Sandbox:Dildar

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]

PBC USG

There are no ultrasound findings associated with primary biliary cirrhosis. However, the ultrasound is mandatory for liver and biliary tree for all cholestatic patients for the differentiation of intrahepatic from extrahepatic cholestasis.

• The ultrasound findings may include:
  • Cholestasis
  • Abdominal lymphadenopathy

Ultrasound examination of the liver and biliary tree is obligatory in all cholestatic patients in order to differentiate intrahepatic from extrahepatic . When the biliary system appears normal and serum AMA are present, no further radiologic workup is necessary. , particularly in the hilar region of the liver, is seen in 80% of patients with PBC

PBC CT

• Findings on CT scan suggestive of advanced primary biliary cirrhosis include:
  • Small heterogeneously attenuating liver
  • Varices
  • Splenomegaly
  • Lymphadenopathy
• Findings on CT scan suggestive of less advanced disease include:
  • Enlarged or normal size liver
  • Smooth contour liver
  • Little atrophy
  • Lacelike fibrosis
  • Regenerative nodules
  • Varices
  • Ascites
  • Lymphadenopathy

Synonoms

• Solitary hyperplastic nodule
• Hepatic hamartoma
• Focal cirrhosis
• Hamartomatous cholangiohepatoma
• Hepatic pseudotumor

Historical Perspective

• In early 1900s,Focal nodular hyperplasia was first described.
• Between 1918-1982,96.625 autopsy studies were conducted out of which 8 percent of nonhemangiomatous lesions were focal nodular hyperplasia.
• In 1994,Working party of the world congresses of gastroenterology suggested a standardized terminology of nodular hepatic lesions that placed Focal noduldar carcinoma in the group of regenerative nodules, as opposed to dysplastic or neoplastic nodules.

Differentiating Focal nodular hyperplasia from Other diseases

Focal nodular hyperplasia must be differentiated from:

• Hepatocellular carcinoma
• Cholangiocarcinoma
• Pancreatic carcinoma
• Liver hemangioma
• Liver abscess
• Cirrhosis
• Inflammatory lesions

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram

Disease	Clinical manifestations													Diagnosis		Comments
	Symptoms									Signs
	Abdominal Pain	Fever	Rigors and chills	Nausea or vomiting	Jaundice	Constipation	Diarrhea	Weight loss	GI bleeding	Hypo- tension	Guarding	Rebound Tenderness	Bowel sounds	Lab Findings	Imaging
Focal nodular hyperplasia	Diffuse	±	−	−	±	−	−	+	+	−	−	−	Normal	Normal Liver function tests Normal AFP Minor elevations of Aspartate Alanine aminotransferase Alkaline phosphatase Gamma glutamyl transpeptidase	Us Multiphasic helical CT scan	Open biopsy if diagnosis can not be established
Hepatocellular carcinoma/Metastasis	RUQ	+	−	+	+	+	+	+	+	+	−	+	Normal Hyperactive if obstruction present	High levels of AFP in serum Abnormal liver function tests Thrombocytopenia	US CT MRI Liver biopsy	Other symptoms: Splenomegaly Variceal bleeding Ascites Spider nevi Asterixis
Cholangiocarcinoma	RUQ	+	−	+	+	−	−	+	−	−	−	+	Normal	Elevated CA 19-9 Increased amylase / lipase Increased stool fat content	Contrast-enhanced ultrasound CT scan Calcification Pseudocyst Dilation of main pancreatic duct MRI	Predisposes to pancreatic cancer
Pancreatic carcinoma	MidEpigastric	−	−	+	+	+	−	+	−	−	−	+	Normal	↑ Alkaline phosphatase ↑ serum bilirubin ↑ gamma-glutamyl transpeptidase ↑ CA 19-9	MDCT with PET/CT MRI EUS	Skin manifestations may include: Bullous pemphigoid Cicatricial pemphigoid Migratory superficial thrombophlebitis (classic Trousseau's syndrome) Pancreatic panniculitis
Disease	Abdominal Pain	Fever	Rigors and chills	Nausea or vomiting	Jaundice	Constipation	Diarrhea	Weight loss	GI bleeding	Hypo- tension	Guarding	Rebound Tenderness	Bowel sounds	Lab Findings	Imaging	Comments
Gallbladder cancer	Midepigastric	−	−	+	+	−	+	+	−	−	−	−	Normal	↑ Alkaline phosphatase ↑ CA 19-9	US CT MRI
Liver hemangioma	Intermittent RUQ	−	−	+	+	−	−	−	−	−	−	−	Normal	Abnormal LFTs	US Single-photon emission computerized tomography(SPECT) MRI	US will reveal hypoechoic lesions
Liver abscess	RUQ	+	−	+	+	−	−	+	−	−	−	−	Normal	Hypoalbuminemia Abnormal liver function tests	US CT
Cirrhosis	RUQ+Bloating	+	−	+	+	−	−	+	−	−	−	−	Normal	Hypoalbuminemia Prolonged PT Abnormal LFTs Hyponatremia Thrombocytopenia	US Nodular, shrunken liver Ascites	Stigmata of liver disease Cruveilhier- Baumgarten murmur
Inflammatory lesions	RUQ	±	−	+	+	−	−	−	−	−	−	−	Normal	Hypoalbuminemia Prolonged PT Abnormal LFTs Hyponatremia Thrombocytopenia	US Nodular,shrunken or coarse liver	Stigmata of liver disease

Focal Nodular Hyperplasia

FNH is typically benign, and usually no treatment is needed. Hemangiomas are the most common and are entirely benign. Treatment is unnecessary unless their expansion causes symptoms

Focal nodular hyperplasia (FNH) is a non-malignant hepatic tumor that is not of vascular origin. In one autopsy series of 96,625 patients, 8 percent of non-hemangiomatous lesions were FNH, representing 66 percent of all benign non-hemangiomatous lesions seen between 1918 and 1982 [1]. In large retrospective studies of patients referred for ultrasound and multidetector computed tomography, the prevalence of focal nodular hyperplasia was 0.2 percent and 1.6 percent, respectively [2,3].

FNH is seen in both sexes and throughout the age spectrum, although it is found predominantly in women (in a ratio of 8 or 9:1) between the ages of 20 and 50 years [4]. FNH comprises up to 2 percent of liver tumors in children [5].

This topic review will focus on the pathogenesis, clinical manifestations and management of FNH. An approach to patients presenting with a focal liver lesion is discussed separately. (See "Solid liver lesions: Differential diagnosis and evaluation".)

PATHOGENESIS — FNH has various labels: solitary hyperplastic nodule, hepatic hamartoma, focal cirrhosis, hamartomatous cholangiohepatoma, and hepatic pseudotumor. This profusion of terms epitomizes the confusion surrounding our understanding of the pathogenesis of the many conditions in which nodules of benign appearing hepatocytes are found. The International Working Party of the World Congresses of Gastroenterology proposed a standardized nomenclature in 1994, which placed FNH in the group of regenerative nodules, as opposed to dysplastic or neoplastic nodules [6]. This fits well with our current understanding of the pathogenesis of FNH. The contention that this lesion is non-neoplastic has been bolstered by the reported polyclonal origin of the hepatocytes [7], although this is disputed by others [8].

Previously considered to be a hamartoma, a neoplasm, a response to ischemia or other injury, or a focal area of regeneration, FNH is now generally accepted to be a hyperplastic (regenerative) response to hyperperfusion by the characteristic anomalous arteries found in the center of these nodules [4,9,10]. Whether vascular injury is also involved is less clear, but FNH is occasionally supplied primarily by portal venous blood due to thrombosis of the anomalous central artery [11].

The association of FNH with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease [12]) and hepatic hemangiomas strengthens the hypothesis that FNH is a congenital vascular anomaly. Two pathology studies found cavernous hemangiomas in 6.5 and 2.3 percent of patients with FNH [13,14] and an imaging study, using ultrasound and dynamic CT, found that 23 percent of FNH patients had associated hemangiomas [15]. Multiple FNH lesions have also been noted in association with hemihypertrophy and vascular malformations (Klippel-Trénaunay-Weber syndrome) [16]. FNH with similar clinical and radiographic features has been documented in identical twins supporting a role of congenital vascular anomalies in its pathogenesis and a possible genetic predisposition to the disease [17].

PATHOLOGY — FNH is most often solitary (80 to 95 percent), and usually less than 5 cm in diameter. Only 3 percent are larger than 10 cm, although FNH as large as 19 cm have been reported [1,13,18]. It has a sharp margin with no capsule and may be pedunculated. The characteristic finding is the presence of a central stellate scar (picture 1) containing an inappropriately large artery with multiple branches radiating through the fibrous septa to the periphery. These branches divide the mass into multiple small nodules or cords of normal appearing hepatocytes (picture 2). The scar-like tissues within FNH nodules are composed of abnormally large portal tracts including large feeding arteries, portal veins, and bile ducts [10].

The arteries drain into adjacent hepatic veins. This radiating, branching pattern produces the spoke and wheel image typically seen on angiography. Although normal bile ducts are absent, bile ductules derived from hepatocyte metaplasia are usually prominent, traveling along the fibrous septa (picture 3). Sinusoids and Kupffer cells are typically present, distinguishing it from hepatocellular adenoma (HA), which usually lacks bile ducts and Kupffer cells [1,13,14,18,19]. The minimal microscopic criteria for the diagnosis of classical FNH are nodular architecture, abnormal vessels, and proliferation of bile ductules [13]. Lymphocyte infiltration, canalicular bile plugs, copper deposition, and feathery degeneration of hepatocytes may suggest cholestasis and/or inactive cirrhosis. Irregular intimal fibrosis or hypertrophy of the media may be seen in large arteries and veins, at times even occluding the lumen [13,14,19]. When present, portal veins are dilated and/or stenotic [10].

Non-classical variants — Non-classical forms of FNH lack either the typical nodular architecture or vascular malformations, but always contain bile ductular proliferation. They almost always lack the characteristic central scar [13]. Three variants have been recognized:

●The most common of these, the telangiectatic type, often presents with multiple FNH. In addition to the lack of a central scar, the mass is characterized by the absence of nodular architecture and the presence of single, quite regular plates of hepatocytes separated by sinusoids fed directly by anomalous arteries [13,20]. The risk of bleeding appears to be similar to the risk observed in patients with a hepatic adenoma [21].

●A mixed hyperplastic and adenomatous form may be difficult to distinguish from HA due to its subtle vascular and bile ductular findings [13,20].

●A third histologic variant consisting of FNH with cytologic atypia resembling dysplasia of large cell type has been proposed [13].

A comprehensive pathological study of 305 lesions failed to identify a macroscopic central stellate scar in 50 percent and noted non-classical histology in 20 percent of the lesions, most showing a telangiectatic variant [13]. The surprisingly high number of lesions without a central scar was almost exclusively due to the large number of masses that had non-classical histology. Ninety-five percent of those with non-classical histology did not have a scar, whereas only 18 percent of those with classical histology lacked a scar [13]. The overall prevalence and clinical significance of these variants remains to be determined.

DIAGNOSIS — The diagnosis of FNH is usually made by demonstrating its characteristic features on imaging tests and excluding other lesions. The latter can typically be accomplished by assessment of the context in which FNH is detected and by obtaining specific radiologic and laboratory testing (table 1). The differential diagnosis includes hepatic adenoma, hepatocellular carcinoma, fibrolamellar carcinoma, cirrhosis, large regenerative nodules, hemangioma, and hypervascular metastases. (See "Solid liver lesions: Differential diagnosis and evaluation".)

Symptoms — The majority of reports have found that symptoms or signs directly attributable to FNH are infrequent. Two-thirds to three-fourths of patients are identified incidentally [18], with the mass noted at the time of surgery, on an abdominal imaging study, or at autopsy. Unlike hepatic adenomas, FNH rarely presents with acute onset of hemorrhage, necrosis, or infarction [22,23].

However, symptomatic presentations have been described. In one series, for example, abdominal discomfort or a palpable liver mass was observed in 25 percent of 41 patients [24]. Another series that included 168 patients found that 60 percent had abdominal pain and 4 percent had an abdominal mass [13]. The high number of symptomatic patients in the second report probably reflects selection bias since all of the patients were identified from pathology specimens obtained at the time of surgical resection [13].

Laboratory tests — Liver tests are most often normal although minor elevations in aspartate and alanine aminotransferase, alkaline phosphatase and gamma glutamyl transpeptidase levels may be seen [13,14,24]. The alpha-fetoprotein is normal.

Imaging tests — A confident diagnosis can usually be made through a combination of imaging modalities; tissue diagnosis is usually not required.

Ultrasonography — Although often first identified on ultrasound examination, FNH is variably hyper, hypo, or isoechoic [24] and US is able to identify the central scar in only 20 percent of cases [25]. The ultrasound characteristics are difficult to distinguish from an adenoma or malignant lesions. Power Doppler ultrasound may help differentiate the arterial flow in FNH from the venous flow in HA [24,26,27].

Contrast-enhanced ultrasonography — Several reports have described improved characterization of focal liver lesions using contrast-enhanced ultrasonography compared with standard ultrasonography [28-30]. While the approach is not approved in the United States, it is available in other countries. Test characteristics compared with other imaging modalities remain incompletely defined, although emerging data suggest its ability for differentiation among solid liver lesions is comparable with MRI [31]. (See "Contrast-enhanced ultrasound for the evaluation of liver lesions".)

CT scan — A properly timed dynamic, triphasic, helical CT scan performed without contrast, and with contrast during the hepatic arterial and portal venous phases, will often be highly suggestive of the diagnosis [32,33]. The lesion may be hypo or isodense on non-contrast imaging with the central scar identified in one-third of patients. The lesion becomes hyperdense during the hepatic arterial phase due to the arterial origin of its blood supply (image 1). FNH is generally isodense during the portal venous phase, although the central scar may become hyperdense as contrast diffuses into the scar. While characteristic of FNH, a central scar may be present in the fibrolamellar variant of HCC. (See "Epidemiology, clinical manifestations, diagnosis, and treatment of fibrolamellar carcinoma", section on 'Imaging'.)

MRI — There may be little to distinguish FNH from normal liver on standard MRI, since it is composed of the same elements as normal liver. An isointense lesion is noted on T1-weighted images, while an isointense to slightly hyperintense mass appears on T2-weighted images (image 2 and image 3) [34]. The scar typically shows high signal intensity on T2-weighted images due to vessels or edema in the scar (image 3) [35]. Gadolinium infusion produces rapid enhancement of the FNH mass due to its arterial blood supply, producing a hyperintense lesion on early films (image 2). On delayed images it becomes more isointense with respect to normal liver. The central scar enhances on delayed imaging as contrast gradually diffuses into the fibrous center of the mass [36-39]. In one study, gadolinium enhanced MRI had a sensitivity and specificity of 70 and 98 percent, respectively [24].

A relatively new MR contrast agent has been introduced into clinical use. Unlike currently used gadolinium-based contrast agents for MRI, this agent, a Gd-BOPTA chelate of Gadobenate Dimeglumine, has a dual route of elimination, through both renal and hepatobiliary excretion (image 4). Thus, it can be useful for distinguishing hepatic adenomas from focal nodular hyperplasia. (See "Solid liver lesions: Differential diagnosis and evaluation".)

Angiography — Although angiography may reveal the diagnostic "spoked wheel" appearance of FNH, its use is rarely indicated [32,40,41].

ROLE OF ORAL CONTRACEPTIVES — FNH was first described in the early 1900s, long before the advent of oral contraceptives (OCPs). It is seen in men and children who do not use OCPs and its incidence remained steady after the introduction of OCPs in 1960, in sharp contrast to the dramatic rise in the incidence of HA with the widespread use of OCPs. Thus use of OCPs is not required for the development of FNH [42-44].

On the other hand, FNH may be responsive to estrogens [11]. Patients taking OCPs tend to have larger, more vascular tumors, have more symptoms, and reports of hemorrhage or rupture in patients with FNH have all occurred in patients taking OCPs [45-48]. However, the magnitude of the risk associated with OCPs is uncertain. In a study of 216 women with FNH, use of OCPs did not appear to influence the size or number of FNH lesions or size changes (which were rare) during follow-up for an average of two years [49]. A case control trial comparing 23 women with histologically confirmed FNH to 94 controls estimated the odds ratio of OCP use to be 2.8 (95% CI, 0.8 to 9.4) for those who had ever used OCPs and 4.5 (95% CI, 1.2 to 16.9) for those who had ≥3 years of use [50].

We generally do not insist that oral contraceptives and other estrogen containing preparations should be discontinued. However, it is reasonable to obtain a follow-up imaging study in 6 to 12 months in women who continue taking these drugs.

MANAGEMENT — The natural history of FNH is one of stability and lack of complications. Lesions generally do not change over time, although they occasionally become smaller [49,51-54]. However, as mentioned above, enlargement of FNH in the setting of OCPs and during pregnancy have been reported [55]. There is no evidence for malignant transformation of FNH [13,24,56,57].

Patients who are suspected of having FNH based upon the evaluation described above should be managed conservatively [24,35,49,51,52,54,58,59]. If a diagnosis remains unclear, a liver biopsy may be helpful, but may also be misleading since only resection will be definitive [60]. Follow-up studies at three and six months will often be sufficient to confirm the stability of the lesion and its benign nature, after which no long-term follow-up is required routinely. Surgery should be reserved for the rare, very symptomatic FNH lesion, and the highly suspicious lesion, which has eluded diagnosis by all other modalities.

We generally do not insist that oral contraceptives and other estrogen containing preparations should be discontinued. However, it is reasonable to obtain a follow-up imaging study in 6 to 12 months in women who continue taking these drugs. Small FNH do not appear to pose a significant risk to a successful pregnancy [49,61], although close observation is strongly recommended and resection may be prudent for large (>8 cm) FNH.

SUMMARY AND RECOMMENDATIONS

●Focal nodular hyperplasia (FNH) is a non-malignant hepatic tumor that is not of vascular origin. It is now generally accepted to be a hyperplastic (regenerative) response to hyperperfusion by the characteristic anomalous arteries found in the center of these nodules. (See 'Pathogenesis' above.)

●FNH is most often solitary (80 to 95 percent) and usually less than 5 cm in diameter. Only 3 percent are larger than 10 cm. (See 'Pathology' above.)

●The majority of reports have found that symptoms or signs directly attributable to FNH are infrequent. (See 'Symptoms' above.)

●The diagnosis of FNH is usually made by demonstrating its characteristic features on imaging tests and excluding other lesions. The latter can typically be accomplished by assessing the context in which FNH is detected and by obtaining specific radiologic and laboratory testing (table 1). (See 'Diagnosis' above and "Solid liver lesions: Differential diagnosis and evaluation".)

●The natural history of FNH is one of stability and a lack of complications. Thus, we suggest that patients who are suspected of having FNH based upon the evaluation described above be managed conservatively (Grade 2B). (See 'Management' above.)

●FNH may be responsive to exogenous estrogens. We generally do not insist that oral contraceptives and other estrogen-containing preparations should be discontinued. However, it is reasonable to obtain a follow-up imaging study in 6 to 12 months in women who continue taking these drugs. (See 'Role of oral contraceptives' above.)

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HCC Differnetial Table

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram

Disease	Clinical manifestations													Diagnosis		Comments
	Symptoms									Signs
	Abdominal Pain	Fever	Rigors and chills	Nausea or vomiting	Jaundice	Constipation	Diarrhea	Weight loss	GI bleeding	Hypo- tension	Guarding	Rebound Tenderness	Bowel sounds	Lab Findings	Imaging
Hepatocellular carcinoma/Metastasis	RUQ	+	−	+	+	+	+	+	+	+	−	+	Normal Hyperactive if obstruction present	High levels of AFP in serum Abnormal liver function tests Thrombocytopenia	US CT MRI Liver biopsy	Other symptoms: Splenomegaly Variceal bleeding Ascites Spider nevi Asterixis
Cholangiocarcinoma	RUQ	+	−	+	+	−	−	+	−	−	−	+	Normal	Elevated CA 19-9 Increased amylase / lipase Increased stool fat content	Contrast-enhanced ultrasound CT scan Calcification Pseudocyst Dilation of main pancreatic duct MRI	Predisposes to pancreatic cancer
Pancreatic carcinoma	MidEpigastric	−	−	+	+	+	−	+	−	−	−	+	Normal	↑ Alkaline phosphatase ↑ serum bilirubin ↑ gamma-glutamyl transpeptidase ↑ CA 19-9	MDCT with PET/CT MRI EUS	Skin manifestations may include: Bullous pemphigoid Cicatricial pemphigoid Migratory superficial thrombophlebitis (classic Trousseau's syndrome) Pancreatic panniculitis
Focal nodular hyperplasia	Diffuse	±	−	−	±	−	−	+	+	−	−	−	Normal	Normal Liver function tests Normal AFP Minor elevations of Aspartate Alanine aminotransferase Alkaline phosphatase Gamma glutamyl transpeptidase	Us Multiphasic helical CT scan	Open biopsy if diagnosis can not be established
Disease	Abdominal Pain	Fever	Rigors and chills	Nausea or vomiting	Jaundice	Constipation	Diarrhea	Weight loss	GI bleeding	Hypo- tension	Guarding	Rebound Tenderness	Bowel sounds	Lab Findings	Imaging	Comments
Gallbladder cancer	Midepigastric	−	−	+	+	−	+	+	−	−	−	−	Normal	↑ Alkaline phosphatase ↑ CA 19-9	US CT MRI
Liver hemangioma	Intermittent RUQ	−	−	+	+	−	−	−	−	−	−	−	Normal	Abnormal LFTs	US Single-photon emission computerized tomography(SPECT) MRI	US will reveal hypoechoic lesions
Liver abscess	RUQ	+	−	+	+	−	−	+	−	−	−	−	Normal	Hypoalbuminemia Abnormal liver function tests	US CT
Cirrhosis	RUQ+Bloating	+	−	+	+	−	−	+	−	−	−	−	Normal	Hypoalbuminemia Prolonged PT Abnormal LFTs Hyponatremia Thrombocytopenia	US Nodular, shrunken liver Ascites	Stigmata of liver disease Cruveilhier- Baumgarten murmur
Inflammatory lesions	RUQ	±	−	+	+	−	−	−	−	−	−	−	Normal	Hypoalbuminemia Prolonged PT Abnormal LFTs Hyponatremia Thrombocytopenia	US Nodular,shrunken or coarse liver	Stigmata of liver disease

Classification

Historical Perspective

Pathophysiology

Causes

Differentiating Splenic Rupture from Other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-Ray

MRI

Other Imaging Findings

Other Diagnostic Studies

Algorithms

Major molecular events in the pathogenesis of HCC

Genomic alterations

Epigenetic modifications

Growthfactor pathway alterations

Gene Mutations

Gene Amplification

DNA methylation micro RNA

Micro RNA

LNC RNA

Major Signaling pathways

•TERT promoter •TP53 •CTNNB1 •AXIN1 •AXIN2 •ATM •RPS6KA3 •JAK1 •IL6R •IL6ST •ARID1 •ARID2

•CCND1 •FGF19 •CDKNA2A •CDKNA2B •AXIN1 •IRF2 •MET

GSTP1 •E-Cadherin •CDKNA2 •RASSF1A •SOCS-3 •MIGMT

•MiR-155 •Mir-122 •Mir-224 •Mir-21

•HULC •HEIH •Dreh •MVIH •HOTAIR •MDIG •LINE1

•Wnt/β –catenin •Tyrosine kinase pathways EGF HGF/c-MET FGF VEGF •IGF •HIF •TGF β •Hedgehog

Elderly Male with jaundice from pancreatic cancer, By James Heilman, MD (Own work) [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons

The incidence of HCC has almost tripled since the early 1980s in the United States where it is the fastest rising cause of cancer-related deaths1. According to population based Surveillance Epidemiology and End Results registry data, the overall HCC age adjusted incidence rates for liver and intrahepatic ducts cancer is as high as 8 per 100,000 underling population in 2010 (Fig. 1) of which at least 6 per 100,000 related to HCC. Men are at approximately three times higher risk than women. Asian men (i.e., Chinese, Korean, Filipino, and Japanese) have the highest age-adjusted incidence rates. However, the largest proportional increases have occurred among Hispanics followed by blacks and non-Hispanic whites, whereas the lowest proportional increases have occurred among Asians. In contrast to Asians/Pacific Islanders, HCC incidence rates are reported to be higher among Hispanics born in the United States than among foreign-born Hispanics2. HCC incidence rates have increased in each successive birth cohort born between 1900 and 19593 (Fig. 2). In addition, the age distribution of HCC patients has shifted to younger ages, with the greatest proportional increases among individuals 45–60 years old (Fig. 2). There is a south to north gradient in the incidence and mortality of HCC; Southern states including Texas, Louisiana, and Mississippi have some of the highest HCC incidence rates in the nation (Fig. 3). In one study, Texas Latino and especially South Texas Latinos had the highest age-adjusted HCC incidence rates (as high as 10.6/100,000)4.

Video codes

Normal video

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Video in table

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Floating video

Title

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Redirect

1. REDIRECTEsophageal web

synonym website

https://mq.b2i.sg/snow-owl/#!terminology/snomed/10743008

Image

Normal versus Abnormal Barium study of esophagus with varices

Image to the right

C. burnetii, the Q fever causing agent

Image and text to the right

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Gallery

• 

  Histopathology of a pancreatic endocrine tumor (insulinoma). Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas

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  Histopathology of a pancreatic endocrine tumor (insulinoma). Chromogranin A immunostain. Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas

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  Histopathology of a pancreatic endocrine tumor (insulinoma). Insulin immunostain. Source:https://librepathology.org/wiki/Neuroendocrine_tumour_of_the_pancreas

References