THERE IS A GREAT ROLE OF TACE PROCEDURE FOR LIVER CANCER, IT CAN BE THE MOST EFFECTIVE AND TIME SAVING FOR HCC CASES.
Primary and secondary liver tumors are a common cause of morbidity and
mortality around the world. While curative therapies for some of these cancers
exist – hepatocellular carcinoma (HCC) can be treated with partial hepatectomy
or liver transplantation – many patients are ineligible for curative liver resection
due to the advanced stage of their cancers; furthermore, widespread implementation of liver transplantation is prevented by a shortage of donor organs.
The same is true for patients with metastatic colorectal or neuroendocrine tumors. Due to these
shortcomings, various palliative therapies have been advanced in the management
of hepatic neoplasms.
These include systemic chemotherapy, radiation therapy, and local and regional percutaneous modalities. The latter group comprises both ablative techniques (chemical and thermal), and the intra-arterial monotherapies.
Unlike healthy hepatocytes, which are supplied largely by the portal venous circulation, both primary and secondary liver tumors receive their vascular supply principally from the hepatic artery.
Thus, occlusion of the hepatic artery would be expected to lead to ischemic necrosis of tumor cells while selectively sparing the native liver. This principle has been exploited in the development of bland transarterial embolization (TAE) and transarterial chemoembolization (TACE).
In both of these approaches, the branches of the hepatic artery that supplies the tumor are occluded with embolic particles.
For chemoembolization, chemotherapeutic agents are added to the embolization mixture for delivery directly into the tumor.
In principle, chemoembolization targets liver lesions by a multifaceted attack. First, embolization of the vascular supply triggers localized tissue ischemia. Second, since the chemotherapeutic agents are delivered directly into the ischemic tumor, their local concentrations and tissue dwell times can be significantly increased [1–5].
Equally importantly, the ischemia induced by chemoembolization may counteract
drug resistance by causing metabolically active cell membrane pumps to fail, thereby
increasing intracellular retention of the chemotherapeutic agents [3,6].
Technique of chemoembolization
Preoperative evaluation for chemoembolization includes imaging, serology, and counseling. A patient should have either a definitive tissue diagnosis or a compelling clinical diagnosis, such as a markedly elevated serum alpha-fetoprotein (AFP) level associated with an HCC-like mass in a cirrhotic liver .
The patient must have a dynamic gadolinium-enhanced MRI or triple-phase CT of the liver.
The extrahepatic disease should be excluded by a bone scan and cross-sectional imaging of the chest, abdomen, and pelvis. Serological studies should include CBC, PT,
PTT, creatinine, liver function tests, and AFP levels. Due to the demanding nature
of this palliative treatment, patients should receive thorough counseling about
their regimens. In particular, this discussion should mention the common postembolization syndrome, the 5–7% risk of serious complications, and the 1–4%
chance of periprocedural mortality. The patient and family members should clearly
understand that chemoembolization is a palliative regimen with the potential for
significant discomfort, risk, and expense.
Patients need not be routinely admitted until the morning of their procedure, but they should be advised to fast overnight.
On the morning of the procedure, patients are hydrated with 0.9% NSS at 200–300 cm3 h−1. Prophylactic medications are administered intravenously, including antibiotics (cefazolin 1 g, metronidazole 500 mg) and antiemetics (odansetron 24 mg, decadron 10 mg, diphenhydramine
The evidence for antibiotic prophylaxis is not compelling except for patients without a functioning sphincter of Oddi (e.g., post-Whipple or biliary stent), and not all practitioners administer them routinely.
The patient is sedated, prepped, and draped. Before any embolization is performed, diagnostic angiography of the celiac and superior mesenteric arteries is performed to determine the arterial supply to the liver and to confirm the patency of the portal vein.
Because non-target embolization of the gut or gallbladder is a significant cause of morbidity, the origins of the right gastric, supraduodenal, cystic, and other potential extrahepatic arteries must be clearly identified .
Once the arterial anatomy has been mapped, a catheter is advanced super selectively into a lobar or segmental branch of the right or left hepatic artery.
Typically, the lobe with the greatest tumor burden is embolized first, with subsequent treatments
targeting the contralateral side.
The chemo-embolic mixture is injected into the segmental artery until nearly complete stasis of blood flow is achieved. Intra-arterial lidocaine (30mg boluses, up to a total of 200mg) and intravenous fentanyl and midazolam should be used to alleviate discomfort during the procedure
Antibiotics, antiemetics, and intravenous hydration are continued after the embolization (3L of 0.9% NSS over 24h).
The common post-embolization syndrome must be managed aggressively with palliation of pain, nausea, and fever.
Specifically, narcotics, perchlorpromazine, odansetron, decadron, and acetaminophen should
be liberally administered.
The patient can be discharged with the resumption of oral intake and the cessation of parenteral narcotic therapy.
Typically, half of the patients are discharged on the first postoperative day, while most of the remainder leave after 2 days .
Oral home medications include antibiotics (5 days), antiemetics, and narcotics when needed. Laboratory studies are repeated in 3 weeks to ensure the normalization of liver enzymes. Depending upon the tumor burden and arterial anatomy, a cycle of chemoembolization will include between one and four procedures. Thus, the patient will return for the next embolization in about 4 weeks; treatments alternate between the left and right lobes, as well as any parasitized
Following completion of the treatment cycle, responseis assessed with repeat cross-sectional imaging and tumor marker serology. If the response has been inadequate, further rounds of chemoembolization can be administered.
Choice of embolic particles
Variousembolicparticlesareavailableon the market.Thoughtheydifferinstructure, no agent has been conclusively demonstrated to be superior to any other.
The first embolic particle to be developed, the gelatin sponge (Gelfoam; Upjohn, Kalamazoo,
MI) has been used in the majority (71%) of chemoembolization trials .
Historically it has been available in various formulations – particles, cubes, pellet, powder,
fragments, and strips – the size of the particles determining how distal the embolization would take place .
Notably, use of the powder formulation has been discontinued because of an unfavorable side-effect profile. In all of these formulations, the gelatin causes only temporary devascularization, allowing recanalization to take place in about 2 weeks.
A similar temporary occlusion agent has also been developed from cross-linked bovine collagen (Angiostat; Regional Therapeutics, Pacific Palisades, CA).
More permanent embolic particles include polyvinyl alcohol (PVA; several vendors) and trisacryl gelatin spheres (Embosphere microspheres; BioSphere Medical, Rockland, MA).
Both of these come in a range of sizes (40–1000 μm), allowing the clinician to select the level of embolization. Less commonly, reports exist of the use of steel coils, starch microspheres, autologous blood clots, and even the herb Bletilla striata to embolize the hepatic artery . Recent studies have begun to assess the feasibility of drug-eluting beads, a new approach that may
offer an improved pharmacokinetic profile compared to traditional chemoembolization .
Choice of chemotherapeutic agents
Several chemotherapeutic agents are available for chemoembolization, for use as monotherapy or in combination.
Doxorubicin and cisplatin are the most commonly used single agents . Most reports from Europe and Asia use doxorubicin or epirubicin, whether alone or in combination with mitomycin-C.
Centers in the United States prefer cisplatin monotherapy or a combination of 100–150 mg
cisplatin, 40–60 mg doxorubicin, and 10–20 mg of mitomycin-C (CAM).
Although at least one case series suggested that cisplatin may confer a survival benefit over doxorubicin , no randomized trial has shown the superiority of any of these agents .
In fact, apparent differences between these agents may be driven by the ability to administer more embolizations in patients treated with cisplatin .In any case, no clear consensus has yet emerged for the superiority of any chemotherapeutic agent or combination.
Choice of emulsion: transarterial oily chemoembolization
The observation that iodized poppyseed oil (Ethiodol; Savage Laboratories, Melville, NY) selectively accumulated in hepatocellular carcinomas led to the incorporation of lipiodol (Guerbet, Aulnay-sous-Bois, France) into chemo-embolic regimens.
This technique, now known as transarterial oily chemoembolization, has the potential to more accurately target the chemotherapeutic drugs.
When iodized oil is injected into the hepatic artery, it travels to the distal arterioles, where it shunts
into the terminal portal venules at the pre-sinusoidal level.
From there, the oil slowly moves into the sinusoids and becomes trapped in the tumor vessels. In
theory, any chemotherapeutic agents suspended in this oily phase would thus be targeted to the liver.
Studies in rabbits  and humans  have demonstrated that the combination of oily chemoembolization with a particulate agent is superior to oily chemoembolization alone .
Such an effect is probably caused by the fact that most chemotherapeutic drugs remain in the aqueous phase of the emulsion. When chemoembolization is performed exclusively with an oily emulsion, continuous arterial inflow elutes out the aqueous drug, even though the oil itself remains
suspended in the liver.
Particulate-only chemoembolization causes relatively proximal occlusion, allowing continued inflow into the tumor from the portal venules, again diluting the chemotherapeutic drugs and resulting in reduced ischemia.
Thus the combination of oil and particles allows the occlusion of both distal arterioles and
portal venules – effectively sandwiching the drugs and maintaining tumor ischemia. Additionally, since this technique increases hepatic drug retention, it has the benefit of reduced systemic toxicity
Efficacy of chemoembolization
Historically, the efficacy of the transarterial embolo- therapies has been somewhat controversial. For example, early studies were inconclusive about the efficacy of chemoembolization in the treatment of hepatocellular carcinoma.
Nevertheless, evidence has emerged during this decade from several randomized trials that a role
exists for chemoembolization in the management of HCC.
Though the evidence is slightly less clear for the management of colorectal and neuroendocrine metastases, chemoembolization has nonetheless become established as an important palliative
therapy in the oncologist’s armamentarium.
Role of chemoembolization in unresectable hepatocellular carcinoma
Initial retrospective cohort studies in the Orient, Europe, and the United States suggested that chemoembolization was effective in the palliation of unresectable HCC: rates of tumor necrosis ranged from 60% to 100% .
Cumulative probability of survival in these studies was 54–88% at one year, 33–64% at 2 years, and 18–51% at 3 years, with the best results obtained by repeated embolizations with a combination
of iodized oil, gelfoam, and chemotherapeutic drugs.
Survival varied directly with oil uptake and retention, and inversely with tumor volume, stage, and Child class.
Nevertheless, early randomized controlled trials failed to demonstrate a survival benefit for patients with unresectable HCC. Chemoembolization with gelfoam/doxorubicin (n = 42 patients) , lipiodol/5-epidoxorubicin (n = 50) , and gelfoam/lipiodol (n = 96)  did not increase survival compared to control subjects who received only palliation of pain.
Interestingly, however, two of these studies [13,14] did demonstrate non-significant trends towards increased survival from chemoembolization, suggesting that they may have been underpowered to
answer this question.
Since that time, however, evidence has begun to mount in favor of chemoembolization in the management of unresectable HCC. In 2002, two randomized studies demonstrated a clear survival benefit from chemoembolization.
In the first study, of 80 patients from Hong Kong, survival in patients treated with cisplatin/
lipiodol/gelatin-sponge chemoembolization was 57%, 31%, and 26% at 1, 2, and 3
years, compared with 32%, 11%, and 3% in those receiving conservative management .
In the second study, of 112 patients from Barcelona, 1-year and 2-year survival was 82% and 63% in patients receiving doxorubicin/gelatin-sponge chemoembolization, 75% and 50% in those treated only with gelatin-sponge bland TAE, and 63% and 27% for those receiving conservative management .
The authors hypothesized that the results of these trials may have differed from earlier studies because of differences in patient demographics and tumor background .
In particular, the studies from Hong Kong and Barcelona were conducted in patients whose HCC arose in the presence of viral hepatitis in 80% of cases, compared to a higher preponderance of alcohol-induced liver disease in the earlier French studies .
The tolerance of patients with alcohol-induced cirrhosis for chemoembolization may have been lower than that of those with viral hepatitis .
A recent meta-analysis of 175 cohort studies and randomized controlled trials (RCTs) of chemoembolization in the treatment of unresectable HCC concluded that chemoembolization does provide a significant survival benefit when compared to conservative therapy (631 patients in nine RCTs, p = 0.0025) .
Interestingly, a sub-analysis of studies comparing chemoembolization to bland TAE (412 patients,
3 RCTs) failed to demonstrate a survival benefit for either methodology, though
chemoembolization trended towards an improved outcome (p = 0.052).
Lastly, chronologically later studies demonstrated improved outcomes in comparison to
earlier trials ; this finding could be partially explained as a result of the improving
proficiency of clinicians.
In summary, evidence indicates that patients with unresectable hepatocellular carcinomas benefit from transarterial chemoembolization, though the benefit of specific choices of chemoembolic combinations remains unproven.
Disagreements between early randomized trials of chemoembolization and newer studies may have
resulted from differences in the patient populations or from the improving proficiency of clinicians.
Role of chemoembolization as a neoadjuvant therapy in HCC
While chemoembolization has become well established as a palliative therapy in the management of unresectable hepatocellular carcinomas, its role as a neoadjuvant therapy for HCC has been more controversial.
In theory, chemoembolization could prevent tumor growth in patients awaiting orthotopic liver transplants, thus decreasing attrition from the transplant waiting list due to tumor progression: as
such, chemoembolization could serve as a bridge to transplantation.
Alternatively, preoperative chemoembolization might be expected to improve outcomes after
partial hepatic resection, and might even convert some unresectable lesions into resectable tumors.
Early support for the role of chemoembolization as a neoadjuvant came from retrospective cohort studies showing that neoadjuvant chemoembolization could induce a reduction in tumor size and thus a downstaging of HCC before hepatic resection or liver transplantation [17,18].
Similarly, while the 6-month drop-out rate from the transplant waiting list is typically between 23% and 46% , those patients who receive neoadjuvant chemoembolization have been reported to have a drop-out rate of only 15% .
Nevertheless, while such early studies were encouraging, it is unclear whether their conclusions can translate to improved outcomes.
For example, the aforementioned study  failed to demonstrate a statistically significant improvement in patient survival, thus calling into question the clinical relevance of the findings.
In fact, the results of later retrospective cohort studies of chemoembolization as a bridge to transplant have been contradictory [19,21], and no RCT has yet been conducted on the issue.
In fact, a recent systematic evidence-based review of the available studies concluded
that at present there is insufficient evidence to claim that chemoembolization could be used as a bridge to transplant, that it would decrease transplant waiting list drop-out rates, or that preoperative chemoembolization could improve posttransplant survival in patients with HCC .
Perhaps the most relevant confounding variable is wait times for listed patients. In regions with short wait times (< 3 months), the drop-out rate is low, so neoadjuvant therapy is not
When wait times are very long, approaching the median time to-progression after image-guided therapy, the benefit from neoadjuvant stabilization is lost.
The wide geographic and temporal variation in wait times makes analysis of the benefit of neoadjuvant therapy from prior literature difficult.
Nevertheless, in the absence of any randomized trials, chemoembolization continues to be used in a non-palliative role in the pre-transplant setting, largely because it at least has not been shown to increase postoperative complications in transplant patients .
The effectiveness of preoperative chemoembolization in patients receiving hepatic resection has been similarly controversial. In theory, the combination of chemoembolization with curative surgery might be expected to improve patient outcomes.
Moreover, since chemoembolization has been shown to be capable of downstaging tumors , it might be able to convert some patients with unresectable lesions into surgical candidates. Indeed, some studies have shown just this, with preoperative chemoembolization significantly improving the 5-year survival of patients undergoing hepatic resection from 19% to 39% .
These findings have been further supported by a large retrospective cohort analysis
However, other prospective trials have failed to show a benefit from neoadjuvant chemoembolization before hepatic resection; one prospective study actually demonstrated worsened actuarial survival in chemoembolized patients due to the delay in curative resection .
A review of various adjuvant and neoadjuvant therapies in HCC has concluded that there is insufficient evidence to claim that neoadjuvant chemoembolization improves patient survival before resection .
Still, in the absence of definitive randomized controlled trials, the issue remains unresolved.
In summary, the role of chemoembolization as a neoadjuvant before liver transplantation or hepatic resection has been rather controversial.
Despite positive findings from some studies, the preponderance of evidence has not yet supported
such an indication. In fact, where the administration of chemoembolization may delay a definitive therapy, chemoembolization may actually worsen patient survival .
Clearly, randomized controlled studies are needed to further clarify these questions.
Toxicity of Chemoembolization
Despite having a more favorable side-effect profile than conventional chemotherapy, chemoembolization is not free of complications.
Thirty-day mortality ranges from 1% to 4%; chemoembolization in the treatment of HCC had a median mortality of 2.4% in a recent meta-analysis of 2858 patients .
Severe complications of chemoembolization occur in 5–7% of subjects, though these rates can be
reduced to 3–4% when patients are properly selected.
Most patients suffer from a self-limited post-embolization syndrome. Major complications of chemoembolization include hepatic insufficiency, abscesses, ischemic complications (cholecystitis,
bile duct necrosis, perforation of the alimentary tract), and renal dysfunction.
Less commonly, chemoembolization can also lead to tumor rupture, occlusion of the hepatic artery, and clinically significant pancreatitis.
The majority of patients (40–86%) [14,38] suffer from a condition termed post-embolization syndrome (PES).
This is generally characterized by fever (74% of patients), abdominal pain (45.2%), nausea/emesis (58.9%), and a transaminitis (54%) .
In most cases PES is self-limited, though its palliation does necessitate hospitalization. On average, patients defervesce within 3 days, their nausea and pain can be medically managed, and their hepatic function gradually returns to normal .
Though previously thought to be indicative of tumor necrosis and thus a successful treatment, neither the presence nor the severity of PES has been shown to correlate to positive patient outcomes .
While reliable clinical predictors of the severity of PES have not yet been identified,PES does trend towards a more indolent course when embolization of the gall bladder is avoided, and when the patient is receiving repeat embolization to previously treated territory .
Acute irreversible hepatic decompensation has been reported to occur in 3% of patients [8,39]. It should be distinguished from the transient and self-limited transaminitis that occurs with post-embolization syndrome.
Irreversible decompensation is more common with the use of high doses of cisplatin and poor
pretreatment hepatic function (high bilirubin, prolonged PT, and advanced cirrhosis) .
Abscess formation affects between 0.2% and 2.5% [40,43] of patients receiving chemoembolization.
The majority of these infections occur in the liver, though 0.4% of patients may suffer from a splenic abscess .
While their proximate cause is an infectious process, their formation is ultimately permitted by local ischemic necrosis.
Abscesses present with localized pain, fever, and leukocytosis,and can be definitively diagnosed by ultrasound or CT .
The likelihood of abscess formation has been strongly linked to a history of a Whipple procedure:
the presence of a bilioenteric anastomosis increases the incidence of a hepatic abscess by an odds ratio of 894 .
Attempts at prophylaxis against the formation of abscesses have led many clinicians to treat patients with broadspectrum antibiotics peri- and postoperatively ; others have even advocated
the addition of antibiotics to the embolic mixture.
However, a recent prospective cohort study from Germany casts doubt on these practices: patients who did not receive treatment with antibiotics had no more infections or other complications than those who received 3 days of intravenous and 7 days of oral broad-spectrum antibiotics .
Severe ischemic complications, other than abscesses, have been reported to occur in 2.1% of patients receiving chemoembolization: these consist of ischemic cholecystitis (1.1%), bile duct necrosis (1.1%) , and perforation of the duo denum (0.05%) .
However, several other studies have quoted the incidence of gastroduodenal erosions and ulcerations to be significantly higher: one retrospective analysis of 280 cases demonstrated an endoscopy-proven incidence of 5.3% .
Since such lesions can result from the reflux of embolic material into the gastric circulation, the importance of meticulous attention to anatomic variants and adherence to selective or superselective embolization is the primary safeguard against this possibility .
Alternatively, at least some of these lesions could be the result of stress ulceration. Similarly, embolization distal to the cystic artery is the primary way of avoiding ischemic cholecystitis .
Nevertheless, since chemoembolization purposefully causes tissue ischemia, some damage to structures that are dependent on the hepatic artery is unavoidable (e.g., the intrahepatic bile
Renal failure has also been documented as a complication of chemoembolization, though its reported incidence varies between 0.05%  and 13%, averaging 1.8% in the aforementioned meta-analysis .
A prospective cohort study revealed an incidence of 8.6%, with 2.9% developing irreversible renal impairment .
Independent risk factors for the development of acute renal failure are the number of chemoembolization sessions, high Child–Pugh class, and a severe course of post-embolization syndrome; irreversible renal dysfunction was predicted only by the presence of diabetes .
The proximate causes of such kidney damage may be
the use of arterial contrast agents, the nephrotoxicity of the chemotherapeutic drugs, and inflammatory factors released from tumor necrosis [8,45].
The less common complications of chemoembolization include tumor rupture, occlusion of the hepatic artery, and clinically significant pancreatitis.
Spontaneous rupture of the treated tumor occurs in 0.15% of patients, most often after the
embolization of a large neoplasm .
Occlusion of the hepatic artery is a complication of repeated embolizations, occurring in 2% of patients following their second or third round of chemoembolization .
Though clinically significant pancreatitis is generally considered a rare complication – Roullet et al. report an incidence of 1.7%  – subclinical elevations in pancreatic enzymes may occur in as many as 15.2% of patients .
The likelihood of suffering severe side effects from chemoembolization is attenuated by both meticulous technique and proper patient selection. In principle, patients must be selected to include only those who will both benefit and tolerate the embolization procedure.
Selecting patients for optimum efficacy
Patients with multiple or unresectable lesions located exclusively or predominantly in the liver are ideal candidates for chemoembolization.
Since liver embolization only targets intrahepatic lesions, patients whose hepatic tumor burden is the primary driver of their symptoms and survival are the most likely to benefit from chemoembolization.
Nevertheless, the presence of some extrahepatic disease is not an absolute contraindication to chemoembolization; some patients whose metastatic disease is minimal or indolent may still be candidates for this therapy.
Selecting patients for optimum tolerability
The fundamental principle underlying the intra-arterial embolo-therapies is the differential blood supply of the hepatic neoplasms (supplied via the hepatic artery) and hepatocytes (supplied via the portal vein). Thus, if the native hepatocytes were to become more dependent on the blood flow from the hepatic artery,embolization of this vessel would be expected to lead to increased side effects.
This has in fact been demonstrated. Conditions that predispose the healthy liver to injury by increasing the relative contribution of blood from the arterial circulation include portal vein thrombi and superimposed liver disease.
Thus, occlusion of the portal vein is a relative contraindication to chemoembolization, though small
case series suggest that patients with the significant collateral flow can still be embolized
Patients with significant liver disease, such as those of Child-Pugh class C, with tumor replacing > 50% of liver , alpha-fetoprotein > 400 U L−1 , lactate dehydrogenase > 425 IU L−1, aspartate aminotransferase > 100 IU L−1, or total bilirubin ≥ 2 mg dL−1, are also at increased risk. Severe liver disease, as indicated by hepatic encephalopathy or jaundice, is an absolute contraindication to embolization.
Biliary pathology is another relative contraindication. Biliary obstruction predisposes patients to biliary necrosis even in the absence of hyperbilirubinemia.
As discussed previously, a surgical biliary anastomosis or stent virtually guarantees the development of a hepatic abscess, at least in the absence of prophylactic antibiotics .
Last, since the chemoembolization procedure must include angiography, patients with contraindications to this procedure cannot be embolized. All of the contraindications for chemoembolization also apply to bland embolization.
New developments in chemoembolization technology
The latest generation of embolic particles are polyvinyl alcohol polymeric beads specifically designed to load chemotherapeutic drugs and elute them over time into the tumor tissue following embolization.
Preclinical bench-top and animal studies have confirmed the ability of these drug-eluting beads to provide enhanced local drug delivery over a prolonged period with minimal systemic exposure
Phase I/II clinical trials for hepatoma in Europe and Asia have shown promising 1-year and 2-year survivals in the 85–90% range, but a disturbing incidence of major complications at around 10%, with a surprising frequency of hepatic abscess [52,53].
Randomized trials against conventional oily chemoembolization have not been completed. These beads are available as bland embolics in the USA and can be loaded with one or more drugs, but such off-label use is discouraged until their safety and efficacy is established in clinical trials, particularly given their high cost.
Transarterial chemoembolization is a powerful and well-established tool in the palliative management of both primary and secondary liver tumors.
While future randomized trials are still needed to unequivocally prove the survival benefits of
chemoembolization in some cancers, its effects on the management of symptoms have been clearly demonstrated.
When performed with meticulous technique, chemoembolization can be efficacious while still maintaining a side-effect profile superior to that of conventional therapies.
Though patient selection remains crucial, the transarterial embolotherapies can be offered to many more patients than traditional hepatic resection or transplantation.
Therefore, familiarity with chemoembolization is essential for any clinician involved in the care of patients with primary or secondary liver tumors.
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35. Ruszniewski P, O’Toole D. Ablative therapies for liver metastases of gastroenteropancreatic
endocrine tumors. Neuroendocrinology 2004; 80 (Suppl 1): 74–8.
36. Touzios JG, Kiely JM, Pitt SC, et al. Neuroendocrine hepatic metastases: does aggressive management improve survival? Ann Surg 2005; 241: 776–83.
37. Ruutiainen AT, Soulen MC, Tuite CM, et al. Chemoembolization and bland embolization of
neuroendocrine tumor metastases to the liver. J Vasc Interv Radiol 2007; 18: 847–55.
38. Wigmore SJ, Redhead DN, Thomson BN, et al. Postchemoembolisation syndrome: tumour
necrosis or hepatocyte injury? Br J Cancer 2003; 89: 1423–7.
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transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma.
Cancer 2001; 94: 1747–52.
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chemoembolization. J Vasc Interv Radiol 2001; 12: 965–8.
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43. Xia J, Ren Z, Ye S,etal. Study of severe and rare complications of transarterial chemoembolization
(TACE) for liver cancer. Eur J Radiol 2006; 59: 407–12.
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in post-transarterial embolization for hepatocellular carcinoma: a retrospective cohort study of
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of liver tumors: frequency and associated risk factors. Pancreatology 2007; 7: 53–62.
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Transarterial chemoembolization 91
High-intensity focused ultrasound (HIFU)
treatment of liver cancer
IMAGING ANATOMY OF PHARYNX & LARYNX is essential to understand subsequent pathology, The upper aerodigestive tract consists of the pharynx and the larynx. The larynx connects pharynx and trachea.
The pharynx is divided into:
• Nasopharynx: extends to inferior portion of soft palate
• Oropharynx: extends from soft palate to hyoid bone
• Hypopharynx (laryngeal part of the pharynx): contains pyriform sinuses and posterior pharynx.
The larynx contains:
• The laryngeal surface of epiglottis. • Aryepiglottic folds
• Arytenoid cartilage
• False cords
• True cords (glottis is the space between vocal cords)
• Subglottic larynx
Para-pharyngeal Space (Fig. 1)
it’s Potential space filled with loose connective tissue.
A pyramidal Space , with the apex directed toward the lesser cornua of the hyoid bone and the base toward the skull base.
It Extends from skull base to mid-oropharynx.
• Lateral: mandible, medial pterygoid muscle
• Medial: superior constrictor muscles of pharynx, tensor and levator veli palatini
• Anterior: buccinator muscle, pterygoid, mandible
• Posterior: carotid sheath.
Lymphatics (Fig. 3)
The parapharyngeal space has abundant lymph node groups.
• Lateral pharyngeal node (Rouvière)
• Deep cervical nodes
• Internal jugular chain, including jugulodigastric node
• Chain of spinal accessory nerve
• Chain of transverse cervical artery
Paraganglia (Fig. 4)
Cells of neuroectodermal origin that are sensitive to changes in oxygen and CO2.
• Carotid body (at carotid bifurcation)
• Vagal bodies
Neoplastic transformation of the jugular bulb ganglion produces the glomus jugulare.
Fluoroscopic Vocal Cord examination (Fig. 5)
Occasionallyperformedtoevaluatethesubglotticregion (Valsalva maneuver), invisible by laryngoscopy.
• Phonation of “E” during expiration: adducts cords.
• Phonation of “reversed E” during inspiration; distends laryngeal ventricles
• Puffed cheeks (modified Valsalva): distends pyriform
• Valsalva: distends subglottic region
• Inspiration: abducts cords.
Nodal Stations (Fig. 6)
• IA: between anterior margins of the anterior bellies of the digastric muscles, above the
hyoid bone and below the mylohyoid muscle (submental) • IB: below mylohyoid muscle, above hyoid bone, posterior to anterior belly of digastric muscle,
and anterior to a line drawn tangential to the posterior surface of the submandibular gland
• Levels II, III, IV: internal jugular nodes II: (jugulodigastric) from skull base to lower body of the hyoid bone, through posterior edge of the sternocleidomastoid muscle and posterior edge of the submandibular gland. Note: A node medial to the carotid artery is classified as a retropharyngeal node. III:hyoid bone to cricoid cartilage IV: cricoid to clavicle
• Level V: skull base to clavicle, between anterior edge of trapezius muscle and posterior edge of
• Level VI:visceral nodes; from hyoid bone, top of manubrium, and between common carotid arteries on each side • Level VII:caudal to top of the manubrium in superior mediastinum (superior mediastinal
Pathologic Adenopathy Size Criteria:
Neck lymphadenopathy by size has poor specificity, and no universal standard exists for determination of adenopathy. Nonetheless, two methods are commonly used: • Long axis: 15mm in levels I and II, 10mm elsewhere • Short axis: 11mm in level II, 10mm elsewhere Retropharyngeal nodes should not exceed 8mm
(long) or 5mm (short).
Emerging technologies such as MRI lymph node imaging with iron nanoparticles or PET may prove to be more specific and sensitive.
IMAGING TECHNIQUES OF PHARYNX AND LARYNX ARE VERY EASY, WE HERE WILL TRY TO SUMMERIZE THEM.
THANKS TO DR/ DAVID SUTTON MD, FRCP, FRCR, DMRD, FCan.AR (Hon) OUR BELOVED TEACHER
Lateral Film is the best film projection, as Pharynx and Larynx clear of the cervical spine . as in Fig (1). The Film is placed against the shoulder and the incident beam is centered on :
Jaw Angle if we want Nasopharynx.
Thyroid Cartilage If we want Larynx.
(A) Some of the structures demonstrated on a plain lateral view of the neck. Xerography, although giving an excellent demonstration of the air-soft-tissue interface, is no longer available because of the high radiation dose used.
(B) High-kV lateral neck gives an adequate demonstration of the soft tissue anatomy.
More benefit to opacify lesions below the crico-pharyngeus that cannot be assessed with a laryngeal mirror.
Tumours of the pharynx will be outlined by barium coating, especially those in the piriform fossae ( difficult to be seen with a mirror).
The normal larynx will appear as a `filling defect’ in the frontal projection with contrast in the piriform fossa on either side.
This is well shown on the oblique projection, obtained with the patient swallowing while the head is turned to one side.
When the larynx fails in its primary function as a protective sphincter for the lungs, ‘spill-over’ will occur to give a `barium laryngogram’.
This problem is seen more and more in an aging people, who dysphagia is due to mild stroke.
Fig . 2
Lateral View of normal Barium Swallow. The epiglottis (arrow) folds over the larynx as barium passes down into the esophagus .
It gives a good demonstration of degustation process.
Passage of the bolus across the back of the tongue with an elevation of the larynx and tilting of the epiglottis down over the closed larynx is shown (Fig. 2).
Contrast then passes through the open cricopharyngeus into the esophagus.
Minor functional disorders of swallowing can only be shown by this technique (Fig. 3).
Videofluoroscopy is an alternative means of assessing swallowing function and a technique for assessment of oral or pharyngeal dysphagia.
Cine barium swallow. Four frames in 1 s, frontal and lateral views. The patient had mild dysphagia due to unilateral vagal paralysis. Various
normal and abnormal features are demonstrated.
1. The vallecula fills with barium and is then partially effaced by the normal backward compression of the tongue.
2. The epiglottis is partially immobile and only tilts down to the transverse position, not fully covering the laryngeal inlet.
3. Barium enters the vestibule of the larynx. This may occasionally be observed in asymptomatic subjects but is usually an indication of failure of the laryngeal sphincters ('spill-over').
4. At the same time the relation of the postphyaryngeal wall to the cervical spine does not change, indicating paralysis of the middle pharyngeal constrictor.
5. Cricopharyngeus contracts and relaxes normally.
6. The epiglottis shows little movement.
7. The right side of the pharynx contracts normally but the left remains flaccid and filled with barium.
8. Cricopharyngeus contracts and releases normally.
CT is now the optimum method of imaging the outlines of the nasopharynx but also shows the soft-tissue structures of the infratemporal fossa and parapharyngeal space, which lie alongside the Naso- and oropharynx.
Formerly this region could be studied radiologically only in an indirect way by examination of surrounding bony structures or by invasive contrast examinations such as sialography and angiography.
The infratemporal fossa is situated below the skull base and is bounded by the pharyngeal musculature medially and the mandible laterally.
The most prominent and easily recognized structures within the infratemporal fossa are the pterygoid muscles.The anatomy of this region is depicted in Fig. 4.
Below, the infratemporal fossa is continuous with the parapharyngeal space. The role of CT for lesions in this region may be defined as: • To complement direct examination of lesions in the postnasal space .• To assess the size and situation and relations of a well-defined mass for prospective surgical removal, or the extent of local deepinfiltration for radiotherapy planning. • To assess the relation of the mass to the great vessels and the parotid gland: by combining CT with contrast enhancement more accurate differentiation becomes possible.Contrast enhancement should be assessed in the vascular phase by intravenous infusion or bolus injection. Further sections in the coronal plane may give more information. Respiratory movement is less of a problem with the new fast scanners.
Scanning is begun at the level of the thyroid bone and sequential scans of 5 min slices are made in a caudal direction.
The shape of the airway alters as sequential scans are viewed. Above the rounded hypopharynx, it is bisected by the crescentic epiglottis.
Further down, the median and lateral glossoepiglottic folds delineate the valleculae.
Below this, the airway assumes a triangular shape and the piriform sinuses are seen as two lateral appendages separated by the aryepiglottic folds.
At the level of the cords the shape changes to the characteristic glottic chink or boat shape with the sharp anterior commissure extending right up to the thyroid cartilage in the midline (Fig. 5).
In the subglottic area, there is an even, symmetric oval shape which gives way at the level of the first tracheal ring to an oval flattened posteriorly, which may he likened to the shape of a horseshoe.
CT provides a non-invasive, quick and effective radiological investigation of the larynx, and is not uncomfortable for the patient.
It can be done without risk in the face of respiratory obstruction, or after suspected laryngeal injury.
It gives an accurate assessment of laryngeal anatomy and involvement by tumor, particularly at the glottic level.
The value of such an assessment is greatly increased if partial laryngectomy is contemplated, but this is an unusual operation in the UK where carcinoma of the larynx is treated with radiotherapy and/or total laryngectomy.
Axial CT of soft tissues below the skull base. (A) Normal section through antra and postnasal space. The arrowheads indicate the openings of
the eustachian tubes. m = ramus of mandible; s = styloid process; p = pterygoid muscles. (B) Section at a slightly lower level passes through the soft palate
(sp). Tensor and levator palatini blend with the pharyngeal constrictors (c) to give a dense muscle mass. The enlarged but otherwise normal parotid gland
has a lower attenuation, i.e. appears darker, than the masseter muscle in front of it but not as dark as the fatty tissue in the parapharyngeal space. Thus the
medial limit of the deep parotid lobe can be defined (arrowhead). These features are best shown by MRI.
Axial CT Scan of the normal Larynx at the level of true vocal cords.
Note the diamond shape of the airway with the cords in abduction.
Contrast is given , so CCA (A) and IJV (I) are shown.
MRI is superior over CT for neck masses.
MRI show neck vessels without the need to contrast.
T1WI gives the best spatial resolution.
T weighted Protocols give the best view of muscle invasion by carcinoma esp in Tongue base.
CT with contrast is superior over MRI in the evaluation of Neck Lymph Nodes, however, none of them can differentiate neoplastic from inflammatory hyperplasia, yet metabolic techniques like FDG-PET, SPECT is promising in that.
Sometimes the presence of Fat can obscure lesions, so fat saturation techniques are very useful, STIR protocol the most dependent one show increase signal intensity from most of the tumors especially Parotid Tumors. But It can’t be used with gadolinium contrast.
Chemical Shift fat saturation techniques can show recurrent tumor after gadolinium injection.
Now Fat Saturation Techniques, used with T1 fast spin echo OR Post-gadolinium T protocols are more useful in defining Neck Lesions .
Fig.6 (A) upper image: Sagittal MRI, T 1 -weighted, shows good differentiation between the tongue muscles, the genioglossi in the floor of the mouth and the surrounding fat, especially in the pre-epiglottic space (arrow). (B) lowe image : Sagittal film in a child revealing subglottic stenosis (arrow)
Chordoma. Sagittal MR section, T,-weighted, shows a nonhomogeneous mass in the nasopharynx and replacing the basisphenoid.The tumor has burst out of its capsule and is displacing the brainstem posteriorly.
PRINCIPLES Of MSK U/S ARE VERY EASY , WE WILL DISCUSS IT AT THIS ARTICLE
THANKS TO DR .AHMED . F. ABOGAMAL FOR HIS GREAT EFFORT
The Sonographic Revolution
For many years the rheumatologist adopted to fight against time to diagnose and follow most of the rheumatic diseases, this fighting continues to occur with no winners until the sonographic revolution has occurred in rheumatology.
Ultrasonography has been shown to be capable of substantially changing the traditional approach to most clinical problems in daily rheumatological practice because of its ability to allow a quick, safe and inexpensive access to otherwise undetectable anatomical information on the early targets of most rheumatic diseases.
Ultrasonography completes the physical examination in a rapid and accurate manner and allows the very early detection of a wide spectrum of pathological findings involving different anatomical structures in the musculoskeletal system.1
Although musculoskeletal ultrasound may be considered as one of the latest developments in ultrasound applications, it was first used, as far back as 1958, in the assessment of the acoustic attenuation of musculoskeletal tissues by K.T Dussik et al.2, 3
Dussik had also been the first to use ultrasound as a medical imaging modality in 1942. 2, 4
Ultrasound developed slowly until 1960 when Donald and colleagues produced the first automatic scanner.2
For the next decade, ultrasound was predominantly limited to the evaluation of abdominal and pelvic diseases.
By 1972 the first B-scan image of a joint was reported in the differentiation of a Baker’s cyst and thrombophlebitis.5
Graf, in 1980, published his landmark paper on the use of ultrasound in the diagnosis of congenital hip joint dislocation.6
In 1988, L. De Flaviis described ultrasound of the hand in rheumatoid patients including erosions, 10 years after Cooperberg described features of synovial thickening and joint effusion in the rheumatoid knee.7, 8
Since this time, particularly in the past decade, there has not only been a rapid development in ultrasound technology, but also widespread use of ultrasound in the investigation of musculoskeletal disorders to the point where it is now firmly established as a key imaging modality.
BASICS OF MUSCULOSKELETAL ULTRASOUND
Ultrasound uses high-frequency sound waves to acquire images for the soft tissues, bones, and nerves of the body.
The ultrasound machine sends an electrical signal to the transducer, which is connected (via a cable) to the monitor and computer processing unit.
This system results in the production of sound waves that are transmitted from the transducer to the soft tissues of the body through acoustic transmission gel.9
The sound waves interact with the tissue interfaces and some reflect back toward the transducer on the surface of the skin.
The ultrasound image is produced from this reflection, which converts sound waves to an electrical current.9
The ultrasound machine then measures the amplitude of the returning electrical signal and records its travel time to determine the depth of the reflected structure.
As the machine generates and records the amplitudes and travel times of the sound beams, it uses the computer software to produce a two-dimensional image of the scanned structures.10
The transducer is an essential element of US equipment, responsible for the generation of a US beam and the detection of returning echoes.
It greatly influences spatial resolution, penetration and signal-to-noise ratio, and in turn its selection affects the quality of the US image.9
Frequency of the Transducer:
To produce an image of optimal quality, it is important to select the proper transducer for the area of interest.
A transducer is described by the range of sound wave frequencies it can produce (MHz).
Higher-frequency transducers produce higher resolution images, but at the expense of beam penetration, because higher-frequency sound is more rapidly absorbed by the tissues.
Lower-frequency transducers are more capable of assessing deeper structures, but they have lower resolution.9
Shape of the Transducer foot plate:
Transducers also can be described as linear or curvilinear.
Linear transducers produce a sound wave that is propagated in a straight line perpendicular to the transducer surface (Fig.1).
Such transducers are best for evaluating linear structures like tendons.
Curvilinear transducers produce an arched beam and are less commonly used, but have some advantages in evaluating deeper structures (Fig. 2) and the small-footprint linear array L shaped transducer (hockey-stick transducer) which is suitable for evaluation of the small joints (Fig. 3).
Commonly used transducers in musculoskeletal ultrasound include the high frequency (20–7 MHz), linear transducer, and the low- to medium frequency (5–2 MHz) curvilinear array transducer.
The examiner should choose the highest-frequency transducer that can adequately image the target structure at the appropriate depth.9
Fig.1: Linear transducers are best for evaluating linear structures like tendons (coated from Jacobson JA, 9).
Fig.2: Curvilinear transducers are used for evaluating deeper structures such as hip, piriformis muscle, and sciatic nerve (coated from Jacobson JA, 9).
Fig.3: The small-footprint linear array transducer is also called a hockey-stick transducer and has higher frequency compared with other transducers. This transducer is used for evaluating small superficial structures such as peripheral nerves (coated from Jacobson JA, 9).
Reducing the width and thickness of the US beam to be limited to the area of interest has definite advantages in terms of contrast and spatial resolution.
In modern linear-array transducers’, focusing is currently not obtained by means of a fixed lens as in the old mechanical sector probes in which degrading of the image quality occurred at a short distance from the focal zone.
Focusing is now produced electronically by activating a series of elements in the array with appropriate delays, so that the trigger pulses to the inner elements are delayed with respect to the pulses to the outer ones.
In this way a curved wave front results from constructive interference bringing the US beam toward a focus. Recently, the introduction and refinement of matrix (1.5D probes) transducers led to further progress.
In these transducers, the single row of long piezoelectric elements found in a conventional probe is replaced by more layers (three to seven) incorporated into a single thin layer to produce parallel rows of short elements.
The slice thickness of the US image is improved by performing dynamic focusing in the elevation plane.
This leads to better spatial and contrast resolution and reduction of partial- volume averaging artifacts.11 A less expensive alternative to 1.5D probes is the use of peculiar acoustic lenses – Hanafy lenses –placed in front of the piezoelectric elements.
The Hanafy lens has nonuniform thickness and resonance properties: it produces a narrow and uniform image slice thickness and, simultaneously, a very broad bandwidth pulse.
The inner portion of the lens is thinner, resonates at higher frequencies and focuses in the near field, whereas its outer portions resonate at lower frequency and are focused in both transmission and reception at the deepest part of the image providing better penetration.12
Fig 4: Hanafy lens (Acuson-Siemens) coated from Claudon et al., 12.
Basic Scanning Techniques:
At first it is important to use enough acoustic transmission gel.
After that the examiner should begin by holding the transducer between the thumb and fingers of their dominant hand, positioning the end of the transducer near the ulnar side of the hand.
It is essential to securely stabilize the transducer on the patient’s body, with either the palm of the imaging hand or the small finger.
After the transducer is properly placed on the patient’s skin, a rectangular image is produced on the monitor.
The top of the image represents the tissues in contact with the transducer; the bottom of the image displays the deeper structures.
The left-to right orientation of the image can be altered using a button on the machine or by rotating the transducer 180 degree (fig 5).9
The image on the screen can be further adjusted and optimized by changing the sound-beam penetration using the depth controls.
Selection of the proper transducer is also critical in evaluating the depth of a structure.
There is an inverse relation between the frequency of the transducer and its depth of penetration, such that higher-frequency transducers are usually best to view superficial structures, whereas lower-frequency transducers are used for deeper structures.10, 13
Fig.5: (A, B) Orientation of the image. The top of the image usually shows the shallow structures and the bottom of the image, the deeper structures. The notch (arrow) of the probe usually represents the left side of the image (asterisk), but an image can be inverted by controls on the machine and it is important to confirm the side of the transducer with the side of the image on the screen. During examinations, t is important to be consistent. Many find it helpful to align the left side of the image with the examiner’s left side, coated from Jacobson JA, 2007.9
The next step in imaging is adjusting the focal zone of the ultrasound beam.
The number of focal zones should be reduced to span the area of interest.
The zone feature is usually displayed on the side of the image as a series of cursors or symbols.
The depth and length of the focal zone position should match the position of the structure of interest.
The examiner may adjust the gain to either increase or decrease the brightness of the echo image.
A standardized approach to the study of the various anatomical regions is advisable even if the choice of the acoustic window is conditioned by the specific diagnostic need.14
Each anatomical area should be explored on various scan planes so as to obtain all of the necessary information.
An in-depth knowledge of the anatomy of the region examined is required for the musculoskeletal US. 14
Advantages and Disadvantages of Musculoskeletal Ultrasound:
When comparing US with other musculoskeletal imaging techniques (radiography, computed tomography, and magnetic resonance imaging), ultrasound offers numerous advantages.
Perhaps the most important of these is that ultrasound offers a hands-on, dynamic examination, allowing the clinician to image in real-time, while interacting with the patient.15
The clinician can ask the patient for assistance during the examination and may accurately localize painful areas by palpating with the transducer and seeking patient feedback.16
The sonographer can also ask the patient to reproduce the abnormal or painful event while scanning dynamically.
Furthermore, ultrasound is less expensive when compared to CT or MRI, can be repeated, and US can be used to compare the finding in the diseased side with the normal side of the same patient in the same session.
Ultrasound transmits no radiation to the patient or user, and thus may be used in special populations, including pregnant women and those with metal implants or other sources of imaging artifacts. 16
In addition, the enhanced sensitivity for detecting low-velocity flow in small tendon and synovium vessels achieved by recent colour Doppler and power Doppler techniques has led to the incorporation of Doppler US in rheumatology.
US allows an immediate correlation between imaging findings and clinical data, which improves diagnosis and management of patients with a range of rheumatic diseases from inflammatory arthritis, vasculitis or osteoarthritis to soft-tissue diseases.16-20
US has demonstrated more sensitivity than clinical evaluation in assessing joint inflammation.21-26
In addition, ultrasound is a bedside tool for performing accurate and safe musculoskeletal injections.27
On the other hand, the primary disadvantage of ultrasound is that it is operator dependent and there is a steep learning curve. Numerous examinations must be performed to establish a reliable diagnostic algorithm.28
Ultrasonographic Tissue Appearance:
Musculoskeletal ultrasound can be used to identify muscles, tendons, ligaments, nerves, bone surface and vessels, at a resolution of less than0.1 mm.
These structures can be characterized and described by their echogenicity. 29
When there is a large difference in impedance at the interface between tissues the sound beam is strongly reflected, creating a bright echo on the image. This process is described as hyperechoic.
If an image displays no echo and is black, it is referred to as anechoic, and when a weak or low echo is produced, it is termed hypoechoic.
When the echogenicity of a structure appears equal to an adjacent structure, it can be described as isoechoic or of equal echogenicity. 29
In general, when interpreting musculoskeletal ultrasound, a practical order of echogenicity is: bone/ligament/tendon/nerve/muscle.
In addition to their echogenicity, tissues are also described by their echotexture, which refers to their internal echo pattern.
Echotexture varies based on whether a structure is imaged longitudinally or transversely.30, 31
Definitions of Basic ultrasound terminology:
Echotexture refers to the coarseness or non-homogeneity of an object. Echogenicity refers to the ability of tissue to reflect ultrasound waves back toward the transducer and produce an echo. The higher the echogenicity of tissues, the brighter they appear on ultrasound imaging. Hyperechoic structures are seen as brighter on conventional US imaging relative to surrounding structures due to higher reflectivity of the US beam. Isoechoic structures of interest are seen as bright as surrounding structures on conventional US imaging due to similar reflectivity to the US beam. Hypoechoic structures are seen as darker relative to the surrounding structures on conventional US imaging due to the US beam being reflected to a lesser extent. Anechoic structures that lack internal reflectors fail to reflect the US beam to the transducer and are seen as homogeneously black on imaging. Longitudinal structure is imaged along the long axis. Transverse structure is imaged perpendicular to the long axis.
1. Grassi W., Filippucci E., and Busilacchi P. Musculoskeletal ultrasound Best Practice & Research
Clinical Rheumatology 2004; 18: No. 6, pp. 813–826.
2. Kane D, Grassi W, Sturrock R et al. A brief history of musculoskeletal ultrasound: ‘From bats and
ships to babies and hips.’ Rheumatology 2004;43:931–933.
3. Dussik KT, Fritch DJ, Kyriazidou M et al. Measurements of articular tissues with ultrasound. Am
J Phys Med 1958;37:160–165.
4. Dussik KT. On the possibility of using ultrasound waves as a diagnostic aid. Z Neurol Psychiatr
5. McDonald DG, Leopold GR. Ultrasound B-scanning in the differentiation of Baker’s cyst and
thrombophelebitis. Br J Radiol 1972;45:729–732.
6. Graf R. The diagnosis of congenital hip-joint dislocation by the ultrasonic combound treatment.
Arch Orthop Trauma Surg 1980;97:117–133.
7. De Flaviis L, Scaglione P, Nessi R et al. Ultrasonography of the hand in rheumatoid arthritis. Acta
8. Cooperberg PL, Tsang I, Truelove L et al. Gray scale ultrasound in the evaluation of rheumatoid
arthritis of the knee. Radiology 1978;126:759–763.
9. Jacobson JA. Fundamentals of musculoskeletal ultrasound. Philadelphia: Saunders Elsevier; 2007.
10. Smith J, Finnoff JT. Diagnostic and interventional musculoskeletal ultrasound: Part 1.
Fundamentals. PM R 2009;1(1):64–75.
11. Rizzatto G. Evolution of US transducers: 1.5 and 2D arrays. Eur Radiol1999;9:304–306
12. Claudon M, Tranquart F, Evans DH et al. Advances in ultrasound. Eur Radiol 2002;12:7–18
13. Kremkau F. Diagnostic ultrasound. Principles and instruments. 6th edition. Philadelphia: WB
Saunders; 2002. p. 428.
14. Backhaus M, Burmester GR, Gerber T, et al. Guidelines for musculoskeletal ultrasound in
rheumatology. Annals of the Rheumatic Diseases 2001; 60: 641–649.
15. O’Neill J. Introduction to musculoskeletal ultrasound. In: O’Neill J, editor. Musculoskeletal
ultrasound. New York: Springer; 2008. p. 3–17.
16. Grassi W, Cervini C. Ultrasonography in rheumatology: an evolving technique. Ann Rheum Dis
17. Wakefield RJ, Brown AK, O´ Connor PJ, et al. Musculoskeletal ultrasonography: what is it and
should training be compulsory for rheumatologists? Rheumatology 2004;43:821–2.
18. Kane D, Grassi W, Sturrock R, Balint PV. Musculoskeletal ultrasoundda state of the art review in
rheumatology. Part 2:
19. Clinical indications for musculoskeletal ultrasound in rheumatology. Rheumatology 2004;43:829–
20. Schmidt WA, Seifert A, Gromnica-Ihle E, et al. Ultrasound of proximal upper extremity arteries to
increase the diagnostic yield in large-vessel giant cell arteritis. Rheumatology 2008;47:96–101.
21. Backhaus M, Kamradt T, Sandrock D, et al. Arthritis of the finger joints: a comprehensive
approach comparing conventional radiography, scintigraphy, ultrasound, and contrast-enhanced
magnetic resonance imaging. Arthritis Rheum 1999;42:1232–45.
22. Kane D, Balint PV, Sturrock RD. Ultrasonography is superior to clinical examination in the
detection and localization of knee joint effusion in rheumatoid arthritis. J Rheumatol
23. Wakefield RJ, Green MJ, Marzo-Ortega H, et al. Should oligoarthritis be reclassified? Ultrasound
reveals a high prevalence of subclinical disease. Ann Rheum Dis 2004;63:382–5.
24. Karim Z, Wakefield RJ, Quinn M, et al. Validation and reproducibility of ultrasonography in the
detection of synovitis in the knee: a comparison with arthroscopy and clinical examination.
Arthritis Rheum 2004;50:387–94.
25. Szkudlarek M, Narvestad E, Klarlund M, et al. Ultrasonography of the metatarsophalangeal joints
in rheumatoid arthritis: comparison with magnetic resonance imaging, conventional radiography,
and clinical examination. Arthritis Rheum 2004;50:2103–12. Chapter One Principles of ultrasound 11
26. Naredo E, Bonilla G, Gamero F, et al. Assessment of inflammatory activity in rheumatoid
arthritis: a comparative study of clinical evaluation with grey scale and power Doppler
ultrasonography. Ann Rheum Dis 2005;64:375–81.
27. Koski JM. Ultrasound-guided injections in rheumatology. J Rheumatol 2000;27:2131–8.
28. Nofsinger C, Konin JD. Diagnostic ultrasound in sports medicine: current concepts and advances.
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NORMAL SONO-ANATOMY OF MSK TISSUES IS VERY IMPORTANT TO KNOW, AND MAKE ABOUT 90% OF THE WAY TO KNOW THE PATHOLOGY.
THANKS TO DR .AHMED . F. ABOGAMAL FOR HIS GREAT EFFORT
Tendons are characterized by their parallel course with respect to the skin surface and by a typical fibrillar echotexture that is clearly detectable in longitudinal scans.
The fibrillar echotexture is generated by parallel running fascicles of collagen fibres, which appear as closely positioned, fine hyperechoic lines with even finer anechoic thin lines in between, corresponding to inter-fascicular ground substance. Fig.6
On tendons with a synovial sheath, a subtle anechoic rim interposed between the sheath and the tendon margin can be detected.1
Fig.7: Tendon transverse:
A: sonographic picture,T= tendon, B= bone.
B: Tissue specimen of the same picture, T= tendon,B= bone.
In transverse scans, tendons appear as round or oval structures, characterized by numerous closely joined dots that are homogeneously distributed and correspond to the intra-tendinous connective fibers.
The tendon’s sonographic characteristics in healthy subjects are fairly homogeneous and have limited intra- and inter-individual variability.1 Fig.7
They are made up of two components: the muscle fibers, which are long and cylindrical in structure, representing the cellular unit of muscle, and stromal connective tissue.
Individual muscle fibers are grouped together in bundles, which are commonly known as fascicles, and several fascicles join together to form an individual muscle (Fig. 8).
Thin connective tissue strands – the endomysium – separate the individual muscle fibers; a more substantial connective sheath with small vessels and nerve endings, the perimysium (also referred to as fibroadipose septa), envelops individual fascicles; a thick fibrous layer, the epimysium, surrounds the entire muscle. 2,3 , Fig.8.
Fig.8: Muscle fiber: cross-section (coated from van Holsbeeck and Introcaso, 2001).3
The fasciculi can be identified as separate structures on ultrasound.2, 3 They are best identified in the longitudinal plane as hypoechoic cylindrical structures, separated by the hyperechoic intervening connective tissue, the perimysium (fig 9,10).
Individual fibers and the endomysium are not individually discernible. The epimysium, fascia, and intermuscular fat are all thin, linear hyperechoic structures on ultrasound.
During contraction of a muscle, the fibers shorten, causing an apparent increase in muscle bulk. When the muscle is contracted, the fascicles have a thicker and more hypoechoic appearance.3
Fig.9: Muscle longitudinal: A: sonographic picture F = fascia, M = muscle. B: Tissue specimen of the same picture, F = fascia, M = muscle. (coated from van Holsbeeck and Introcaso, 2001).3
Fig.10: Muscle Transverse: A: sonographic picture F = fascia, M = muscle. B: Tissue specimen of the same picture, F = fascia, M = muscle. (coated from van Holsbeeck and Introcaso, 2001).3
Ligaments are fibrous structures appearing similar to tendons. However, they are less compact and are composed of a more diverse pattern of collagen bundles.4
Ligaments are usually well defined and easily visible on ultrasound examination. However, when they occur as a focal thickening of a joint capsule, they may not be distinguishable as distinct structures.
Ligaments display a hyperechoic, linear appearance on ultrasound and are optimally evaluated when they are stretched.5, Fig.11
Similar to tendons, ligaments appear fibrillar during longitudinal scanning and have a broom-end appearance on transverse scans.
However, ligaments can be distinguished from tendons by tracing them back to the bony structures to which they attach.4
Fig.11: Ultrasound image of medial collateral ligament reveals the superficial ligament (arrows) and meniscofemoral ligament (mf) and meniscotibial ligament (mt) attached to the meniscus (asterisk).
A peripheral nerve is a cordlike structure containing a large number of individual nerve fibers.
The nerve fibers are grouped together into bundles known as fascicles Fig.12. The fascicles are enclosed in a connective tissue sheath or membrane known as the epineurium.
Each fascicle is in turn covered by a sheath of connective tissue, the perineurium. The individual nerve fibers within the fascicle are also enclosed by a sheath of connective tissue, the endoneurium.
Extending inward from the epineurium is the interfascicular epineurium, which is thin septae adding further support to the nerve bundles and their vascular supply. 6, 7.
Fig.12: Peripheral nerve: cross section (coated from van Holsbeeck and Introcaso, 2001).3
Ultrasound, in the longitudinal axis of the nerve, demonstrates a fascicular pattern of uninterrupted hypoechoic bands with intervening linear interrupted hyperechoic bands Fig.13.
The hypoechoic bands represent the fasciculi and the hyperechoic bands the supporting interfascicular epineurium.
The epineurium is hyperechoic and of similar appearance to perineural fat and may not be separable on ultrasound.
In the axial study, the nerve is composed of fasciculi seen as multiple hypoechoic dots, which may be of varying size, intermingled in a hyperechoic background of the supporting connective tissue.2, 8–10
Fig.13: Ultrasound image of median nerve (A= long axis, B= short axis) shows hypoechoic nerve
fascicles (arrowheads). t = flexor digitorum tendon, p = palmaris longus tendon, R = radius, L = lunate.
Ultrasound provides limited views of bones. It can display vivid anatomic details of the cortical surfaces of the superficial bone.5
Bones appear with well-defined, linear, and smooth hyperechoic borders. This hyperechoic appearance is caused by the high reflectivity of the acoustic interface.
Because nearly the entire sound beam is reflected, ultrasound is unable to image beyond the bone surface or that of other calcified structures, so the image beyond the interface appears black; this is referred to as posterior acoustic shadowing.4
Because of this phenomenon, Ultrasound can provide information only about the superficial portion of bones Fig.14.
Fig.14: US appearance of normal bone: surface echotexture. a Longitudinal 12–5 MHz US image obtained over the diaphysis of the radius demonstrates the bone surface as a continuous straight hyperechoic line (arrows) produced by a strong reflection of sound due to the marked difference in acoustic impedance of the soft tissues and bone. Reverberation artifact (arrowheads) projecting in the shadow beyond the bone can be seen.
Synovial joints are the most common joints examined with ultrasound. They are formed by articulating bone surfaces, fibrous capsules, and ligaments, and other intraarticular structures (ligaments, menisci, labra, and fat pads) 2, Fig.15.
Ultrasound examination of joint surfaces reveals a homogeneously smooth hypoechoic smooth linear band (the hyaline cartilage).11,12
The joint capsule appears as a hyperechoic line merging with the para-articular tissues.2 The deeper subchondral bone is a regular, continuous, bright, hyperechoic line.
Fig (15): Elbow joint anterior longitudinal veiw:A: sonographic picture, M= muscle, F= fat pad, CA= cartilage, R=Radius phalanx, H= humerus,JS= joint space. B: Tissue specimen of the same picture. (coated from van Holsbeeck and Introcaso, 2001).3
Cartilage can be divided into hyaline cartilage, white fibrocartilage, and elastic or yellow fibrocartilage.
The latter is present in only select regions, e.g., the auricle of the external ear.
Articular hyaline cartilage is of varying thickness, being thicker in points of greater stress and on convex rather than concave surfaces.
It provides a degree of elasticity and shock absorption, as well as helping to dissipate stress across a joint.6,7 On ultrasound, it has a smooth, well-defined surface and border and is uniformly hypoechoic.3, Fig.17.
Fig.17: Articular hyaline cartilage:A: sonographic picture, S= Skin, C= cartilage, B=bone. B: Tissue specimen of the same picture(coated from van Holsbeeck and Introcaso, 2001).3
It’s a variable mixture of white fibrous tissue and cartilaginous tissue with a large component of collagen fibrils.
It provides elasticity and flexibility. The menisci of the knee, temporomandibular and sternoclavicular joints, the glenoid and hip labra, and the triangular fibrocartilage of the wrist are composed of fibrocartilage.
On ultrasound, fibrocartilage is hyperechoic with well-delineated borders. Because of its position within joints, it is not always fully accessible to a full ultrasound examination.3, Fig.18
Fig.18: Fibrocartilage. The posterior glenoid labrum (arrow) is demonstrated here as a well-defined, hyperechoic triangular structure between the articulating surfaces of the glenoid (G) and humerus (H).
Normal bursae in healthy subjects are not always easily visualized. They appear as a thin hypoechoic space delimited by echoic borders corresponding to the tissue–fluid interface.
Bursitis is characterized by an increase in the synovial fluid that usually appears as a sharply defined anechoic area.13, Fig.16.
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