Endoscopic Ultrasonography

Number: 0446

Policy

1. Aetna considers endoscopic ultrasonography (EUS) medically necessary for any of the following indications:
    
   1. Diagnosis of common bile duct stones; or
   2. Evaluating abnormalities of the biliary tree; or
   3. Evaluating abnormalities of the gastrointestinal tract wall or adjacent structures; or
   4. Evaluating abnormalities of the pancreas, including masses, pseudocysts and chronic pancreatitis; or
   5. Evaluating adenopathy and masses of the posterior mediastinum (endoscopic ultrasonography with fine-needle aspiration); or
   6. Gallbladder drainage for acute cholecystitis; or
   7. Pre-operative staging of gastric cancer; or
   8. Providing endoscopic therapy under ultrasonographic guidance; or
   9. Sampling tissue of lesions within, or adjacent to, the wall of the gastrointestinal tract; or
   10. Staging of lung cancer (endoscopic ultrasonography with fine-needle aspiration); or
   11. Staging tumors of the gastrointestinal tract (including the esophagus, the stomach, the rectum), pancreas and bile ducts; or 
   12. Surveillance of certain gastric subepithelial masses (asymptomatic glomus tumors or small (less than 3 cm) gastrointestinal stromal tumors).
        
2. Aetna considers EUS experimental and investigational for all other indications (not an all-inclusive list) because of insufficient evidence in the peer-reviewed literature, including the following conditions:
    
   1. Diagnosis of esophageal varices; and
   2. EUS-elastography (for differentiation of benign and malignant pancreatic masses; differential diagnosis of malignant lymph nodes; for adrenal glands, hepatobiliary/gastrointestinal tract pathology (including anal canal), lung, mediastinum, and urogenital tract); and 
   3. Staging of tumors shown to be metastatic by other imaging methods (unless the results are the basis for therapeutic decisions); and  
   4. When the results will not alter care of the member.

Background

Endoscopic ultrasonography (EUS) incorporates high-frequency ultrasound into the tip of the endoscope to visualize the gastrointestinal wall and surrounding structures.  Using endoscopy, ultrasound probes can be placed in close proximity to the target anatomy, thereby enhancing resolution of the gastrointestinal wall and adjacent structures.  Tissue samples can be obtained and therapy can be performed by passing instruments under ultrasonographic guidance.

Endoscopic ultrasonography is used for staging tumors of the gastrointestinal tract, pancreas and bile ducts; the most notable application is in staging esophageal, gastric, and rectal tumors.  Studies show that EUS is the most accurate imaging modality for staging depth of tumor invasion, with pre-operative accuracy in the 80 % to 90 % range when compared with surgical pathology.  However, biopsy and histopathologic evaluation are needed to identify the specific histology.  Endoscopic ultrasonography can not reliably distinguish an inflammatory process from a neoplastic process.  In addition, EUS has proved less accurate in staging lymph node than in staging depth of tumor invasion because the node has to be located and then identified as benign or malignant.

A recent advance of EUS is high-frequency ultrasound probe sonography (HFUPS).  This has been researched as a method of providing ultrasound imaging of visible lesions without endoscope exchange as it can be performed through the biopsy channel of an endoscope.  Two commercially available probes, the Olympus UM-2R/UM-3R Ultrasonic Probes (Olympus Optical Co.) and the Fujinon Sonoprobe SP-701 (Fujinon, Inc.), have received 510(k) status from the Food and Drug Administration.  High-frequency ultrasound probe sonography has been used in the staging of esophageal, gastric, ampullary, pancreatobiliary, and colonic neoplasms; however, there is limited information on the clinical impact of HFUPS.  The American Society for Gastrointestinal Endoscopy (ASGE) reviewed the medical literature on HFUPS and concluded that HFUPS can provide detailed imaging of the gastrointestinal wall for the evaluation and staging of mucosal and submucosal lesions of the gastrointestinal tract and pancreatico-biliary tree.  It may also provide useful information that could affect therapeutic strategies in patients with superficial lesions; however, the technique should be reserved for use by centers with significant experience in EUS.  In addition, further studies on the clinical impact of HFUPS are necessary.

Endoscopic ultrasonography has been proven a reliable and accurate diagnostic tool for staging tumors of the gastrointestinal tract, pancreas and bile ducts; evaluating abnormalities of the gastrointestinal tract wall or adjacent structures; tissue sampling of lesions within, or adjacent to, the wall of the gastrointestinal tract; evaluation of abnormalities of the pancreas, including masses, pseudocysts and chronic pancreatitis; evaluation of abnormalities of the biliary tree; and providing endoscopic therapy under ultrasonographic guidance.  These indications for EUS were supported by the guidelines on the Appropriate Use of Gastrointestinal Endoscopy (1997) developed by the ASGE with the assistance and support of the American Gastroenterological Association, the American College of Gastroenterology, the Society for Surgery of the Alimentary Tract, the Society of American Gastrointestinal Endoscopic Surgeons, and the American Society for Colon and Rectal Surgery.

Sreenarasimhaiah (2005) stated that the emergence of EUS has given promise to improved staging with its ability to examine tumors from within the gastrointestinal lumen with extremely close proximity.  An additional advantage is the ability to perform fine-needle aspiration (FNA) biopsy to confirm or exclude tumor involvement.  Many studies have demonstrated superior accuracy in staging with EUS and EUS-FNA for tumors of the esophagus, stomach, pancreas, rectum, and mediastinum, including lung cancer.  This is in agreement with previous findings. 

Guidelines from the ASGE (Jacobson et al, 2003) concluded that EUS-FNA is indicated for the evaluation of adenopathy and masses of the posterior mediastinum.  The guidelijnes state that it is the procedure-of-choice for tissue sampling of such lesions in the subcarinal, subaortic (aorto-pulmonary window), and peri-esophageal stations found on cross-sectional imaging.  The guidelines state that EUS-FNA should also be considered in the pre-operative staging of patients with non-small cell lung cancer without definite adenopathy on cross-sectional imaging.

The medical position on the management of patients with gastric subepithelial masses from the American Gastroenterological Association Institute (Hwang and Kimmey, 2006) noted that patients with symptoms that can be attributed to the mass should undergo endoscopic or surgical resection of the mass.  Current evidence does not allow making a firm recommendation on the optimal management of the patient with an incidentally detected, asymptomatic gastric subepithelial mass.  Options include performing no further testing or monitoring, following the mass with periodic endoscopic or EUS surveillance, and endoscopic or surgical resection of the mass.  These management options should be discussed with the patient and whenever possible guided by EUS imaging and tissue sampling information, because the clinical significance of the mass is highly variable.  This guideline recommended EUS surveillance for asymtomatic patients with glomus tumor or gastrointestinal stromal tumor that is less than 3 cm in diameter.

In a meta-analysis and systematic review, Puli et al (2009) evaluated the accuracy of EUS in diagnosing nodal metastasis of rectal cancers.  The authors concluded that the sensitivity and specificity of EUS is moderate.  They stated that further refinement in EUS technologies and diagnostic criteria are needed to improve the diagnostic accuracy.

Shirakawa et al (2004) noted that peripheral lung lesions are increasing in numbers.  Since conventional diagnostic procedures have limitations in availability and results, endoscopic diagnosis is essential for the prevention of unnecessary operations.  The authors concluded that: when the lesion can be correctly described by endobronchial ultrasonography from inside the lesion, endobronchial ultrasonography is useful to guide transbronchial lung biopsy, can contribute to a reduction in patient discomfort and improves the accuracy of diagnosis.  Kramer and colleagues (2004) concluded that EUS-FNA can replace more than half of the surgical staging procedures in lung cancer patients with mediastinal and/or upper retroperitoneal positron emission tomography hot spots, thereby saving 40 % of staging costs.

The Canadian Agency for Drugs and Technologies in Health's report on endobronchial ultrasound (EBUS) for lung cancer diagnosis and staging (Ho et al, 2009) noted that EBUS is a new technology that involves the introduction of an ultrasound probe into the thoracic region via the bronchial airway while patients are under conscious sedation or general anesthesia.  The probe is used to generate images of pulmonary and mediastinal structures.  Its use allows minimally invasive sampling of peripheral pulmonary lesions, and mediastinal and hilar lesions.  The development of the built-in linear probe, as opposed to a radial probe, enables real time guidance during EBUS-transbronchial needle aspiration (EBUS-TBNA).  These investigators reviewed published literature by cross-searching Embase and Medline databases between 2004 and April 2009.  Parallel searches were performed on PubMed and The Cochrane Library (Issue 1, 2009) databases.  The websites of regulatory agencies, and health technology assessment and related agencies, were searched, as were specialized databases.  The Google search engine was used to search for information on the Internet.

These researchers identified 1 health technology assessment (HTA), 1 meta-analysis, 2 cost analyses, and 3 observational studies on the use of EBUS for lung cancer diagnosis and staging.  The HTA examined the safety and effectiveness of EBUS for detection and staging in patients with suspected or established lung cancer.  No meta-analysis was performed, and the conclusions that were presented came from individual trials.  The HTA found a statistically significantly increased diagnostic yield for mediastinal lymph nodes when EBUS-TBNA was compared to conventional TBNA.  In the 2009 meta-analysis, the overall diagnostic accuracy of EBUS-TBNA in detecting metastatic mediastinal lymph nodes in patients who were suspected of having lung cancer was assessed.  Endobronchial ultrasound-guided transbronchial needle aspiration had a pooled sensitivity of 0.93 (95 % confidence interval [CI]: 0.91 to 0.94) and a pooled specificity of 1.00 (95 % CI: 0.99 to 1.00) for lung cancer detection and staging.  When compared directly, EBUS-TBNA was found to be more sensitive than conventional TBNA.  The findings from recent trials were in agreement with the findings of the meta-analysis on EBUS-TBNA diagnostic accuracy.  The authors concluded that based on the existing evidence, EBUS is an accurate and safe tool for use in lung cancer diagnosis and staging.

In a systematic review on the safety and effectiveness of EBUS-TBNA, Varela-Lema et al (2009) reviewed a total of 20 publications.  Of these, 14 were original studies that examined the clinical usefulness of the technique in visualizing and staging lymph nodes in patients with suspected or established lung cancer.  Sensitivity ranged 85 % to 100 % and negative predictive value ranged 11 % to 97.4 %.  Three studies evaluated the clinical usefulness of the technique in the diagnosis of sarcoidosis.  EBUS-TBNA was diagnostic in 88 % to 93 % of patients.  One retrospective study evaluated the use of EBUS-TBNA in the diagnosis of lymphoma.  None of the studies included in the present review reported important complications.  Endobronchial ultrasound-guided transbronchial needle aspiration is a safe and highly accurate procedure for the examination and staging of mediastinal and hilar lymph nodes in patients with known or suspected lung malignancy.  The evidence is promising for sarcoidosis but is insufficient for lymphoma.

Adams et al (2009) carried out a systematic review of published studies evaluating EBUS-TBNA for mediastinal lymph node staging to ascertain the pooled sensitivity and specificity of this investigation.  A literature search was constructed and performed by a professional medical librarian to identify the literature from 1960 to February 2008.  Pooled specificity and sensitivity was estimated from the extracted data with an exact binomial rendition of the bivariate mixed-effects regression model.  Of 365 publications, 25 were identified in which EBUS-TBNA was specifically focused on mediastinal node staging.  Of these, only 10 had data suitable for extraction and analysis.  The overall test performance was excellent with an area under the summary receiver operating characteristics curve of 0.99 (95 % CI: 0.96 to 1.00); similarly, EBUS-TBNA had excellent pooled specificity of 1.00 (95 % CI: 0.92 to 1.00) and good pooled sensitivity of 0.88 (95 % CI: 0.79 to 0.94).  The authors concluded that EBUS-TBNA has excellent overall test performance and specificity for mediastinal lymph node staging in patients with lung cancer.  The results compare favorably with published results for computed tomography (CT) and positron emission tomography.

Cameron and colleagues (2010) stated that EBUS-TBNA is a recently developed, accurate, safe and cost-effective technique that allows sampling of mediastinal lymph nodes and peri-bronchial lesions including pulmonary and mediastinal lesions.  Its major indications are the nodal staging of non-small cell carcinomas of the lung, their re-staging following chemotherapy and/or radiation, the diagnosis of sarcoidosis and of metastases from extra-thoracic malignancies, and the diagnosis of mediastinal lymphadenopathy and masses of unknown etiology.

In a pilot study, Aumiller et al (2009) examined the feasibility of detecting pulmonary embolism (PE) in the central airways by EBUS.  Consecutive patients underwent flexible bronchoscopy with a convex EBUS probe under local anesthesia and moderate sedation within 24 hrs after angio-CT had documented a central PE.  The EBUS images were compared to the CT findings.  Among 32 patients (mean age of 69 years, 20 men), angio-CT documented 101 PE, of which 97 (96 %) were also detected with EBUS.  The 4 emboli not detected consisted of 1 in a middle lobe and 3 in a left upper lobe artery.  At least 1 embolus was detected with EBUS in every patient, which is sufficient to confirm a diagnosis of central PE.  No bronchoscopic complications were observed.  Mean procedure time was reduced from 5 mins in the first 16 patients to 3 mins in the last 16.  The authors concluded that EBUS was a feasible and safe approach to detecting central pulmonary emboli.  Moreover, they stated that blinded, comparative trials are needed to evaluate its use as a primary tool for diagnosing these emboli.

Soja et al (2009) examined the use of EBUS for the assessment of bronchial wall remodeling in patients with asthma.  In 35 patients with asthma and 23 control subjects, high-resolution CT (HRCT) scanning and EBUS were used to measure bronchial wall thickness in the 10th segment of the right lung.  With a radial 20-MHz probe, EBUS identified the 5-laminar structure of the bronchial wall.  Layer 1 (L(1)) and layer 2 (L(2)) were analyzed separately, and layers 3 through 5 (L(3-5)), which corresponded to cartilage, were analyzed jointly.  Digitalized EBUS images were used for the quantitative assessment of bronchial wall thickness and the wall area (WA) of the layers.  Finally, bronchial biopsy specimens were taken for measuring the thickness of the reticular basement membrane (RBM).  The thickness and WA of the bronchial wall layers, which were assessed using EBUS, were correlated with FEV(1) and RBM.  There was no significant difference in the measurements of total bronchial wall thickness using EBUS and HRCT scanning.  The thickness and WA of the bronchial wall and its layers were significantly greater in patients with asthma than in the control subjects.  A negative correlation among the thicknesses of L(1), L(2), and L(3-5) and FEV(1), and a positive correlation with RBM were observed only in the patients with asthma.  The authors concluded that EBUS allows precise measurement of the thickness and WA of bronchial wall layers.  The correlation of these parameters with asthma severity suggested implementation of EBUS in the assessment of bronchial wall remodeling in patients with asthma.

In a meta-analysis, Wu et al (2011) evaluated the accuracy of EUS elastography by pooling data of existing trials.  A total of 7 studies involving 368 patients with 431 lymph nodes (LNs) were included.  Pooling was conducted in a fixed-effect model or a random-effect model.  The pooled sensitivity of EUS elastography for the differential diagnosis of benign and malignant LNs was 88 % (95 % CI: 0.83 to 0.92), and the specificity was 85 % (95 % CI: 0.79 to 0.89).  The area under the curve under summary receiver operating characteristic (SROC) was 0.9456.  The pooled positive likelihood ratio was 5.68 (95 % CI: 2.86 to 11.28), and the negative likelihood ratio was 0.15 (95 % CI: 0.10 to 0.21).  The subgroup analysis by excluding the outliers provided a sensitivity of 85 % (95 % CI: 0.79 to 0.90) and a specificity of 91 % (95 % CI: 0.85 to 0.95) for the differential diagnosis of benign and malignant LNs.  The area under the curve under SROC was 0.9421.  The authors concluded that EUS elastography is a promising, non-invasive method for differential diagnosis of malignant LNs and may prove to be a valuable supplemental method to EUS-guided FNA.

Will and Meyer (2012) stated that endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) are considered the gold standard in the interventional treatment of biliary obstruction, in particular, with palliative intention.  If ERCP and PTC are not possible, an alternative drainage procedure such as the endoscopic ultrasound-guided cholangiodrainage (EUCD) can be used.  Endoscopic US-guided cholangiodrainage is an endoscopic/sonografic procedure, which is used in case of post-operatively changed anatomy of the upper gastro-intestinal tract (BII gastric resection, pylorus-preserving pancreas head resection, Whipple procedure, [sub-]total gastrectomy, Roux-en-Y reconstruction) and, thus, if papilla of Vater (papilla) can not be reached or catheterized or if the patient denies PTC; and in subjects with recurrent, advanced or metastasized tumor lesion(s) of the upper abdomen, hepatobiliary system as well as pancreas and associated obstruction of the biliary tree/jaundice.  The authors stated that with regard to the limited diffusion process, EUCD can not be considered a standard procedure yet.  The advantages comprise low tissue trauma, primary internal drainage and the possible endoscopic re-intervention in case of complications.  The high technical challenge in performing EUCD is an unfavorable aspect for broader use in clinical practice.  However, the disclosed treatment results demonstrating an acceptable complication rate show that EUCD can be competitively considered to ERCP und PTC with a great chance for primary success.  These investigatros concluded that EUCD is an elegant, not yet fully established, but rather still experimental procedure of interventional endoscopy/EUS, which needs great expertise of the endoscopist in an inter-disciplinary center of visceral medicine as one of the main predictions.  In experienced hands, a safe procedure can be provided, for which a systematic follow-up and a multi-center evaluation of peri-interventional management are still needed in order to achieve a final assessment of EUCD for guideline approval.

Cardoso et al (2012) stated that accurate pre-operative staging is important in determining the appropriate treatment of gastric cancer.  Recently, EUS has been introduced as a staging modality.  However, reported test characteristics for EUS in gastric cancer vary.  These investigators identified, synthesized, and evaluated findings from all articles on the performance of EUS in the pre-operative staging of gastric cancer.  Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 1, 2009.  All search titles and abstracts were independently rated for relevance by a minimum of 2 reviewers.  Meta-analysis for the performance of EUS was analyzed by calculating agreement (Kappa statistic), and pooled estimates of accuracy, sensitivity, and specificity for all EUS examinations, using histopathology as the reference standard. Subgroup analyses were also performed.  A total of 22 articles met inclusion criteria and were included in the review.  Endoscopic ultrasonography pooled accuracy for T staging was 75 % with a moderate Kappa (0.52); EUS was most accurate for T3 disease, followed by T4, T1, and T2.  Endoscopic ultrasonography pooled accuracy for N staging was 64 %, sensitivity was 74 %, and specificity was 80 %.  There was significant heterogeneity between the included studies.  Subgroup analyses found that annual EUS volume was not associated with EUS T and N staging accuracy (p = 0.836, 0.99, respectively).  The authors concluded that EUS is a moderately accurate technique that seems to describe advanced T stage (T3 and T4) better than N or less advanced T stage.  Stratifying by EUS annual volume did not affect EUS performance in staging gastric cancer.

The National Comprehensive Cancer Network’s clinical practice guideline on gastric cancers (including cancer in the proximal 5 cm of the stomach) (NCCN, 2013) states that “clinical staging has greatly improved with the availability of diagnostic modalities such as endoscopic ultrasound (EUS) …. EUS performed prior to any treatment is important in the initial clinical staging of gastric cancer …. This is especially important in patients who are being considered for EMR [endoscopic mucosal resection]”.

Xu and associates (2013) stated that EUS elastography is a novel method for visualization of tissue elasticity modulus during a conventional EUS examination.  The reported yield of EUS elastography for the differentiation of benign and malignant pancreatic masses has shown variable results.  In a systemic review and meta-analysis, these investigators examined the accuracy of EUS elastography by pooling data of available trials.  The Medline, PubMed, Embase, and Cochrane Central Trials databases were used to retrieve all the studies that assessed the diagnostic accuracy of EUS elastography for the differentiation of benign and malignant pancreatic masses.  Pooling was carried out using a fixed-effect model when significant heterogeneity was not present; otherwise, the random-effect model was used.  If there were less than 4 studies using the same diagnostic standard, forest plots were constructed without pooling.  In 6 studies using the qualitative color pattern as the diagnostic standard, the sensitivity was 99 % (95 % CI: 98 to 100 %) and the specificity was 74 % (95 % CI: 65 to 82 %).  The area under the curve under the summary receiver-operating characteristic was 0.9624.  In 3 studies using the quantitative hue histogram value as the diagnostic standard, the sensitivity was 85 to 93 % and the specificity was 64 to 76 %.  The authors concluded that EUS elastography is a promising non-invasive technique for the differentiation of pancreatic masses with a high sensitivity, and may prove to be a valuable complementary method to EUS-FNA.

In a meta-analysis, Mei and colleagues (2013) evaluated the accuracy of EUS elastography for diagnosis of solid pancreatic masses.  A total of 13 articles for EUS elastography diagnosing solid pancreatic masses were selected.  The Mantel-Haenszel and DerSimonian Laird methods were used to analyze pooled results.  This study involved 1,044 patients.  Main outcome measures included the pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio, and summary receiver operating characteristic (sROC) curve.  The pooled sensitivity, specificity, and diagnostic odds ratio of EUS elastography distinguishing benign from malignant solid pancreatic masses were 0.95 (95 % CI: 0.94 to 0.97), 0.67 (95 % CI: 0.61 to 0.73), and 42.28 (95 % CI: 26.90 to 66.46), respectively.  The sROC area under the curve was 0.9046.  The subgroup analysis based on excluding the outliers showed that the heterogeneity was eliminated, and the pooled sensitivity and specificity were 0.95 (95 % CI: 0.93 to 0.97) and 0.7 (95 % CI: 0.63 to 0.76), respectively.  The sROC area under the curve was 0.8872.  The authors concluded that EUS elastography is a reliable technique for the characterization of solid pancreatic masses and may be a useful complementary tool for EUS-guided FNA.  However, they stated that a more accurate computer-aided diagnosis method for EUS elastography is in demand to reduce various biases and improve the accuracy of EUS elastography for diagnosis of solid pancreatic masses.

Furthermore, the NCCN’s clinical practice guideline on “Pancreatic adenocarcinoma” (Version 1.2014) does not mention the use of EUS elastography as a management tool.

The World Gastroenterology Organization’s clinical practice guideline on “Esophageal varices” (WGO, 2014) stated that “Esophagogastroduodenoscopy (EGD) is the gold standard for the diagnosis of esophageal varices.  If the gold standard is not available, other possible diagnostic steps would be Doppler ultrasonography of the blood circulation (not endoscopic ultrasonography)”.

Dietrich et al (2014) stated that real-time elastography (RTE) performed during EUS is a relatively new technique that allows the evaluation of tissue stiffness, with the intent of better characterizing lesions during EUS examinations.  These investigators described the technique of RTE-EUS, as well as the clinical applications, including the study of pancreatic lesions, but also hepatobiliary, gastro-intestinal (GI) tract pathology (including anal canal), lymph nodes, adrenal glands, lung and mediastinum, as well as urogenital applications.  The authors stated that one of the advantages of the RTE-EUS technique is the possibility to be used in various locations accessible from the GI tract; they also discussed future developments of elastography -- a technique that will certainly not replace biopsy, but will rather be an adjunct during EUS examinations.

Diagnosis of Common Bile Duct Stones:

Giljaca et al (2015) stated that there has been no systematic review of the accuracy of EUS and magnetic resonance cholangio-pancreatography (MRCP) in the diagnosis of common bile duct stones using appropriate reference standards. In a Cochrane review, these researchers compared the accuracy of EUS and MRCP for the diagnosis of common bile duct stones.  They searched MEDLINE, EMBASE, Science Citation Index Expanded, BIOSIS, and Clinicaltrials.gov until September 2012.  They searched the references of included studies to identify further studies and of systematic reviews identified from various databases (Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Medion, and ARIF (Aggressive Research Intelligence Facility)).  These investigators did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively.  They included studies that provided the number of true positives, false positives, false negatives, and true negatives for EUS or MRCP.  They only accepted studies that confirmed the presence of common bile duct stones by extraction of the stones (irrespective of whether this was done by surgical or endoscopic methods) for a positive test, and absence of common bile duct stones by surgical or endoscopic negative exploration of the common bile duct or symptom free follow-up for at least 6 months for a negative test, as the reference standard in people suspected of having common bile duct stones.  They included participants with or without prior diagnosis of cholelithiasis; with or without symptoms and complications of common bile duct stones, with or without prior treatment for common bile duct stones; and before or after cholecystectomy.  At least 2 authors independently screened abstracts and selected studies for inclusion.  Two authors independently collected the data from each study.  They used the bi-variate model to obtain pooled estimates of sensitivity and specificity.  These researchers included a total of 18 studies involving 2,366 participants (976 participants with common bile duct stones and 1,390 participants without common bile duct stones); 11 studies evaluated EUS alone, and 5 studies evaluated MRCP alone; 2 studies evaluated both tests.  Most studies included patients who were suspected of having common bile duct stones based on abnormal liver function tests; abnormal trans-abdominal US; symptoms such as obstructive jaundice, cholangitis, or pancreatitis; or a combination of the above.  The proportion of participants who had undergone cholecystectomy varied across studies; not 1 of the studies was of high methodological quality.  For EUS, the sensitivities ranged between 0.75 and 1.00 and the specificities ranged between 0.85 and 1.00.  The summary sensitivity (95 % CI) and specificity (95 % CI) of the 13 studies that evaluated EUS (1,537 participants; 686 cases and 851 participants without common bile duct stones) were 0.95 (95 % CI: 0.91 to 0.97) and 0.97 (95 % CI: 0.94 to 0.99).  For MRCP, the sensitivities ranged between 0.77 and 1.00 and the specificities ranged between 0.73 and 0.99.  The summary sensitivity and specificity of the 7 studies that evaluated MRCP (996 participants; 361 cases and 635 participants without common bile duct stones) were 0.93 (95 % CI: 0.87 to 0.96) and 0.96 (95 % CI: 0.90 to 0.98).  There was no evidence of a difference in sensitivity or specificity between EUS and MRCP (p = 0.5).  From the included studies, at the median pre-test probability of common bile duct stones of 41 % the post-test probabilities (with 95 % CI) associated with positive and negative EUS test results were 0.96 (95 % CI: 0.92 to 0.98) and 0.03 (95 % CI: 0.02 to 0.06).  At the same pre-test probability, the post-test probabilities associated with positive and negative MRCP test results were 0.94 (95 % CI: 0.87 to 0.97) and 0.05 (95 % CI: 0.03 to 0.09).  The authors concluded that both EUS and MRCP have high diagnostic accuracy for detection of common bile duct stones.  People with positive EUS or MRCP should undergo endoscopic or surgical extraction of common bile duct stones and those with negative EUS or MRCP do not need further invasive tests.  However, if the symptoms persist, further investigations will be indicated.  The 2 tests were similar in terms of diagnostic accuracy and the choice of which test to use would be determined by the availability and contra-indications to each test.  Moreover, they stated that it should be noted that the results were based on studies of poor methodological quality and so the results should be interpreted with caution; further studies that are of high methodological quality are needed to determine the diagnostic accuracy of EUS and MRCP for the diagnosis of common bile duct stones.

British Society of Gastroenterology guidelines on the management of common bile duct stones (Williams, et al., 2008) states: "EUS appears comparable to ERCP as a diagnostic test for CBDS, and performs better than either USS or CT. Unlike ERCP, EUS does not require instrumentationof the sphincter of Oddi and does not subject patients to the associated risk of pancreatitis. With regards to MR, systematic reviewof prospective studies has failed to show a statistically significant difference in performance when the two modalities are compared, though for small CBD stones EUS may still be more sensitive. However, it should be noted that, unlike MR, EUS has yet to become widely available. In addition, it requires the patient to undergo endoscopy, does not provide images of the intra-hepatic ducts and may be difficult to perform on patients with altered gastric or duodenal anatomy."

Diagnosis of Pelvic Lesions:

Han and colleagues (2015) stated that pre-operative diagnosis of pelvic lesions remains challenging despite advances in imaging technologies. Endoscopic ultrasonography-guided biopsy is an effective diagnostic modality for sampling the digestive tract and surrounding areas.  However, a meta-analysis summarizing the diagnostic effectiveness of EUS-guided biopsy for pelvic lesions has not been published.  In a systematic review and meta-analysis, these investigators evaluated the utility of EUS-guided biopsy in the diagnosis of pelvic lesions.  Articles were identified via structured database search; only studies where pelvic lesions were confirmed by surgery or clinical follow-up were included.  Data extracted were selected with strict criteria.  A fixed-effects model was used to estimate the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR).  A summary receiver operating characteristic curve (SROC) was also constructed.  A total of 10 studies containing a total of 246 patients were included.  The pooled sensitivity of EUS-guided biopsy for differential diagnosis of pelvic masses was 0.89 (95 % CI: 0.83 to 0.94), and the specificity was 0.93 (95 % CI: 0.86 to 0.97).  The area under the SROC was 0.9631.  The combined PLR, NLR, and DOR were 11.75 (95 % CI: 5.90 to 23.43), 0.12 (95 % CI: 0.07 to 0.20), and 100.06 (95 % CI: 37.48 to 267.10), respectively.  There is potential presence of publication bias in this meta-analysis.  The authors concluded that the finding of this meta-analysis showed that EUS-guided biopsy is a powerful tool for differentiating pelvic masses with a high sensitivity and specificity.  Moreover, they stated that EUS-guided biopsy is a safe procedure with low rate of complication, although more high-quality prospective studies are needed to be done.

Nisenblat et al (2016) noted that approximately 10 % of women of reproductive age suffer from endometriosis. Endometriosis is a costly chronic disease that causes pelvic pain and subfertility.  Laparoscopy, the gold standard diagnostic test for endometriosis, is expensive and carries surgical risks.  Currently, no non-invasive tests that can be used to accurately diagnose endometriosis are available in clinical practice.  In a Cochrane review, these investigators provided estimates of the diagnostic accuracy of imaging modalities for the diagnosis of pelvic endometriosis, ovarian endometriosis and deeply infiltrating endometriosis (DIE) versus surgical diagnosis as a reference standard.  They described performance of imaging tests for mapping of deep endometriotic lesions in the pelvis at specific anatomical sites.  Imaging tests were evaluated as replacement tests for diagnostic surgery and as triage tests that would assist decision-making regarding diagnostic surgery for endometriosis.  The authors concluded that none of the evaluated imaging modalities was able to detect overall pelvic endometriosis with enough accuracy that they would be suggested to replace surgery.  Specifically for endometrioma, TVUS qualified as a SpPin triage test; MRI displayed sufficient accuracy to suggest utility as a replacement test, but the data were too scant to permit meaningful conclusions.  Trans-vaginal ultrasound (TVUS) could be used clinically to identify additional anatomical sites of DIE compared with MRI, thus facilitating pre-operative planning.  Recto-sigmoid endometriosis was the only site that could be accurately mapped by using TVUS, trans-rectal ultrasonography (TRUS), MRI or multi-detector computerized tomography enema (MDCT-e).  Studies evaluating recent advances in imaging modalities such as TVUS with bowel preparation (TVUS-BP), rectal water contrast during trans-vaginal ultrasonography (RWC-TVS,), 3.0T MRI and MDCT-e were observed to have high diagnostic accuracies, but were too few to allow prudent evaluation of their diagnostic role.  They stated that in view of the low quality of most of the included studies, the findings of this review should be interpreted with caution; future well-designed diagnostic studies undertaken to compare imaging tests for diagnostic test accuracy and costs are recommended.

Management of Acute Cholecystitis:

An UpToDate reviewof acute cholecystitis (Vollmer, et al., 2016) states that transmural drainage utilizes endoscopic ultrasound guidance to access the inflamed gallbladder with a needle puncture, followed by dilation and stent placement over a guidewire. The review stated that the transmural drainage technique is technically successful in most cases (97 percent) and resolves acute cholecystitis in over 95 percent of patients The review states that, in high risk patients, endoscopic transmural drainage is used as a bridge to definitive gallbladder surgery. 

Choi and Lee (2015) noted that w the evolution of the linear echo-endoscope and the improved ability to direct a needle within the field of interest, the therapeutic potential of EUS has greatly expanded. Endoscopic ultrasonography-guided trans-mural gallbladder drainage (EUS-GBD) may be the next frontier for therapeutic EUS.  Since EUS-GBD was first described in 2007, recent reports have suggested it as an alternative to external gallbladder drainage for acute cholecystitis;  EUS-GBD includes EUS-guided trans-mural nasogallbladder drainage, EUS-guided gallbladder aspiration, and EUS-guided trans-mural gallbladder stenting.

Penas-Herrero et al (2015) stated that EUS-GBD has been introduced as an alternative to percutaneous trans-hepatic GBD for the treatment of acute cholecystitis in non-surgical candidates. These investigators performed a systematic review of the English language literature through PubMed search until June 2014.  A total of 155 patients with acute cholecystitis treated with EUS-GBD in 8 studies and 12 case reports, and 2 patients with EUS-GBD for other causes were identified.  Overall, technical success was obtained in 153 patients (97.45 %) and clinical success in 150 (99.34 %) patients with acute cholecystitis.  Adverse events developed in less than 8 % of patients, all of them managed conservatively.  Endoscopic ultrasound-GBD has been performed with plastic stents, nasobiliary drainage tubes, standard or modified tubular self-expandable metal stents (SEMS) and lumen-apposing metal stents (LAMS) by different authors with apparently similar outcomes.  No comparison studies between stent types for EUS-GBD have been reported.  The authors concluded that EUS-GBD is a promising novel alternative intervention for the treatment of acute cholecystitis in high surgical risk patients.  Feasibility, safety and effectiveness in published studies from expert centers were very high compared to currently available alternativess.  Moreover, they stated that further studies are needed to establish the safety and long-term outcomes of this procedure in other practice settings before EUS-GBD can be widely disseminated.

Re-Staging of Locally Advanced Rectal Cancer:

Zhao et al (2014) stated that endorectal EUS can provide accurate and reliable information for initial staging of locally advanced rectal cancer (LARC) in both the depth of rectal cancer penetration (T-stage) and regional lymph node involvement (N-stage). However, there is still no consensus about its accuracy in re-staging LARC after neoadjuvant chemoradiotherapy (NAT).  These investigators retrieved previous studies and performed a meta-analysis for evaluating the accuracy of EUS for re-staging of LARC after NAT.  It was found the accuracy of EUS for T re-staging of LARC was relatively low and over-staging was common, although the accuracy for assessing T3/4 was significantly higher than T0 to T2 stage.  The specificity of EUS for assessing N stage was relatively high, but the sensitivity was relatively low.  The authors concluded that data obtained in this study confirmed the overall accuracy of EUS is insufficient to serve as a basis for decisions on re-staging; exploring the possible application of new techniques is needed for better re-staging.

NCCN guidelines on rectal cancer (2016) state that "MRI, CT and EUS are the most commonly used modalities for restaging after neoadjuvant treatment, but the accuracy of these techniques for determining T stage and lymph node involvement is limited ." 

CPT Codes / HCPCS Codes / ICD-10 Codes
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered if selection criteria are met:
31652 - 31653	Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with endobronchial ultrasound (EBUS) guided transtracheal and/or transbronchial sampling (eg, aspiration[s]/biopsy[ies])
31654	Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with transendoscopic endobronchial ultrasound (EBUS) during bronchoscopic diagnostic or therapeutic intervention(s) for peripheral lesion(s) (List separately in addition to code for primary procedure[s])
43231	Esophagoscopy, flexible, transoral; with endoscopic ultrasound examination
43232	with transendoscopic ultrasound-guided intramural or transmural fine needle aspiration/biopsy(s)
43237	Esophagogastroduodenoscopy, flexible, transoral; with endoscopic ultrasound examination limited to the esophagus, stomach or duodenum, and adjacent structures
43238	with transendoscopic ultrasound-guided intramural or transmural fine needle aspiration/biopsy(s), (includes endoscopic ultrasound examination limited to the esophagus, stomach or duodenum, and adjacent structures)
43242	with transendoscopic ultrasound-guided intramural or transmural fine needle aspiration/biopsy(s) (includes endoscopic ultrasound examination of the esophagus, stomach, and either the duodenum or a surgically altered stomach where the jejunum is examined distal to the anastomosis)
43259	with endoscopic ultrasound examination, including the esophagus, stomach, and either the duodenum or a surgically altered stomach where the jejunum is examined distal to the anastomosis
45341	Sigmoidoscopy, flexible; with endoscopic ultrasound examination
45342	with transendoscopic ultrasound guided intramural or transmural fine needle aspiration/biopsy(s)
45391	Colonoscopy, flexible; with endoscopic ultrasound examination limited to the rectum, sigmoid, descending, transverse, or ascending colon and cecum, and adjacent structures
45392	with transendoscopic ultrasound guided intramural or transmural fine needle aspiration/biopsy(s), includes endoscopic ultrasound examination limited to the rectum, sigmoid, descending, transverse, or ascending colon and cecum, and adjacent structures
76975	Gastrointestinal endoscopic ultrasound, supervision and interpretation
ICD-10 codes covered if selection criteria are met (not all inclusive):
C15.3 - C15.9	Malignant Neoplasm of the esophagus
C16.0 - C16.9	Malignant neoplasm of the stomach
C17.0 - C17.9	Malignant neoplasm of small intestine
C18.0 - C18.9	Malignant neoplasm of colon
C19 - C21.8	Malignant neoplasm of rectum, rectosigmoid junction and anus
C22.1	Intrahepatic bile duct carcinoma
C24.0 - C24.9	Malignant neoplasm of other and unspecified parts of biliary tract
C25.0 - C25.9	Malignant neoplasm of pancreas [not covered for differentiation of benign and malignant pancreatic masses]
C26.0 - C26.9	Malignant neoplasm of other and ill-defined digestive organs
C33 - C34.92	Malignant neoplasm of trachea, bronchus, and lung
C38.1 - C38.3	Malignant neoplasm of mediastinum
C48.0 - C48.8	Malignant neoplasm of retroperitoneum and peritoneum
C78.00 - C78.89	Secondary malignant neoplasm of respiratory and digestive systems
D00.0 - D01.9	Carcinoma in situ of digestive organs
D13.0 - D13.9	Benign neoplasm of other part and ill-defined parts of digestive system
D14.1 - D14.4 D15.2, D19.0	Benign neoplasm of larynx, trachea, bronchus and lung, pleura, and mediastinum
D37.1 - D38.6	Neoplasms of uncertain behavior of stomach, intestines, and rectum, liver and biliary passages, retroperitoneum and peritoneum, other and unspecified digestive organs, larynx, trachea, bronchus, and lung, pleura, thymus, and mediastinum
K80.30-K80.71	Calculus of bile duct with cholangitis
K81.0	Acute cholecystitis
R19.00 - R19.09	Intra-abdominal and pelvic swelling, mass and lump
R22.2	Localized swelling, mass and lump, trunk
R59.0 - R59.9	Enlarged lymph nodes
ICD-10 codes not covered for indications listed in the CPB:
C77.0 - C77.9	Secondary and unspecified malignant neoplasm of lymph nodes [for differential diagnosis of malignant lymph nodes]
C78.80 - C78.89	Secondary malignant neoplasm of other digestive organs [for differentiation of benign and malignant pancreatic masses]
D13.6	Benign neoplasm of pancreas [for differentiation of benign and malignant pancreatic masses]
D13.7	Benign neoplasm of endocrine pancreas [for differentiation of benign and malignant pancreatic masses]
D36.0	Benign neoplasm of lymph nodes [for differential diagnosis of malignant lymph nodes]
D37.8 - D37.9	Neoplasm of uncertain behavior of other and unspecified digestive organs [for differentiation of benign and malignant pancreatic masses]
D49.0	Neoplasm of unspecified nature of digestive system [for differentiation of benign and malignant pancreatic masses]
E24.0 - E27.9	Disorders of the adrenal gland
I85.00 - I85.11	Esophageal Varices
N00.0 - N99.89	Diseases of the genitourinary system

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