DIAGNOSIS of INCISIONAL HERNIA: DYNAMIC ULTRASOUND versus CT

Femoral hernias, Henry Robert Whalen, Gillian A Kidd, Patrick J O’Dwyer

BMJ2011;343doi: http://dx.doi.org/10.1136/bmj.d7668(Published 8 December 2011)

Cite this as:BMJ2011;343:d7668

 

An overweight 65 year old woman visits her general practitioner with discomfort in her right groin. On examination, the suggestion of a reducible groin lump is noted. She is routinely referred to the surgical outpatient clinic with a possible diagnosis of inguinal hernia. However, two weeks later and before her surgical appointment, she again visits her general practitioner, this time with vomiting, diarrhoea, and colicky abdominal pain. She is immediately referred to the emergency department. An abdominal radiograph shows small bowel obstruction. She is admitted to the surgical ward with a diagnosis of obstructed femoral hernia and has a small bowel resection and emergency hernia repair.

What is a femoral hernia?

A femoral hernia is the protrusion of a peritoneal sac through the femoral ring into the femoral canal, posterior and inferior to the inguinal ligament. The sac may contain preperitoneal fat, omentum, small bowel, or other structures.

How common are femoral hernias?

·         About 5000 femoral hernia repairs are carried out in the United Kingdom each year

·         Femoral hernias account for a fifth of all groin hernias in females but less than 1% of groin hernias in males

·         The 40% of femoral hernias that present acutely are associated with a 10-fold increased risk of mortality1 2

Why is a femoral hernia missed?

Evidence is scarce as to the reason why femoral hernias are often missed and present as emergencies. Patients may be aware of groin discomfort or a groin lump, but they may not realise its clinical importance and may be reluctant to seek medical help. Initially some patients present to primary care with vague symptoms including groin discomfort that may be attributed to other disease such as osteoarthritis. As femoral hernias are typically small, they may be easily missed on examination, particularly in obese patients. Furthermore, owing to the difficulty in clinically distinguishing groin hernias, femoral hernias may be mistaken for inguinal hernias and referred for surgical opinion on a non-urgent basis.3

In an emergency, patients may present with signs of bowel obstruction, which include colicky abdominal pain, vomiting, and abdominal distension. About a third of patients do not complain of symptoms directly attributable to a hernia,4 and a groin lump is not always present. Other diagnoses, such as gastroenteritis, enlarged groin lymph node, diverticulitis, or constipation, may be made in error.⇓

Inguinal hernias are usually reducible and above the inguinal ligament. Femoral hernias are often irreducible and below the inguinal ligament. Adapted with permission from Ellis H. Clinical anatomy. 6th ed. Blackwell Scientific, 1977

Retrospective studies have observed that about 40% of hernias causing symptoms of acute bowel obstruction are missed owing to a lack of groin examination.5 6 The researchers concluded that female patients and all patients with femoral hernia were less likely to have a groin examination, despite signs of bowel obstruction being noted.5

Why does this matter?

Although femoral hernias are less common than inguinal, they are associated with higher rates of acute complication. The cumulative probability of strangulation for femoral hernias is 22% three months after diagnosis, rising to 45% 21 months after diagnosis, whereas the probability of strangulation for an inguinal hernia is 3% and 4.5% respectively over the same time period.7

Several studies have shown that acute femoral hernias and their subsequent complications are associated with increased morbidity and mortality.1 2 8 9 10 Examples of morbidity resulting from acute presentation include increased rates of bowel resection, wound infection, and cardiovascular and respiratory complications.10 As elective femoral hernia repair has been shown to be a relatively safe procedure (even in patients aged over 80), it is generally accepted that femoral hernias should be referred urgently and repaired electively.2 10 11 12

Missed femoral hernia at emergency presentation delays time to surgery.5 One study has shown an increased likelihood of bowel resection if surgery is undertaken more than 12 hours after the onset of acute symptoms.13 Preoperative delay is clearly linked with an increase in bowel resection, and this is associated with mortality rates that are about 20 times higher than those for patients having elective hernia repair (which would not require a bowel resection).2

How is it diagnosed?

Clinical

Classically, femoral hernias present as mildly painful, non-reducible groin lumps, located inferolateral to the pubic tubercle. In contrast, inguinal hernias are found superomedially. However, femoral hernias tend to move superiorly to a position above the inguinal ligament, where they may be mistaken for an inguinal hernia. Differentiation of groin hernias on clinical grounds is therefore unreliable, irrespective of the experience of the examining doctor.14 In patients presenting electively, only about 1% of groin hernias in males are likely to be femoral, whereas the likelihood in females is about 20%.1 Clinical examination alone is inaccurate in differentiating groin hernia.14 Therefore in females, owing to the greater prevalence of femoral hernia, consider all groin hernia to be femoral until proved otherwise.

Femoral hernias may also present without a palpable lump and with only vague symptoms of abdominal or groin pain. However, symptoms may vary and there is a lack of evidence to predict the likelihood of a particular symptom indicating the presence of a femoral hernia. Patients may present later with clinical features of bowel obstruction. Undertake a detailed groin examination in all patients presenting with bowel obstruction.

Investigations

Ultrasonography, magnetic resonance imaging, and computed tomography (CT) have all been shown to be accurate in detecting and differentiating groin hernias.

Ultrasonography is widely available, non-invasive, and highly accurate in differentiating inguinal from femoral hernia—with sensitivities and specificity of 100% being reported in two studies.15 16 Its accuracy is, however, operator dependent.

Magnetic resonance imaging has been reported to be more accurate than ultrasonography in detecting inguinal hernia.17 However, there is a lack of evidence for whether magnetic resonance imaging is better than ultrasonography in detecting and differentiating groin hernia. Therefore ultrasonography should be the first choice for electively investigating suspected groin hernia as it is more widely available, less costly, and accurate.

CT scanning has been shown to be accurate in differentiating groin hernias. One retrospective study reports the correct identification of 74 of 75 hernias (28 femoral and 47 inguinal), which were later confirmed at operation.18 This is broadly comparable with the non-invasive modalities outlined above, but as there is a substantial radiation dose associated with CT scanning, it should not be used electively for investigating suspected groin hernia. In the acute abdomen, however, consider CT as the first choice for investigating suspected small bowel obstruction in the presence of a negative clinical examination.

How is it managed?

In males, a groin hernia suspected as being femoral on clinical examination requires urgent referral, due to the risks of acute complications outlined above. All groin hernia in females should be urgently referred for assessment.

Electively, both open and laparoscopic repair using mesh have significantly lower recurrence rates than repair using sutures only.1 Open repair has the advantage that it can be performed under local anaesthetic. No evidence suggests superiority of either method in the acute setting.

Some research has suggested that femoral hernias may be overlooked during repair of suspected inguinal hernias.19 So during surgical repair of all groin hernias examine the femoral canal if an obvious inguinal hernia is not observed.

Key points

·         Femoral hernias are more common in females and in people aged over 65 years and are associated with higher rates of complications such as strangulation

·         Emergency surgery for femoral hernia is associated with a 10-fold increased risk of mortality, which is further increased by preoperative delays

·         Clinical examination is unreliable in differentiating femoral from inguinal hernia

·         Refer all females with groin hernia for urgent assessment and management

·         Examine the groins of all patients presenting with signs of small bowel obstruction

·         Ultrasound is the first line elective investigation for suspected uncomplicated groin hernia, but in acute small bowel obstruction, CT scanning is first choice

 

ULTRASOUND for DIAGNOSIS of SKULL FRACTURES in CHILDREN

Accuracy of Point-of-Care Ultrasound for Diagnosis of Skull Fractures in Children, Joni E. Rabiner, Lana M. Friedman, Hnin Khine,  Jeffrey R. Avner,  and James W. Tsung

Abstract

OBJECTIVE: To determine the test performance characteristics for point-of-care ultrasound performed by clinicians compared with computed tomography (CT) diagnosis of skull fractures.

METHODS: We conducted a prospective study in a convenience sample of patients ≤21 years of age who presented to the emergency department with head injuries or suspected skull fractures that required CT scan evaluation. After a 1-hour, focused ultrasound training session, clinicians performed ultrasound examinations to evaluate patients for skull fractures. CT scan interpretations by attending radiologists were the reference standard for this study. Point-of-care ultrasound scans were reviewed by an experienced sonologist to evaluate interobserver agreement.

RESULTS: Point-of-care ultrasound was performed by 17 clinicians in 69 subjects with suspected skull fractures. The patients’ mean age was 6.4 years (SD: 6.2 years), and 65% of patients were male. The prevalence of fracture was 12% (n = 8). Point-of-care ultrasound for skull fracture had a sensitivity of 88% (95% confidence interval [CI]: 53%–98%), a specificity of 97% (95% CI: 89%–99%), a positive likelihood ratio of 27 (95% CI: 7–107), and a negative likelihood ratio of 0.13 (95% CI: 0.02–0.81). The only false-negative ultrasound scan was due to a skull fracture not directly under a scalp hematoma, but rather adjacent to it. The κ for interobserver agreement was 0.86 (95% CI: 0.67–1.0).

CONCLUSIONS: Clinicians with focused ultrasound training were able to diagnose skull fractures in children with high specificity.

Ultrasound Technique

Before the start of the study, all enrolling PEM attending and fellow physicians attended a 30-minute didactic session to learn how to use ultrasound to evaluate the skull for fracture and to standardize the method in which bedside ultrasound was performed by participating physicians, followed by a 30-minute hands-on practical session.

A reference manual complete with instructions and images was available throughout the study. All study sonologists except for one were novices to musculoskeletal ultrasound at the start of the study. We defined an experienced sonologist as having performed egal or more 25 musculoskeletal ultrasound examinations, which is the minimum recommended number of scans for ultrasound credentialing per American College of Emergency Physicians Emergency Ultrasound Guidelines.

SonoSite ultrasound systems (SonoSite Inc, Bothell, WA) with high-frequency linear transducer probes (10–5 MHz) were used to perform focused ultrasound examinations to evaluate for skull fracture. Ultrasound gel was layered onto the ultrasound probe, and then the probe was lightly applied to the scalp to avoid pressure on the injured skull. The transducer was placed over the area of soft tissue swelling, hematoma, point of impact, or point of maximal tenderness (Fig 1). Scans were performed in 2 perpendicular  planes, and still pictures and video clips were recorded in each orientation. Skull suture lines were differentiated from skull fractures by following suspected sutures to a fontanelle. If a suspected fracture crossed a suture line or fontanelle, the contralateral area on the skull was imaged for comparison.

The sagittal, coronal, and metopic sutures can be traced to the anterior fontanelle, and the lambdoid sutures can be traced to the posterior fontanelle. The squamous sutures, however, may be difficult to follow to an open fontanelle, but sonologists were encouraged to scan the contralateral area of the skull for comparison. A diagram of suture anatomy was included in the study reference manual.

DISCUSSION

We have demonstrated in the largest cohort of patients to date that with a 1-hour, focused musculoskeletal ultrasound training session, novice sonologists are able to quickly and accurately diagnose skull fractures with high specificity. Previous data on ultrasound by radiologists for skull fracture diagnosis revealed high accuracy.17,20 In addition, studies of ultrasound by clinicians with focused training have also revealed rapid and accurate diagnosis of skull fractures with point-of-care ultrasound. 15,18,19 In our study, as with most ultrasound applications, the specificity was higher than the sensitivity (Table 3).

Clinical assessment may not be completely reliable for predicting skull fractures and intracranial injuries in children. 24 In our data, 2 of 39 (5%)patients assessed to have a 2% to 25% likelihood of fracture and 3 of 9 (33%)assessed to have a 26% to 50% likelihood of fracture after obtaining the history and physical examination had confirmed skull fractures (Table 2). In addition, of the 4 patients in our study who had reported palpable skull fractures on physical examination, only 2 (50%) had confirmed skull fracture by CT scan.

In current practice, head CT serves as the gold standard diagnostic test to evaluate for skull fractures and intracranial bleeding after head trauma. However, there are several advantages of using point-of-care ultrasound in the detection of skull fractures. First,ultrasound can be performed rapidly, which can allow earlier detection of skull fracture as a marker for suspected intracranial injury and neurosurgical consultation. Second, point-of-care ultrasound has the potential to reduce CT use and ionizing radiation exposure in children. The estimated lifetime risk of cancer froma head CT is substantially higher for children than for adults because of a longer latency period and the greater sensitivity of developing organs to radiation. 4–7 However, intracranial injury may occur without skull fracture, and clinicians must use clinical judgment or decision rules25–28 for obtaining CT scan regardless of the presence or absence of skull fracture. In addition, ultrasound can also be performed in young children without the need for sedation.

Point-of-care ultrasound for skull fracturesmay be especially useful in places without access to CT scan. It has been estimated by the World Health Organization that up to two-thirds of the world’s population does not have access to diagnostic imaging technology, 29 and portable ultrasound may be mplemented in these resource-scarce locations.30 In addition, ultrasound may be useful for triage in mass casualty disasters31 or in austere environments.32 Last, ultrasound may be used in pediatricians’offices or in urgent care centers for patients with suspected isolated skull fracture without ready access to CT scan.

Ultrasound may diagnose minimally or nondisplaced skull fractures that can be missed on CT scan. Recent research has revealed that ultrasound has superior sensitivity to radiography in certain types of fractures, 33 and it has been shown to detect nondisplaced fractures as small as 1 mm. 34 Our study included a case of a 16-year-old male who presented with a boggy frontal scalp hematoma after an assault. Skull ultrasound performed by a novice sonologist was interpreted as positive for fracture and confirmed on expert review (Fig 5B). The CT was read as negative for skull fracture, and the patient was discharged from the ED. On telephone follow-up, the patient was asymptomatic.

Knowledge of suture anatomy is essential in performing ultrasound examinations of infant skulls.18,19 A suture appears symmetric and regular and leads to a fontanelle, whereas a fracture is jagged andmay be displaced. All enrolling sonologists in our study were taught to differentiate sutures from skull fractures by following sutures to a fontanelle. If a suspected fracture crossed a suture or fontanelle, the contralateral area of the skull was imaged for comparison. No errors in our study were due to sutures. There have been several recent studies published on ultrasound for diagnosis of skull fractures in children that involved small sample sizes ofchildren. 15,18,19 Our study adds the largest cohort to the current literature. In addition, pooling our data with these similar studies to forma cohort of 185 patients reveals ultrasound to be highly sensitive and specific for diagnosing skull fractures in children (Table 4). The study by Weinberg et al 15 looked at fracture detection for all bones and included a small subset of patients with suspected skull fracture. In the study by Riera and Chen, 19 few enrolling sonologists with no formalized skull ultrasound training performed skull ultrasound. Parri et al 18 reported a very high prevalence of skull  fracture because they enrolled patients with localizing evidence of trauma. However, all of these studies used clinician sonologists who performed blinded point-of-care ultrasound imaging and compared skull ultrasound with CT as the reference standard. Skull ultrasound may be particularly useful in well-appearing patients with suspected isolated skull fracture on the basis of history and physical examination and low risk for clinically important traumatic brain injury. The question remains whether the absence of skull fracture on ultrasound in selected patients with head injury in the presence of single isolated risk factors for intracranial bleeding can obviate the need for CT scan. Two children in our study, one with isolated scalp hematoma and another with isolated loss of consciousness, had no skull fracture detec ted on ultrasound or CT scan but were subsequently found to have intracranial hemorrhage. Thus, caution is warranted in using ultrasound to rule out intracranial injury, and additional research is needed to fully answer this question.

Our study has several limitations. Our study population consisted of a convenience sample of patients enrolled when a trained physician was available,but the prevalence of skull fractures of 12% in our study is similar to other studies. 15,19,24 Ultrasound is an operator-dependent modality, but because a novice group of sinologists was trained to performskull ultrasound with such high specificity, we believe that our results may be generalizable to other clinicians with focused training. Last, there was a limitation in our ultrasound scanning technique. Our only false-negative result was due to a skull fracture that was adjacent to but not directly beneath the scalp hematoma,and therefore this fracture was missed on ultrasound but confirmed on CT scan(Fig 4). We now recommend scanning the areas around the scalp hematoma if a skull fracture is not visualized directly beneath it, similar to the method proposed by Riera and Chen.19

CONCLUSIONS

Clinicians with focused, point-of-care ultrasound training were able to diagnose skull fractures in children with head trauma with high specificity and high negative predictive value. In addition, almost perfect agreement was observed between novice and experienced sonologists. Pooled analysis of published studies for skull fracture reveals high specificities with variable sensitivities. Future research is needed to determine if ultrasound can reduce the use of CT scans in children with head injuries.

Ultrasound for Diagnosis of Skull Fractures and reduction of ionizing radiation exposure,     Niccolo Parri, Liviana Da Dalt, University of Padova, Department of Pediatrics, Treviso, Italy

To the Editors, We read with interest the paper by Rabiner et al.(1). They demonstrated, in the largest cohort ever reported, the high sensitivity of ultrasound (US) for the diagnosis of skull fractures (SF). Their results seem to be particularly useful for everyday practice because head US have been performed by many unexperted sonographers. However the study seem to suffer from some limitations that, may question the validity of results and conclusions. There is no question that ionizing

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To the Editors, We read with interest the paper by Rabiner et al.(1). They demonstrated, in the largest cohort ever reported, the high sensitivity of ultrasound (US) for the diagnosis of skull fractures (SF). Their results seem to be particularly useful for everyday practice because head US have been performed by many unexperted sonographers. However the study seem to suffer from some limitations that, may question the validity of results and conclusions. There is no question that ionizing radiation exposure in children must be reduced and that US has the potential to reduce it. The authors enrolled a convenience sample of patients < 21 years who underwent a CT because of a head trauma and/or suspected SF based on the decision of the treating physician. It would be worthwhile to state more explicitly that some clinical practice guidelines recommend imaging with CT for head-injured children whose only risk factor is SF. Since the reduction of CT can be obtained by identifying children at very low risk of clinically important traumatic brain injuries (ciTBI), we have concerns about the methods proposed in the article. The Pediatric Emergency Care Applied Research Network (PECARN) derived and validated a high-quality, well-performing clinical prediction rule for identifying children < 18 years at very low risk of ciTBI for whom CT could be obviated.(2) The rule might not be perfect, but represent the best current scientific evidence. PECARN as well as multiple prior studies have considered scalp findings to be a risk factor for children < 2 years. For older children the only signs of basal skull fractures give a higher risk for ciTBI.(2) The authors enrolled 69 patients discovering 8 SF (12%) in children < 21 years; without any information about the patients for whom SF probably have the most diagnostic importance as predictors of intracranial injury there is a concern that some of the older patients could probably had underwent a CT scan only for the suspicious of SF. The Authors found 8 (12%) SF on 69 patients with external signs of head trauma (soft tissue swelling/hematoma, point of impact/maximal tenderness). A general higher incidence of SF is reported in the younger age group. Moreover, the presence of scalp hematoma is 80%-100% sensitive for an associated SF since most fractures have an overlying hematoma or soft tissue swelling (>90%).(3) Therefore there's concern regarding the possibility of a unacceptable interobserver agreement in the assessment of physical examination findings in children with blunt head trauma. Finally, since this is a comparative study we think that a blind expert should have reviewed both ultrasound and CT images for the 2nd false positive patient. The authors correctly report a higher sensitivity for radiology, since it can detect non-displaced fractures as small as 1 mm. Even though one more true positive patient would have a small contribution to increase the sensitivity and specificity of the test, this would have strengthen the test since the other 2 missed patients can be ascribed to errors on the US technique.

THYROID NODULES: COMPARISON ULTRASOUND ELASTOGRAPHY to B-MODE ULTRASOUND CRITERIA

ABSTRACT :

OBJECTIVE. The purpose of this article is to present, through systematic review of recent literature, a comparative effectiveness analysis of ultrasound elastography versus B-mode ultrasound features for differentiating thyroid nodules.

MATERIALS AND METHODS. We conducted an extensive literature search of PubMed and other medical and general purpose databases from January 1966 through March 2012. Eligible studies were published in English, reported diagnostic performance of elastography (using elasticity score or strain ratio) with or without B-mode ultrasound in differentiation of thyroid nodules, and used histology or cytology as the reference standard. Summary diagnostic performance measures were assessed for each of the elasticity measuring methods and ultrasound features by means of a bivariate random effects model.

RESULTS. Twenty-four studies provided relevant information on more than 2624 patients and 3531 thyroid nodules (927 malignant and 2604 benign). Six ultrasound features (echogenicity, calcifications, margins, halo sign, shape, and color Doppler flow pattern) were compared with elasticity score and strain ratio. The respective sensitivities and specificities were as follows: elasticity score, 82% and 82%; strain ratio, 89% and 82%; hypoechogenicity, 78% and 55%; microcalcifications, 50% and 80%; irregular margins, 66% and 81%; absent halo sign, 56% and 57%; nodule vertical development, 46% and 77%; and intranodular vascularization, 40% and 61%.

CONCLUSION. Evaluation of thyroid nodules with ultrasound elastography appears to be both more sensitive and specific than each of the ultrasound features. The former is a safe and effective technique that warrants further rigorous investigation or use in the clinical diagnosis of thyroid nodules.

TESTICULAR CANCER

Summary

Imaging studies play a vital role in the diagnosis and management of testicular cancer. Ultrasound is primarily used for initial diagnosis, and CT is the standard for cancer staging. MRI provides an equally powerful diagnostic alternative to CT for use in certain circumstances. The use of PET is limited in tumor characterization, but, with the advent of new tracers, PET is gaining acceptance for the evaluation of treatment response as well as recurrence.

Diagnosis

Sonographic imaging of the testes represents the reference standard imaging evaluation, with sensitivity of near 100% when combined with physical examination (Fig. 1).

Ultrasound can distinguish intra- and extra-testicular lesions and is undertaken in most cases before orchiectomy [9]. Testicular tumors are typically well defined and hypoechoic compared with normal testicular tissue but can be heterogeneous with calcification or cystic changes [10]. Increased vascularity of a lesion is not specific to testicular tumors.

In cases in which the diagnosis is in question, additional information can be gained with MRI. Solid testicular tumors have lower signal intensity on T2-weighted MRI in contrast with the high signal intensity of normal testicular parenchyma. One study evaluated MRI of the testes before orchiectomy in 33 patients with T1- and T2-weighted images using a 1.5-T MRI unit.

The sensitivity and specificity of MRI in differentiating benign from malignant intratesticular lesions were 100% and 87.5%, respectively.

Furthermore, the accuracy of MRI for assigning pathologically confirmed T category was 92.8% [11]. The role of MRI of the testis in place of ultrasound remains to be clearly determined. However, it offers reliable and detailed information in the case of equivocal ultrasound findings or in the absence of a skilled sonographer. On occasion, the initial presentation may be a retroperitoneal mass, with testicular imaging not revealing an evident lesion. In these cases, a testicular malignancy must be considered because the primary testicular tumor may have “burned out” and no longer be evident or it may appear more subtle on imaging [12, 13] (Fig. 2). A more unusual presentation would be that of an extragonadal GCT. Extragonadal GCTs are essentially of the same histology as testicular malignancies but develop outside of the testis, commonly in the pineal gland, mediastinum, retroperitoneum, or sacrum [14, 15]. In either of these situations, tumor markers or biopsy may provide insight to the diagnosis.

The finding of testicular microlithiasis (Fig. 3) is commonly present on ultrasound imaging in patients with testicular malignancy. Historically, the contribution of testicular microlithiasis to the risk of malignancy has been controversial; however, more recent data have shown that the presence of microlithiasis on an otherwise normal testicular ultrasound does not predispose the patient to testicular malignancy [16]. One study of sonographic screening in 1504 healthy United States Army Reserve recruits revealed an incidence of testicular microlithiasis of 5%, or 1000 times greater than the incidence of testicular malignancy [17]. It appears the presence or absence of testicular microlithiasis is not significantly associated with risk for malignancy, and there is no good evidence to support a role for imaging surveillance in the absence of additional risk factors [18, 19].

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.