Search Questions | ResearchGate

Hepatocellular carcinoma (HCC, also called malignant hepatoma) is a primary malignancy (cancer) of the liver. Most cases of HCC are secondary to either a viral hepatitide infection (hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis).[1] In countries where hepatitis is not endemic, most malignant cancers in the liver are not primary HCC but metastasis (spread) of cancer from elsewhere in the body, e.g., the colon. Treatment options of HCC and prognosis are dependent on many factors but especially on tumor size and staging. Tumor grade is also important. High-grade tumors will have a poor prognosis, while low-grade tumors may go unnoticed for many years, as is the case in many other organs, such as the breast, where a ductal carcinoma in situ (or a lobular carcinoma in situ) may be present without any clinical signs and without correlate on routine imaging tests, although in some occasions it may be detected on more specialized imaging studies like MR mammography.

The usual outcome is poor, because only 10 - 20% of hepatocellular carcinomas can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually deadly within 3 to 6 months.[2] This is partially due to late presentation with large tumours, but also the lack of medical expertise and facilities. This is a rare tumor in the United States. A new receptor tyrosine kinase inhibitor, sorafenib has been shown in a Spanish phase III clinical trial to add two months to the lifespan of late stage HCC patients with well preserved liver function [3].

-Risk factors

The main risk factors for hepatocellular carcinoma are

Alcoholism

Hepatitis B

Hepatitis C

Aflatoxin

Cirrhosis of the liver

Wilsons disease[citation needed]

When hepatocellular adenomas grow to a size of more than 6–8 cm, they are considered cancerous and thus become a risk of hepatocellular carcinoma.

Diabetics are also at risk for adenomas. Also, those individuals who abuse anabolic steroids are also at risk to develop hepatic adenomas.[4]

Although hepatocellular carcinoma most commonly affects adults, children who are affected with biliary atresia, infantile cholestasis, glycogen-storage diseases, and other cirrhotic diseases of the liver are predisposed to developing hepatocellular carcinoma.

Children and adolescents are unlikely to have chronic liver disease, however, if they suffer from congenital liver disorders, this fact increases the chance of developing hepatocellular carcinoma.[5]

-Signs and symptoms

HCC may present with jaundice, bloating from ascites, easy bruising from blood clotting abnormalities or as loss of appetite, unintentional weight loss, abdominal pain,especially in the upper -right part, nausea, emesis, or fatigue.[6]

-Pathogenesis

Main article: Carcinogenesis

Hepatocellular carcinoma, like any other cancer, develops when there is a mutation to the cellular machinery that causes the cell to replicate at a higher rate and/or results in the cell avoiding apoptosis. In particular, chronic infections of hepatitis B and/or C can aid the development of hepatocellular carcinoma by repeatedly causing the body's own immune system to attack the liver cells, some of which are infected by the virus, others merely bystanders. While this constant cycle of damage followed by repair can lead to mistakes during repair which in turn lead to carcinogenesis, this hypothesis is more applicable, at present, to hepatitis C. Chronic hepatitis C causes HCC through the stage of cirrhosis. In chronic hepatitis B, however, the integration of the viral genome into infected cells can directly induce a non-cirrhotic liver to develop HCC. Alternatively, repeated consumption of large amounts of ethanol can have a similar effect. Besides, cirrhosis is commonly caused by alcoholism, chronic hepatitis B and chronic hepatitis C. The toxin aflatoxin from certain Aspergillus species of fungus is a carcinogen and aids carcinogenesis of hepatocellular cancer by building up in the liver. The combined high prevalence of rates of aflatoxin and hepatitis B in settings like China and West Africa has led to relatively high rates of heptatocellular carcinoma in these regions. Other viral hepatitides such as hepatitis A have no potential to become a chronic infection and thus are not related to hepatocellular carcinoma.

-Diagnosis

Hepatocellular carcinoma (HCC) most commonly appears in a patient with chronic viral hepatitis (hepatitis B or hepatitis C, 20%) or/and with cirrhosis (about 80%). These patients commonly undergo surveillance with ultrasound due to the cost-effectiveness.

In patients with a higher suspicion of HCC (such as rising alpha-fetoprotein and des-gamma carboxyprothrombin levels), the best method of diagnosis involves a CT scan of the abdomen using intravenous contrast agent and three-phase scanning (before contrast administration, immediately after contrast administration, and again after a delay) to increase the ability of the radiologist to detect small or subtle tumors. It is important to optimize the parameters of the CT examination, because the underlying liver disease that most HCC patients have can make the findings more difficult to appreciate.

On CT, HCC can have three distinct patterns of growth:

A single large tumor

Multiple tumors

Poorly defined tumor with an infiltrative growth pattern

A biopsy is not needed to confirm the diagnosis of HCC if certain imaging criteria are met.

The key characteristics on CT are hypervascularity in the arterial phase scans, washout or de-enhancement in the portal and delayed phase studies, a pseudocapsule and a mosaic pattern. Both calcifications and intralesional fat may be appreciated.

CT scans use contrast agents, which are typically iodine or barium based. Some patients are allergic to one or both of these contrast agents, most often iodine. Usually the allergic reaction is manageable and not life threatening.

An alternative to a CT imaging study would be the MRI. MRI's are more expensive and not as available because fewer facilities have MRI machines. More important MRI are just beginning to be used in tumor detection and fewer radiologists are skilled at finding tumors with MRI studies when it is used as a screening device. Mostly the radiologists are using MRIs to do a secondary study to look at an area where a tumor has already been detected. MRI's also use contrast agents. One of the best for showing details of liver tumors is very new: iron oxide nano-particles appears to give better results. The latter are absorbed by normal liver tissue, but not tumors or scar tissue.

In a review article of the screening, diagnosis and treatment of hepatocellular carcinoma, 4 articles were selected for comparing the accuracy of CT and MRI in diagnosing this malignancy.[7] Radiographic diagnosis was verified against post-transplantation biopsy as the gold standard. With the exception of one instance of specificity, it was discovered that MRI was more sensitive and specific than CT in all four studies.

-Pathology

Micrograph of hepatocellular carcinoma. Liver biopsy. Trichrome stain.Macroscopically, liver cancer appears as a nodular or infiltrative tumor. The nodular type may be solitary (large mass) or multiple (when developed as a complication of cirrhosis). Tumor nodules are round to oval, grey or green (if the tumor produces bile), well circumscribed but not encapsulated. The diffuse type is poorly circumscribed and infiltrates the portal veins, or the hepatic veins (rarely).

Microscopically, there are four architectural and cytological types (patterns) of hepatocellular carcinoma: fibrolamellar, pseudoglandular (adenoid), pleomorphic (giant cell) and clear cell. In well differentiated forms, tumor cells resemble hepatocytes, form trabeculae, cords and nests, and may contain bile pigment in cytoplasm. In poorly differentiated forms, malignant epithelial cells are discohesive, pleomorphic, anaplastic, giant. The tumor has a scant stroma and central necrosis because of the poor vascularization.[8]

-Staging

Important features that guide treatment include: -

size

spread (stage)

involvement of liver vessels

presence of a tumor capsule

presence of extrahepatic metastases

presence of daughter nodules

vascularity of the tumor

MRI is the best imaging method to detect the presence of a tumor capsule.

-Management

This article's factual accuracy may be compromised because of out-of-date information. Please help improve the article by updating it. There may be additional information on the talk page. (January 2010)

Liver transplantation to replace the diseased liver with a cadaveric liver or a living donor graft. Historically low survival rates (20%-36%). During 1996–2001 the rate had improved to 61.1% , likely related to adoption of the Milan criteria at US transplantation centers. Expanded Shanghai criteria in China resulted in overall survival and disease-free survival rates similar to the Milan criteria[9]. Studies from the late 2000 obtained higher survival rates ranging from 67% to 91%[10]. If the liver tumor has metastasized, the immuno-suppressant post-transplant drugs decrease the chance of survival. Considering this objective risk in conjunction with the potentially high rate of survival, some recent studies conclude that: "LTx can be a curative approach for patients with advanced HCC without extrahepatic metastasis"[11]. For those reasons, and others, it is considered nowadays that patient selection is a major key for success[12].

Surgical resection to remove a tumor together with surrounding liver tissue while preserving enough liver remnant for normal body function. This treatment offers the best prognosis for long-term survival, but unfortunately only 10-15% of patients are suitable for surgical resection. This is often due to extensive disease or poor liver function. Resection in cirrhotic patients carries high morbidity and mortality. The expected liver remnant should be more than 25% of the total size for a non-cirrhotic liver, while that should be more than 40% of the total size for a cirrhotic liver. The overall recurrent rate after resection is 50-60%.

Percutaneous ethanol injection (PEI) well tolerated, high RR in small (<3 cm) solitary tumors; as of 2005, no randomized trial comparing resection to percutaneous treatments; recurrence rates similar to those for postresection.

Transcatheter arterial chemoembolization (TACE) is usually performed for unresectable tumors or as a temporary treatment while waiting for liver transplant. TACE is done by injecting an antineoplastic drug (e.g. cisplatin) mixed with a radioopaque contrast (e.g. Lipiodol) and an embolic agent (e.g. Gelfoam) into the right or left hepatic artery via the groin artery. As of 2005, multiple trials show objective tumor responses and slowed tumor progression but questionable survival benefit compared to supportive care; greatest benefit seen in patients with preserved liver function, absence of vascular invasion, and smallest tumors. TACE is not suitable for big tumors (>8 cm), presence of portal vein thrombus, tumors with portal-systemic shunt and patients with poor liver function.

Radiofrequency ablation (RFA) uses high frequency radio-waves to destroy tumor by local heating. The electrodes are inserted into the liver tumor under ultrasound image guidance using percutaneous, laparoscopic or open surgical approach. It is suitable for small tumors (<5 cm). A large randomised trial comparing surgical resection and RFA for small HCC showed similar 4 years-survival and less morbidities for patients treated with RFA.[13]

Selective internal radiation therapy can be used to destroy the tumor from within (thus minimizing exposure to healthy tissue). There are currently two products available, SIR-Spheres and TheraSphere The latter is an FDA approved treatment for primary liver cancer (HCC) which has been shown in clinical trials to increase survival rate of low-risk patients. SIR-Spheres are FDA approved for the treatment of metastatic colorectal cancer but outside the US SIR-Spheres are approved for the treatment of any non-resectable liver cancer including primary liver cancer. This method uses a catheter (inserted by a radiologist) to deposit radioactive particles to the area of interest.

Intra-arterial iodine-131–lipiodol administration Efficacy demonstrated in unresectable patients, those with portal vein thrombus. This treatment is also used as adjuvant therapy in resected patients (Lau at et, 1999). It is believed to raise the 3-year survival rate from 46 to 86%. This adjuvant therapy is in phase III clinical trials in Singapore and is available as a standard medical treatment to qualified patients in Hong Kong.

Combined PEI and TACE can be used for tumors larger than 4 cm in diameter, although some Italian groups have had success with larger tumours using TACE alone.

High intensity focused ultrasound (HIFU) (not to be confused with normal diagnostic ultrasound) is a new technique which uses much more powerful ultrasound to treat the tumour. Still at a very experimental stage. Most of the work has been done in China. Some early work is being done in Oxford and London in the UK.

Hormonal therapy Antiestrogen therapy with tamoxifen studied in several trials, mixed results across studies, but generally considered ineffective Octreotide (somatostatin analogue) showed 13-month MS v 4-month MS in untreated patients in a small randomized study; results not reproduced.

Adjuvant chemotherapy: No randomized trials showing benefit of neoadjuvant or adjuvant systemic therapy in HCC; single trial showed decrease in new tumors in patients receiving oral synthetic retinoid for 12 months after resection/ablation; results not reproduced. Clinical trials have varying results.[14]

Palliative: Regimens that included doxorubicin, cisplatin, fluorouracil, interferon, epirubicin, or taxol, as single agents or in combination, have not shown any survival benefit (RR, 0%-25%); a few isolated major responses allowed patients to undergo partial hepatectomy; no published results from any randomized trial of systemic chemotherapy.

Cryosurgery: Cryosurgery is a new technique that can destroy tumors in a variety of sites (brain, breast, kidney, prostate, liver). Cryosurgery is the destruction of abnormal tissue using sub-zero temperatures. The tumor is not removed and the destroyed cancer is left to be reabsorbed by the body. Initial results in properly selected patients with unresectable liver tumors are equivalent to those of resection. Cryosurgery involves the placement of a stainless steel probe into the center of the tumor. Liquid nitrogen is circulated through the end of this device. The tumor and a half inch margin of normal liver are frozen to -190°C for 15 minutes, which is lethal to all tissues. The area is thawed for 10 minutes and then re-frozen to -190°C for another 15 minutes. After the tumor has thawed, the probe is removed, bleeding is controlled, and the procedure is complete. The patient will spend the first post-operative night in the intensive care unit and typically is discharged in 3 – 5 days. Proper selection of patients and attention to detail in performing the cryosurgical procedure are mandatory in order to achieve good results and outcomes. Frequently, cryosurgery is used in conjunction with liver resection as some of the tumors are removed while others are treated with cryosurgery. Patients may also have insertion of a hepatic intra-arterial catheter for post-operative chemotherapy. As with liver resection, the surgeon should have experience with cryosurgical techniques in order to provide the best treatment possible.

There is a new drug Sorafenib which was originally used for Renal Cell Cancer that has shown promising results when used with Hepatocellular Cancer

Interventional radiology

Agaricus blazei mushrooms inhibited abnormal collagen fiber formation in human hepatocarcinoma cells in an in vitro experiment.[15]

Abbreviations: HCC, hepatocellular carcinoma; TACE, transarterial embolization/chemoembolization; PFS, progression-free survival; PS, performance status; HBV, hepatitis B virus; PEI, percutaneous ethanol injection; RFA, radiofrequency ablation; RR, response rate; MS, median survival.

A systematic review assessed 12 articles involving a total of 318 patients with hepatocellular carcinoma treated with Yttrium-90 radioembolization.[16] Excluding a study of only one patient, post-treatment CT evaluation of the tumor showed a response ranging from 29 to 100 % of patients evaluated, with all but two studies showing a response of 71 % or greater.

A group of researchers studied the use of Sorafenib in patients with advanced hepatocellular carcinoma. Sorafenib is a small molecule that inhibits tumor-cell proliferation and tumor angionesis. It also increases the rate of apoptosis in other tumor models. The results indicated that single-agent sorafenib might have a beneficial therapeutic effect. In this study, for instance, the median overall survival was of 9.2 months and the median time to progression was of 5.5 months. Also, the survival benefit represented a 31% relative reduction in the risk of death.[17]

-Prevention

Since hepatitis B or C is one of the main causes of hepatocellular carcinoma, prevention of this infection is key to then prevent hepatocellular carcinoma. Thus, childhood vaccination against hepatitis B may reduce the risk of liver cancer in the future.[18]

In the case of patients with cirrhosis, alcohol consumption is to be avoided. Also, screening for hemochromatosis may be beneficial for some patients.[19]

-Prognosis

Please help improve this article by expanding it. Further information might be found on the talk page. (January 2010)

The usual outcome is poor, because only 10 - 20%[citation needed] of hepatocellular carcinomas can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually fatal within 3 – 6 months. However, survival can vary, and occasionally people will survive much longer than 6 months. The prognosis for metastatic or unresectable hepatocellular carcinoma has recently improved due to the approval of nexavar for advanced hepatocellular carcinoma.

-Epidemiology

Age-standardized death from liver cancer per 100,000 inhabitants in 2004.[20]

no data

less than 7.5

7.5-15

15-22.5

22.5-30

30-37.5

37.5-45

45-52.5

52.5-60

60-67.5

67.5-75

75-110

more than 110HCC is one of the most common tumors worldwide. The epidemiology of HCC exhibits two main patterns, one in North America and Western Europe and another in non-Western countries, such as those in sub-Saharan Africa, central and Southeast Asia, and the Amazon basin. Males are affected more than females usually and it is most common between the age of 30 to 50[1] Hepatocellular carcinoma causes 662,000 deaths worldwide per year[21], about half of them in China.

-Non-Western Countries

In some parts of the world, such as sub-Saharan Africa and Southeast Asia, HCC is the most common cancer, generally affecting men more than women, and with an age of onset between late teens and 30s. This variability is in part due to the different patterns of hepatitis B and hepatitis C transmission in different populations - infection at or around birth predispose to earlier cancers than if people are infected later. The time between hepatitis B infection and development into HCC can be years, even decades, but from diagnosis of HCC to death the average survival period is only 5.9 months according to one Chinese study during the 1970-80s, or 3 months (median survival time) in Sub-Saharan Africa according to Manson's textbook of tropical diseases. HCC is one of the deadliest cancers in China where chronic hepatitis B is found in 90% of cases. In Japan, chronic hepatitis C is associated with 90% of HCC cases. Food infected with Aspergillus flavus (especially peanuts and corns stored during prolonged wet seasons) which produces aflatoxin poses another risk factor for HCC.

-North America and Western Europe

Most malignant tumors of the liver discovered in Western patients are metastases (spread) from tumors elsewhere.[1] In the West, HCC is generally seen as a rare cancer, normally of those with pre-existing liver disease. It is often detected by ultrasound screening, and so can be discovered by health-care facilities much earlier than in developing regions such as Sub-Saharan Africa.

Acute and chronic hepatic porphyrias (acute intermittent porphyria, porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria) and tyrosinemia type I are risk factors for hepatocellular carcinoma. The diagnosis of an acute hepatic porphyria (AIP, HCP, VP) should be sought in patients with hepatocellular carcinoma without typical risk factors of hepatitis B or C, alcoholic liver cirrhosis or hemochromatosis. Both active and latent genetic carriers of acute hepatic porphyrias are at risk for this cancer, although latent genetic carriers have developed the cancer at a later age than those with classic symptoms. Patients with acute hepatic porphyrias should be monitored for hepatocellular carcinoma.

-Research

Current research includes the search for the genes that are disregulated in HCC,[22] protein markers,[23] and other predictive biomarkers.[24][25] As similar research is yielding results in various other malignant diseases, it is hoped that identifying the aberrant genes and the resultant proteins could lead to the identification of pharmacological interventions for HCC.[26]

-References

- a b c Kumar V, Fausto N, Abbas A (editors) (2003). Robbins & Cotran Pathologic Basis of Disease (7th ed.). Saunders. pp. 914–7. ISBN 978-0-721-60187-8.

- Hepatocellular carcinoma MedlinePlus, Medical Encyclopedia

- http://content.nejm.org/cgi/content/abstract/359/4/378

- "Hepatocellular Carcinoma and Diseases". http://www.hepatocellular.org/. Retrieved May 12, 2010.

- "Pathophysiology". http://emedicine.medscape.com/article/986988-overview. Retrieved May 12, 2010.

- http://www.mayoclinic.com/health/liver-cancer/DS00399/DSECTION=symptoms

- El-Serag HB, Marrero JA, Rudolph L, Reddy KR (May 2008). "Diagnosis and treatment of hepatocellular carcinoma". Gastroenterology 134 (6): 1752–63. doi:10.1053/j.gastro.2008.02.090. PMID 18471552. http://linkinghub.elsevier.com/retrieve/pii/S0016-5085(08)00426-5.

- Hepatocellular carcinoma (Photo) ATLAS OF PATHOLOGY

- Jia Fan; Guang-Shun Yang; Zhi-Ren Fu; Zhi-Hai Peng; Qiang Xia; Chen-Hong Peng; Jian Zhou; Yang Xu et al. (2009). "Liver transplantation outcomes in 1,078 hepatocellular carcinoma patients: a multi-center experience in Shanghai, China". Journal of Cancer Research and Clinical Oncology 135 (10): 1403-1412. doi:10.1007/s00432-009-0584-6. http://www.springerlink.com/content/m20156148046t6g8/fulltext.pdf.

- Vitale, Alessandro; Gringeri, Enrico; Valmasoni, Michele; D'Amico, Francesco; Carraro, Amedeo; Pauletto, Antonio; D'Amico, Francesco Jr.; Polacco, Marina; D'Amico, Davide Francesco; Cillo, Umberto (2007). "Longterm results of liver transplantation for hepatocellular carcinoma: an update of the University of Padova experience". Transplantation Proceedings 39 (6): 1892-1894. doi:10.1016/j.transproceed.2007.05.031. http://cat.inist.fr/?aModele=afficheN&cpsidt=19021177.

- Aiman Obed; Tung-Yu Tsui; Andreas A. Schnitzbauer; Manal Obed; Hans J. Schlitt; Heinz Becker; Thomas Lorf (2009). "Liver transplantation as curative approach for advanced hepatocellular carcinoma: is it justified?". Langenbeck's Archives of Surgery 393 (2): 147-141. doi:10.1007/s00423-007-0250-x. http://www.springerlink.com/content/em42670j1802m171/fulltext.pdf.

- Liver Transplantation for Hepatocellular Carcinoma: Need for a New Patient Selection Strategy. 240. 2004. pp. 924-925. doi:10.1007/s00423-007-0250-x. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1356504/.

- Chen, Min-Shan; Li, Jin-Qing; Zheng, Yun; Guo, Rong-Ping; Liang, Hui-Hong; Zhang, Ya-Qi; Lin, Xiao-Jun; Lau, Wan Y (2006). "A Prospective Randomized Trial Comparing Percutaneous Local Ablative Therapy and Partial Hepatectomy for Small Hepatocellular Carcinoma". Annals of Surgery 243 (3): 321–8. doi:10.1097/01.sla.0000201480.65519.b8. PMID 16495695.

- American Society of Clinical Oncology, 2005 Annual Meeting, Abstracts on Hepatobiliary Cancer

- Sorimachi, K; Akimoto, K; Koge, T (2008). "Inhibitory effect of Agaricus blazei Murill components on abnormal collagen fiber formation in human hepatocarcinoma cells". Biosci Biotechnol Biochem 72 (2): 621–3. doi:10.1271/bbb.70700. PMID 18256462

- Vente MA, Wondergem M, van der Tweel I, et al (April 2009). "Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis". Eur Radiol 19 (4): 951–9. doi:10.1007/s00330-008-1211-7. PMID 18989675.

- "Sorafenib in Advanced Hepatocellular Carcinoma". http://content.nejm.org/cgi/content/full/359/4/378. Retrieved May 12, 2010.

- "Hepatocellular carcinoma". https://health.google.com/health/ref/Hepatocellular+carcinoma. Retrieved May 12, 2010.

- "Prevention". http://www.nlm.nih.gov/medlineplus/ency/article/000280.htm. Retrieved May 12, 2010.

- "WHO Disease and injury country estimates". World Health Organization. 2009. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved Nov. 11, 2009.

- "Cancer". World Health Organization. February 2006. http://www.who.int/mediacentre/factsheets/fs297/en/. Retrieved 2007-05-24.

- Genetic research in HCC Stanford Asian Liver Center

- Huntington Medical Research Institute News, May 2005

- Journal of Clinical Oncology, Special Issue on Molecular Oncology: Receptor-Based Therapy, April 2005

- Lau W, Leung T, Ho S, Chan M, Machin D, Lau J, Chan A, Yeo W, Mok T, Yu S, Leung N, Johnson P (1999). "Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial". Lancet 353 (9155): 797–801. doi:10.1016/S0140-6736(98)06475-7. PMID 10459961.

- Thomas M, Zhu A (2005). "Hepatocellular carcinoma: the need for progress". J Clin Oncol 23 (13): 2892–9. doi:10.1200/JCO.2005.03.196. PMID 15860847. http://www.jco.org/cgi/content/full/23/13/2892.

regards

Prof. Mohammed Abdulwahab AlKhateeb

-MD.,FICMS.,-INTERNAL MEDICINE - IRAQ - BAGHDAD,1993.

-Membership in international society of Iraqi scientists - MISIS - USA

-Active membership of New York Academy of Scientists)-AMNYAS-USA, 1984.

-European Society of digestive Oncology - ESDO MEMBERSHIP-AUSTERIA

-Acive membership of American Cancer Society / Cancer Survivors Network-USA. (http://csn.cancer.org/user/130076)

-Mayoclinic center health responder (physicianupdate.mayoclinic.org) & sharing.mayoclinic.org)-USA.

-Membership and Founder of "internal medicine & Clinical Pharmacology group" in ResearchGate – USA, (http://www.researchgate.net/profile/Mohammed_Alkhateeb/ )

-NOW WORKING IN ERBIL/IRAQ

…

Acute coronary syndrome (ACS)-news-internal medicine-part-3-

Question

Nov 2010

Acute coronary syndrome (ACS)

is usually one of three diseases that involved the coronary arteries: ST elevation myocardial infarction (30%), non ST elevation myocardial infarction (25%), or unstable angina (38%).[1]

These types are named according to the appearance of the electrocardiogram (ECG/EKG) as non-ST segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI).[2] There can be some variation as to which forms of MI are classified under acute coronary syndrome.[3]

ACS should be distinguished from stable angina, which develops during exertion and resolves at rest. In contrast with stable angina, unstable angina occurs suddenly, often at rest or with minimal exertion, or at lesser degrees of exertion than the individual's previous angina ("crescendo angina"). New onset angina is also considered unstable angina, since it suggests a new problem in a coronary artery.

Though ACS is usually associated with coronary thrombosis, it can also be associated with cocaine use.[4] Cardiac chest pain can also be precipitated by anemia, bradycardias (excessively slow heart rate) or tachycardias (excessively fast heart rate).

-Signs and symptoms

The cardinal sign of decreased blood flow to the heart is chest pain experienced as tightness around the chest and radiating to the left arm and the left angle of the jaw. This may be associated with diaphoresis (sweating), nausea and vomiting, as well as shortness of breath. In many cases, the sensation is "atypical", with pain experienced in different ways or even being completely absent (which is more likely in female patients and those with diabetes). Some may report palpitations, anxiety or a sense of impending doom and a feeling of being acutely ill.

The description of the chest discomfort as a pressure has little utility in aiding a diagnosis as it is not specific for ACS.[5]

-Diagnosis

Classification of acute coronary syndromes.[6]-Electrocardiogram

In the setting of acute chest pain, the electrocardiogram is the investigation that most reliably distinguishes between various causes.[7] If this indicates acute heart damage (elevation in the ST segment, new left bundle branch block), treatment for a heart attack in the form of angioplasty or thrombolysis is indicated immediately (see below). In the absence of such changes, it is not possible to immediately distinguish between unstable angina and NSTEMI.

-Imaging and blood tests

As it is only one of the many potential causes of chest pain, the patient usually has a number of tests in the emergency department, such as a chest X-ray, blood tests (including myocardial markers such as troponin I or T, and a D-dimer if a pulmonary embolism is suspected), and telemetry (monitoring of the heart rhythm).

-Prediction scores

The ACI-TIPI score can be used to aid diagnosis; using 7 variables from the admission record, this score predicts crudely which patients are likely to have myocardial ischemia.[8] For example according to a randomized controlled trial, males having chest pain with normal or non diagnostic ECG are at higher risk for having acute coronary syndrome than women. [9] In this study, the sensitivity was 65.2% and specificity was 44%. This particular study had an 8.4% prevalence of acute coronary syndrome, which means the positive predictive value of being a male with chest pain and having coronary syndrome is 9.6% and negative predictive value is 93.2% ( click here to adjust these results for patients at higher or lower risk of acute coronary syndrome).

In a second cohort study, exercise electrocardiography was similarly found to be a poor predictor of acute coronary syndrome at follow-up. [10] Of the patients who had a coronary event at 6 years of follow up, 47% had a negative ECG at the start of the study. With an average follow up of 2.21 years the receiver operating characteristic curves gave resting ECG a score of 0.72 and exercise ECG a score of 0.74.

-Prevention

Acute coronary syndrome often reflects a degree of damage to the coronaries by atherosclerosis. Primary prevention of atherosclerosis is controlling the risk factors: healthy eating, exercise, treatment for hypertension and diabetes, avoiding smoking and controlling cholesterol levels; in patients with significant risk factors, aspirin has been shown to reduce the risk of cardiovascular events. Secondary prevention is discussed in myocardial infarction.

After a ban on smoking in all enclosed public places was introduced in Scotland in March 2006, there was a 17 percent reduction in hospital admissions for acute coronary syndrome. 67% of the decrease occurred in non-smokers.[11]

-Treatment

-STEMI

Main article: Myocardial infarction

If the ECG confirms changes suggestive of myocardial infarction (ST elevations in specific leads, a new left bundle branch block or a true posterior MI pattern), thrombolytics may be administered or primary coronary angioplasty may be performed. In the former, medication is injected that stimulates fibrinolysis, destroying blood clots obstructing the coronary arteries. In the latter, a flexible catheter is passed via the femoral or radial arteries and advanced to the heart to identify blockages in the coronaries. When occlusions are found, they can be intervened upon mechanically with angioplasty and usually stent deployment if a lesion, termed the culprit lesion, is thought to be causing myocardial damage. Data suggest that rapid triage, transfer and treatment is essential.[12] The time frame for door-to-needle thrombolytic administration according to American College of Cardiology (ACC) guidelines should be within 30 minutes, whereas the door-to-balloon Percutaneous Coronary Intervention (PCI) time should be less than 90 minutes. It was found that thrombolysis is more likely to be delivered within the established ACC guidelines among patients with STEMI as compared to PCI according to a case control study . [13]

-NSTEMI and NSTE-ACS

If the ECG does not show typical changes, the term "non-ST segment elevation ACS" is applied. The patient may still have suffered a "non-ST elevation MI" (NSTEMI). The accepted management of unstable angina and acute coronary syndrome is therefore empirical treatment with aspirin, heparin (usually a low-molecular weight heparin such as enoxaparin) and clopidogrel, with intravenous glyceryl trinitrate and opioids if the pain persists.

A blood test is generally performed for cardiac troponins twelve hours after onset of the pain. If this is positive, coronary angiography is typically performed on an urgent basis, as this is highly predictive of a heart attack in the near-future. If the troponin is negative, a treadmill exercise test or a thallium scintigram may be requested.

If there is no evidence of ST segment elevation on the electrocardiogram, delaying urgent angioplasty until the next morning is not inferior to doing so immediately.[14]

In a cohort study comparing NSTEMI and STEMI, patients with NSTEMI had statistically similar mortality at one year after PCI as compared to patients with STEMI (3.4% vs 4.4%). [15] However, NSTEMI had significantly more "major cardiac events" (death, myocardial infarction, disabling stroke, or requiring revascularization) at one year (24.0% vs 16.6%).

Cocaine associated ACS should be managed in a manner similar to other patients with acute coronary syndrome except beta blockers should not be used and benzodiazepines should be administered early.[16]

-Prognosis

-TIMI score

The TIMI risk score can identify high risk patients[17] and has been independently validated.[18][19]

-Biomarkers for diagnosis

The aim of diagnostic markers is to identify patients with ACS even when there is no evidence of heart muscle damage.

Ischemia-Modified Albumin (IMA) - In cases of Ischemia - Albumin undergoes a conformational change and loses its ability to bind transitional metals (copper or cobalt). IMA can be used to assess the proportion of modified albumin in ischemia. Its use is limited to ruling out ischemia rather than a diagnostic test for the occurrence of ischemia.

Myeloperoxidase (MPO) - The levels of circulating MPO, a leukocyte enzyme, elevate early after ACS and can be used as an early marker for the condition.

Glycogen Phosphorylase Isoenzyme BB-(GPBB) is an early marker of cardiac ischemia and is one of three isoenzyme of Glycogen Phosphorylase.

Troponin is a late cardiac marker of ACS

-Biomarkers for Risk Stratification

The aim of prognostic markers is to reflect different components of pathophysiology of ACS. For example:

Natriuretic peptide - Both B-type natriuretic peptide (BNP) and N-terminal Pro BNP can be applied to predict the risk of death and heart failure following ACS.

Monocyte chemo attractive protein (MCP)-1 - has been shown in a number of studies to identify patients with a higher risk of adverse outcomes after ACS.

-References

This article needs additional citations for verification.

Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (January 2008)

- Torres M, Moayedi S (May 2007). "Evaluation of the acutely dyspneic elderly patient". Clin. Geriatr. Med. 23 (2): 307–25, vi. doi:10.1016/j.cger.2007.01.007. PMID 17462519.

- Grech ED, Ramsdale DR (June 2003). "Acute coronary syndrome: unstable angina and non-ST segment elevation myocardial infarction". BMJ 326 (7401): 1259–61. doi:10.1136/bmj.326.7401.1259. PMID 12791748. PMC 1126130. http://bmj.com/cgi/pmidlookup?view=long&pmid=12791748.

- "Dorlands Medical Dictionary:acute coronary syndrome". http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?pg=/ppdocs/us/common/dorlands/dorland/nine/14170699.htm.

- Achar SA, Kundu S, Norcross WA (2005). "Diagnosis of acute coronary syndrome". Am Fam Physician 72 (1): 119–26. PMID 16035692. http://www.aafp.org/afp/20050701/119.html.

- Woo KM, Schneider JI (November 2009). "High-risk chief complaints I: chest pain--the big three". Emerg. Med. Clin. North Am. 27 (4): 685–712, x. doi:10.1016/j.emc.2009.07.007. PMID 19932401.

- Alpert JS, Thygesen K, Antman E, Bassand JP. (2000). "Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction". J Am Coll Cardiol 36 (3): 959–69. doi:10.1016/S0735-1097(00)00804-4. PMID 10987628.

- Chun AA, McGee SR (2004). "Bedside diagnosis of coronary artery disease: a systematic review". Am. J. Med. 117 (5): 334–43. doi:10.1016/j.amjmed.2004.03.021. PMID 15336583.

- Selker HP, Griffith JL, D'Agostino RB (1991). "A tool for judging coronary care unit admission appropriateness, valid for both real-time and retrospective use. A time-insensitive predictive instrument (TIPI) for acute cardiac ischemia: a multicenter study". Medical care 29 (7): 610–27. PMID 2072767.

- Goodacre, S; Pett, P; Arnold, J; Chawla, A; Hollingsworth, J; Roe, D; Crowder, S; Mann, C et al. (2009). "Clinical diagnosis of acute coronary syndrome in patients with chest pain and a normal or non-diagnostic electrocardiogram.". Emergency medicine journal : EMJ 26 (12): 866–70. doi:10.1136/emj.2008.064428. PMID 19934131.

- Sekhri, N; Feder, GS; Junghans, C; Eldridge, S; Umaipalan, A; Madhu, R; Hemingway, H; Timmis, AD (2008). "Incremental prognostic value of the exercise electrocardiogram in the initial assessment of patients with suspected angina: cohort study.". BMJ(Clinical research ed.) 337: a2240. doi:10.1136/bmj.a2240. PMID 19008264.

- Pell JP, Haw S, Cobbe S et al. (2008). "Smoke-free Legislation and Hospitalizations for Acute Coronary Syndrome". New England Journal of Medicine 359 (5): 482. doi:10.1056/NEJMsa0706740. PMID 18669427.

- Blankenship JC and Skelding KA. Rapid Triage, Transfer, and Treatment with Percutaneous Coronary Intervention for Patients with ST-Segment Elevation Myocardial Infarction. Acute Coronary Syndromes. 2008;9(2):59–65

- Janda, SP; Tan, N (2009). "Thrombolysis versus primary percutaneous coronary intervention for ST elevation myocardial infarctions at Chilliwack General Hospital.". The Canadian journal of cardiology 25 (11): e382–4. PMID 19898701.

- Montalescot G, Cayla G, Collet JP, Elhadad S, Beygui F, Le Breton H et al. (2009). "Immediate vs delayed intervention for acute coronary syndromes: a randomized clinical trial.". JAMA 302 (9): 947-54. doi:10.1001/jama.2009.1267. PMID 19724041.

- Cox, DA; Stone, GW; Grines, CL; Stuckey, T; Zimetbaum, PJ; Tcheng, JE; Turco, M; Garcia, E et al. (2006). "Comparative early and late outcomes after primary percutaneous coronary intervention in ST-segment elevation and non-ST-segment elevation acute myocardial infarction (from the CADILLAC trial).". The American journal of cardiology 98 (3): 331–7. doi:10.1016/j.amjcard.2006.01.102. PMID 16860018.

- McCord J, Jneid H, Hollander JE, et al. (April 2008). "Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology". Circulation 117 (14): 1897–907. doi:10.1161/CIRCULATIONAHA.107.188950. PMID 18347214.

- Antman EM, Cohen M, Bernink PJ, et al. (2000). "The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making". JAMA 284 (7): 835–42. doi:10.1001/jama.284.7.835. PMID 10938172.

- Pollack CV, Sites FD, Shofer FS, Sease KL, Hollander JE (2006). "Application of the TIMI risk score for unstable angina and non-ST elevation acute coronary syndrome to an unselected emergency department chest pain population". Academic emergency medicine : official journal of the Society for Academic Emergency Medicine 13 (1): 13–8. doi:10.1197/j.aem.2005.06.031. PMID 16365321.

- Chase M, Robey JL, Zogby KE, Sease KL, Shofer FS, Hollander JE (2006). "Prospective validation of the Thrombolysis in Myocardial Infarction Risk Score in the emergency department chest pain population". Annals of emergency medicine 48 (3): 252–9. doi:10.1016/j.annemergmed.2006.01.032. PMID 16934646.

regards

Prof. Mohammed Abdulwahab AlKhateeb

-MD.,FICMS.,-INTERNAL MEDICINE - IRAQ - BAGHDAD,1993.

-Membership in international society of Iraqi scientists-MISIS- Detroit,Michigan,USA (http://www.issiraq.org/ISSMembers/ISSMembers.htm)

-Active membership of New York Academy of Scientists)-AMNYAS-USA, 1984.

-European Society of digestive Oncology - ESDO MEMBERSHIP-AUSTERIA

-Acive membership of American Cancer Society / Cancer Survivors Network-USA. (http://csn.cancer.org/user/130076)

-Mayoclinic center health responder (physicianupdate.mayoclinic.org) & sharing.mayoclinic.org)-USA.

-Membership and Founder of "internal medicine & Clinical Pharmacology group" in ResearchGate – USA, (http://www.researchgate.net/profile/Mohammed_Alkhateeb2/ )

-Membership of Cancer Survivors Network society (http://csn.cancer.org/node/203981)

-WIKIDOC-Internal medicine & clinical pharmacology - Editor-In-Chief (http://www.wikidoc.org/index.php/Internal AND http://www.wikidoc.org/index.php/Clinical_pharmacology)

-NOW WORKING IN ERBIL/IRAQ

…

Discover the world's scientific knowledge

With 160+ million publication pages, 25+ million researchers and 1+ million questions, this is where everyone can access science