Intraductal ultrasound for evaluating the pancreaticobiliary ductal system

INTRODUCTION — Intraductal ultrasound (IDUS) of the pancreaticobiliary ductal system utilizes a small caliber ultrasound catheter (also referred to as a mini-catheter). Because the ultrasound catheter ranges in size from 2 to 3 mm, it can be passed through the accessory channel of a duodenoscope and into the pancreatic or bile duct. The ultrasound catheter's small caliber, wire-guided design, flexibility, and high resolution imaging facilitate the evaluation of biliary, pancreatic, and ampullary disorders (table 1).

This topic will discuss the imaging principles, procedure technique, and clinical applications of IDUS. We generally use IDUS to complement endoscopic and radiographic imaging during endoscopic retrograde cholangiopancreatography (ERCP), which has evolved into mostly a therapeutic procedure. An overview of ERCP is discussed separately. (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults".)

The role of small caliber ultrasound catheters for evaluating other parts of the gastrointestinal tract is discussed elsewhere. (See "Endoscopic ultrasound (EUS): Use of miniprobes for evaluating gastrointestinal lesions".)

PROCEDURE

Patient preparation — The preprocedure preparation for patients undergoing IDUS is similar to the preparation for patients undergoing ERCP, and these issues are discussed separately. (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults", section on 'Patient preparation'.)

Imaging principles — IDUS produces higher resolution images than standard endoscopic ultrasound (EUS) [1]. Close proximity of the ultrasound transducer to the duct wall permits the use of high frequency, high resolution sound waves. The pancreatic and bile ducts have a tubular anatomy, are fluid filled, and are only slightly larger in caliber than the IDUS catheter. In addition, the IDUS catheter operates at higher frequencies (12 to 20 MHz) than standard EUS imaging [1,2]. The use of high frequencies produces high resolution images and detailed examination of ductal and periductal tissues. However, the limited depth of penetration prevents detailed examination of the surrounding tissue and more distant sites.

Equipment — Commercially-available systems for performing IDUS are listed in the table (table 2).

Mechanical ultrasound catheters include the following components:

●A single transducer mounted on the tip of a wire that allows the transducer to rotate and produce a 360-degree image

●A cable that excites the transducer and transfers signals to the image processor

●A flexible protective housing

Some ultrasound catheters provide biplane imaging by allowing the transducer to move in both radial and linear planes.

Design variations exist for IDUS systems, and some systems incorporate the use of a guidewire (picture 1 and picture 2). Mechanical catheters with a guidewire port permit mechanical rotating sector scanning and linear scanning with three-dimensional reconstruction.

Technique

Evaluating the biliary tract — The procedural technique for IDUS in the biliary tract is summarized as follows:

●Accessing the bile duct – We typically perform IDUS by inserting the ultrasound catheter through the ampulla of Vater during endoscopic retrograde cholangiopancreatography (ERCP), but IDUS can also be performed using a percutaneous approach. The small caliber of the wire-guided ultrasound catheter (ie, 2 to 3 mm in diameter) facilitates cannulating an intact biliary sphincter [3-5]. If endoscopic sphincterotomy is planned for patients with biliary obstruction, we perform IDUS prior to sphincterotomy to help retain fluid and minimize insufflation of the biliary tree. An intact biliary sphincter optimizes acoustic coupling and image quality. Patients with tight biliary strictures may require balloon or catheter dilation to facilitate inserting the ultrasound catheter. However, we target a post-dilation diameter that will allow catheter insertion but avoid excessive tissue disruption because it may impact bile duct wall thickness and overall appearance.

The total time for performing IDUS, including catheter insertion and imaging time, is approximately 5 to 10 minutes [1,6]. This does not include time required to perform ERCP. (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults".)

●Imaging technique – All IDUS catheters are mechanical. We usually perform IDUS using a pullback imaging technique. We maintain the elevator of the duodenoscope in the down (relaxed) position while the catheter is being withdrawn. In our experience, this minimal elevator technique reduces tension on the rotating cable of the catheter and extends the lifespan of the catheter. In some settings, using a stiffer guidewire (ie, 0.035 inches in diameter) may facilitate this technique. As an example, we use a stiffer guidewire to help advance the catheter in patients with proximal biliary strictures. (See "Endoscopic biliary sphincterotomy", section on 'Guidewires'.)

IDUS produces high quality imaging of the biliary system and surrounding structures, such as the right hepatic artery, portal vein, and the hepatoduodenal ligament (image 1 and image 2). Examination of more distant tissues is hindered by its limited depth of penetration [7-10]. IDUS may also have limited value in evaluating lymph nodes, and unlike EUS, IDUS provides diagnostic assessment only and cannot be used to perform fine needle aspiration. (See "Endoscopic ultrasound-guided fine needle aspiration in the gastrointestinal tract".)

●Imaging appearance – The normal bile duct appears as either two or three layers, which is similar to that seen during EUS [2,11,12]. The normal bile duct wall is 0.31 to 0.79 mm thick, with smooth inner and outer surfaces and homogeneous internal echoes [13]. When visualized as a two-layer structure, an internal hypoechoic layer is seen, which represents the mucosa, muscularis propria (fibromuscular layer), and fibrous layer of the subserosa [14,15]. An outer hyperechoic layer represents the adipose layer of the subserosa, the serosa, and the interface echo between the serosa and surrounding organs. A third inner hyperechoic layer, representing an interface, will occasionally be identified. It may not be possible to differentiate the fibromuscular layer from the perimuscular connective tissue in some patients in whom they appear as a single hypoechoic layer.

Evaluating the pancreatic ducts — The technique for performing IDUS of the pancreatic duct is similar to the technique for examination of the bile duct (see 'Evaluating the biliary tract' above):

●Accessing the pancreatic duct – We typically perform IDUS by inserting the ultrasound catheter into the pancreatic duct, although the proximal portion of the pancreatic duct may be tortuous [6,16]. However, cannulating the pancreatic duct does not typically require pancreatic sphincterotomy. In a study including 153 patients who underwent ERCP, the IDUS catheter was successfully passed into the pancreatic head, body, and tail in 94, 89, and 55 percent of patients, respectively [6].

●Imaging appearance – The ultrasound appearance of the wall of the main pancreatic duct varies from a single hyperechoic layer to three layers. When three layers are present, the inner and outer layers are hyperechoic, with an intervening hypoechoic layer [12].

Adverse events — Adverse events attributed to IDUS are uncommon but may include pancreatitis and catheter fracture [3,6,17-19]. However, most studies do not typically distinguish adverse events related specifically to IDUS from events due to the ERCP itself. (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults", section on 'Adverse events'.)

Limited data suggested that performing IDUS during ERCP was not associated with increased risk of post-ERCP pancreatitis. In two studies including 443 patients who underwent IDUS, four patients (0.9 percent) developed mild pancreatitis [6,16]. The incidence, risk factors, and prevention of post-ERCP pancreatitis are discussed separately. (See "Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis".)

Post-procedure care — After the procedure, patients are recovered from sedation or anesthesia. (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults", section on 'Post-procedure care'.)

The equipment is cleaned per procedural protocol. (See "Preventing infection transmitted by gastrointestinal endoscopy".)

CONTRAINDICATIONS AND LIMITATIONS — Contraindications to IDUS are similar to those for ERCP and include (see "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults", section on 'Contraindications'):

●Patients who cannot tolerate moderate sedation, monitored anesthesia care, or general anesthesia. (See "Anesthesia for gastrointestinal endoscopy in adults".)

●Patients who are hemodynamically unstable.

Limitations of IDUS include that it is invasive, uses specialized equipment, requires expertise in advanced endoscopy, increases overall cost, and may not be widely available.

CLINICAL APPLICATIONS

Diagnostic role of IDUS — IDUS can assist in the evaluation of patients with a variety of pancreaticobiliary disorders (table 1). The most common indications for IDUS of the biliary tract are obstructive jaundice and evaluating indeterminate biliary strictures. IDUS is useful for determining the cause of biliary obstruction and can also assist in local tumor staging.

Biliary disease

Bile duct strictures — We may use IDUS to evaluate biliary strictures by assessing for the following sonographic features that are suggestive of malignancy (image 3) [4,7,19-25]:

●A hypoechoic mass, especially if infiltrating surrounding tissues or >7 mm in thickness

●Heterogeneity of the internal echo

●Notching or irregularity of the outer border

●A papillary surface

●Disruption of the normal bile duct structure

●Suspicious lymph nodes (hypoechoic, round and smooth bordered)

Malignant biliary strictures may be related to tumors such as cholangiocarcinoma or pancreatic cancer, and the diagnostic evaluation and staging of these tumors is discussed in detail separately. (See "Clinical manifestations and diagnosis of cholangiocarcinoma" and "Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer".)

Biliary strictures that do not have sonographic characteristics of malignancy may be related to a variety of nonmalignant conditions:

●Post-surgical biliary complications (eg, cholecystectomy) (see "Complications of laparoscopic cholecystectomy" and "Liver transplantation in adults: Long-term management of transplant recipients", section on 'Biliary complications')

●Primary sclerosing cholangitis (see "Primary sclerosing cholangitis in adults: Clinical manifestations and diagnosis")

●Autoimmune pancreatitis (see "Autoimmune pancreatitis: Clinical manifestations and diagnosis")

●Chronic pancreatitis (see "Overview of the complications of chronic pancreatitis", section on 'Biliary obstruction')

●Infectious or ischemic cholangiopathy, including chronic bacterial cholangitis, recurrent pyogenic cholangitis, and biliary parasitosis (see "Recurrent pyogenic cholangitis")

Studies suggested that IDUS demonstrated better overall test performance than other methods for distinguishing malignant from nonmalignant strictures [4,19,20,24,25]. In a study including 234 patients with indeterminate bile duct strictures who underwent endoscopic retrograde cholangiopancreatography (ERCP) with IDUS in addition to endoscopic ultrasound (EUS), computed tomography (CT), and endoscopic transpapillary biopsy, 136 patients (58 percent) had a malignant stricture that was confirmed by surgical histology or median follow-up of 34 months [24]. IDUS had a higher accuracy (ie, ability to correctly differentiate malignant from nonmalignant strictures) compared with EUS, CT, or transpapillary biopsy (91 versus 74, 73, and 59 percent, respectively). For 55 patients who were diagnosed with pancreatic adenocarcinoma, IDUS had higher accuracy compared with EUS or CT (90 versus 81 and 76 percent, respectively) [24]. In another study including 193 patients with indeterminate biliary strictures, 97 patients were diagnosed with malignancy (confirmed by tissue sampling, surgery, and/or long-term follow up) [19]. The sensitivity and specificity of IDUS were 97 and 79 percent, respectively. The accuracy of IDUS (ie, ability to correctly differentiate malignant from nonmalignant strictures) was higher for proximal compared with distal biliary strictures (98 versus 83 percent). Malignant strictures were longer (20 versus 14 mm) and had greater wall thickness (7 versus 3 mm) compared with nonmalignant strictures.

Other potential applications of IDUS in patients with indeterminate bile duct strictures but negative or nondiagnostic tissue sampling include:

●Surveillance – IDUS may be useful for surveillance of indeterminate biliary strictures with negative tissue sampling. In a study including 86 patients with indeterminate bile duct strictures who had multiple tests including cholangiography, brush cytology, intraductal biopsy, digital image analysis (DIA), and fluorescence in situ hybridization (FISH), 21 patients (24 percent) with initially negative tissue sampling were later diagnosed with malignant stricture [25]. IDUS had higher sensitivity for diagnosing malignancy compared with combined FISH/DIA, FISH alone, or DIA alone (86 versus 67, 62, and 14 percent, respectively).

●Providing US guidance for tissue sampling – We may use IDUS to target sampling of polypoid or localized bile duct lesions in the setting of an otherwise normal bile duct wall [26].

●Identifying possible indications for surgery – Preliminary studies suggested that some lesion characteristics (eg, a lesion involving and disrupting the bile duct wall) may be an indication for surgical exploration, even in patients with negative tissue sampling [26-28]. Additional studies are needed to confirm these findings before using these IDUS-related lesion characteristics as indications for surgery.

Primary sclerosing cholangitis — For patients with primary sclerosing cholangitis (PSC), we use IDUS to assess biliary strictures for features of malignancy (eg, irregular foci) and facilitate targeted tissue sampling [22,25]. In a study of 40 patients with a PSC-related dominant biliary stricture who underwent ERCP, tissue sampling, and IDUS, eight patients (20 percent) had cholangiocarcinoma [22]. Compared with cholangiography, IDUS had higher sensitivity and specificity for diagnosing malignancy (88 versus 63 percent and 91 versus 53 percent, respectively). However, studies suggested that overall accuracy of IDUS (ie, ability to correctly differentiate malignant from nonmalignant strictures) is lower for PSC-related strictures compared with non-PSC-related strictures (62 versus 82 percent) [25]. (See "Primary sclerosing cholangitis in adults: Clinical manifestations and diagnosis", section on 'Dominant biliary strictures' and 'Bile duct strictures' above.)

Cholangiocarcinoma — IDUS is useful for characterizing malignant bile duct strictures and for local tumor staging of cholangiocarcinoma. IDUS detects early lesions, determines the longitudinal tumor extent, and identifies tumor extension into adjacent organs (eg, pancreas) and major blood vessels (eg, portal vein, hepatic artery) [8,9,29-31]. The use of IDUS for local staging and preoperative planning is discussed separately. (See "Clinical manifestations and diagnosis of cholangiocarcinoma", section on 'Intraductal ultrasound'.)  

Distinguishing tumor spread from peritumoral bile duct wall inflammation is challenging with IDUS and other noninvasive imaging techniques. Studies suggested that the following factors may facilitate detailed visualization using IDUS [3,19,31-33]:

●Procedure timing – For patients with malignant biliary obstruction, we perform IDUS ideally prior to or within a few days of biliary stent placement [3,26]. The evaluation of bile duct wall thickening may be impacted by stent-induced inflammation and epithelial hyperplasia that may lead to overestimation of the longitudinal extent of the tumor [26].

●Thresholds for bile duct thickness – Assessing bile duct wall thickness with IDUS may be helpful in distinguishing inflammatory from malignant conditions. In a study comparing IDUS findings in 23 patients with IgG4-related sclerosing cholangitis (IgG4-SC) with 11 patients with cholangiocarcinoma, bile duct wall thickness >0.8 mm in non-strictured areas on cholangiography was highly suggestive of IgG4-SC, with sensitivity and specificity of 95 and 91 percent, respectively [31,33].

Choledocholithiasis — The use of IDUS for evaluating patients with suspected choledocholithiasis is generally reserved for those with nondiagnostic imaging (eg, magnetic resonance cholangiopancreatography [MRCP]) and as an option for confirming bile duct clearance following endoscopic stone removal [18,34-39]. The evaluation of suspected choledocholithiasis is discussed in detail separately. (See "Choledocholithiasis: Clinical manifestations, diagnosis, and management".)

●Suspected choledocholithiasis in patients with nondiagnostic studies – Both larger caliber bile ducts (>10 mm) and smaller stones (<3 mm) reduce the sensitivity of both MRCP and ERCP [18,36,37]. However, IDUS maintains high sensitivity and specificity in both conditions [18,36,37]. In a study including 92 patients with suspected biliary pancreatitis and negative cholangiogram, IDUS demonstrated bile duct stones (mean stone size, 1.9 mm) in 33 patients (36 percent), and the diagnosis was confirmed with endoscopic stone extraction [37]. During mean follow-up of 24 months, two patients (2 percent) had recurrent biliary pancreatitis. However, both patients had stones on IDUS but did not undergo cholecystectomy. In a study including 95 patients with jaundice and suspected choledocholithiasis who had negative cholangiography, bile duct stones were detected by IDUS in 31 patients (33 percent), and stones were confirmed by endoscopic stone removal in all patients [34]. Stone diameter ranged from 1 to 7 mm (mean stone size, 2.9 mm). In addition, IDUS showed biliary sludge in 24 patients (25 percent), which was confirmed by sludge extraction in 21 patients (88 percent). In a study including 32 patients with suspected biliary pancreatitis who had radiologic imaging (transabdominal US, CT, and MRCP) that was followed by ERCP with IDUS, choledocholithiasis was confirmed in 20 patients by stone extraction [18]. The sensitivity of US, CT, MRCP, ERCP and IDUS for identifying choledocholithiasis was 20, 40, 80, 90, and 95 percent, respectively, and specificity was 83, 92, 83, 92, and 92 percent, respectively. Of note, the sensitivity of MRCP decreased with bile duct dilation (bile duct diameter >10 mm, 73 versus 89 percent).

●Confirming duct clearance – Using IDUS to confirm stone clearance has been associated with lower rates of stone recurrence. Although IDUS adds time to ERCP (ie, an additional 5 to 10 minutes), it facilitates achieving complete duct clearance during the index procedure [38,39]. In a study comparing 59 patients who underwent IDUS after ERCP-guided biliary stone removal with 129 patients who had ERCP with stone removal only, rates of stone recurrence after three years were lower in the IDUS group (3 versus 13 percent) [38]. During the index procedure, 14 patients (24 percent) in the IDUS group had residual common bile duct stones (mean stone size, 4.9 mm). In a study of 70 patients with choledocholithiasis based on radiologic imaging (eg, US, MRCP) who underwent ERCP with sphincterotomy and stone extraction followed by IDUS, 28 patients (40 percent) had residual bile duct stones (mean size, 2.2 mm) that were addressed during the index procedure [39]. Although randomized trials are lacking, these data support the use of IDUS for confirming bile duct clearance after endoscopic removal.

Pancreatic disease — Technical advances, test performance, and safety of other methods for pancreatic imaging (eg, CT, magnetic resonance imaging [MRI], EUS) have essentially eliminated the need for ERCP with diagnostic invasive pancreatography. Thus, the role of IDUS of the pancreatic duct is limited to selected patients [5,17,40]:

●Pancreatic cystic neoplasms – For patients with suspected pancreatic cystic neoplasms (table 3), IDUS has been studied for detecting small lesions, determining the extent of intraductal disease, and assessing for parenchymal invasion. Evaluation with IDUS may help guide surgical planning for patients with mucin-producing tumors involving the main pancreatic duct or for patients with side-branch disease by identifying papillary tumor projections into the main pancreatic duct.

However, other imaging studies provide accurate diagnostic and presurgical assessment such that IDUS is not performed in most patients with pancreatic cystic neoplasms. The diagnosis, classification, and management of pancreatic cystic neoplasms is discussed in detail separately. (See "Classification of pancreatic cysts" and "Pancreatic cystic neoplasms: Clinical manifestations, diagnosis, and management".)

Data from randomized trials and observation studies suggested that IDUS was useful for surgical planning in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas (picture 3 and image 4) [5,17,40,41]. In a trial including 40 patients with IPMN who underwent preoperative testing followed by surgical resection, assessment with IDUS resulted in lower rates of surgical modifications based on intraoperative frozen sections compared with no IDUS (15 versus 50 percent) [5]. Preoperative IDUS also resulted in lower rates of recurrent disease after mean follow-up of 50 months (5 versus 20 percent). In a study including 24 patients with branch duct IPMN who underwent IDUS prior to surgical resection, the sensitivity and specificity of IDUS for detecting lateral tumor spread into the main pancreas duct was 92 and 91 percent, respectively [40]. One false negative occurred in a patient with flat atypia in the main pancreas duct, and one false positive arose in a patient with fibrosis and inflammation in the wall of the main duct.

Management of IPMN of the pancreas is discussed in more detail separately. (See "Intraductal papillary mucinous neoplasm of the pancreas (IPMN): Evaluation and management".)

●Other pancreatic disorders – IDUS may be used for evaluating indeterminate pancreatic strictures when the diagnosis is uncertain despite advanced imaging and when ERCP is planned for tissue sampling or therapeutic intervention [16]. The diagnostic evaluation of suspected pancreatic cancer is discussed separately. (See "Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer".)

Ampullary lesions — We use IDUS for evaluating the size and extent of ampullary lesions in selected patients (eg, patients with an adenoma in whom the extent of pancreas or biliary ductal infiltration requires clarification prior to endoscopic resection or in whom ampullary carcinoma cannot be excluded). This approach is consistent with society guidelines [42]. However, we do not use IDUS to evaluate all patients with ampullary lesions because of the potential risk of pancreatitis, additional procedure time, and cost. IDUS provides detailed visualization of the papilla and can reliably differentiate the sphincter of Oddi musculature from the papillary orifice [10,42].

Studies suggested that accuracy of IDUS for T-staging of ampullary lesions ranged from 87 to 95 percent [10,43]. In a meta-analysis including five studies, the pooled sensitivity and specificity of IDUS for T1 tumors was 90 and 88 percent, respectively; for T2 tumors, 73 and 91 percent, respectively, and for T3 tumors, 79 and 97 percent, respectively [10]. However, the pooled sensitivity for N-staging was 61 percent. In a study including 48 patients with ampullary lesions who underwent surgical or endoscopic resection, IDUS had higher sensitivity for detecting bile duct infiltration compared with EUS (71 versus 43 percent), while both techniques had good specificity (90 versus 98 percent) [43].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Endoscopic retrograde cholangiopancreatography (ERCP)".)

SUMMARY AND RECOMMENDATIONS

●Background – Intraductal ultrasound (IDUS) of the pancreaticobiliary system utilizes a small caliber ultrasound catheter that can be passed through the accessory channel of a duodenoscope and into the pancreatic or bile duct. The ultrasound catheter's small caliber, wire-guided design, flexibility, and high resolution imaging are beneficial for evaluating a variety of biliary, pancreatic, and ampullary disorders (table 1). The use of high frequencies allows for detailed examination of ductal and periductal tissues (image 1 and image 2). However, the limited depth of penetration prevents examination of more distant sites. (See 'Introduction' above.)

●Procedure – IDUS is typically performed by inserting the ultrasound catheter through the ampulla of Vater during endoscopic retrograde cholangiopancreatography (ERCP):

•Pre- and post-procedure care – Pre- and post-procedure care is similar to that for patients who undergo ERCP alone. (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults", section on 'Patient preparation'.)

•Contraindications – There are few contraindications that are mainly related to ERCP itself, including inability to tolerate anesthesia/sedation and/or hemodynamic instability. (See 'Contraindications and limitations' above and "Endoscopic ultrasound (EUS): Use of miniprobes for evaluating gastrointestinal lesions", section on 'Contraindications'.)

•Adverse events – Adverse events associated with IDUS are uncommon. Limited data suggested that performing IDUS during ERCP was not associated with increased risk of post-ERCP pancreatitis. (See 'Adverse events' above.)

Limitations of IDUS include that it is invasive, uses specialized equipment, requires expertise in advanced endoscopy, and may not be widely available.

●Clinical applications – Clinical applications of IDUS include (see 'Clinical applications' above):

•Indeterminate biliary strictures – IDUS can help differentiate malignant from nonmalignant biliary strictures based on sonographic features such as hypoechoic mass, heterogeneity of the internal echo, and irregularity of the outer border (image 3). (See 'Bile duct strictures' above.)

•Cholangiocarcinoma – IDUS detects early lesions, determines the longitudinal tumor extent, and identifies tumor extension into adjacent organs (eg, pancreas) and major blood vessels (eg, portal vein, hepatic artery). (See 'Cholangiocarcinoma' above and "Clinical manifestations and diagnosis of cholangiocarcinoma", section on 'Intraductal ultrasound'.)

•Suspected but unconfirmed choledocholithiasis – IDUS may be useful for demonstrating choledocholithiasis when other imaging studies (eg, magnetic resonance cholangiopancreatography [MRCP] and/or cholangiography) are nondiagnostic. (See 'Choledocholithiasis' above.)

•Pancreatic disease – For patients with intraductal papillary mucinous neoplasm (IPMN), IDUS may distinguish main duct disease from branch duct disease and determine the extent of tumor spread and parenchymal invasion. (See 'Pancreatic disease' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Michael J Levy, MD (deceased), who contributed to earlier versions of this topic review.