Ovarian Stromal Tumors: A Rare Cause of Postmenopausal Virilization

DISCUSSION

Androgen-secreting ovarian tumors represent about 1% of all ovarian neoplasms.  Steroid cell tumors  (SCT)  are among  the less common variants, which account for less than 0.1% of all ovarian  tumors.

1,2  The SCTs  are  tumors composed of cells that resemble steroid hormone-secreting cells.  The three major categories of SCTs  are  stromal luteoma,  Leydig  cell tumors  that lack Sertoli cell  or stromal component, and steroid cell tumor not otherwise specified (NOS).3,4 

In a review of 105 steroid cell tumors of the  ovary, stromal luteomas account  for about 22% of cases.5 These benign functional neoplasms, first described by Scully in 1964, are believed to be of stromal derivation, originating from luteinized cells or their precursors,  or undifferentiated spindle cells of the ovarian stroma.6 About 60% of cases present  with estrogenic manifestations,  and only 12% of cases are androgenic.1,2  They are usually encountered in postmenopausal women, typically  during workup for abnormal bleeding or for virilizing/feminizing symptoms.2,6 Occasionally, they may occur as unsuspected findings during surgery.7  Some reported estrogenic manifestations include endometrial hyperplasia and well-differentiated endometrioid adenocarcinoma.2

A previously reported case  of an undifferentiated NOS steroid cell tumor presented with hirsutism, amenorrhea, clitoromegaly, and temporal baldness.8 In our  patient’s case, hirsutism was associated with signs of virilization in the form of  deepening  voice, clitoromegaly, frontal baldness and increased muscularity.  In androgen-secreting ovarian tumors,  serum testosterone levels are often high, but DHEA-S levels are low.  Our patient also had grossly elevated serum testosterone but normal DHEA-S levels. The diagnosis of these  rare tumors can be problematic, especially  in the case of a small ovarian tumor. These tumors are  typically less than 3 cm in diameter,  which explains  poor  visualization with ultrasonography  and computerized  tomography.4  In previous case reports, selective venous sampling have been shown  to be highly effective in tumor localization.9  However, this is an invasive and operator-dependent procedure with the risk of hemorrhage. A few case reports  have previously described gonadotropin-dependent stromal luteoma, but these tumors could not be localized with imaging techniques. Testosterone, FSH and LH were markedly inhibited following the administration of a GnRH analogue, suggesting a gonadotropin-dependent, testosterone-secreting ovarian tumor; and  implying that a stromal luteoma is not autonomous but is gonadotropin-dependent.10  In our case, computerized tomography incidentally  detected a left adnexal mass, which was not clinically palpable; and was subsequently confirmed  by transvaginal ultrasonography. A different kind of luteoma can appear in pregnancy. In the Philippines, one case of a maternal pregnancy luteoma responsible for virilization of both newborn and mother was  reported, which was not the case in this patient.12

Microscopically, stromal luteomas are composed of round polyhedral cells present in nests that form nodules. Crystalloids of Reinke are conspicuously absent, a distinguishing feature of  stromal luteomas  from Leydig cell tumors.2 In difficult cases, immunocytochemistry provides diagnostic accuracy. The most useful immunohistochemical marker for their identification is alpha-inhibin, which is positive in most neoplasms in the sex cord-stromal group.4  Stromal hyperthecosis has been found in association with stromal luteomas in the surrounding or contralateral ovary in 90% of cases, a feature not seen in our patient.2,12 

In the evaluation of postmenopausal androgen excess, the history and physical examination direct the appropriate laboratory and radiologic evaluation. Testosterone and DHEA-S are the primary hormonal  tests that should be measured.13 A testosterone  level  above  200  ng/dL or DHEA-S level more than  800  ng/mL suggest  the need to evaluate for a tumor of the ovary or adrenal. In a study of 478 women (both premenopausal and post-menopausal) with signs and symptoms of hyperandrogenism, 11  had testosterone  level above 250 ng/dL. However, only one of these 11 had  a  tumor. Of the 10 women with DHEA-S level above  600 ng/mL, none had an adrenal tumor.14

Several reports  have also more recently confirmed that absolute levels  of elevation  of these steroid hormones do not  clearly  differentiate the  etiologies. Some have suggested a 2-  to 5-day  low  dose dexamethasone suppression test.  Failure to suppress baseline elevation of testosterone or DHEA-S is thought  to indicate an ovarian source.15  However, this approach has not been studied among the postmenopausal women.

Pelvic ultrasonography  or magnetic resonance imaging (MRI) is useful in women with elevated testosterone levels to evaluate the ovary. The expertise of the ultrasonographer may influence detection, as most tumors are quite small. A CT or MRI of the adrenals is indicated in the evaluation of patients with high DHEA-S, or signs and symptoms and laboratory abnormalities suggestive of adrenal Cushing’s syndrome.  Although most patients with isolated elevation of testosterone  have an ovarian source of hyperandrogenism, there are rare case reposts of testosterone-secreting adrenal adenomas.16 Thus, imaging the adrenals is useful before proceeding to ovarian surgery.

Data  is  limited concerning the frequency and severity of androgen excess in the menopause. No data  is available concerning long-term effects of altering androgen levels. However, high androgens adversely alter lipid profile with increase LDL, decrease in HDL and  increase triglyceride levels.17,18 There have been recent associations reported between levels of advance glycation end-products and testosterone levels in post-menopausal women, independent of insulin resistance. High testosterone and estrogen  are both  associated with worsening insulin resistance and can worsen hypertension and fluid retention. Recent studies have shown that high testosterone  in women correlate with increased risk for breast cancer and cardiac risk.

18,19 In a group of 390 postmenopausal  women, 104  of these  with history of irregular cycles and hyperandrogenemia had more evidence of coronary artery disease by angiogram, as well as more obesity, metabolic syndrome and diabetes.18,20 This emphasizes the need for thorough evaluation and treatment in postmenopausal women who present with hyperandrogenism.  An interdisciplinary approach to management is strongly recommended.

CONCLUSION

This case highlights the importance of a thorough evaluation in postmenopausal women who present with virilization and hyperandrogenism. The  physical manifestations of androgen excess also portend the serious health risks associated with this condition.The cardiometabolic consequences of hyperandrogenemia, particularly due to underlying  insulin resistance, leading to diabetes, dyslipidemia and worsening hypertension, should also be evaluated and treated. 

SIÊU ÂM DOPPLER ĐÁNH GIÁ THẬN TIỂU ĐƯỜNG TYPE 2

Discussion


In this study, the renal volume of the diabetic patients was significantly higher than that of the nondiabetic controls. The kidney volume corrected for body surface area (renal area index) was increased by 26% in the diabetic patients. Stratifying for the degree of proteinuria, the greatest degree of nephromegaly was present in the normoalbuminuric patients with normal renal function (Figures 2 and 3). Diabetic kidney hypertrophy-hyperfunction syndrome is a well-established phenomenon that precedes changes in albuminuria by several years and predicts progression into microalbuminuria and overt renal disease. Renal enlargement occurs shortly after the induction of hyperglycemia, and it has been shown that the protein content rises in parallel to the kidney weight. Similarly, an increased protein to DNA ratio has been measured after a few days, indicating hypertrophy of the cells. In a longitudinal study of 146 normoalbuminuric patients, an increased kidney volume at baseline, but not hyperfiltration, was a predictor of progression to microalbuminuria in 27 patients.



The increase in renal volume during the early phase of diabetic nephropathy observed in diabetic patients could be associated with a reduction in the surface ratio of capillaries to tubules and might cause reduced perfusion and interstitial fibrosis. Hyperfiltration and hypertrophy are the first abnormalities seen in the kidneys in both types of diabetes and can be ideal parameters for intervention because the GFR is well preserved. The structural and functional changes are all reversible and can be decreased by improving metabolic control, strict blood pressure control, and treatment with angiotensin-converting enzyme inhibition or angiotensin 2 receptor blockade. From a clinical viewpoint, hyperfiltration is not a parameter of practical value for daily management of patients because it is too problematic to measure, whereas kidney volume measurement could be a potential tool for early identification of diabetic nephropathy. In this study, nephromegaly was the only detectable alteration in the diabetic patients during the prealbuminuric phase, when renal abnormalities are not detectable by the noninvasive methods normally used and recommended by the scientific community for diabetic nephropathy screening.

In animal models, prevention of early hypertrophy-hyperfunction has already been shown to avoid the development of diabetic nephropathy. Future studies will need to address the independent role of nephromegaly not only in the evolution of albuminuria but also in the subsequent decline of the GFR and whether it is a marker of glycemic control or exerts a pathogenetic role in human diabetic nephropathy.

In this study, higher RI values were also observed on Doppler sonography in the diabetic patients (Figures 1B and 4). Major variations were detected at advanced stages of diabetic nephropathy but less so in the early course of nephropathy (Figure 4 and Table 2).

The RI used to grade intrarenal resistance with sonography represents the intrarenal resistance downstream of the measuring site. It is the easiest of all known resistance parameters to record, correlates with biopsy results, and might aid in the management of renal disease. Radermacher et al  reported an RI of 0.8 or higher to be the strongest predictor of allograft loss among  risk factors included in a multivariate analysis, and the RI was correlated with several histologic markers of intrarenal damage.

The RI increase in our group of diabetic patients did not depend on the chronologic age but on the duration of diabetes. This finding can be an indication of a disease-specific alteration. How much the 3 different renal vascular beds (preglomerular vessels, glomerular capillaries, and postglomerular vessels) contribute to the elevated RI is unclear. In diabetic patients, renal artery disease is more frequent in the intrarenal vessels than in the main renal artery, and it is possible that during the very early prealbuminuric phase, patients have more pronounced vasoconstriction, even without overt nephropathy.

A possible explanation for our study results may be the following: (1) at an early stage of the disease, renal damage is located primarily in the glomeruli, in which case, a normal RI would be expected; and (2) at an advanced stage of the disease, the glomeruli become sclerotic, and tubules become atrophic with increasing interstitial fibrosis. All of these factors can lead to an increase in the RI. Moreover, advanced arteriosclerosis in intrarenal arteries at an advanced stage of diabetic nephropathy may contribute to the increase in the RI. Therefore, renal hypertrophy and the increase in the RI could represent two different phases: renal enlargement is a prealbuminuric reversible step of renal involvement in diabetes mellitus, whereas the RI increase indicates the progression of disease with renal scarring, which precedes the appearance of albuminuria.

There is evidence that suggests that the risk of developing diabetic nephropathy begins when urinary albumin excretion values are still in the normoalbuminuric range; however, excluding biopsy, no humoral or imaging parameter exists that can reveal earlier stages of nephropathy. Diabetic nephropathy is a progressive condition that often heralds increasing creatinine as the final manifestation, and as it evolves, the risk of cardiovascular complications increases. At present, treatment during the later stages of the condition is unable to preserve renal function or alter the burden of cardiovascular events. Future research could evaluate whether the progression of nephropathy and cardiovascular morbidity and mortality could be prevented by early treatment in patients with an increased renal volume, a higher RI, or both. Sonography may identify patients with nephropathy at a very early stage and may contribute to early diagnosis and prevention of disease progression.

Abbreviations:
GFR=glomerular filtration rate, MR=magnetic resonance, RI=resistive index

© 2013 by the American Institute of Ultrasound in Medicine

Cervical Elastography for Prediction of Successful Induction of Labor at Term

Discussion

The exact process from cervical ripening to effacement and dilatation is not clearly established. However, several elements, including ecorin, hyaluronic acid, hormones,cytokines, and proteases, are involved in this process, reducing collagen levels and cell components within the cervix while increasing the water content, all leading to the softening of the cervix.  Cervix shortening may follow ripening but not always, as seen in cases of term deliveries with a reduced cervical length measured from the mid second trimester. Thus, evaluation of not only the cervical length but also the mechanical properties of the cervix should be included to predict successful induction of labor.

Only a few attempts have been made to objectively evaluate the cervical consistency with  sonography. One study  reported that cervical consistency can be evaluated by measuring the difference of echogenicity in the anterior and posterior cervical lips on a vaginal grayscale sonographic histogram. A disadvantage is that the echogenicity of the cervix can be affected by gain and artifacts such as reverberation.  Thus, another way to measure cervical consistency is needed, based on the physical properties of the cervix. The main issue with elastography of the cervix is the lack of reference tissue for comparison. Elastography is most useful when there is adjacent tissue of differing stiffness (ie, tumor imaging). Thus, elastography of malignant tumors can be useful because it increases the contrast between adjacent tissues of differing stiffness. However, the cervix is nearly uniform and changed in toto. Considering the limitations of cervical elastography, this study was performed and showed that it was possible to quantify the whole elastographic data of the cervix and that imaging analysis could be applied to cervical elastography to predict successful induction of labor in nulliparous women at term. Moreover, the intraobserver and interobserver variability for cervical elastographic data shows that imaging analysis was reliable and reproducible.

The application of elastography in the cervix of pregnant woman is at a rudimentary stage. In particular, the elastographic method used to evaluate solid tumors in the prostate, breast, and thyroid gland cannot be directly transferred to measuring the cervix in a pregnant woman.

A tumor in a solid organ is relatively round and can be compared with surrounding normal tissue. However, a normal cervix in a pregnant woman has no abnormal tissue or a typical shape that is different from round. In addition, to adequately assess the status of the cervix, data obtained from the entire cervix are needed. If the analytic method of elastography used for solid tumors is applied to the cervix of a pregnant woman, the predicted problems are as follows: the color in a cervical elastographic image is not homogeneous, and the area colored the same is not circular but very irregularly shaped. Thus, the scoring method using color in small circular areas of the cervix in previous studies seldom reflects the whole cervix and is subjective. Especially, if the uterine cervix is shortened or funneled, it is difficult to select and score the several small circular areas in the cervix. However, these problems can be resolved by the imaging analysis technique introduced in this study. By using a different imaging analysis technique, the whole cervix can be included for evaluation; the area can be selected regardless of shape; and the data are objective and automatically calculated by a computer.

During the prenatal period, the main changes in the cervix include softening, ripening, and dilatation.  If the cervical length or cervical area is correlated with cervical dilatation, the softening and ripening of the cervix can be reflected by cervical elastography. In this study, the combinations of cervical length or cervical area + mean elastographic index or cervical hard area were modeled to improve prediction. This study indicates that elastography is a technique that can be applied to examine the cervix of pregnant women.

Although the imaging analysis used in this study was able to resolve some problems originated by the application of elastography in the cervix of pregnant women, other limitations remain. There were no reference data to show the elastographic status of the cervix according to the gestational age in normal pregnant women. The physiologic modifications of breathing and arterial pulsation could play a role in the variability of tissue displacement. The elastographic image can be changed by pressing the probe with different pressure levels. To overcome this problem, we tried to apply no pressure and just touch the cervix with the probe after insertion. Of course, although we tried to maintain steady pressure, we could not stop all minimal shaking. Therefore, to evaluate whether the changes made by this minimal shaking could affect the elastographic results, we performed the intraobserver and interobserver reproducibility test for imaging analysis of the elastographic results. There were 2 limitations to the intraobserver and interobserver test in this study. For intraobserver reproducibility, a minimum 2-week interval is required between reviews of the same image to avoid recall bias. The periods between each review in our study were just 20 minutes. The other limitation was that there were some large 95% CI values. Nevertheless, imaging analysis of cervical elastography can be a good method for evaluating the cervical status when used together with the cervical length. This finding can be applied to other clinical studies, such as the prediction of preterm birth, breast cancer detection, and thyroid mass evaluation.

In conclusion, imaging analysis of cervical elastography to predict successful induction of labor in nulliparous women at term is objectively quantifiable, reliable, and reproducible. Future studies should be performed to determine the effect of the combination of cervical length and cervical elastographic parameters and to resolve the remaining limitations of cervical elastography.

CYSTIC PARATHYROID ADENOMA

Girish M Parmar, et al: Cystic Parathyroid Adenoma in Four Patients from India,

JAFES,  Vol. 27 No. 2 November 2012

 

DISCUSSION

 

Here we describe  4  cases with cystic lesions of the parathyroid gland. Three of these (Cases  1,2  and  3) had parathyroid adenomas with cystic degeneration whereas Case 4 had  a  true parathyroid cyst. Cystic lesions of the parathyroid gland are rare (0.5%–1% of all parathyroid pathologies).  Macroscopic cysts larger than 1 cm in diameter are referred to as parathyroid cysts and necessitate further investigation. Some investigators have suggested that the true prevalence of parathyroid cysts remains uncertain and that these lesions may occur more frequently than is generally appreciated.Cystic lesions of the  parathyroid gland can be  either due to true parathyroid cyst  as seen in Case 4, or due to cystic degeneration of parathyroid adenoma as seen in Cases 1, 2 and 3. Most of the parathyroid gland adenomas are solid while cystic degeneration is seen in 1-2% of patients with primary hyperparathyroidism.

 

Approximately 90% of true parathyroid cysts are classified as nonfunctioning cysts  with normal calcium concentrations  and 10% are functioning cysts  with elevated calcium concentration. However,  in one study, functioning parathyroid cysts were more common. A true parathyroid cyst needs to be differentiated from  a parathyroid adenoma with cystic degeneration. Parathyroid cysts are more frequent in females between 20 to  60 years of age,  whereas parathyroid adenomas are more common after 50 years of age.

 

Patients with true nonfunctional parathyroid cysts present with compressive symptoms. On the other hand, patients with true functional parathyroid cysts  and patients with cystic  parathyroid adenoma  present with signs and symptoms of hypercalcemia. 

 

Parathyroid cysts are of variable sizes, ranging from 1 to 10 cm in greatest dimension, with the average cyst measuring approximately 3 to 5 cm. In 85  - 90% of cases, they are located in the neck and often involve the inferior parathyroid glands. In 5 - 10% of cases they have been detected  at ectopic sites  anywhere from the angle of the mandible to the mediastinum. The mediastinal location of the parathyroid cyst can be ascribed to two factors. First, the cyst may descend into the mediastinum because of  its weight and negative intrathoracic pressure. Second, an aberrant mediastinal parathyroid gland may give rise to the cyst.  

 

 

Degeneration of an existing parathyroid adenoma secondary to hemorrhage into the adenoma, also results in cyst formation. The other different theories proposed are: (1) retention of glandular secretions, (2) persistence of vestigial pharyngobranchial ducts, (3) persistence of Kursteiner's canals, (4) enlargement of a microcyst, or (5) coalescence of the microcysts. None of these theories are

universally applicable, and the processes leading to cyst formation may well differ from one person to the next.

Ultrasonography may reveal a nonspecific cystic structure. Analysis of the aspirate generally reveals elevated PTH level, diagnostic of parathyroid cyst.Nonfunctional parathyroid cysts  have  high  fluid PTH

concentrations, in conjunction with normal serum PTH concentrations.

In functional parathyroid cysts, cystic fluid PTH levels can reach several million pg/ml.PTH levels in the cystic fluid were measured only in the fourth patient. 

 

The histologic distinction between a cystic parathyroid adenoma and the rare functional parathyroid cyst is made by the former having a preponderance of chief cells with multilocular degenerative thick-walled cysts and the latter usually consisting of a unilocular thin-walled cyst. 

 

Treatment strategies for parathyroid cysts include surgical excision or aspiration or injection of sclerosing agents.Surgical treatment seems to be the preferred intervention for functional and symptomatic parathyroid cysts as in our patient. Fine-needle aspiration yields the diagnosis and may be considered the treatment of choice for nonfunctional parathyroid cysts. It  leads  to cystic regression without recurrence.

Several reports in the literature support fine-needle aspiration as a therapeutic modality.  For recurrent  nonfunctional parathyroid cysts, sclerotherapy with use of tetracycline and alcohol has also been described. It has been effective but is associated with the risk of subsequent fibrosis and recurrent laryngeal nerve palsy.If  aspiration cannot be done safely or the cyst recurs  after successful aspiration, surgical excision should be done.

Ultrasound-Guided HIFU Used for Treatment of Breast Fibroadenomas

Ultrasound-Guided HIFU Used for Treatment of Breast Fibroadenomas

  

A new noninvasive therapeutic application using ultrasound-guided, high-intensity focused ultrasound (HIFU) is currently being employed for a specifically localized ablation with no skin damage. The ultrasound waves are focused on a small area where the rise in temperature leads to tissue necrosis. This precision avoids injuring healthy tissues around the lesion.

The echotherapy is a technique that enables clinicians to visualize and simultaneously treat a tumor such as fibroadenoma with no incision or scar.

Theraclion (Paris, France; www.theraclion.com), a specialist in cutting-edge medical technology that develops echotherapy technology that uses HIFU, has received the CE marking approval for the noninvasive treatment of breast fibroadenomas, a first for this indication.

“The CE marking widens the use of our technology in the major area of breast fibroadenoma.

Our technology can now be offered to all women suffering from this pathology in Europe. They can benefit from a noninvasive outpatient treatment without general anesthesia which puts an end to the embarrassment and anxiety triggered by this kind of tumor. Noninvasive focused ultrasound surgery guided by real-time ultrasound imaging is consistent with the logic of developing lesser invasive treatments and a reduction of health costs.

This market authorization in Europe will allow us to grow by creating noninvasive surgery centers based on our resulting echotherapy solution within leading hospitals and clinics. Other tumors beside breast fibroadenomas will be treated in a noninvasive manner in the near future,” said Jean-Yves Burel, CEO of Theraclion.

Fibroadenoma is the most widely spread breast benign tumor, with 10% of women risk developing it in their lifetime. It represents more than half of breast biopsies. This disorder hits women of all ages but is a lot more frequent with women under 30.

Estimates show that 50,000 fibroadenoma tumors are detected each year in France, with 320,000 in Europe and 640,000 in the United States.

“I used the EchoPulse to treat 11 patients during a clinical trial at the American Hospital of Paris from January to October 2012. The results from this technique are encouraging with a 60% volume reduction of fibroadenoma in an average period of six months. EchoPulse could represent an interesting alternative to classical surgery,” added Dr. Marc Abehsera from the medical imaging service at the American Hospital of Paris.

“It is interesting [to be able to] participate in the assessment of echotherapy in breast fibroadenoma in the French trial. We are hoping to participate in a multicenter trial that will measure the effects of this type of treatment in breast cancer,” stated Dr. Edouard Poncelet from the woman imaging service at the Valenciennes Hospital Center).

A clinical trial on 40 patients has shown the efficiency and the excellent tolerance of echotherapy for this type of pathology. Currently, fibroadenomas have been treated in three French centers (Lille Jeanne de Flandres Hospital, the Valenciennes Hospital, and the American Hospital of Paris) and one center in Bulgaria (the University Hospital of Sofia), with considerable volume reductions accompanied by the resolution of symptoms.

EchoPulse, the medical device developed by Theraclion, uses ultrasound imaging as a targeting system and HIFU for tissue necrosis, thereby eliminating the need for patients to undergo a surgical procedure. EchoPulse is unique as it combines in the same device an imaging monitoring and treatment system while remaining compact and mobile. In addition to its ergonomic benefits, it provides excellent image quality, a millimetric accuracy of wave shots, and an integrated cooling system for the patient’s safety. The benefits offered by EchoPulse are beneficial for the patients (non-invasive, scarless, and mobile treatment, conscious sedation) but also for the practitioners (fast, effective, and harmless) and hospital centers (efficient, less hospitalization costs, one device for several pathologies).

SIÊU ÂM THEO DỎI GAN GHÉP

Download

Liver Transplantation

www.kosmos-design.co.uk/EFSUMB-ECB/ecb-ch27-livertransplant.pdf‎

 

ELASTO ULTRASOUND and LIVER FIBROSIS / EASL 2013 NETHERLANDS

AMSTERDAM -- Although biopsy remains the gold standard for diagnosing liver fibrosis, imaging tests increasingly appear to be a viable way to garner equivalent information with less patient discomfort and risk, researchers said here. In presentations at the meeting of the European Association for the Study of the Liver, scientists from across Europe reported on the strengths and weaknesses of various imaging modalities as tools for routine clinical practice. There was no clear winner among transient elastography, magnetic resonance elastography (MRE), real-time shear wave elastography (RTSWE), and acoustic radiation force impulse (ARFI) imaging, but all appeared to be nearly as accurate as liver biopsy in quantitative assessment of fibrosis and for predicting outcomes such as death and cirrhotic decompensation. The role of liver imaging for these purposes in the U.S. has recently come to the fore with the FDA's clearance last week of the Fibroscan transient elastography device. Fibroscan is the established leader in noninvasive fibrosis imaging and, according to its French manufacturer, Echosens, the U.S. is the last major market to approve its device. All these forms of elastography work by setting up shear waves in the liver. Patterns of propagation of these waves correspond to the degree of liver stiffness, which in turn correlates with the level of fibrosis. All but MRE use ultrasound to generate the waves. Studies presented here evaluated one or more of these technologies against another, with or without liver biopsy as a reference standard, and in a variety of patient populations.

Transient Elastography Versus Biopsy

Perhaps the most direct assessment was reported by Juan Macias, MD, of Hospital Universitario de Valme in Seville, Spain. He reported a retrospective analysis of 297 patients coinfected with HIV and hepatitis C virus (HCV) who had been tested with liver biopsy as well as transient elastography, with these tests performed within a year of each other. The study period covered 2005 to 2011. Findings indicated that fibrosis stage as established from biopsies and liver stiffness measurements from transient elastography were equally accurate in predicting overall mortality and decompensation of cirrhosis. Kaplan-Meier curves for patients with stage F4 fibrosis (overt cirrhosis) and for those with elastography measurements in the highest quintile (21 kPa and above) were nearly identical through up to 6 years of follow-up, for both all-cause death and for decompensation of cirrhosis, Macias reported. Point estimates of the increased risk for these outcomes were somewhat higher in models based on biopsy findings than in the elastography-based analyses, but the error bars in the latter were markedly smaller. For example, the risk of decompensation doubled with each increase in fibrosis stage (hazard ratio 2.00, 95% CI 1.32 to 3.00), whereas each 5-kPa increase in liver stiffness corresponded to a hazard ratio of 1.42 (95% CI 1.31 to 1.55). "The noninvasive nature of [transient elastography] should favor its use instead of liver biopsy when the only issue is predicting the clinical outcome of liver disease in HIV-HCV coinfection," Macias told attendees.

ARFI Versus Transient Elastography

Acoustic radiation force impulse imaging is another up-and-coming imaging method for liver disease. Like transient elastography, it uses ultrasound to generate mechanical waves within the liver, but the nature of the waves and the interpretation of the resultant patterns differs. Derek Bardou of CHU Angers in Angers, France, noted that the two technologies have been compared head-to-head in previous studies, with pooled data suggesting that ARFI is less accurate. But transient elastography has a significant drawback -- it doesn't work on obese patients. Bardou pointed out that the previous analyses were all conducted on a per-protocol basis, such that patients for whom the transient elastography attempt failed to yield usable results were excluded. He argued that a more stringent "intent-to-diagnose" analysis would be a better reflection of the utility of the two methods in routine practice. From 2009 to early 2013, he and his colleagues used both methods on a total of 267 patients with chronic, noncancerous liver disease (patients with cirrhotic complications or sepsis were excluded) who also underwent liver biopsies. Areas under the receiver-operating characteristic (AUROC) curves for classifying patients' liver disease stage were calculated for both test types, with biopsy results serving as the reference standard. The researchers found that, on a per-protocol basis, AUROC values with ARFI were indeed lower -- indicating poorer accuracy -- than those seen with transient elastography. In this analysis, Bardou and colleagues excluded 6.7% of patients in whom transient elastography could not be performed. ARFI failed in fewer than 1%. But in the intent-to-diagnosis analysis involving all 267 patients, there was no significant difference in AUROC values for the two methods. Bardou added that whole-liver results with ARFI were more accurate than findings only in the right lobe, the "classical" way to perform ARFI, he explained. RTSWE Versus Transient Elastography Versus Biopsy Another study reported here sought to validate real-time shear wave elastography as an alternative -- not necessarily superior -- to liver biopsy. Giovanna Ferraioli, MD, of Italy's University of Pavia, presented findings from 88 patients with chronic liver disease of varied origin and 33 healthy controls. Patients underwent both RTSWE (using the ElastPQ system) and transient elastography as well as biopsy. The controls had only the noninvasive testing. RTSWE, in this study, involved a fixed "sample box" located a maximum of 70 mm below the Glisson's capsule within the liver. Patients held their breath for 2 to 4 seconds and 10 images were collected, with the median stiffness value in kPa used as the final result. As the name suggests, and unlike transient elastography, RTSWE delivers readings almost immediately. In some studies, it has appeared to be more accurate as well. Both imaging methods showed stiffness values that progressed upward with the degree of fibrosis ascertained with the biopsies. RTSWE yielded somewhat more detail, in that the median values for each patient group stratified according to fibrosis stage (F0/1 to F4) tracked steadily higher. Transient elastography results for patients with F2 fibrosis, on the other hand, were nearly identical to those with F0/1 disease (5.45 versus 5.5 kPa). Ferraioli and colleagues found that, as expected, RTSWE values in the healthy controls were lower than in patients with liver disease (median 3.3 kPa, interquartile range 3.7 to 4.0). Transient elastography readings tended to be higher (median 3.8 kPa, interquartile range 4.5 to 5.0) and overlapped in the controls with those from patients with liver disease (median in F2 patients 5.45, interquartile range 4.3 to 8.0). RTSWE "compares favorably" with transient elastography, Ferraioli concluded.

MR Elastography Versus Biopsy

Use of MRI equipment to analyze liver stiffness is an even newer approach. It, too, can be used to generate vibrations that propagate through the liver. Rocio Gallego-Duran, also of the Hospital Universio de Valme, reported on a validation study in which artificial neural networks were used to generate elastography values from MRI scans. Her study involved 63 patients with biopsy-confirmed non-alcoholic fatty liver disease, including 32 with non-alcoholic steatohepatitis (NASH) and 25 with significant fibrosis. The first 22 of these patients were used as a "training cohort" for fine-tuning the software settings to match biopsy results as closely as possible. The resulting model was then tested in the remaining 41 patients, serving as a validation cohort. For diagnosing NASH, the model showed sensitivity of 77% and specificity of 90%, Gallego-Duran reported. Positive and negative predictive values were 89% and 79%, respectively. The model was not quite as good at diagnosing fibrosis. With the best-performing cutoff values, sensitivity was 87% but specificity was only 63%. As a result, the positive predictive value was just 59%, although the negative predictive value was a respectable 89%. Gallego-Duran told attendees that the MRI-based technique holds some potential advantages over the ultrasound-based methods. Because it produces high-resolution images of the entire liver, it may provide a fuller picture of liver disease and can also reveal other types of liver injury. Patients' body fat also is not an issue for image quality, as it is for transient elastography, she said.

None of the studies had commercial funding.

All of the presenters declared that they had no relevant financial interests.

Primary source: European Association for the Study of the Liver Source reference: Macias J, et al "Performance of liver stiffness compared with liver biopsy to predict survival and decompensations of cirrhosis among HIV/HCV-coinfected patients" EASL 2013; Abstract 20.

Additional source: European Association for the Study of the Liver Source reference: Bardou D, et al "First intention-to-diagnose comparison of ARFI and Fibroscan in chronic liver diseases" EASL2013; Abstract 15. Additional source: European Association for the Study of the Liver Source reference: Ferraioli G, et al "Performance of ELASTPQ® shear wave elastography technique for assessing fibrosis in chronic viral hepatitis" EASL 2013; Abstract 16.

HÌNH ẢNH vài BỆNH NHIỄM KÝ SINH TRÙNG ở GAN

Download bài từ EFSUMB-ECB

US in Tropical disease

 

http://www.kosmos-design.co.uk/EFSUMB-ECB/ecb-ch26-tropicaldiseases.pdf