Contrast-enhanced Harmonic Endoscopic Ultrasonography Research Articles

Tissue harmonic versus contrast-enhanced harmonic endoscopic ultrasonography for the diagnosis of pancreatic tumors: Prospective multicenter study.

This prospective multicenter study aimed to assess and compare the accuracy of tissue harmonic endoscopic ultrasonography (TH-EUS) and contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for differentiating pancreatic carcinoma from other pancreatic tumors. Consecutive patients with solid pancreatic tumors were prospectively enrolled between August 2013 and December 2014. To assess the accuracy of TH-EUS and CH-EUS, we compared four parameters of TH-EUS (fuzzy edge, irregular periphery, hypoechogenicity, and heterogeneous internal echogenicity) and four parameters of CH-EUS (hypoenhancement and heterogeneous enhancement in the early and late phases, respectively) to investigate which parameter of each method was most suitable to diagnose pancreatic carcinomas. Interobserver agreement and the diagnostic ability of pancreatic carcinoma using TH-EUS and CH-EUS were assessed and compared. A total of 204 patients were enrolled. For the diagnosis of pancreatic carcinoma, interobserver agreement by experts and nonexperts was 0.33-0.50 and 0.35-0.50 for TH-EUS, respectively, and 0.72-0.74 and 0.20-0.54 for CH-EUS, respectively. Irregular periphery was the most accurate diagnostic parameter among TH-EUS findings for differentiating pancreatic carcinomas, with sensitivity, specificity, and accuracy of 95.0%, 42.9%, and 78.9%, respectively. Late phase hypoenhancement was the most accurate diagnostic parameter among CH-EUS findings for differentiating pancreatic carcinomas, with sensitivity, specificity, and accuracy of 90.8%, 74.6%, and 85.8%, respectively. The accuracy of CH-EUS (late phase hypoenhancement) for diagnosis of pancreatic carcinoma was significantly higher than that of TH-EUS (irregular periphery) (p < 0.001). In comparison with TH-EUS, CH-EUS increased the diagnostic ability and reproducibility for the diagnosis of pancreatic carcinoma. UMIN (000011124).

Role of CH-EUS as guidance for EUS-biliary drainage malignant obstruction.

Endoscopic ultrasound (EUS)-guided biliary drainage is the usual method of choice for patients with biliary obstructions difficult to treat by endoscopic retrograde cholangiopancreatography. In some patients, however, the bile duct is difficult to detect during EUS-guided biliary drainage. Contrast-enhanced harmonic endoscopic ultrasound has reportedly been useful for interventional EUS procedures. This study describes five patients who underwent EUS-guided biliary drainage with contrast-enhanced harmonic imaging between April 2017 and March 2020 for malignant biliary obstruction due to bile duct cancer. The procedure was performed through an intrahepatic bile duct approach in three patients and through an extrahepatic bile duct approach in the other two. Although fundamental B-mode EUS was unable to detect the target intrahepatic bile duct because the duct was filled with debris, contrast-enhanced harmonic imaging was able to detect the bile duct by clarifying its border with the hepatic parenchyma. Similarly, in patients who underwent extrahepatic bile duct approach, fundamental B-mode EUS could not distinguish between debris and tumor, whereas contrast-enhanced harmonic EUS was able to differentiate between them. The procedure was technically and clinically successful in all five patients. One patient experienced bleeding as an adverse event. In conclusion, EUS-guided biliary drainage with contrast-enhanced harmonic imaging is useful in detecting the fluid space in bile ducts filled with debris or filled with debris and tumor invasion.

Efficacy of Contrast-Enhanced Harmonic Endoscopic Ultrasound for Pancreatic Solid Tumors with a Combination of Qualitative and Quantitative Analyses: A Prospective Pilot Study

Image evaluation of contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) and additional time-intensity curve (TIC) analysis enable qualitative and quantitative analyses of pancreatic tumor based on real-time perfusion imaging. To evaluate the efficacy of CEH-EUS with a combination of qualitative and quantitative analyses of pancreatic solid tumors. Patients were scheduled to undergo EUS-guided fine needle aspiration (FNA) for pancreatic solid tumors were prospectively enrolled between 11/2016 and 12/2018 and underwent CEH-EUS. The vascular and enhancement patterns were qualitatively evaluated and heterogeneous enhancement was defined to be indicative of malignancy. The echo intensity change during 60s in the tumor was quantitatively evaluated by time intensity curve analysis. In total, 100 patients were enrolled in this study. The final diagnoses were malignant lesions in 87 patients and benign legions in 13 patients. There were four categories of enhancement and patterns: hypovascular with heterogeneous, hypovascular with homogeneous, hypervascular heterogeneous, and hypervascular homogeneous enhancement. The diagnostic capability of qualitative analysis was the sensitivity, specificity, and accuracy of 89%, 62%, and 85%, respectively. With respect to time intensity curve analysis, the time to peak of malignant lesions was significantly shorter than those of benign lesions (P = 0.0009) with an optimal cutoff value of 12.81s on the receiver operating characteristic curve analysis. With the combination of qualitative and quantitative analyses, the sensitivity, specificity, and accuracy were improved to 100%, 54%, and 94%, respectively. CEH-EUS with combined qualitative and quantitative analyses for pancreatic tumors might be useful as a complement for EUS-FNA. The UMIN Clinical Trials Registry (UMIN000025192).

Evaluation of Peritoneal Deposits in Undiagnosed Ascites by Advanced Endoscopic Ultrasound Imaging Techniques

AbstractEtiology of ascites can be usually determined with ascitic fluid cytological and biochemical evaluation. Occasionally, the cause of ascites cannot be determined despite repeated ascitic fluid evaluations. These patients with undiagnosed ascites usually undergo diagnostic laparotomy/laparoscopy for etiological diagnosis. Endoscopic ultrasound (EUS) can help in resolving the diagnostic conundrum of undiagnosed ascites by visualizing as well as sampling peritoneal and omental deposits/thickening. However, rarely fine-needle aspiration from deposits may be falsely negative and patient may need repeat sampling. Newer EUS imaging techniques such as elastography and contrast-enhanced harmonic EUS by providing additive information on stiffness and enhancement pattern of the lesion can help in differential diagnosis.

Comparison of contrast-enhanced versus conventional EUS-guided FNA/fine-needle biopsy in diagnosis of solid pancreatic lesions: a randomized controlled trial

Contrast-enhanced harmonic EUS (CEH-EUS) is useful in the differential diagnosis of solid pancreatic lesions (SPLs). However, there is lack of verification about the usefulness of CEH-EUS-guided FNA/fine-needle biopsy (FNB) sampling. This study aimed to investigate the usefulness of CEH-EUS-guided FNA/FNB sampling without on-site cytopathology. Patients with SPLs were prospectively enrolled and randomly assigned (1:1) to 2 parallel groups, the interventional group (CEH-EUS) or the control group (conventional EUS). The diagnostic sensitivity and optimal number of needle passes for pathologic diagnosis were investigated and compared between groups. Two hundred forty patients were enrolled from March 2016 to September 2019, with 120 patients assigned to each group. Pancreatic malignancies and neuroendocrine tumors were found in 202 (90.83%) and 9 (3.75%) patients, respectively. There was no statistically significant difference between the groups in terms of age, sex, lesion size (30.96 ± 12.09mm in the CEH-EUS group vs 33.09 ± 16.39mm in the conventional EUS group; P= .252), lesion location, adverse event rate, and disease distribution. The diagnostic sensitivity values in the CEH-EUS and conventional EUS groups were 85.8% and 88.3%, respectively (P= .564). All patients in the conventional EUS group and most in the CEH-EUS group received a pathologic diagnosis within 3 needle passes. Diagnostic sensitivity for SPLs was not different between the CEH-EUS and conventional EUS groups, and no independent factors were found that could improve diagnostic sensitivity. CEH-EUS-guided FNA/FNB sampling does not need to be used routinely and may be selectively considered for small, indeterminate lesions. (Clinical trial registration number: KCT 0001840.).

Utility of multiphase contrast enhancement patterns on CEH-EUS for the differential diagnosis of IPMN-derived and conventional pancreatic cancer

BackgroundIntraductal papillary mucinous neoplasm (IPMN) is reported as a high-risk factor for pancreatic cancer (PC) that includes IPMN-derived cancers (IPMC) and the development of invasive pancreatic ductal adenocarcinoma (PDAC) concomitant with IPMN. Since invasive IPMC and PDAC exhibit different oncological behaviors, their differentiation is clinically important. We aimed to investigate the use of contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) for the differential diagnosis between invasive IPMC and PDAC. MethodsThis study involved 183 consecutive patients with PC (invasive IPMC: 42, PDAC concomitant with IPMN: 9, without IPMN: 132) who underwent CEH-EUS preoperatively. While investigating the patterns, enhanced effects in the solid part of the tumor were compared with those in the surrounding pancreatic parenchyma after administration of Sonazoid® and evaluated as hyperenhanced, isoenhanced, or hypoenhanced. We retrospectively compared the enhanced pattern of CEH-EUS by using multiphasic analysis and clinicopathological factors between invasive IPMC and PDAC. ResultsIn multiphase evaluations at 20, 40 and 60 s in CEH-EUS, 75.2% (106/141) of PDACs were hypoenhanced (−) at ≥2 of the 3 time points, with significant differences from those of invasive IPMC (P < 0.001). The solid tumor diameter was significantly larger in PDAC than in invasive IPMC, and the tumor stage and preoperative serum carbohydrate antigen 19-9 level were higher. After propensity score matching of stage and solid tumor diameter, contrast enhancement patterns were significantly more persistent in invasive IPMC than in PDAC (P = 0.0013). ConclusionsMultiphase evaluation using CEH-EUS is a useful method for differentiating between invasive IPMC and PDAC.

Utility of contrast-enhanced harmonic endoscopic ultrasonography for predicting the prognosis of pancreatic neuroendocrine neoplasms.

Pancreatic neuroendocrine neoplasms (PanNENs), including Grade 1 (G1) or G2 tumors, can have a poor prognosis. This study investigated the value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for predicting the prognosis of PanNENs. This single-center, retrospective study included 47 consecutive patients who underwent CH-EUS and were diagnosed with PanNEN by surgical resection or EUS-guided fine needle aspiration between December 2011 and February 2016. Patients were divided into aggressive and non-aggressive groups according to the degree of clinical malignancy. CH-EUS was assessed regarding its capacity for diagnosing aggressive PanNEN, the correspondence between contrast patterns and pathological features, and its ability to predict the prognosis of PanNEN. There were 19 cases of aggressive PanNEN and 28 cases of non-aggressive PanNEN. The aggressive group included three G1, four G2, three G3 tumors, three mixed neuroendocrine non-neuroendocrine neoplasms, and six neuroendocrine carcinomas. CH-EUS was superior to contrast-enhanced computed tomography for the diagnosis of aggressive PanNEN (P<0.001): hypo-enhancement on CH-EUS was an indicator of aggressive PanNEN, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94.7%, 100%, 100%, 96.6%, and 97.9%, respectively. Among G1/G2 PanNENs, cases with hypo-enhancement on CH-EUS had a poorer prognosis than those with hyper/iso-enhancement (P=0.0009). Assessment of 36 resected specimens showed that hypo-enhancement on CH-EUS was associated with smaller and fewer vessels and greater degree of fibrosis. Contrast-enhanced harmonic endoscopic ultrasonography may be useful for predicting the prognosis of PanNENs.

A Prospective, Randomised Controlled Trial Investigating the Diagnostic Sensitivity of Contrast‐Enhanced Harmonic Endoscopic Ultrasound-Guided Versus Conventional Endoscopic Ultrasound‐Guided Fine-Needle Aspiration/Biopsy for Solid Pancreatic Lesions

Background: Contrast‐enhanced harmonic endoscopic ultrasound (CEH‐EUS) is useful in the differential diagnosis of solid pancreatic lesions (SPLs). This study aimed to investigate the usefulness of CEH‐EUS-guided fine-needle aspiration/biopsy (FNA/B), without on-site cytopathology. Methods: This randomised controlled trial was conducted at two university hospitals in Korea. Patients with SPLs were prospectively enrolled and randomly assigned (1:1) using a table of random sampling numbers, to two parallel groups, the interventional group (CEH-EUS) or the control group (conventional EUS). The investigators, endoscopists, patients, and pathologists were unmasked to the group assigned. The diagnostic sensitivity and optimal number of needle passes for pathologic diagnosis were investigated and compared between groups. Clinical trial number: KCT0001840. Findings: In total, 252 patients with SPLs were screened and 240 were enrolled from March 2016 to September 2019, with 120 patients assigned to each group. Pancreatic malignancies and neuroendocrine tumours were found in 202 (90·83%) and nine (3·75%) patients, respectively. There was no statistically significant difference between the groups in terms of age, sex, lesion size (30·96±12·09 mm in the CEH-EUS group vs 33·09±16·39 mm in the conventional EUS group; p=0·252), location, adverse event rate (2·5% vs 2·5%; p=0·999), and disease distribution (malignancy, neuroendocrine tumour, and benign masses, p=0·395). The diagnostic sensitivity values in the CEH-EUS and conventional EUS groups were 85·8% and 88·3%, respectively (p=0·564). All the patients in the conventional EUS group and most of those in the CEH-EUS group received a pathological diagnosis within three needle passes. Interpretation: This prospective, randomised trial showed that the diagnostic sensitivity for SPLs was not different between the CEH‐EUS and conventional EUS groups, and there were no independent factors that could improve diagnostic sensitivity. CEH-EUS-guided FNA/B will not need to be used routinely for the diagnosis of SPLs. CEH-EUS may be selectively considered in small, indeterminate lesion. Trial Registration: (Clinical trial registration at https://cris.nih.go.kr/cris; KCT0001840) Funding Statement: None. Declaration of Interests: There are no conflicts of interest to declare. Ethics Approval Statement: This study was approved by the Institutional Review Board (GAIRB2016-026) and conducted in accordance with the principles set forth in the Declaration of Helsinki. Written informed consent was obtained from all patients.

Meta-analysis of contrast-enhanced ultrasound and contrast-enhanced harmonic endoscopic ultrasound for the diagnosis of gallbladder malignancy

BackgroundThe diagnosis between benign and malignant gallbladder lesions is sometimes difficult. The objective of this study is to assess whether contrast-enhanced ultrasound (CEUS) and contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) can be an accurate method for detecting gallbladder malignancy and to determine which imaging signs can be indicative of malignancy.MethodsA study search of PubMed, Elsevier, and Sciencedirect was performed in May 2019. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve were used to examine the accuracy of CEUS and CH-EUS.ResultsTwenty-one studies were included in the meta-analysis. The pooled sensitivities of CEUS and CH-EUS were 0.81 (0.75–0.86) and 0.92 (0.86–0.95); the specificities were 0.94 (0.90–0.96) and 0.89 (0.69–0. 97); the DORs were 64 (32–127) and 89 (22–354); and the area under the SROC curves were 0.90 (0.87–0.92) and 0.92 (0.90–0.94). On CEUS, the diagnostic criterion for gallbladder malignancy according to four features were analyzed. Sensitivity and specificity were 0.75 (0.65–0.83) and 0.98 (0.85–1.00) for integrity of gallbladder wall; 0.69 (0.55–0.81) and 0.89 (0.77–0.95) for heterogeneous enhancement; 0.81 (0.71–0.88) and 0.88 (0.76–0.94) for irregular vessels; and 0.81 (0.66–0.91) and 0.75 (0.59–0.86) for washout time within 28 s. On CH-EUS, heterogeneous enhancement could be indicative of malignant lesions with a sensitivity of 0.94 (0.85–0.97); and the specificity was 0.92 (0.71–0.98).ConclusionsCEUS and CH-EUS are promising and reliable imaging modalities with a high sensitivity and specificity for the diagnosis of gallbladder malignancy. CH-EUS might be more sensitive than CEUS with a higher sensitivity. In addition, irregular tralesional vessels and washout time within 28 s on CEUS and heterogeneous enhancement on CH-EUS are indicative of malignancy. However, larger scale and well-designed studies are warranted to verify our results.

Improved detection of liver metastasis using Kupffer-phase imaging in contrast-enhanced harmonic EUS in patients with pancreatic cancer (with video)

Kupffer-phase imaging visualized by perfluorobutane (Sonazoid) distribution into normal liver tissues upon phagocytosis by Kupffer cells potentially aids in improving detection of liver metastasis compared with fundamental B-mode EUS (FB-EUS). However, the diagnostic performance of Kupffer-phase imaging in contrast-enhanced harmonic EUS (CH-EUS) remains unclear. Hence, this study aimed to evaluate the usefulness of CH-EUS-based Kupffer-phase imaging for diagnosing liver metastasis from pancreatic cancer. We retrospectively analyzed consecutive patients with pancreatic cancer who underwent contrast-enhanced CT (CE-CT) and FB-EUS, followed by CH-EUS, from 2011 to 2017. The diagnostic ability of CH-EUS against that of CE-CT and FB-EUS for metastasis in the left liver lobe was compared. Subsequently, the influences of CH-EUS on the determination of clinical stage and patient management for pancreatic cancer were assessed. We enrolled 426 patients with pancreatic cancer. Metastasis in the left liver lobe was present in 27.2% of patients. The diagnostic accuracy of CE-CT, FB-EUS, and CH-EUS was 90.6%, 93.4%, and 98.4%, respectively. The sensitivity and diagnostic accuracy of CH-EUS for metastasis in the left liver lobe were significantly higher than those of FB-EUS or CE-CT. The sensitivity of CH-EUS for detecting small liver metastasis (<10mm) was considerably higher than that of CE-CT or FB-EUS (P< .001). In 2.1% of patients, only CH-EUS could detect a single distant metastasis of the left liver lobe, thereby upgrading the tumor staging and altering the clinical management. CH-EUS-based Kupffer-phase imaging increased the detectability of metastasis in the left liver lobe. This technique could be a reliable pretreatment imaging modality for clinical decision-making in patients with pancreatic cancer.

Contrast Harmonic Endoscopic Ultrasound in Pancreatic Diseases

Endoscopic ultrasound (EUS) was first described in 1986, with the aim of overcoming the problems affecting transabdominal ultrasound imaging, mainly problems related to the interposition of gas, and artifacts produced by bone or fat. Now, EUS can be considered as the best method for the analysis of pancreatic diseases, overtaking the diagnostic accuracy of computed tomography and magnetic resonance imaging. However, fundamental B-mode imaging is limited for the diagnosis of solid pancreatic lesions, because most of them are depicted as heterogeneous and hypo-echoic, and it is difficult to differentiate between benign and malignant lesions. Similar to how perfusion patterns obtained by computed tomography or magnetic resonance imaging after injection of contrast agents allow for the characterization of focal lesions, EUS has also recently been introduced to the use of contrast agents for performing contrast-enhanced harmonic EUS (CEH-EUS), which has the capability to distinguish the type of perfusion between lesions and surrounding tissue. CEH-EUS has shown its usefulness for the diagnosis and characterization of solid pancreatic lesions. Moreover, CEH-EUS is also highly accurate for distinguishing non-neoplastic from neoplastic cysts in pancreatic lesions. Another potential role of CEH-EUS is its ability to direct EUS-guided tissue acquisition.

Can contrast-enhanced harmonic endoscopic ultrasonography accurately diagnose main pancreatic duct involvement in intraductal papillary mucinous neoplasms?

BackgroundMain pancreatic duct (MPD) involvement in branch duct-type intraductal papillary mucinous neoplasms (BD-IPMNs) is a high risk finding for malignant IPMNs. However, discrepancies exist in the identification of MPD involvement between imaging findings and pathological diagnosis. The purpose of this study was to evaluate the diagnostic accuracy of preoperative assessment of MPD involvement in IPMNs using contrast-enhanced harmonic endoscopic ultrasound (CH-EUS). MethodsThis study involved 166 consecutive patients with BD-IPMNs who underwent surgical resection. CH-EUS was used to evaluate the MPD involvement according to the presence of mural nodules (MN) that advanced into the MPD or involved the MPD. The CH-EUS findings were compared with the pathological findings. Additionally, we analyzed the risk factors for malignant BD-IPMNs using multivariate analysis. ResultsA total of 77, 51, and 38 patients were pathologically diagnosed with low-grade or intermediate-grade dysplasia, high-grade dysplasia and invasive IPMNs, respectively. MPD involvement was diagnosed using CH-EUS (MPD-inv.-EUS) in 90 (54.2%) patients with a sensitivity, specificity and accuracy of 83.5%, 87.0% and 84.9%, respectively. The malignancy rate in patients with MPD-inv.-EUS was 71.6% (63/90). Multivariate logistic regression analysis showed that MPD-inv.-EUS (OR, 3.61; 95% CI:1.45–8.98), age (OR, 5.70; 95% CI: 1.47–22.2), cyst size (OR, 2.45; 95% CI:1.04–5.78) and MN size (OR, 7.05; 95% CI:2.48–20.0) were significant for malignant BD-IPMNs. ConclusionsMPD-inv.-EUS accurately represents the pathological involvement of IPMN and may be a useful predictor of malignant BD-IPMNs.

Sa1464 QUANTITATIVE CONTRAST-ENHANCED ENDOSCOPIC ULTRASOUND IN PANCREATIC DUCTAL ADENOCARCINOMA AND PANCREATIC NEUROENDOCRINE TUMORS: CAN WE PREDICT SURVIVAL USING PERFUSION PARAMETERS?

Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) parameters may be used to predict prognosis of pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (pNET). The perfusion parameters obtained through time intensity curve (TIC) analysis may have different degrees of impact on overall survival (OS). The aim of this study was to investigate the association between several perfusion parameters on CEH-EUS performed before treatment and survival outcome in patients with PDAC or pNET. Patients with PDAC or pNET who underwent CEH-EUS at our institution between 2017-2019 were included in the study. Quantitative analysis of tumor vascularity was performed using TIC analysis-derived parameters, obtained from processing CEH-EUS recordings with a commercially available software. Cox proportional hazards models were used to determine associations with survival outcome Twenty-two patients with PDAC (tumor size on EUS: median, 33 mm; range, 23–45 mm) and eight patients with pNET (tumor size: median, 40mm; range, 18-65mm) were identified. During CEH-EUS, all PDACs were hypoenhanced in all phases, while pNETs appeared as hyperenhancing masses in the arterial phase. Median OS for PDAC patients was 9.61 months (95%CI, 0.1-38.7) while the median OS for pNET patients was 15.81 months (95%CI, 5.8-24.5). In a multivariate model for OS, a lower peak enhancement (HR=1.76, P=0.02) and a lower wash-in area under the curve (HR=1.06, P=0.001) were associated with worse survival outcome for patients with PDAC. CEH-EUS parameters may be used as a surrogate to predict PDAC aggressiveness and survival before treatment. After validation by large-scale studies, CEH-EUS perfusion parameters have the potential to be used in pretreatment risk stratification of patients with PDAC and in evidence-based clinical decision support.

Diagnostic value of contrast-enhanced harmonic endoscopic ultrasonography in predicting the malignancy potential of submucosal tumors: a systematic review and meta-analysis.

Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) utilizes the second-harmonic signals from contrast microbubbles located in the vessels to improve the detectability of microcirculation. Many studies have used CH-EUS to stratify the malignancy risk of submucosal tumors (SMTs), discriminate gastrointestinal stromal tumors (GISTs) from benign SMTs, and predict the malignancy of GISTs based on the regularity of vessels or enhancing patterns. The aim of this study was to conduct a meta-analysis to evaluate the diagnostic performance of CH-EUS in the differential diagnosis of SMTs. After searching the Medline, Embase, and Cochrane databases systematically, studies that evaluated the diagnostic accuracy of CH-EUS for the prediction of the malignancy potential of SMTs were pooled. The diagnostic accuracy was computed using a stochastic effect model. The overall test performance was summarized with the summary receiver operating characteristic curve. Six studies discriminated GISTs from benign lesions, and three studies discriminated low-risk from high-risk GISTs, covering a total of 354 cases of SMT. The overall accuracy of CH-EUS in predicting malignancy risk can be assessed as follows: sensitivity 0.87 (95% CI 0.82-0.91), specificity 0.82 (95% CI 0.74-0.89), positive likelihood ratio of 3.55 (95% CI 2.39-5.27), negative likelihood ratio of 0.21 (95% CI 0.13-0.33), and diagnostic odds ratio of 22.17 (95% CI 10.43-47.10). The overall area under the curve was 0.89. Subgroup analysis of the sensitivity and specificity for studies discriminating low-risk from high-risk GISTs were 0.93 (95% CI 0.77-0.99) and 0.81 (95% CI 0.63-0.93), respectively. There was evidence of significant heterogeneity, but no proof of publication bias. CH-EUS is an effective tool for improving the diagnostic accuracy of conventional EUS for discriminating SMTs and is superior to other imaging techniques. However, due to the limited number of well-designed control studies, we should take into consideration the uncertainty of this method when altering a treatment plan.

Contrast-enhanced EUS for evaluation of thickened omentum.

A 68-year-old man presented with upper abdominal pain. He had undergone a Whipple procedure 32 months earlier for pancreatic adenocarcinoma. Clinical examination, liver function tests, serum CA19-9, and US of the abdomen showed normal results. Contrast-enhanced CT revealed thickened omentum. On EUS, thickened omentum was visualized as a sheetlike hypoechoic structure adjacent to the gastric wall (A). Contrast-enhanced harmonic EUS (CH-EUS) by the use of Sonovue (Bracco, Milan, Italy) was done at a low mechanical index of 0.12.

Utility of Contrast-Enhanced Harmonic Endoscopic Ultrasound for the Guidance and Monitoring of Endoscopic Radiofrequency Ablation.

Background/AimsInterventional endoscopists may utilize contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) for image guidance during radiofrequency ablation (RFA) because of its capability to delineate real-time tumor perfusion dynamics. The purpose of this study was to assess the utility of CEH-EUS for the guidance and monitoring of endoscopic RFA.MethodsNineteen consecutive patients with solid abdominal tumors who underwent CEH-EUS and endoscopic RFA were included. The extent of the ablation was assessed by CEH-EUS at 5 to 7 days after RFA. Additional RFAs were performed under CEH-EUS guidance.ResultsThe diagnoses were as follows nonfunctioning neuroendocrine tumor (n=13), solid pseudopapillary neoplasm (SPN) (n=2), insulinoma (n=1), left adrenal adenoma (n=2), and left adrenal oligometastasis (n=1). Pre-CEH-EUS findings revealed that 17 cases showed hyperenhanced patterns and two cases of SPN showed isoenhanced patterns. CEH-EUS-assisted RFA was technically feasible in all 19 patients. After the first RFA session, seven patients of the treated tumors showed the disappearance of intratumoral enhancement on CEH-EUS, whereas 12 showed residual contrast enhancement. Twelve patients with incomplete ablation were further treated with additional RFA under real-time CEH-EUS guidance. Radiologic complete response was observed in 13 patients (68.4%). Among the 35 ablation procedures, the only adverse events were two episodes of pancreatitis (5.7%; 1 moderate and 1 mild). During the median follow-up of 28 months, the local recurrence rate was 7.7%.ConclusionsThe application of CEH-EUS for RFA could be helpful in assessing early treatment response after ablation and targeting residual viable tumors during additional ablation sessions.

Utility of Contrast-Enhanced Harmonic Endoscopic Ultrasonography for Early Diagnosis of Small Pancreatic Cancer.

This study aimed to assess whether contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS), compared to multidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI), is useful for early diagnosis of small pancreatic cancer (PC). Between March 2010 and June 2018, all three imaging modalities and surgery were performed for patients with a pancreatic solid lesion measuring ≤20 mm; diagnostic ability was compared among modalities. Fifty-one of 60 patients were diagnosed with PC (PC size in 41 patients: 11–20 mm; 10 patients: ≤10 mm). The sensitivity, specificity, and accuracy of CH-EUS, MDCT, and MRI for PC (11–20 mm) detection were 95%/83%/94%, 78%/83%/79%, and 73%/33%/68%, respectively. The diagnostic ability of CH-EUS was significantly superior compared with MDCT and MRI (p = 0.002 and p = 0.007, respectively). The sensitivity, specificity, and accuracy of CH-EUS, MDCT, and MRI for PC (≤10 mm) detection were 70%/100%/77%, 20%/100%/38%, and 50%/100%/62%, respectively. The diagnostic ability of CH-EUS tended to be superior to that of MDCT (p = 0.025). The sensitivity of MDCT for PC (≤10 mm) detection was significantly lower than that for PC (11–20 mm) detection (20% vs. 78%; p = 0.001). CH-EUS, compared to MDCT and MRI, is useful for diagnosing small PCs.

Role of endoscopic ultrasound in the screening and follow-up of high-risk individuals for familial pancreatic cancer.

Managing familial pancreatic cancer (FPC) is challenging for gastroenterologists, surgeons and oncologists. High-risk individuals (HRI) for pancreatic cancer (PC) (FPC or with germline mutations) are a heterogeneous group of subjects with a theoretical lifetime cumulative risk of PC over 5%. Screening is mainly based on annual magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). The goal of screening is to identify early-stage operable cancers or high-risk precancerous lesions (pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasms with high-grade dysplasia). In the literature, target lesions are identified in 2%-5% of HRI who undergo screening. EUS appears to provide better identification of small solid lesions (0%-46% of HRI) and chronic-pancreatitis-like parenchymal changes (14%-77% of HRI), while MRI is probably the best modality to identify small cystic lesions (13%-49% of HRI). There are no specific studies in HRI on the use of contrast-enhanced harmonic EUS. EUS can also be used to obtain tissue samples. Nevertheless, there is still limited evidence on the accuracy of imaging procedures used for screening or agreement on which patients to treat. The cost-effectiveness of screening is also unclear. Certain new EUS-related techniques, such as searching for DNA abnormalities or protein markers in pancreatic fluid, appear to be promising.

Contrast‑enhanced harmonic endoscopic ultrasonography for the differential diagnosis of pancreatic masses: A systematic review and meta‑analysis

Understanding the difference between malignant and benign pancreatic masses is critical in terms of diagnosis, although this is difficult to determine in clinical practice. The contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) technique was introduced in 2010, although, to the best of the authors' knowledge, there has been no systematic review or meta-analysis to date evaluating its diagnostic performance for the differentiation of pancreatic masses. The aim of the present study was to systematically evaluate the diagnostic performance of CH-EUS for the differentiation of pancreatic masses. Search key words and inclusion and exclusion criteria were initially presented. Two independent authors read and extracted the relevant information from the included studies. Disagreements were resolved through discussion with another two experienced authors. Metadisc and Stata software were used for the meta-analysis and the evaluation of bias. A total of 16 studies comprising 1,325 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of CH-EUS were used to distinguish between malignant and benign tumors, and the values obtained were 93% [95% confidence interval (CI): 91-94%], 84% (95% CI: 80-87%), 5.58 (95% CI: 3.90-7.97), 0.09 (95% CI: 0.07-0.11) and 72.56 (95% CI: 48.93-107.60), respectively. The area under the summary receiver operating characteristic curve was determined to be 0.96. No publication bias was identified in this meta-analysis. Taken together, these results confirm that CH-EUS has a high accuracy rate for distinguishing between benign and malignant pancreatic space-occupying lesions, and it may therefore be used as an effective diagnostic tool for pancreatic masses.

Endoscopic ultrasonography for pancreatic solid lesions.

The incidence and mortality rates of pancreatic cancer, which has a poor prognosis, are rising rapidly. Endoscopic ultrasonography (EUS) provides superior spatial resolution compared with other imaging modalities such as transabdominal ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), and it is considered among the most reliable and efficient diagnostic modalities for pancreatic diseases. In this review, we show that EUS is useful for detection of pancreatic solid lesions and staging of pancreatic cancer. EUS also plays an important role in screening patients with high-risk factors for pancreatic cancer. Although EUS is useful for detection of small pancreatic lesions, pancreatic lesions are difficult to characterize using this modality, because most pancreatic solid lesions appear hypoechoic on EUS. From this point of view, contrast-enhanced harmonic EUS (CH-EUS) plays an important role in the differential diagnosis of pancreatic lesions. EUS and CH-EUS are also useful for staging pancreatic cancer. Moreover, EUS-guided fine-needle aspiration (EUS-FNA) is superior to other modalities in terms of cytopathological diagnosis. Although EUS-FNA has a high diagnostic ability for pancreatic cancer, the combination of EUS-FNA and CH-EUS improves the diagnostic ability by decreasing the number of false-negative cases. Thus, conventional EUS, EUS-FNA, and CH-EUS are essential in clinical practice for the diagnosis of pancreatic solid lesions.