; Lawrence, Richard A.; Lane, James M.

    1980-01-01

    Paraquat and diquat facilitate formation of superoxide anion in biological systems, and lipid peroxidation has been postulated to be their mechanism of toxicity. Paraquat has been shown to be more toxic to selenium-deficient mice than to controls, presumably as the result of decreased activity of the selenoenzyme glutathione peroxidase. The present study was designed to measure lipid peroxidation and to assess toxicity in control and selenium-deficient rats given paraquat and diquat. Lipid peroxidation was measured by determining ethane production rates of intact animals; toxicity was assessed by survival and by histological and serum enzyme evidence of liver and kidney necrosis. Paraquat and diquat were both much more toxic to selenium-deficient rats than to control rats. Diquat (19.5 μmol/kg) caused rapid and massive liver and kidney necrosis and very high ethane production rates in selenium-deficient rats. The effect of paraquat (78 μmol/kg) was similar to that of diquat but was not as severe. Acutely lethal doses of paraquat (390 μmol/kg) and diquat (230 μmol/kg) in control rats caused very little ethane production and no evidence of liver necrosis. These findings suggest that paraquat and diquat exert their acute toxicity largely through lipid peroxidation in selenium-deficient rats. Selenium deficiency had no effect on superoxide dismutase activity in erythrocytes or in 105,000 g supernate of liver or kidney. Glutathione peroxidase, which represents the only well-characterized biochemical function of selenium in animals, was dissociated from the protective effect of selenium against diquat-induced lipid peroxidation and toxicity by a time-course study in which selenium-deficient rats were injected with 50 μg of selenium and later given diquat (19.5 μmol/kg). Within 10 h, the selenium injection provided significant protection against diquat-induced lipid peroxidation and mortality even though this treatment resulted in no rise in glutathione peroxidase

  9. Protein arginine N-methyltransferase 1 promotes the proliferation and metastasis of hepatocellular carcinoma cells.

    PubMed

    Gou, Qing; He, ShuJiao; Zhou, ZeJian

    2017-02-01

    Hepatocellular carcinoma is the most common subtype of liver cancer. Protein arginine N-methyltransferase 1 was shown to be upregulated in various cancers. However, the role of protein arginine N-methyltransferase 1 in hepatocellular carcinoma progression remains incompletely understood. We investigated the clinical and functional significance of protein arginine N-methyltransferase 1 in a series of clinical hepatocellular carcinoma samples and a panel of hepatocellular carcinoma cell lines. We performed suppression analysis of protein arginine N-methyltransferase 1 using small interfering RNA to determine the biological roles of protein arginine N-methyltransferase 1 in hepatocellular carcinoma. In addition, the expression of epithelial-mesenchymal transition indicators was verified by western blotting in hepatocellular carcinoma cell lines after small interfering RNA treatment. Protein arginine N-methyltransferase 1 expression was found to be significantly upregulated in hepatocellular carcinoma cell lines and clinical tissues. Moreover, downregulation of protein arginine N-methyltransferase 1 in hepatocellular carcinoma cells by small interfering RNA could inhibit cell proliferation, migration, and invasion in vitro. These results indicate that protein arginine N-methyltransferase 1 may contribute to hepatocellular carcinoma progression and serves as a promising target for the treatment of hepatocellular carcinoma patients.

  10. Nonapoptotic cell death in acute kidney injury and transplantation.

    PubMed

    Linkermann, Andreas

    2016-01-01

    Acute tubular necrosis causes a loss of renal function, which clinically presents as acute kidney failure (AKI). The biochemical signaling pathways that trigger necrosis have been investigated in detail over the past 5 years. It is now clear that necrosis (regulated necrosis, RN) represents a genetically driven process that contributes to the pathophysiology of AKI. RN pathways such as necroptosis, ferroptosis, parthanatos, and mitochondrial permeability transition-induced regulated necrosis (MPT-RN) may be mechanistically distinct, and the relative contributions to overall organ damage during AKI in living organisms largely remain elusive. In a synchronized manner, some necrotic programs induce the breakdown of tubular segments and multicellular functional units, whereas others are limited to killing single cells in the tubular compartment. Importantly, the means by which a renal cell dies may have implications for the subsequent inflammatory response. In this review, the recent advances in the field of renal cell death in AKI and key enzymes that might serve as novel therapeutic targets will be discussed. As a consequence of the interference with RN, the immunogenicity of dying cells in AKI in renal transplants will be diminished, rendering inhibitors of RN indirect immunosuppressive agents.

  11. Specific diagnosis of hepatocellular carcinoma by delayed hepatobiliary imaging

    SciTech Connect

    Hasegawa, Y.; Nakano, S.; Ibuka, K.; Hashizume, T.; Noguchi, A.; Sasaki, Y.; Imaoka, S.; Fujita, M.; Kawamoto, S.; Kasugai, H.

    1986-01-15

    For assessment of the value of delayed hepatobiliary imaging with technetium 99m (/sup 99m/Tc)-(Sn)-N-pyridoxyl-5-methyltryptophan (/sup 99m/Tc-PMT) for specific diagnosis of hepatocellular carcinoma, 88 patients with various malignant and benign liver diseases (49 with hepatocellular carcinoma, 4 with cholangiocellular carcinoma, 10 with metastatic liver carcinoma, 2 with liver cysts, 2 with liver hemangioma, 1 with liver abscess, 2 with intrahepatic lithiasis, 12 with liver cirrhosis, and 6 with chronic hepatitis) were studied. In 20 (41%) of the 49 patients with hepatocellular carcinoma, greater uptake of /sup 99m/Tc-PMT by the tumor than by the surrounding liver tissue was seen in delayed hepatobiliary images, whereas in eight patients (16%), equilibrated uptake was seen. No increased uptake of the radioisotope by hepatic lesions was seen in 21 patients with localized liver diseases other than hepatoma. Moreover, in 18 patients with diffuse liver diseases, no focal accumulation of the radioisotope was seen in delayed /sup 99m/Tc-PMT images. In addition, of 28 patients with hepatocellular carcinoma in whom the serum alpha-fetoprotein level showed little or no increase, 12 showed increased uptake of /sup 99m/Tc-PMT by the tumor. In assessing delayed /sup 99m/Tc-PMT images, however, it was necessary to consider following complications: accumulation of tracer in obstructed and dilated biliary trees; retention of radioactivity in nonneoplastic liver tissues; difficulties in evaluating /sup 99m/Tc-PMT uptake by small hepatic tumors; overlapping of radioactivity in the gut and gallbladder in delayed /sup 99m/Tc-PMT images of tumors. This study indicates that delayed /sup 99m/Tc-PMT images can be useful in the diagnosis of hepatocellular carcinoma.

  12. Flap Necrosis after Palatoplasty in Patients with Cleft Palate

    PubMed Central

    Rossell-Perry, Percy

    2015-01-01

    Palatal necrosis after palatoplasty in patients with cleft palate is a rare but significant problem encountered by any cleft surgeon. Few studies have addressed this disastrous complication and the prevalence of this problem remains unknown. Failure of a palatal flap may be attributed to different factors like kinking or section of the pedicle, anatomical variations, tension, vascular thrombosis, type of cleft, used surgical technique, surgeon's experience, infection, and malnutrition. Palatal flap necrosis can be prevented through identification of the risk factors and a careful surgical planning should be done before any palatoplasty. Management of severe fistulas observed as a consequence of palatal flap necrosis is a big challenge for any cleft surgeon. Different techniques as facial artery flaps, tongue flaps, and microvascular flaps have been described with this purpose. This review article discusses the current status of this serious complication in patients with cleft palate. PMID:26273624

  13. Synovial fat necrosis associated with ischemic pancreatic disease.

    PubMed

    Smukler, N M; Schumacher, H R; Pascual, E; Brown, S; Ryan, W E; Sadeghian, M R

    1979-05-01

    A 59-year-old man with ischemic pancreatic disease, polyarthritis, and cutaneous nodules has shown histopathologic findings indicative of disseminated fat necrosis in a percutaneous biopsy specimen from the right knee. The histopathologic findings in the synovium included necrotic fat cells, distorted fat cells and adjacent lymphocytes, lipid laden histiocytes, and giant cells. In prior histopathologic studies of the joint involvement associated with this disorder, fat cell necrosis has been found only in the periarticular tissues, and the synovium has appeared normal or showed nonspecific inflammation. However, the present study shows that the synovial membrane may also be the site of fat necrosis and an associated inflammatory reaction; thus patients with this disorder may manifest arthritis in addition to periarthritis.

  14. Tongue necrosis as first symptom of giant cell arteritis (GCA).

    PubMed

    Brodmann, M; Dorr, A; Hafner, F; Gary, T; Pilger, E

    2009-06-01

    Giant cell arteritis (GCA) is the most common systemic vasculitis affecting people over the age of 50 years, especially in the western world. Nevertheless, the initial diagnosis can be tricky, as some of the patients present at first time with a real unusual initial manifestation. One of these can be tongue necrosis, which is according to the literature in accordance with scalp necrosis, the rarest initial manifestation form of GCA. We describe two patients who presented with tongue necrosis as initial symptom of GCA. The diagnosis was made by the American College of Rheumatology criteria, biopsy and duplex sonography of their temporal arteries. A typical halo was seen as a sign of intimal edema. The patients were put on corticosteroids immediately after diagnosis was proven and their symptoms improved quickly.

  15. Cannabinoids act as necrosis-inducing factors in Cannabis sativa.

    PubMed

    Shoyama, Yoshinari; Sugawa, Chitomi; Tanaka, Hiroyuki; Morimoto, Satoshi

    2008-12-01

    Cannabis sativa is well known to produce unique secondary metabolites called cannabinoids. We recently discovered that Cannabis leaves induce cell death by secreting tetrahydrocannabinolic acid (THCA) into leaf tissues. Examinations using isolated Cannabis mitochondria demonstrated that THCA causes mitochondrial permeability transition (MPT) though opening of MPT pores, resulting in mitochondrial dysfunction (the important feature of necrosis). Although Ca(2+) is known to cause opening of animal MPT pores, THCA directly opened Cannabis MPT pores in the absence of Ca(2+). Based on these results, we conclude that THCA has the ability to induce necrosis though MPT in Cannabis leaves, independently of Ca(2+). We confirmed that other cannabinoids (cannabidiolic acid and cannabigerolic acid) also have MPT-inducing activity similar to that of THCA. Moreover, mitochondria of plants which do not produce cannabinoids were shown to induce MPT by THCA treatment, thus suggesting that many higher plants may have systems to cause THCA-dependent necrosis.

  16. 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

  17. [The diagnostic approach to hepatocellular carcinoma].

    PubMed

    Schacherer, D; Schoelmerich, J; Zuber-Jerger, I

    2007-10-01

    Risk factors and symptoms of hepatocellular carcinoma (HCC): The main risk factors of HCC include infection with hepatitis B or C virus, as well as alcohol consumption. There are no specific symptoms of HCC, making early diagnosis and detection of the disease difficult. When HCC presents with specific clinical symptoms, the tumour is typically very far advanced. Surveillance in liver cirrhosis: The most common serological marker used in HCC diagnosis is alpha-fetoprotein (AFP), but other tumour markers such as the des-gamma-carboxyprothrombin (DGCP) or fractions of AFP (AFP-L3) exist and there use is discussed in this context. Surveillance should be done by sonography at 6 (to 12) months intervals. The single nodule in the cirrhotic liver: Ultrasound is the most commonly used imaging modality for detecting HCC tumour nodules with a large range of reported sensitivities. HCC may appear as a hypoechoic, isoechoic, or hyperechoic round or oval lesion with intratumoural flow signals on Doppler or power Doppler sonography. The differentiation of smaller malignant lesions in cirrhotic livers can be improved by contrast-enhanced ultrasound (CEUS). Spiral computed tomography (CT) and magnetic resonance imaging (MRI) with and without contrast enhancement play an important role in the diagnosis and staging of HCC. If the vascular pattern on imaging is not typical, biopsy becomes necessary. The patient with known HCC: Different tumour markers are used in the evaluation of tumour progression, prediction of patient outcome and treatment efficacy. Among the various staging systems used in the context of HCC, the Barcelona-Clinic-Liver-Cancer (BCLC) staging system is currently the only staging system that takes into account tumour stage, liver function, physical status and cancer-related symptoms. Beside surgical resection, non-surgical treatments such as percutaneous ethanol injection (PEI), radiofrequency thermoablation (RFTA) and trans-arterial chemoembolisation (TACE) are

  18. Imaging of cavitary necrosis in complicated childhood pneumonia.

    PubMed

    Hodina, M; Hanquinet, S; Cotting, J; Schnyder, P; Gudinchet, F

    2002-02-01

    The aim of this study was to illustrate the chest radiographs (CR) and CT imaging features and sequential findings of cavitary necrosis in complicated childhood pneumonia. Among 30 children admitted in the Pediatric Intensive Care Unit for persistent or progressive pneumonia, respiratory distress or sepsis despite adequate antibiotic therapy, a study group of 9 children (5 girls and 4 boys; mean age 4 years) who had the radiographic features and CT criteria for cavitary necrosis complicated pneumonia was identified. The pathogens identified were Streptococcus pneumoniae( n=4), Aspergillus( n=2), Legionella( n=1), and Staphylococcus aureus( n=1). Sequential CR and CT scans were retrospectively reviewed. Follow-up CR and CT were evaluated for persistent abnormalities. Chest radiographs showed consolidations in 8 of the 9 patients. On CT examination, cavitary necrosis was localized to 1 lobe in 2 patients and 7 patients showed multilobar or bilateral areas of cavitary necrosis. In 3 patients of 9, the cavitary necrosis was initially shown on CT and visualization by CR was delayed by a time span varying from 5 to 9 days. In all patients with cavities, a mean number of five cavities were seen on antero-posterior CR, contrasting with the multiple cavities seen on CT. Parapneumonic effusions were shown by CR in 3 patients and in 5 patients by CT. Bronchopleural fistulae were demonstrated by CT alone ( n=3). No purulent pericarditis was demonstrated. The CT scan displayed persistent residual pneumatoceles of the left lower lobe in 2 patients. Computed tomography is able to define a more specific pattern of abnormalities than conventional CR in children with necrotizing pneumonia and allows an earlier diagnosis of this rapidly progressing condition. Lung necrosis and cavitation may also be associated with Aspergillus or Legionella pneumonia in the pediatric population.

  19. [Acute pancreatitis].

    PubMed

    Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A

    2014-03-01

    Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.

  20. Bronchitis - acute

    MedlinePlus

    ... to breathe. Other symptoms of bronchitis are a cough and coughing up mucus. Acute means the symptoms ... diagnosed with chronic bronchitis, you must have a cough with mucus on most days for at least ...

  1. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is inflammation of your bronchial tree. The bronchial tree consists of tubes that carry air into your ... weeks or months. This happens because the bronchial tree takes a while to heal. A lasting cough ...

  2. In Silico Analysis of Tumor Necrosis Factor α-Induced Protein 8-Like-1 (TIPE1) Protein

    PubMed Central

    Su, Zhaoliang; Wang, Shengjun; Xu, Huaxi

    2015-01-01

    Tumor necrosis factor α-induced protein 8 (TNFAIP8)-like protein 1 (TIPE1) was a member of TNFAIP8 family. Previous studies have shown that TIPE1 could induce apoptosis in hepatocellular carcinoma. In this study, we attempted to predict its potential structure. Bioinformatic analysis of TIPE1 was performed to predict its potential structure using the bioinfomatic web services or softwares. The results showed that the amino acid sequences of TIPE1 were well conserved in mammals. No signal peptide and no transmembrane domain existed in human TIPE1. The aliphatic index of TIPE1 was 100.75 and the theoretical pI was 9.57. TIPE1 was a kind of stable protein and its grand average of hydropathicity was -0.108. Various post-translational modifications were also speculated to exist in TIPE1. In addition, the results of Swiss-Model Server and Swiss-Pdb Viewer program revealed that the predicted three-dimensional structure of TIPE1 protein was stable and it may accord with the rule of stereochemistry. TIPE1 was predicted to interact with FBXW5, caspase8 and so on. In conclusion, TIPE1 may be a stable protein with no signal peptide and no transmembrane domain. The bioinformatic analysis of TIPE1 will provide the basis for the further study on the function of TIPE1. PMID:26207809

  3. A new geographic and host record for infectious pancreatic necrosis

    USGS Publications Warehouse

    Parisot, T.J.; Yasutake, W.T.; Bressler, V.

    1963-01-01

    The occurrence of infectious pancreatic necrosis in rainbow trout (Salmo gairdneri), brook trout (Salvelinus fontinalis), and cutthroat trout (Salmo clarki) has been experimentally authenticated for the first time in the western United States. The cutthroat trout represents a new host. Brook trout fin tissue culture inoculated with bacteria-free filtrate from the diseased fish tissue showed marked degenerative changes after 24 hours. Chinook salmon (Oncorhynchus tshawytscha), kokanee (O. nerka), and silver salmon (O. kisutch) were not susceptible to the virus when inoculated. Histologically, extensive pancreatic necrosis was observed in the original and experimental materials, but striated muscle hyalinization was detected only in the original material.

  4. Possible Mechanism of Liver Necrosis Caused by Aromatic Organic Compounds

    PubMed Central

    Brodie, Bernard B.; Reid, Watson D.; Cho, Arthur K.; Sipes, Glenn; Krishna, Gopal; Gillette, James R.

    1971-01-01

    Treatment of rats with phenobarbital, which stimulates the activity of the drug-metabolizing enzymes in the liver, potentiates hepatic necrosis elicited by bromobenzene and a number of other chemically inert halogenated aromatic hydrocarbons. Radioautographic studies indicate that [14C]bromobenzene is covalently bound at the sites of necrosis. From these results, it is inferred that the hepatotoxic effects of the halogenated aromatic hydrocarbons are mediated by chemically active metabolites formed in hepatocytes. In accord with this view, a number of aromatic halogenated hydrocarbons are converted by microsomes in vitro to active intermediates which form covalent complexes with glutathione (GSH). Images PMID:4395686

  5. Drug-Eluting Beads Loaded With Doxorubicin (DEBDOX) Chemoembolisation Before Liver Transplantation for Hepatocellular Carcinoma: An Imaging/Histologic Correlation Study

    SciTech Connect

    Pauwels, Xavier Azahaf, Mustapha; Lassailly, Guillaume; Sergent, Géraldine; Buob, David; Truant, Stéphanie Boleslawski, Emmanuel; Louvet, Alexandre; Gnemmi, Vivianne; Canva, Valérie Mathurin, Philippe; Pruvot, François-René; Leteurtre, Emmanuelle; and others

    2015-06-15

    Purpose Most transplant centers use chemoembolisation as locoregional bridge therapy for hepatocellular carcinoma (HCC) before liver transplantation (LT). Chemoembolisation using beads loaded with doxorubicin (DEBDOX) is a promising technique that enables delivery of a large quantity of drugs against HCC. We sought to assess the imaging–histologic correlation after DEBDOX chemoembolisation.Materials and Methods All consecutive patients who had undergone DEBDOX chemoembolisation before receiving liver graft for HCC were included. Tumour response was evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST) and modified RECIST (mRECIST) criteria. The result of final imaging made before LT was correlated with histological data to predict tumour necrosis.ResultsTwenty-eight patients underwent 43 DEBDOX procedures for 45 HCC. Therapy had a significant effect as shown by a decrease in the mean size of the largest nodule (p = 0.02) and the sum of viable part of tumour sizes according to mRECIST criteria (p < 0.001). An objective response using mRECIST criteria was significantly correlated with mean tumour necrosis ≥90 % (p = 0.03). A complete response using mRECIST criteria enabled accurate prediction of complete tumour necrosis (p = 0.01). Correlations using RECIST criteria were not significant.ConclusionOur data confirm the potential benefit of DEBDOX chemoembolisation as bridge therapy before LT, and they provide a rational basis for new studies focusing on recurrence-free survival after LT. Radiologic evaluation according to mRECIST criteria enables accurate prediction of tumour necrosis, whereas RECIST criteria do not.

  6. Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats.

    PubMed

    Pradeep, Kannampalli; Park, Sang Hyun; Ko, Kyong Cheol

    2008-06-10

    observations were supported by the histopathological findings. Thus, oral administration of hesperidin was found to offer protection against gamma-irradiation induced hepatocellular damage and oxidative stress in rats, probably by exerting a protective effect against hepatocellular necrosis via its free radical scavenging and membrane stabilizing ability.

  7. α-Hispanolol sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis via death receptor up-regulation

    SciTech Connect

    Mota, Alba; Jiménez-Garcia, Lidia; Herránz, Sandra; Heras, Beatriz de las; Hortelano, Sonsoles

    2015-08-01

    Hispanolone derivatives have been previously described as anti-inflammatory and antitumoral agents. However, their effects on overcoming Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance remain to be elucidated. In this study, we analyzed the cytotoxic effects of the synthetic hispanolone derivative α-hispanolol (α-H) in several tumor cell lines, and we evaluated the induction of apoptosis, as well as the TRAIL-sensitizing potential of α-H in the hepatocellular carcinoma cell line HepG2. Our data show that α-H decreased cell viability in a dose-dependent manner in HeLa, MDA-MB231, U87 and HepG2 cell lines, with a more prominent effect in HepG2 cells. Interestingly, α-H had no effect on non-tumoral cells. α-H induced activation of caspase-8 and caspase-9 and also increased levels of the proapoptotic protein Bax, decreasing antiapoptotic proteins (Bcl-2, X-IAP and IAP-1) in HepG2 cells. Specific inhibition of caspase-8 abrogated the cascade of caspase activation, suggesting that the extrinsic pathway has a critical role in the apoptotic events induced by α-H. Furthermore, combined treatment of α-H with TRAIL enhanced apoptosis in HepG2 cells, activating caspase-8 and caspase-9. This correlated with up-regulation of both the TRAIL death receptor DR4 and DR5. DR4 or DR5 neutralizing antibodies abolished the effect of α-H on TRAIL-induced apoptosis, suggesting that sensitization was mediated through the death receptor pathway. Our results demonstrate that α-H induced apoptosis in the human hepatocellular carcinoma cell line HepG2 through activation of caspases and induction of the death receptor pathway. In addition, we describe a novel function of α-H as a sensitizer on TRAIL-induced apoptotic cell death in HepG2 cells. - Highlights: • α-Hispanolol induced apoptosis in the human hepatocellular carcinoma cell line HepG2. • α-Hispanolol induced activation of caspases and the death receptor pathway. • α-Hispanolol enhanced

  8. TIPE2 inhibits TNF-α-induced hepatocellular carcinoma cell metastasis via Erk1/2 downregulation and NF-κB activation.

    PubMed

    Zhang, Yue Hua; Yan, Hong Qiong; Wang, Fang; Wang, Yan Yan; Jiang, Yi Na; Wang, Yi Nan; Gao, Feng Guang

    2015-01-01

    Tumor necrosis factor-α-induced protein 8-like 2 (TNFAIP8L2, TIPE2), which belongs to the TNF-α-induced protein 8 family, is a negative regulator of immune homeostasis. Although pro-inflammatory cytokines such as TNF-α have been reported to be involved in liver carcinoma metastasis, the effect of TIPE2 on hepatocellular carcinoma metastasis remains unknown. We demonstrate that TNF-α clearly augments MMP-13/MMP-3 expression and promotes cell migration in HepG2 cells through activation of the Erk1/2-NF-κB pathways. Interestingly, in addition to human PBLs, macrophages and fibroblasts, liver cancer cells specifically express TNF-α following LPS treatment. Most importantly, TIPE2 overexpression efficiently abrogates the effects of LPS on TNF-α secretion and abolishes the effects of TNF-α on MMP-13/MMP-3 upregulation, cell migration and Erk1/2-NF-κB activation. Taken together, these findings demonstrate that TIPE2 was able to suppress TNF-α-induced hepatocellular carcinoma metastasis by inhibiting Erk1/2 and NF-κB activation, indicating that both TNF-α and TIPE2 might be potential targets for the treatment of HCC metastasis.

  9. Acute and chronic pancreatitis: surgical management.

    PubMed

    Dzakovic, Alexander; Superina, Riccardo

    2012-08-01

    Pancreatitis is becoming increasingly prevalent in children, posing new challenges to pediatric health care providers. Although some general adult treatment paradigms are applicable in the pediatric population, diagnostic workup and surgical management of acute and chronic pancreatitis have to be tailored to anatomic and pathophysiological entities peculiar to children. Nonbiliary causes of acute pancreatitis in children are generally managed nonoperatively with hydration, close biochemical and clinical observation, and early initiation of enteral feeds. Surgical intervention including cholecystectomy or endoscopic retrograde cholangiopancreatography is often required in acute biliary pancreatitis, whereas infected pancreatic necrosis remains a rare absolute indication for pancreatic debridement and drainage via open, laparoscopic, or interventional radiologic procedure. Chronic pancreatitis is characterized by painful irreversible changes of the parenchyma and ducts, which may result in or be caused by inadequate ductal drainage. A variety of surgical procedures providing drainage, denervation, resection, or a combination thereof are well established to relieve pain and preserve pancreatic function.

  10. The role of death receptor 3 in the biological behavior of hepatocellular carcinoma cells

    PubMed Central

    ZHANG, YOU CHENG; GUO, LIU QING; CHEN, XIAO; WANG, GEN NIAN; NI, RI; WANG, MAN CAI; WEI, FENG XIAN

    2015-01-01

    Death receptor 3 (DR3) belongs to the tumor necrosis factor (TNF) receptor superfamily, primarily found in lymphoid tissues. Reports have determined that DR3 may also be distributed in numerous types of tumors. Therefore, it is thought that DR3 may have an important role in the process of tumorigenesis. The aim of the present study was to observe the effect of silencing DR3 expression on hepatocarcinoma cell growth, apoptosis and invasion in order to elucidate the role of DR3 in tumor development. The hepatocarcinoma cell lines (HepG2, Huh7, SMMC7721 and Bel-7402) and normal human liver cells (HL-7702) were transfected with three stealth RNA interference (RNAi) sequences that target the DR3 gene. Reverse transcription quantitative polymerase chain reaction was used to detect the expression levels of DR3 in hepatocarcinoma cell lines and normal liver HL-7702 cells. MTT assay and flow cytometry (FCM) were used to determine the rates of cell proliferation and apoptosis, respectively. Following silencing of the DR3 gene, western blot analysis was used to determine the protein expression of P53, Fas, Caspase8, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Caspase3. DR3 messenger RNA (mRNA) expression in hepatocarcinoma cell lines was significantly increased compared with that in the normal liver cell line. Three targeted DR3 gene small interfering RNAs significantly inhibited DR3 gene expression in Bel-7402 cells at the nucleic acid level. AF02670.1_stealth_883 and cocktail demonstrated the most efficient inhibition of DR3 gene expression at 48 and 72 h following transfection, with mRNA inhibition rates of 89.46 and 92.75%, and 90.53 and 94.25% (P<0.01), respectively. Cell viability was significantly reduced by AF02670.1_stealth_883 and RNAi cocktail at 24, 48 and 72 h following transfection. The inhibition rates of cell proliferation were 50.76 and 61.76% (P<0.05) at 72 h following transfection. FCM revealed that AF02670.1_stealth_883 and

  11. Severe Raynaud's phenomenon-A streamlined approach to acute management.

    PubMed

    Lee, Regent; Lomas, Oliver; Handa, Ashok

    2011-01-01

    Raynaud's phenomenon is an exaggerated vasospastic response to cold or emotional stress which not only may cause the patient severe pain but also critical ischaemia and necrosis of the digits. We report the case of a 69-year-old woman who presented with rest pain, impending ulceration and necrosis of finger tips due to an episode of left-sided Raynaud's phenomenon. Intravenous prostacyclin was administered successfully as a bridge to endoscopic thoracic sympathectomy. Vascular surgery units are ideally positioned for the acute management of severe Raynaud's phenomenon to provide continuity of care to patients with profound digital ischaemia and impending tissue loss.

  12. MDCT Versus MRI Assessment of Tumor Response After Transarterial Chemoembolization for the Treatment of Hepatocellular Carcinoma

    SciTech Connect

    Kloeckner, Roman; Otto, Gerd; Biesterfeld, Stefan; Oberholzer, Katja; Dueber, Christoph; Pitton, Michael B.

    2010-06-15

    The purpose of this study was to compare the ability of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) to evaluate treatment results after transarterial chemoembolization (TACE), with a special focus on the influence of Lipiodol on calculation of tumor necrosis according to EASL criteria. A total of 115 nodules in 20 patients (17 males, 3 females; 69.5 {+-} 9.35 years) with biopsy-proven hepatocellular carcinoma were treated with TACE. Embolization was performed using a doxorubicin-Lipiodol emulsion (group I) or DC Beads loaded with doxorubicin (group II). Follow-up included triphasic contrast-enhanced 64-row MDCT (collimation, 0.625 mm; slice, 3 mm; contrast bolus, 120 ml iomeprol; delay by bolus trigger) and contrast-enhanced MRI (T1 native, T2 native; five dynamic contrast-enhanced phases; 0.1 mmol/kg body weight gadolinium-DTPA; slice thickness, 4 mm). Residual tumor and the extent of tumor necrosis were evaluated according to EASL. Contrast enhancement within tumor lesions was suspected to represent vital tumor. In the Lipiodol-based TACE protocol, MDCT underestimated residual viable tumor compared to MRI, due to Lipiodol artifacts (23.2% vs 47.7% after first, 11.9% vs 31.2% after second, and 11.4% vs 23.7% after third TACE; p = 0.0014, p < 0.001, and p < 0.001, respectively). In contrast to MDCT, MRI was completely free of any artifacts caused by Lipiodol. In the DC Bead-based Lipiodol-free TACE protocol, MRI and CT showed similar residual tumor and rating of treatment results (46.4% vs 41.2%, 31.9 vs 26.8%, and 26.0% vs 25.6%; n.s.). In conclusion, MRI is superior to MDCT for detection of viable tumor residuals after Lipiodol-based TACE. Since viable tumor tissue is superimposed by Lipiodol artifacts in MDCT, MRI is mandatory for reliable decision-making during follow-up after Lipiodol-based TACE protocols.

  13. [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.

  14. Investigation of SP94 Peptide as a Specific Probe for Hepatocellular Carcinoma Imaging and Therapy

    PubMed Central

    Li, Yanli; Hu, Yan; Xiao, Jie; Liu, Guobing; Li, Xiao; Zhao, Yanzhao; Tan, Hui; Shi, Hongcheng; Cheng, Dengfeng

    2016-01-01

    SP94 (SFSIIHTPILPL), a novel peptide, has shown specific binding to hepatocellular carcinoma (HCC) cells. We aimed to investigate the capability of SP94 as a targeting probe for HCC imaging and therapy following labeling with technetium-99m (99mTc) and rhenium-188 (188Re). HYNIC-SP94 was prepared by solid phase synthesis and then labeled with 99mTc. Cell competitive binding, internalization assay, in vitro and in vivo stability, biodistribution and micro-single photon emission computed tomography /computed tomography (SPECT/CT) imaging studies were performed to investigate the capability of 99mTc tricine-EDDA/HYNIC-SP94 as a specific HCC imaging probe. Initial promising targeting results inspired evaluation of its therapeutic effect when labeled by 188Re. HYNIC-SP94 was then labeled again with 188Re to perform cell apoptosis, microSPECT/CT imaging evaluation and immunohistochemistry. Huh-7 cells exhibited typical apoptotic changes after 188Re irradiation. According to 99mTc tricine-EDDA/HYNIC-SP94 microSPECT/CT imaging, tumor uptake was significantly decreased compared with that of pre-treatment with 188Re-HYNIC-SP94. The immunohistochemistry also displayed obvious necrosis and apoptosis as well as inhibition of proliferation in the 188Re-HYNIC-SP94 treatment group. The results supported that 99mTc tricine-EDDA/HYNIC-SP94 is able to target HCC cells and 188Re-HYNIC- SP94 holds potential as a therapeutic agent for HCC, making 99mTc/188Re-HYNIC-SP94 a promising targeting probe for HCC imaging and therapy. PMID:27649935

  15. Host nucleotide polymorphism in hepatitis B virus-associated hepatocellular carcinoma

    PubMed Central

    Mathew, Shilu; Abdel-Hafiz, Hany; Raza, Abbas; Fatima, Kaneez; Qadri, Ishtiaq

    2016-01-01

    Hepatocellular carcinoma (HCC) is etiologically linked with hepatitis B virus (HBV) and is the leading cause of death amongst 80% of HBV patients. Among HBV affected patients, genetic factors are also involved in modifying the risk factors of HCC. However, the genetic factors that regulate progression to HCC still remain to be determined. In this review, we discuss several single nucleotide polymorphisms (SNPs) which were reportedly associated with increased or reduced risk of HCC occurrence in patients with chronic HBV infection such as cyclooxygenase (COX)-2 expression specifically at COX-2 -1195G/A in Chinese, Turkish and Egyptian populations, tumor necrosis factor α and the three most commonly studied SNPs: PAT-/+, Lys939Gln (A33512C, rs2228001) and Ala499Val (C21151T, rs2228000). In genome-wide association studies, strong associations have also been found at loci 1p36.22, 11q22.3, 6p21 (rs1419881, rs3997872, rs7453920 and rs7768538), 8p12 (rs2275959 and rs37821974) and 22q11.21. The genes implicated in these studies include HLA-DQB2, HLA-DQA1, TCF19, HLA-C, UBE2L3, LTL, FDX1, MICA, UBE4B and PG. The SNPs found to be associated with the above-mentioned genes still require validation in association studies in order to be considered good prognostic candidates for HCC. Screening of these polymorphisms is very beneficial in clinical experiments to stratify the higher or lower risk for HCC and may help in designing effective and efficient HCC surveillance programs for chronic HBV-infected patients if further genetic vulnerabilities are detected. PMID:27057306

  16. Modified AS1411 Aptamer Suppresses Hepatocellular Carcinoma by Up-Regulating Galectin-14

    PubMed Central

    Lee, Jeong-Hoon; Lee, Dong Hyeon; Cho, Eun Ju; Yu, Su Jong; Kim, Yoon Jun; Kim, Jong In; Im, Jong Hun; Lee, Jung Hwan; Oh, Eun Ju; Yoon, Jung-Hwan

    2016-01-01

    Aptamers are small synthetic oligonucleotides that bind to target proteins with high specificity and affinity. AS1411 is an aptamer that binds to nucleolin, which is overexpressed in the cytoplasm and occurs on the surface of cancer cells. We investigated the therapeutic potential of aptamers in hepatocellular carcinoma (HCC) by evaluating anti-tumor effects and confirming the affinity and specificity of AS1411- and modified AS1411-aptamers in HCC cells. Cell growth was assessed using the MTS assay, and cell death signaling was explored by immunoblot analysis. Fluorescence-activated cell sorting was performed to evaluate the affinity and specificity of AS1411-aptamers in SNU-761 HCC cells. We investigated the in vivo effects of the AS1411-aptamer using BALB/c nude mice in a subcutaneous xenograft model with SNU-761 cells. Treatment with a modified AS1411-aptamer significantly decreased in vitro (under normoxic [P = 0.035] and hypoxic [P = 0.018] conditions) and in vivo (under normoxic conditions, P = 0.041) HCC cell proliferation compared to control aptamers. AS1411- and control aptamers failed to control HCC cell proliferation. However, AS1411- and the modified AS1411-aptamer did not induce caspase activation. Decrease in cell growth by AS1411 or modified AS1411 was not prevented by caspase or necrosis inhibitors. In a microarray, AS1411 significantly enhanced galectin-14 expression. Suppression of HCC cell proliferation by the modified AS1411-aptamer was attenuated by galectin-14 siRNA transfection. Modified AS1411-aptamer suppressed HCC cell growth in vitro and in vivo by up-regulating galectin-14 expressions. Modified AS1411-aptamers may have therapeutic potential as a novel targeted therapy for HCC. PMID:27494117

  17. Extrahepatic Blood Supply to Hepatocellular Carcinoma: Angiographic Demonstration and Transcatheter Arterial Chemoembolization

    SciTech Connect

    Miyayama, Shiro Matsui, Osamu; Taki, Keiichi; Minami, Tetsuya; Ryu, Yasuji; Ito, Chiharu; Nakamura, Koichi; Inoue, Dai; Notsumata, Kazuo; Toya, Daisyu; Tanaka, Nobuyoshi; Mitsui, Takeshi

    2006-02-15

    Purpose. To evaluate the incidence of each extrahepatic collateral pathway to hepatocellular carcinoma (HCC) and to assess technical success rates and complications of transcatheter arterial chemoembolization (TACE) through each collateral. Methods. We retrospective evaluated extrahepatic collateral pathways to HCC on angiography in 386 procedures on 181 consecutive patients. One hundred and seventy patients had previously undergone TACE. TACE through extrahepatic collaterals using iodized oil and gelatin sponge particles was performed when a catheter was advanced into the tumor-feeding branch to avoid nontarget embolization. Results. A single collateral was revealed in 275 TACE procedures, two were revealed in 74, and three or more were revealed in 34. Incidences of collateral source to HCC were 83% from the right inferior phrenic artery (IPA), 24% from the cystic artery, 13% from the omental artery, 12% from the right renal capsular artery (RCA) and left IPA, 8% from the right internal mammary artery (IMA) and right intercostal artery (ICA), and 7% from the right inferior adrenal artery (IAA). Technical success rates of TACE were 53% in the right ICA, 70% in the cystic artery, 74% in the omental artery, 93% in the left IPA, 96% in the right IPA, and 100% in the right RCA, right IMA, and right IAA. Complications included skin necrosis after TACE through the right IMA (n = 1), cholecystitis after TACE through the cystic artery (n = 1), and ulcer formation after TACE through the right gastric artery (n = 1), in addition to pleural effusion and basal atelectasis after TACE through the IPA and IMA. Conclusion. Our study suggests that TACE through extrahepatic collaterals is possible with high success rates, and is also relatively safe.

  18. Successful surgical resection of solitary plasmacytoma of the liver mimicking hepatocellular carcinoma. A case report.

    PubMed

    Mirarchi, Mariateresa; De Raffele, Emilio; Bacci, Francesco; Cuicchi, Dajana; Lecce, Ferdinando; Cola, Bruno

    Solitary extramedullary plasmacitomas (SEMP) of the liver are very rare. We report the case of an elderly woman with a huge symptomatic SEMP of the liver mimicking hepatocellular carcinoma (HCC). The patient was a 89-year-old woman who presented with severe abdominal pain and a huge solid mass in the right hypochondrium. The laboratory data on admission revealed normal liver function tests. A multiphasic computed tomography (CT) showed a huge solid mass of the left hemiliver, hypoattenuating on noncontrast images, dishomogeneously hyperenhancing in the late arterial phase, with washout in the portal venous and equilibrium phases. A 18F-FDG positron emission tomography (18F-FDG PET)-CT scan documented a marked FDG uptake within the lesion, without evidence of extrahepatic metastases. We considered the clinical and radiologic findings consistent with the diagnosis of high-grade HCC with areas of intratumoral necrosis preluding to possible tumour rupture. Surgical resection was ultimately considered feasible with a reasonable risk and the patient underwent left hepatectomy with diaphragmatic resection. Pathological examination exhibited an extramedullary plasmacytoma. At immunohistochemical analysis neoplastic cells were positive for CD45, CD38, IRF4, HTPD52, kappa-chain, but negative for lambda- chain; Mib-1 proliferation index was 50%. Subsequent clinical evaluation excluded any sign of multiple myeloma, so that a diagnosis of truly localized SEMP of the liver was finally established. To our knowledge, this is the first case of a solitary extramedullary plasmacitoma of the liver undergoing successful radical liver resection. The patient is alive and well 5 years after surgery without evidence of local recurrence and of systemic disease.

  19. Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma

    PubMed Central

    Salman, A.; Simoneau, E.; Hassanain, M.; Chaudhury, P.; Boucher, L.M.; Valenti, D.; Cabrera, T.; Nudo, C.; Metrakos, P.

    2016-01-01

    Background and Aims In this pilot study, we assessed the safety and tolerability of combining sorafenib with 90Y radioembolization for the treatment of unresectable hepatocellular carcinoma (hcc). Methods The study, conducted prospectively during 2009–2012, included eligible patients with unresectable hcc and a life expectancy of at least 12 weeks. Each patient received sorafenib (400 mg twice daily) for 6–8 weeks before 90Y treatment. Safety and tolerability were assessed. Results Of the 40 patients enrolled, 29 completed treatment (combined therapy). In the initial cohort, the most common cause of hcc was hepatitis C (32.5%), and most patients were staged Child A (82.5%). The 29 patients who completed the study had similar baseline characteristics. Grades 1 and 2 toxicities accounted for 77.8% of all adverse events reported. The most common toxicities reported were fatigue (19.0%), alteration in liver function (7.9%), and diarrhea (6.3%). There were 12 grade 3 and 2 grade 4 toxicity events reported. One patient died of liver failure within 30 days after treatment. During the study, the sorafenib dose was reduced in 6 patients (20.7%), and sorafenib had to be interrupted in 4 patients (13.8%) and discontinued in 4 patients (13.8%). The disease control rate was 72.4% per the modified Response Evaluation Criteria in Solid Tumors, and tumour necrosis was observed in 82.8% of patients. Overall survival in patients undergoing combined therapy was 12.4 months. Conclusions Preliminary results demonstrate the safety and tolerability of combining 90Y radioembolization and sorafenib for advanced hcc. A larger prospective study is needed to determine the extent of the survival benefit. PMID:27803608

  20. Efficacy and safety of intraoperative radiofrequency ablation in management of hepatocellular carcinoma.

    PubMed

    Rizk, Hesham; Magdy, Mohamed; Reda, Mahmoud; Alaa, Taha; El-Shafie, M Mohamed; Ghanem, Mahmoud; Saed, Tarek

    2008-12-01

    The present study is a prospective one involving 15 consecutive patients with hepatocellular carcinoma (HCC) from January 2003 to December 2005. Clinical and laboratory examinations, abdominal ultrasonography & spiral CT scanning were performed. All patients were subjected to intraoperative radiofrequency ablation of HCC after confirmation by core biopsy. Enhanced dynamic CT was done at 1 month postoperative and every 3 months during follow-up period. Males were 12 with age of 41-69 year (53.2 +/- 7.4). Underlying cirrhosis due to viral hepatitis was in all, and HCV was the most common (75%), and patients (85%) werecategorized in Child B classification. Serum alpha feto protein was above 400 ng/ml in 60%. 12 patients had unifocal HCC (nodules mean diameter of less than 3 cm in 6, 3 to 5 cm in 4, and more than 5 cm in 2), and 3 patients had multifocal HCC (nodules mean number of less than 3 cm in 2 and 3 to 5 cm in 1). The mean number of RF application session to achieve complete necrosis in patients with were 1.52 (unifocal) & 2.49 (multifocal HCC). The mean hospital stay was 14.9 days, with neither mortality nor major complications, but Minor complications in 30%. After one month, complete ablation of HCC nodules was achieved in 10 patients with reduction of alpha fetoprotein in 11 patients. 2/5 with partial ablation were multifocal nodules. Total mortality during follow-up in late post-operative period (1 year) was 6 out of 15 patients. 5 of them are the patients with partial ablation. 3 patients out of 9 patients developed evidence of local recurrence detected by enhanced dynamic CT & raising of serum alpha fetoprotein.

  1. Comparison of Types of Cell Death: Apoptosis and Necrosis.

    ERIC Educational Resources Information Center

    Manning, Francis; Zuzel, Katherine

    2003-01-01

    Cell death is an essential factor in many biological processes including development. Discusses two types of cell death: (1) necrosis (induced by sodium azide); and (2) apoptosis (induced by sodium chromate). Illustrates key features that differ between these two types of cells death including loss of membrane integrity and internucleosomal DNA…

  2. Inhibition of Prostaglandin D Synthase Suppresses Muscular Necrosis

    PubMed Central

    Mohri, Ikuko; Aritake, Kosuke; Taniguchi, Hidetoshi; Sato, Yo; Kamauchi, Shinya; Nagata, Nanae; Maruyama, Toshihiko; Taniike, Masako; Urade, Yoshihiro

    2009-01-01

    Duchenne muscular dystrophy is a fatal muscle wasting disease that is characterized by a deficiency in the protein dystrophin. Previously, we reported that the expression of hematopoietic prostaglandin D synthase (HPGDS) appeared in necrotic muscle fibers from patients with either Duchenne muscular dystrophy or polymyositis. HPGDS is responsible for the production of the inflammatory mediator, prostaglandin D2. In this paper, we validated the hypothesis that HPGDS has a role in the etiology of muscular necrosis. We investigated the expression of HPGDS/ prostaglandin D2 signaling using two different mouse models of muscle necrosis, that is, bupivacaine-induced muscle necrosis and the mdx mouse, which has a genetic muscular dystrophy. We treated each mouse model with the HPGDS-specific inhibitor, HQL-79, and measured both necrotic muscle volume and selected cytokine mRNA levels. We confirmed that HPGDS expression was induced in necrotic muscle fibers in both bupivacaine-injected muscle and mdx mice. After administration of HQL-79, necrotic muscle volume was significantly decreased in both mouse models. Additionally, mRNA levels of both CD11b and transforming growth factor β1 were significantly lower in HQL-79-treated mdx mice than in vehicle-treated animals. We also demonstrated that HQL-79 suppressed prostaglandin D2 production and improved muscle strength in the mdx mouse. Our results show that HPGDS augments inflammation, which is followed by muscle injury. Furthermore, the inhibition of HPGDS ameliorates muscle necrosis even in cases of genetic muscular dystrophy. PMID:19359520

  3. Licensed DNA Vaccines against Infectious Hematopoietic Necrosis Virus (IHNV).

    PubMed

    Alonso, Marta; Leong, Jo-Ann C

    2013-04-01

    This article reviews some of the recent patents on DNA vaccines against fish viruses, in particular against the novirhabdovirus infectious hematopoitic necrosis virus (IHNV). Although very effective in protecting fish against IHNV, only one DNA vaccine has been approved to date for use in Canada. In Europe and in US, its commercialization is restricted due to safety concerns.

  4. [Survival benefit with intraarterial techniques in hepatocellular carcinoma].

    PubMed

    Sangro, Bruno

    2014-07-01

    The two intraarterial techniques used in the treatment of hepatocellular carcinoma (HCC) are the transarterial chemoembolization (TACE) and radioembolization (RE). TACE includes various procedures whose objective is to expose tumor cells to a chemotherapy agent and induce acute ischemia in the tumor. The survival benefit obtained by adding a chemotherapy agent or lipiodol to simple particle embolization has not been demonstrated in 2 meta-analyses, which suggests that the antitumor effect is primarily ischemic. RE is a form of brachytherapy that consists of an intraarterial injection of microspheres loaded with yttrium 90 as the source of radiation, a pure beta emitter with a mean tissue penetration of 2mm. TACE is performed in several sessions every 4-8 weeks, while RE is generally a single procedure. The guidelines adopted by the main research societies support the use of TACE for the palliative treatment of patients with intermediate stage HCC. This is a level 1 recommendation based on the positive results of 2 randomized clinical trials and 3 meta-analyses and on several uncontrolled studies with thousands of patients with unresectable HCC. Survival in clinical practice studies is heterogeneous due to the heterogeneity of the treated population. The survival rate varies from 8% to 26% at 5 years, and the median is 16-40 months in the early stage and 15-27 months in the intermediate stage. TACE with drug-eluting beads (DEB-TACE) has not shown superiority versus conventional TACE in terms of improved survival or tumor response, but it decreases the severe chemotherapy-related adverse events. One of its advantages is the standardization of the procedure, while its primary disadvantage is the onset of biliary complications when used nonselectively. There is level 2 evidence to support the use of RE in HCC, evidence that comes from patient cohorts with consistent results and case-control studies. The treated population includes mainly patients with unresectable

  5. Urinary granzyme A mRNA is a biomarker to diagnose subclinical and acute cellular rejection in kidney transplant recipients.

    PubMed

    van Ham, S Marieke; Heutinck, Kirstin M; Jorritsma, Tineke; Bemelman, Fréderike J; Strik, Merel C M; Vos, Wim; Muris, Jettie J F; Florquin, Sandrine; Ten Berge, Ineke J M; Rowshani, Ajda T

    2010-11-01

    The distinction between T-cell-mediated rejection (TCMR) and other causes of kidney transplant dysfunction such as tubular necrosis requires biopsy. Subclinical rejection (SCR), an established risk factor for chronic allograft dysfunction, can only be diagnosed by protocol biopsy. A specific non-invasive biomarker to monitor immunological graft status would facilitate diagnosis and treatment of common transplantation-related complications. To identify possible markers, we measured urinary mRNA levels of several cytolytic proteins by quantitative PCR. Our cohort of 70 renal transplant recipients had biopsy proven type I and type II TCMR, acute tubular necrosis, SCR, calcineurin inhibitor-toxicity, cytomegalovirus infection, and stable graft function with normal histology. Granzyme A (GzmA) mRNA was significantly higher in subclinical and acute cellular rejection compared to patients with stable grafts or those with tubular necrosis with 80% sensitivity and up to 100% specificity. Granzyme B and perforin mRNA levels could significantly discriminate acute rejection from stable or tubular necrosis, but were not significantly elevated during SCR. Importantly, only GzmA mRNA remained below detection limits from grafts that were stable and most with tubular necrosis. Hence, the presented data indicate that urinary GzmA mRNA levels may entail a diagnostic non-invasive biomarker to distinguish patients with subclinical and acute cellular rejection from those with tubular necrosis or stable grafts.

  6. Drug induced acute pancreatitis: incidence and severity.

    PubMed Central

    Lankisch, P G; Dröge, M; Gottesleben, F

    1995-01-01

    To determine the incidence and severity of drug induced acute pancreatitis, data from 45 German centres of gastroenterology were evaluated. Among 1613 patients treated for acute pancreatitis in 1993, drug induced acute pancreatitis was diagnosed in 22 patients (incidence 1.4%). Drugs held responsible were azathioprine, mesalazine/sulfasalazine, 2',3'-dideoxyinosine (ddI), oestrogens, frusemide, hydrochlorothiazide, and rifampicin. Pancreatic necrosis not exceeding 33% of the organ was found on ultrasonography or computed tomography, or both, in three patients (14%). Pancreatic pseudocysts did not occur. A decrease of arterial PO2 reflecting respiratory insufficiency, and an increase of serum creatinine, reflecting renal insufficiency as complications of acute pancreatitis were seen in two (9%) and four (18%) patients, respectively. Artificial ventilation was not needed, and dialysis was necessary in only one (5%) case. Two patients (9%) died of AIDS and tuberculosis, respectively; pancreatitis did not seem to have contributed materially to their death. In conclusion, drugs rarely cause acute pancreatitis, and drug induced acute pancreatitis usually runs a benign course. PMID:7489946

  7. Acute hepatopathy associated with mitotane administration in a dog.

    PubMed

    Webb, Craig B; Twedt, David C

    2006-01-01

    An adult dog with a persistent elevation in alkaline phosphatase enzyme activity was started on mitotane for suspected hyperadrenocorticism. One month later, the dog was presented for intermittent anorexia and acute icterus. The dog's liver enzyme activities and total bilirubin were markedly elevated, prothrombin time was prolonged, and blood urea nitrogen and glucose were low. Histopathology revealed marked, centrilobular, hepatocellular loss. After discontinuation of the mitotane, the dog recovered with supportive care and was normal 3 months later, which was consistent with mitotane-associated hepatic failure.

  8. Radiomics and circulating tumor cells: personalized care in hepatocellular carcinoma?

    PubMed

    Hesketh, Richard L; Zhu, Andrew X; Oklu, Rahmi

    2015-01-01

    Personalized care in oncology is expected to significantly improve morbidity and mortality, facilitated by our increasing understanding of the molecular mechanisms driving tumors and the ability to target those drivers. Hepatocellular carcinoma has a very high mortality to incidence ratio despite localized disease being curable, emphasizing the importance of early diagnosis. Radiomics, the use of imaging technology to extrapolate molecular tumor data, and the detection of circulating tumor cells (CTCs) are two new technologies that could be incorporated into the clinical setting with relative ease. Here we discuss the molecular mechanisms leading to the development of hepatocellular carcinoma focusing on the latest developments in liver magnetic resonance imaging, CTC, and radiomic technology and their potential to improve diagnosis, staging, and therapy.

  9. Simple Sugar Intake and Hepatocellular Carcinoma: Epidemiological and Mechanistic Insight

    PubMed Central

    Laguna, Juan Carlos; Alegret, Marta; Roglans, Núria

    2014-01-01

    Sugar intake has dramatically increased during the last few decades. Specifically, there has been a clear trend towards higher consumption of fructose and high fructose corn syrup, which are the most common added sugars in processed food, soft drinks and other sweetened beverages. Although still controversial, this rising trend in simple sugar consumption has been positively associated with weight gain and obesity, insulin resistance and type 2 diabetes mellitus and non-alcoholic fatty liver disease. Interestingly, all of these metabolic alterations have also been related to the development of hepatocellular carcinoma. The purpose of this review is to discuss the evidence coming from epidemiological studies and data from animal models relating the consumption of simple sugars, and specifically fructose, with an increased risk of hepatocellular carcinoma and to gain insight into the putative molecular mechanisms involved. PMID:25533006

  10. Fibrolamellar Hepatocellular Carcinoma: a Case Report with Distinct Radiological Features

    PubMed Central

    Haritanti, Afrodite; Economou, Ipoliti

    2010-01-01

    Introduction We report a rare case of a 23-year-old male who presented with abdominal discomfort for 15 days. An ultrasound was performed which showed a hypoechoic, heterogenous mass in the left lobe of the liver and distended portal vein, followed by further investigation with computed tomography (CT), MRI, and MRA. Serum alpha-fetoprotein was not elevated and hepatitis B antigen was negative. Methods CT scan depicted a nodular mass in left liver lobe with occlusion of both the central part and the two main branches of intrahepatic portal vein. Result Biopsy of the liver mass led to a diagnosis of fibrolamellar hepatocellular carcinoma. Conclusion Fibrolamellar carcinoma is an uncommon variant of hepatocellular carcinoma. The diagnosis is suggested by radiographic studies and is confirmed by histological examination. PMID:19960280

  11. Hepatocellular carcinoma in a research subject with ornithine transcarbamylase deficiency.

    PubMed

    Wilson, James M; Shchelochkov, Oleg A; Gallagher, Renata C; Batshaw, Mark L

    2012-02-01

    A 66 year old woman who is a manifesting heterozygote for ornithine transcarbamylase deficiency (OTCD) presented with hepatocellular carcinoma (HCC). Fourteen years prior to this presentation she participated in a phase I gene therapy study which used an adenoviral vector, thought to be non-oncogenic, to deliver a normal OTC gene to hepatocytes [1]. A recent review of data collected through a national longitudinal study of individuals with urea cycle defects [2,3] suggests that early urea cycle disorders (UCDs) are associated with hepatocellular damage and liver dysfunction in many cases. This may predispose an affected individual to a substantially increased risk of developing HCC, as has been observed in certain other inborn errors of metabolism. We speculate that the underlying urea cycle defect may be the cause of HCC in this individual.

  12. Gadolinium chloride pretreatment ameliorates acute cadmium-induced hepatotoxicity.

    PubMed

    Kyriakou, Loukas G; Tzirogiannis, Konstantinos N; Demonakou, Maria D; Kourentzi, Kalliopi T; Mykoniatis, Michael G; Panoutsopoulos, Georgios I

    2013-08-01

    Cadmium is a known industrial and environmental pollutant. It causes hepatotoxicity upon acute administration. Features of cadmium-induced acute hepatoxicity encompass necrosis, apoptosis, peliosis and inflammatory infiltration. Gadolinium chloride (GdCl3) may prevent cadmium-induced hepatotoxicity by suppressing Kupffer cells. The effect of GdCl3 pretreatment on a model of acute cadmium-induced liver injury was investigated. Male Wistar rats 4-5 months old were injected intraperitoneally with normal saline followed by cadmium chloride (CdCl2; 6.5 mg/kg) or GdCl3 (10 mg/kg) followed by CdCl2 (6.5 mg/kg; groups I and II, respectively). Rats of both the groups were killed at 9, 12, 16, 24, 48 and 60 h after cadmium intoxication. Liver sections were analyzed for necrosis, apoptosis, peliosis and mitoses. Liver regeneration was also evaluated by tritiated thymidine incorporation into hepatic DNA. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also determined. Hepatic necrosis, hepatocyte and nonparenchymal cell apoptosis and macroscopic and microscopic types of peliosis hepatis were minimized by gadolinium pretreatment. Serum levels of AST and ALT were also greatly diminished in rats of group II. Tritiated thymidine incorporation into hepatic DNA was increased in gadolinium pretreatment rats. Kupffer cell activation was minimal in both the groups of rats. Gadolinium pretreatment attenuates acute cadmium-induced liver injury in young Wistar rats, with mechanisms other than Kupffer cell elimination.

  13. Transarterial Chemoembolization for Hepatocellular Carcinoma with a New Generation of Beads: Clinical–Radiological Outcomes and Safety Profile

    SciTech Connect

    Spreafico, Carlo Cascella, Tommaso; Facciorusso, Antonio Sposito, Carlo; Rodolfo, Lanocita Morosi, Carlo Civelli, Enrico M. Vaiani, Marta; Bhoori, Sherrie; Pellegrinelli, Alessandro; Marchianò, Alfonso; Mazzaferro, Vincenzo

    2015-02-15

    PurposeTo evaluate the short-term safety and efficacy of the new generation of 70–150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT).MethodsForty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response.ResultsAll patients had well-compensated cirrhosis (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1–6) and 43 mm (range 10–190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2–4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures).ConclusionDEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.

  14. Diaphragmatic Hernia After Radiofrequency Ablation for Hepatocellular Carcinoma

    SciTech Connect

    Yamagami, Takuji Yoshimatsu, Rika; Matsushima, Shigenori; Tanaka, Osamu; Miura, Hiroshi; Nishimura, Tsunehiko

    2011-02-15

    We describe a 71-year-old woman with a hepatocellular carcinoma who underwent percutaneous radiofrequency ablation (RF) with a single internally cooled electrode under computed tomography (CT) fluoroscopic guidance. Nine months after the procedure, CT images showed herniation of the large intestine into the right pleural cavity. To our knowledge this complication of RF performed with a single internally cooled electrode under CT guidance has not been previously reported.

  15. Hepatocellular carcinoma HBsAg positive in pregnancy.

    PubMed

    Gonçalves, C S; Pereira, F E; de Vargas, P R; Ferreira, L S

    1984-01-01

    The authors present a case of hepatocellular carcinoma diagnosed in a pregnant woman (four months pregnancy). The clinical evolution was complicated because of a severe hypoglicemia and the patient died 12 weeks after admission. The fetus died before a tentative of surgical delivery. The patient was HBsAg positive and five out of eight sons (inclusively the fetus), were HBsAg positive. There was not indication that the pregnancy had enhanced the tumor evolution.

  16. Prognostic markers in acute pancreatitis.

    PubMed

    Gomatos, Ilias P; Xiaodong, Xu; Ghaneh, Paula; Halloran, Christopher; Raraty, Michael; Lane, Brian; Sutton, Robert; Neoptolemos, John P

    2014-04-01

    Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.

  17. Euforia-induced acute hepatitis in a patient with scleroderma

    PubMed Central

    Jiménez-Encarnación, Esther; Ríos, Grissel; Muñoz-Mirabal, Angel; Vilá, Luis M

    2012-01-01

    Euforia, a supplement containing a variety of natural ingredients, is widely used as an antioxidant and anti-inflammatory formula. It is not approved by the US Food and Drug Administration and its side effects are unknown. We report a 45-year-old woman with limited systemic sclerosis who presented with jaundice and marked elevation of serum transaminases. One month before, she started taking Euforia juice. A liver biopsy disclosed submassive hepatocellular necrosis with histopathological changes consistent with toxic hepatitis. The patient's symptoms resolved with cessation of Euforia. Six months later, she persisted with abnormal liver function tests, but these resolved 18 months after discontinuation of Euforia. The mechanism by which Euforia causes liver injury is unknown. Some ingredients contained in this supplement (green tea, Aloe vera, noni and goji) are linked to hepatic injury. To our knowledge, this is the first report of hepatotoxicity associated with Euforia. PMID:23257938

  18. Acute liver injury secondary to sertraline.

    PubMed

    Suen, Christopher F D Li Wai; Boyapati, Ray; Simpson, Ian; Dev, Anouk

    2013-09-26

    Sertraline is widely prescribed to treat depression and anxiety disorders. However, hepatitis secondary to its use is a rare entity. We report the case of a 26-year-old woman in her 20th week of pregnancy presented with nausea, vomiting, malaise and dark urine. This occurred 6 months after sertraline 50 mg daily was started for the treatment of depression. Three weeks prior to her presentation, the dose of sertraline was increased to 100 mg daily. The patient's liver biochemical profile demonstrated increased transaminases. The biopsy of the liver showed lobular hepatitis, with a mild prominence of eosinophils, suggestive of a drug-induced or toxin-induced aetiology. Extensive biochemical work-up failed to show any other pathology to account for her hepatitis. Liver function tests normalised after cessation of sertraline, indicating a probable association between sertraline use and acute hepatocellular injury in our patient.

  19. Low-dose steroid-induced tumor lysis syndrome in a hepatocellular carcinoma patient.

    PubMed

    Kim, Jin Ok; Jun, Dae Won; Tae, Hye Jin; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Choi, Ho Soon; Yoon, Byung Chul; Hahm, Joon Soo

    2015-03-01

    Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition of tumor lysis syndrome. Although the patient received adequate hydration, severe metabolic acidosis and acute kidney injury progressed unabated. He finally developed multiple organ failure, and died 3 days after admission. This was a case of tumor lysis syndrome caused by administration of low-dose steroid in a patient with HCC.

  20. Low-dose steroid-induced tumor lysis syndrome in a hepatocellular carcinoma patient

    PubMed Central

    Kim, Jin Ok; Tae, Hye Jin; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Choi, Ho Soon; Yoon, Byung Chul; Hahm, Joon Soo

    2015-01-01

    Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition o