Ken Kamata

Characterization of Small Solid Tumors in the Pancreas: The Value of Contrast-Enhanced Harmonic Endoscopic Ultrasonography

OBJECTIVES:Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS), a novel technology, visualizes parenchymal perfusion in the pancreas. This study prospectively evaluated how accurately CH-EUS characterizes pancreatic lesions and compared its diagnostic ability with that of contrast-enhanced multidetector-row computed tomography (MDCT) and endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA).METHODS:A total of 277 consecutive patients with pancreatic solid lesions that were detected by conventional EUS underwent CH-EUS for evaluation of vascularity. After infusing an ultrasound contrast, CH-EUS was performed by using an echoendoscope and a specific mode for contrast harmonic imaging. On the basis of the intensity of enhancement, the lesions were categorized into four patterns: nonenhancement, hypoenhancement, isoenhancement, and hyperenhancement. For comparison, all patients underwent MDCT. The ability of CH-EUS to differentiate ductal carcinomas from the other solid tumors, particularly small lesions (≤2 cm in diameter) was assessed, and compared with the differentiating abilities of MDCT and EUS-FNA.RESULTS:In terms of reading the CH-EUS images, the κ-coefficient of the interobserver agreement test was 0.94 (P<0.001). CH-EUS-depicted hypoenhancement diagnosed ductal carcinomas with a sensitivity and specificity of 95.1% (95% confidence interval (CI) 92.7–96.7%) and 89.0% (95% CI 83.0–93.1%), respectively. For diagnosing small carcinomas by CH-EUS, the sensitivity and specificity were 91.2 % (95% CI 82.5–95.1%) and 94.4% (95% CI 86.2–98.1%), respectively. CH-EUS-depicted hypervascular enhancement diagnosed neuroendocrine tumors with a sensitivity and specificity of 78.9% (95% CI 61.4–89.7%) and 98.7% (95% CI 96.7–98.8%), respectively. Although CH-EUS and MDCT did not differ significantly in diagnostic ability with regard to all lesions, CH-EUS was superior to MDCT in diagnosing small (≤2 cm) carcinomas (P<0.05). In 12 neoplasms that MDCT failed to detect, 7 ductal carcinomas and 2 neuroendocrine tumors had hypoenhancement and hyperenhancement on CH-EUS, respectively. When CH-EUS was combined with EUS-FNA, the sensitivity of EUS-FNA increased from 92.2 to 100%.CONCLUSIONS:CH-EUS is useful for characterizing conventional EUS-detected solid pancreatic lesions. EUS equipped with contrast harmonic imaging may play an important role in the characterization of small tumors that other imaging methods fail to depict and may improve the diagnostic yield of EUS-FNA.

Value of EUS in early detection of pancreatic ductal adenocarcinomas in patients with intraductal papillary mucinous neoplasms.

BACKGROUND AND STUDY AIMS Pancreatic ductal adenocarcinomas (PDAC) sometimes arise in patients with intraductal papillary mucinous neoplasms (IPMNs). This study examined the incidence of PDACs concomitant to or derived from branch duct IPMNs. The usefulness of endoscopic ultrasonography (EUS) relative to other imaging methods for detecting these tumors was also assessed. PATIENTS AND METHODS This retrospective study used data from clinical records and imaging studies that were collected prospectively. During 2001-2009, 167 consecutive patients with IPMNs underwent EUS, ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). The 102 patients whose branch duct IPMNs lacked mural nodules/symptoms and thus did not qualify for resection were followed up by semiannual EUS and annual ultrasonography, CT, and MRI. The sensitivity and specificity with which the four modalities detected IPMN-derived and -concomitant PDACs at the first examination and throughout the study period were evaluated. The rate of PDAC development during follow-up was analyzed by the Kaplan-Meier method. RESULTS A total of 17 IPMN-derived and 11 IPMN-concomitant PDACs were diagnosed at the first examination. Lesions that did not qualify for resection or chemotherapy were followed up for a median of 42 months. Seven IPMN-concomitant PDACs and no IPMN-derived PDACs were detected during follow-up. The 3- and 5-year rates of IPMN-concomitant PDAC development were 4.0% and 8.8%, respectively. At the first examination, EUS was superior to other imaging modalities in terms of IPMN-derived and -concomitant PDAC detection. Throughout the study period, including follow-up, EUS was significantly better at detecting IPMN-concomitant PDACs than the other modalities. CONCLUSIONS IPMN-concomitant PDACs are quite often found at diagnosis and during follow-up. EUS examination of the whole pancreas plays an important role in the management of IPMNs as it allows the early detection of these small invasive carcinomas.

EUS-Guided Broad Plexus Neurolysis Over the Superior Mesenteric Artery Using a 25-Gauge Needle

OBJECTIVES:Endoscopic ultrasonography (EUS)-guided celiac plexus neurolysis (EUS-CPN) is safe and effective but not beneficial for some patients with extended abdominal cancer. We compared the effectiveness of standard EUS-CPN and EUS-guided broad plexus neurolysis (EUS-BPN) that extends over the superior mesenteric artery (SMA) using a 25-gauge needle.METHODS:Consecutive patients referred to our quaternary EUS centers were eligible for inclusion. To evaluate the neurolytic spread, contrast was mixed with the neurolytic agent and post-procedure computed tomography scanning was performed. The regions containing the celiac, superior, and inferior mesenteric arteries were divided on the frontal plane into six areas: upper right and left, middle right and left, and lower right and left. The number of contrast-bearing areas after EUS-CPN and EUS-BPN were related to the degree of pain relief achieved.RESULTS:A total of 67 patients with advanced abdominal cancer were included (34 EUS-CPN and 33 EUS-BPN). The qualitative variables of the two groups did not differ significantly. The EUS-BPN group had more patients with six contrast-bearing areas (42%) than the EUS-CPN group (0%). These patients had significantly better short-term and long-lasting pain relief than patients with less than five contrast-bearing areas. EUS-BPN patients exhibited significantly greater reductions in days 7 and 30 visual analog pain scale scores than EUS-CPN patients.CONCLUSIONS:Our preliminary data suggested that EUS-BPN using a 25-gauge needle provides patients with advanced abdominal cancer with better pain relief than standard EUS-CPN, and without incurring serious complications. Moreover, it seems that broad neurolysis over the SMA may provide superior analgesia.

Estimation of malignant potential of GI stromal tumors by contrast-enhanced harmonic EUS (with videos)

BACKGROUND Contrast-enhanced harmonic EUS (CEH-EUS) is a new sonographic technique that uses US contrast agents and depicts intratumoral vessels in real time. OBJECTIVE To evaluate whether assessment of tumor vascularity by CEH-EUS can predict the preoperative malignancy risk of GI stromal tumors (GISTs). DESIGN Prospective study to observe GIST vascularity. SETTING Kinki University School of Medicine. PATIENTS Between June 2007 and September 2009, 76 consecutive patients suspected of having subepithelial lesions underwent CEH-EUS. INTERVENTION CEH-EUS was performed by using a prototype echoendoscope in an extended pure harmonic detection mode. MAIN OUTCOME MEASUREMENTS Resected GIST specimens in 29 patients who underwent surgical resection were divided into high-grade (n=16) and low-grade (n=13) malignancy groups based on mitotic activity. The abilities of EUS-guided FNA and CEH-EUS to diagnose the malignant potential were compared. The sensitivities with which contrast-enhanced multidetector CT, power-Doppler EUS, and CEH-EUS detected intratumoral vessels in high-grade malignancy GISTs also were compared. RESULTS CEH-EUS identified irregular vessels and thereby predicted GIST malignancies with a sensitivity, specificity, and accuracy of 100%, 63%, and 83%, respectively. Diagnosis of high-grade malignancy GISTs by EUS-guided FNA had a sensitivity, specificity, and accuracy of 63%, 92%, and 81%, respectively. Contrast-enhanced multidetector CT, power-Doppler EUS, and CEH-EUS detected intratumoral vessels in high-grade malignancy GISTs with sensitivities of 31%, 63%, and 100%, respectively (P<.05). LIMITATIONS A single center was involved in this study. CONCLUSIONS CEH-EUS successfully visualized intratumoral vessels and may play an important role in predicting the malignancy risk of GISTs.

Characterization of intra-abdominal lesions of undetermined origin by contrast-enhanced harmonic EUS (with videos).

BACKGROUND The diagnosis of intra-abdominal lesions of undetermined origin is often a challenge for endoscopists and radiologists. OBJECTIVE To evaluate the microvasculature of benign and malignant intra-abdominal lesions by contrast-enhanced harmonic EUS (CEH-EUS) and to investigate its usefulness for discriminating between malignant and benign lesions. DESIGN The vascularity of intra-abdominal lesions of undetermined origin was observed by using CEH-EUS. The lesions were classified according to their vascular patterns. The effectiveness of CEH-EUS in differentiating malignant from benign lesions was evaluated. SETTING Kinki University School of Medicine, Osaka, Japan. PATIENTS Forty-three patients, each with a lesion of undetermined origin, were evaluated prospectively by CEH-EUS between March 2007 and March 2009. INTERVENTIONS CEH-EUS was performed by using a prototype echoendoscope and the extended pure harmonic detection mode (a specific mode for contrast harmonic imaging). MAIN OUTCOME MEASUREMENTS The lesions were categorized by 2 physicians as having no, homogeneous, or heterogeneous enhancement. A consensus was reached for each case offline. How the benign and malignant groups differed in terms of their enhancement patterns was examined. RESULTS The kappa coefficient of the interobserver agreement test was 0.953 (P < .001). Of the 27 malignant lesions, 26 (96.3%) exhibited heterogeneous enhancement. The 1 remaining malignant lesion (3.7%) showed homogeneous enhancement. Of the 16 benign lesions, none displayed heterogeneous enhancement, and 12 (75%) and 4 (25%) exhibited homogeneous and no enhancement, respectively. The malignant and benign lesion groups differed significantly in terms of homogeneous and heterogeneous enhancement (P < .001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy with which CEH-EUS differentiated malignant from benign lesions were 96.3%, 100%, 100%, 94.1%, and 97.6%, respectively. LIMITATIONS A single medical unit with a limited number of patients. CONCLUSIONS CEH-EUS depicted the microvasculature of intra-abdominal lesions of undetermined origin very clearly and may be useful for characterizing such lesions.

Diagnosis of pancreatic tumors by endoscopic ultrasonography.

Pancreatic tumors are highly diverse, as they can be solid or cystic, and benign or malignant. Since their imaging features overlap considerably, it is often difficult to characterize these tumors. In addition, small pancreatic tumors, especially those less than 2 cm in diameter, are difficult to detect and diagnose. For characterizing pancreatic tumors and detecting small pancreatic tumors, endoscopic ultrasonography (EUS) is the most sensitive of the imaging procedures currently available. This technique also provides good results in terms of the preoperative staging of pancreatic tumors. EUS-guided fine needle aspiration (EUS-FNA) has also proved to be a safe and useful method for tissue sampling of pancreatic tumors. Despite these advantages, however, it is still difficult to differentiate between benign and malignant, solid or cystic pancreatic tumors, malignant neoplasms, and chronic pancreatitis using EUS, even when EUS-FNA is performed. Recently, contrast-enhanced EUS with Doppler mode (CE-EUS) employing ultrasound contrast agents, which indicate vascularization in pancreatic lesions, has been found to be useful in the differential diagnosis of pancreatic tumors, especially small pancreatic tumors. However, Doppler ultrasonography with contrast-enhancement has several limitations, including blooming artifacts, poor spatial resolution, and low sensitivity to slow flow. Consequently, an echoendoscope was developed recently that has a broad-band transducer and an imaging mode that was designed specifically for contrast-enhanced harmonic EUS (CEH-EUS) with a second-generation ultrasound contrast agent. The CEH-EUS technique is expected to improve the differential diagnosis of pancreatic disease in the future. This review describes the EUS appearances of common solid and cystic pancreatic masses, the diagnostic accuracy of EUS-FNA, and the relative efficacies and advantages of CE-EUS and CEH-EUS along with their relative advantages and their complementary roles in clinical practice.

Contrast-enhanced harmonic endoscopic ultrasonography for differential diagnosis of pancreatic cysts

BACKGROUND AND STUDY AIM Comparison of fundamental B-mode endoscopic ultrasonography (FB-EUS) and contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) in the differential diagnosis of pancreatic cysts according to presence of mural nodules. PATIENTS AND METHODS Between April 2007 and April 2012, FB-EUS and CH-EUS data were prospectively collected from 581 consecutive patients with pancreatic cysts, and were retrospectively analyzed from 70 with subsequent cyst resection. Presence and height of mural nodules as detected on FB-EUS and CH-EUS were evaluated, and thence accuracies of both methods for diagnosing mucinous versus nonmucinous and malignant versus benign cysts. RESULTS On pathological examination 48 cysts were mucinous and 22 were nonmucinous; 30 cysts were malignant (high grade dysplasia or invasive carcinoma) and 40 were benign. If presence of a mural nodule was considered to indicate a mucinous cyst, FB-EUS and CH-EUS accuracies did not differ significantly (respectively: sensitivity 85 % vs. 79 %; specificity 46 % vs. 96 %; accuracy 73 % vs. 84 %, P = 0.057). If presence of mural nodule was considered to indicate malignancy, CH-EUS was significantly more accurate than FB-EUS (respectively: sensitivity 97 % vs. 97 %; specificity 75 % vs. 40 %; accuracy 84 % vs. 64 %, P = 0.0001). For diagnosing malignancy by evaluating mural nodule height, the area under the receiver operating characteristic (AUROC) was 0.84 and 0.93 for FB-EUS and CH-EUS, respectively (P = 0.028). Presence of a mural nodule of height ≥ 4 mm on CH-EUS was a sign of malignancy (false-positive fraction 0.2; true-positive fraction 0.93; odds ratio 56.0). CONCLUSIONS CH-EUS is more accurate than FB-EUS for diagnosing malignant pancreatic cysts.

Endoscopic Ultrasound-Guided Neurolysis in Pancreatic Cancer

Abdominal pain in patients with pancreatic cancer is a common symptom that is often difficult to manage. Opioids are frequently used in an attempt to mitigate pain; however, side effects may develop. Celiac plexus neurolysis (CPN) affords effective pain control in patients with pancreatic cancer and is not associated with opioid side effects. Endoscopic ultrasound (EUS)-guided CPN has demonstrated safety and efficacy due to real-time imaging and anterior access to the celiac plexus from the posterior gastric wall, thereby avoiding complications related to the puncture of spinal nerves, arteries and the diaphragm, and is now practiced widely. Furthermore, two new techniques of EUS-guided neurolysis for abdominal pain management in pancreatic cancer patients have recently been developed. The first technique is EUS-guided celiac ganglia neurolysis (EUS-CGN) in which EUS facilitates CGN by enabling direct injection into the individual celiac ganglion, and the second technique is EUS-guided broad plexus neurolysis (EUS-BPN) which extends over the superior mesenteric artery. This review provides evidence for the efficacy of EUS-CPN. Particular attention is paid to the two new techniques of EUS-guided neurolysis, EUS-CGN and EUS-BPN.

Contrast-enhanced harmonic endoscopic ultrasonography for assessment of lymph node metastases in pancreatobiliary carcinoma.

AIM To assess the usefulness of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for lymph node metastasis in pancreatobiliary carcinoma. METHODS All patients suspected of pancreatobiliary carcinoma with visible lymph nodes after standard EUS between June, 2009 and January, 2012 were enrolled. In the primary analysis, patients with successful EUS-fine needle aspiration (FNA) were included. The lymph nodes were assessed by several standard EUS variables (short and long axis lengths, shape, edge characteristic and echogenicity), color Doppler EUS variable [central intranodal blood vessel (CIV) presence] and CH-EUS variable (heterogeneous/homogeneous enhancement patterns). The diagnostic accuracy relative to EUS-FNA was calculated. In the second analysis, N-stage diagnostic accuracy of CH-EUS was compared with EUS-FNA in patients who underwent surgical resection. RESULTS One hundred and nine patients (143 lymph nodes) fulfilled the criteria. The short axis cut-off ≥ 13 mm predicted malignancy with a sensitivity and specificity of 72% and 85%, respectively. These values were 72% and 63% for the long axis cut-off ≥ 20 mm, 62% and 75% for the round shape variable, 81% and 30% for the sharp edge variable, 66% and 61% for the hypoechogenicity variable, 70% and 72% for the CIV-absent variable, and 83% and 91% for the heterogeneous CH-EUS-enhancement variable, respectively. CH-EUS was more accurate than standard and color Doppler EUS, except the short axis cut-off. Notably, three patients excluded because of EUS-FNA failure were correctly N-staged by CH-EUS. CONCLUSION CH-EUS complements standard and color Doppler EUS and EUS-FNA for assessment of lymph node metastases.

Contrast-enhanced harmonic endoscopic ultrasonography for pancreatobiliary diseases.

The combination of second‐generation ultrasound contrast agents and an endoscopic ultrasonography (EUS) system with a broad‐band transducer has allowed contrast‐enhanced harmonic imaging in the field of EUS. In contrast‐enhanced harmonic EUS (CH‐EUS), diffuse homogeneous enhancement is obtained in normal parenchyma of the pancreas. The bile duct and pancreatic duct are depicted as non‐enhanced ductal structures with strong contrast in comparison to the surrounding parenchyma. CH‐EUS identifies pancreatic adenocarcinomas as solid lesions exhibiting hypo‐enhancement with a sensitivity and specificity of 88–96% and 88–94%, respectively. In particular, 80–100% of false‐negative cases in endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) are correctly classified by CH‐EUS, suggesting CH‐EUS complements EUS‐FNA. Moreover, CH‐EUS improves depiction of some subtle lesions in conventional EUS, thus facilitating EUS‐FNA. For quantitative perfusion analysis, a time–intensity curve (TIC) for the region of interest can be generated during CH‐EUS. The maximum intensity gain and the echo intensity reduction rate from the peak at 1 min obtained by TIC can be used for differentiation of pancreatic adenocarcinoma from other tumors. CH‐EUS is also useful for differentiation of invasive intraductal papillary mucinous neoplasms (IPMN) from non‐invasive IPMN, identification of malignant lesions in the gallbladder, and T‐ and N‐staging of pancreatobiliary tumors.