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Endoscopic ultrasonography (EUS) provides high spatial resolution and more detailed images than other diagnostic modalities. Furthermore, EUS-guided tissue acquisition (EUS-TA), such as EUS-guided fine needle aspiration or biopsy (EUS-FNA/FNB), is an indispensable tool in pancreaticobiliary disease diagnostics, supporting a conclusive pathological diagnosis. In this review, we evaluate the current status and the usefulness of EUS-TA for the diagnostics of the following biliary tract diseases: (A) biliary stricture diagnostics, (B) biliary tract cancer (BTC) itself, and (C) staging of advanced BTC. Previous reports have shown that EUS-FNA for biliary lesions is a safe procedure that is useful in differentiating biliary cancer from benign lesions and in the staging of BTC. On the other hand, the diagnostic performance of EUS-TA for bile duct lesions is reported to be similar to that of transpapillary biopsy. Overall, EUS-TA for biliary lesions may be a safe and effective method, but it should be performed with an understanding of the risk of serious adverse events such as bile leakage and peritoneal dissemination of cancer. It is recommended for distal biliary stricture lesions for which endoscopic retrograde cholangiopancreatography cannot confirm the diagnosis or gallbladder lesions if they do not require the needle to pass through the biliary lumen., (© 2024. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Contrast-enhanced endoscopic ultrasound (CE-EUS) has emerged as a promising diagnostic modality for assessing biliary diseases. CE-EUS is a noninvasive imaging technique that utilizes contrast agents to enhance the visualization of blood vessels and perfusion within target tissues. In the context of biliary diseases, CE-EUS allows for improved characterization of biliary lesions, aiding in differential diagnosis and treatment planning. This review highlights several key findings regarding the usefulness of CE-EUS in biliary disease assessment and therapeutic procedures., (© 2023. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Endoscopic ultrasonography (EUS) provides high spatial and contrast resolution and is a useful tool for evaluating the pancreato-biliary regions. Recently, contrast-enhanced harmonic EUS (CH-EUS) has been used to evaluate lesion vascularity, especially for the diagnosis of pancreatic tumors. CH-EUS adds two major advantages when diagnosing pancreatic cystic lesions (PCL). First, it can differentiate between mural nodules and mucous clots, thereby improving the accurate classification of PCL. Second, it helps with evaluation of the malignant potential of PCL, especially of intraductal papillary mucinous neoplasms by revealing the vascularity in the mural nodules and solid components. This review discusses the use and limitations of CH-EUS for the diagnosis of PCL., (© 2023. The Author(s).)

Endoscopic ultrasound (EUS) is an important tool for the evaluation of lymphadenopathy, especially in intra-thoracic or intra-abdominal regions. EUS also provides tissue diagnosis via EUS fine-needle aspiration or biopsy. To select the target for biopsy or aspiration, conventional B-mode images are used for the evaluation, but this approach still lacks diagnostic accuracy. Contrast-enhanced EUS has been used to evaluate the vascularity of lesions. Most malignant lymphadenopathy shows heterogenous enhancement or defect of enhancement, while quantitative studies using time-intensity curves in contrast-enhanced harmonic EUS show a rapid decline in enhancement pattern. These findings are useful as an auxiliary method for tissue diagnosis or in cases in which tissue diagnosis is contraindicated., (© 2023. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Purpose: Pancreatic cystic lesions (PCLs) include various types of cysts. Accurate preoperative diagnosis is essential to avoid unnecessary surgery on benign cysts. In this study, we aimed to identify the factors associated with misdiagnosis in preoperative endoscopic ultrasound (EUS) imaging and clinicopathological findings for PCLs., Methods: This study included 302 surgically resected patients with PCLs who underwent preoperative EUS. The preoperative EUS findings were re-evaluated and compared with the pathological diagnosis. Additionally, the factors associated with misdiagnosis of PCLs were investigated by multivariate analysis., Results: The preoperative diagnoses of PCLs were intraductal papillary mucinous neoplasm (IPMN) in 213 patients (70.5%), mucinous cystic neoplasm (MCN) in 33 patients (10.9%), serous neoplasm (SN) in 7 patients (2.3%), cystic degeneration cyst of solid tumor in 46 patients (15.2%), and pancreatic cancer with cystic degeneration in three patients (1.0%). A discrepancy between preoperative and postoperative diagnosis was found in 47 patients (15.6%). Based on the pathological diagnosis, the sensitivity of preoperative EUS imaging was IPMN 97.6% (206/211), MCN 90.0% (18/19), cystic degeneration 87.1% (27/31), and SN 15.4% (2/13). Multivariate analysis revealed that main pancreatic duct (MPD) communication ( - ) (odds ratio (OR), 4.54; 95% confidence interval (CI) 1.29-15.9), honeycomb-like structure ( +) (OR, 14.7; 95% CI 2.61-83.3), and MPD size ≦ 2 mm (OR, 16.3; 95% CI 3.93-67.6) were independently associated with misdiagnosis., Conclusion: For cases in which MCN and cystic degeneration of solid tumor are presumed based on preoperative EUS imaging and cases with PCLs with a honeycomb-like structure, diagnosis with multimodalities or fluid analysis with EUS-guided fine-needle aspiration should be considered., (© 2022. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

The diagnosis of autoimmune pancreatitis (AIP) is challenging and should be achieved through the comprehensive evaluation of clinical, radiological, serological, and pathological evidence, as there is currently no single reliable diagnostic modality. Endoscopic ultrasonography (EUS) can reveal pancreatic parenchymal and ductal features in much more detail than any other existing imaging modality. In this article, we focused on three applications of EUS, i.e., conventional EUS imaging, EUS elastography (EUS-EG), and contrast-enhanced harmonic EUS (CEH-EUS), for the diagnosis of AIP. Diffuse hypoechoic areas, diffuse enlargement, bile duct wall thickening, and peripancreatic hypoechoic margins on conventional EUS are characteristic features of AIP, and the frequencies of these findings are significantly higher in AIP than in pancreatic cancer (PC). EUS-EG of the pancreatic parenchyma in AIP showed homogenous stiffness and that the elasticity of the pancreas may change after steroid therapy. CEH-EUS revealed focal or diffuse iso-enhancement in most AIP cases and hypo-enhancement in most PC cases. However, some AIP cases show a contrast enhancement pattern similar to that of PC. It should be noted that EUS findings of AIP may differ depending on its stage or disease activity. Differentiation from PC has become an increasingly important issue in the process of diagnosing AIP, and EUS, including elastography and contrast enhancement, could be a promising imaging modality for this purpose., (© 2021. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Purpose: Shear wave elastography (SWE) using transabdominal ultrasonography (US) is widely used for diagnosis of tissue stiffness. Ultrasound shear wave dispersion (SWD) enables evaluation of tissue viscosity using SWE. The objective of this study was to investigate the reliability and clinical significance of SWD in pancreatic screening., Methods: SWE and SWD were measured in 76 patients examined by US in pancreatic screenings performed between November 2017 and November 2018. The median pancreatic elastic modulus (PEM) and dispersion slope were obtained from at least five measurements. The reproducibility of these values and their correlations with patient characteristics, pancreatic echogenicity, and the pancreas-to-spleen attenuation ratio (P/S) on plain CT, which is associated with fatty change in pancreatic parenchyma, were investigated retrospectively., Results: The median PEM and dispersion slope were 7.4 kPa and 15.7 (m/sec)/kHz, respectively, and both values had high intraclass correlation coefficients, showing high reproducibility (ρ = 0.869 and ρ = 0.867, respectively). The interquartile range/median value of PEM and dispersion slope were 0.36 and 0.28, respectively. PEM had a positive correlation with age (r s  = 0.348, p = 0.002), and dispersion slope was positively correlated with age (r s  = 0.278, p = 0.016) and BMI (r s  = 0.397, p < 0.001). The hyperechoic pancreas had significantly higher PEM (6.6 vs. 7.8 kPa, p = 0.037) and dispersion slope (13.2 vs. 16.3 (m/sec)/kHz, p < 0.001). On plain CT performed in 50 patients, the P/S was not correlated with PEM (r s  = - 0.180, p = 0.221), but was inversely correlated with dispersion slope (r s  = - 0.338, p = 0.019)., Conclusion: Measurement of SWD in pancreatic screening was highly reproducible and may permit objective evaluation of fatty change of the pancreas.

Endoscopic ultrasonography (EUS) is a modality with high spatial resolution that enables comprehensive observation of the entire pancreas and plays an important role in the diagnosis of pancreatic lesions. Recent advances in diagnostic imaging methods such as ultrasound, computed tomography, and magnetic resonance imaging have increased the incidental detection of pancreatic cystic lesions (PCLs). EUS has been recognized as an essential diagnostic method for the detection and evaluation of PCLs. EUS has two important roles: as a detailed (high-resolution) imaging diagnostic method and as an approach for collecting cyst fluid content by EUS-guided fine needle aspiration for pathological diagnosis or biomarker evaluation. Furthermore, in recent years, the usefulness of contrast-enhanced EUS for the differential diagnosis of PCLs or evaluation of grade of malignancy, and a novel imaging technique called needle-based confocal laser endomicroscopy to observe intraductal structures through a needle, has been reported. An understanding of the morphological characteristics of PCLs depicted by ultrasound imaging and of the benefits and limitations of EUS diagnosis in daily practice is needed.

Purpose: To assess the feasibility and the clinical usefulness of a newly developed endoscopic ultrasonography (EUS) shear-wave elastography technique (EUS shear-wave measurement: EUS-SWM) in the diagnosis and treatment of autoimmune pancreatitis (AIP)., Methods: Tissue elasticity was measured in the pancreas in 160 patients. The success rate of EUS-SWMs, the velocity of the shear wave (Vs, m/s), and the reliability index of the Vs measurement (VsN) were evaluated, and the elasticity (median Vs) was compared between AIP patients (n = 14) and normal controls., Results: A total of 3837 EUS-SWMs were performed without adverse events. Overall, 97.6% (3743/3837) were successful. The median VsN was 74%. The median Vs values of the pancreas were as follows: 2.22 m/s in the pancreatic head (push position), 2.36 m/s in the head (pull position), 1.99 m/s in the body, and 2.25 m/s in the tail. The median Vs of the AIP group (2.57 m/s) was significantly higher than that of the normal controls (1.89 m/s) (P = 0.0185). The mean Vs significantly decreased from 3.32 m/s to 2.46 m/s after steroid therapy (n = 6) (P = 0.0234)., Conclusion: EUS-SWM is feasible and generates credible results. EUS-SWM was a useful method for assessment of the effect of steroid therapy in AIP patients.

Purpose: Pancreatic fibrosis or fibrosing reactions have been reported in intraductal papillary-mucinous neoplasm (IPMN) patients. We assessed whether a higher elastic modulus (EM) measured using shear wave elastography (SW-EG) correlated with the existence of branch-duct (BD) IPMN., Methods: In total, 183 normal pancreas (NP) and 123 BD-IPMN cases were enrolled. First, we assessed the difference in pancreatic EM (PEM) at different sites (head or tail side of the cyst). Second, a comparison was done between the median PEM of the NP and the BD-IPMN cases. Receiver-operating characteristic analysis was performed to determine the BD-IPMN diagnostic capabilities. Finally, in patients whose cyst was not visualized, the test-positive rate was determined., Results: No significant difference was seen between the cyst head side PEM (4.61 kPa) and the tail side PEM (5.35 kPa) (P = 0.471). Among these cases matched by age, 73 were selected each from NP and BD-IPMN cases (median age 65 years). The median PEM of the BD-IPMN cases (5.18 kPa) was significantly higher than that of the NP cases (3.17 kPa) (P < 0.001). When the cut-off value was set at 4.75 kPa, the sensitivity, specificity, PPV, NPV, and accuracy were 75.3%, 64.4%, 72.3%, 67.9%, and 69.9%, respectively. The cut-off value of 4.75 kPa helped for the indirect selection of BD-IPMN patients (10/17, 58.8%) whose cyst was not detected on B-mode ultrasonography., Conclusion: SW-EG measurement of the underlying pancreatic parenchyma may correlate with the presence of BD-IPMN.

Purpose: Abdominal ultrasound (US) can visualize the esophagogastric junction (EGJ) as a hyperechoic area in the dorsal portion of the lateral segment of the liver. We prospectively evaluated the EGJ using US elastography (US-EG) in patients with reflux esophagitis (RE) to examine prediction of distal esophageal function., Methods: Of 108 patients undergoing US-EG and esophagogastroduodenoscopy, 102 in whom the EGJ was observed for ≥ 15 s were included. The subjects were divided into a RE group (n = 41, Grade M/A/B:24/13/4 according to modified Los Angeles Classification) and a non-RE group (n = 61). Direct strain elastography (LOGIQ E9, GE Healthcare), which gives a semi-quantitative elasticity index within a region of interest including the lateral segment, was used as a standard for measurement of the change in stiffness (CS) at the EGJ., Results: The number of CS as determined by US-EG was 6.0 (5.5-6.7) in the RE group and 8.6 (6.6-10.0) in the non-RE group (P < 0.0001). In ROC analysis, the AUC was 0.8415 for diagnosis of RE using the number of CS. At a cut-off of 7.7, the sensitivity, specificity, and accuracy for diagnosis were 92.7, 65.6, and 74.5%, respectively., Conclusion: The presence of RE can be predicted based on US-EG.

Purpose: To evaluate the efficacy and safety of gemcitabine plus cisplatin in Japanese patients with unresectable gallbladder cancer (GBC)., Methods: Chemo-naïve patients with histologically proven unresectable GBC were enrolled in this study. The patients received gemcitabine (1000 mg/m 2 ) and cisplatin (25 mg/m 2 ) on days 1 and 8, every 21 days. A response assessment was done by CT scan every 4 weeks. The primary end points were to determine the response rates [RR; complete response (CR) + partial response (PR)] and the disease control rate [DCR; CR + PR + stable disease (SD)]. The secondary end points were to evaluate toxicity, progression-free survival (PFS), and overall survival (OS)., Results: From March 2012 to February 2015, 14 patients from seven different institutions were enrolled in the study, and 13 cases were evaluable for assessment. Eleven cases (84.6%) had distant metastases, and 8 cases (61.5%) had obstructive jaundice. There was no CR, 1 PR (7.7%), 11 SD (84.6%), and 1 progressive disease (PD) (7.7%). The RR was 7.7%, whereas the DCR was 92.3%. The median PFS was 3.1 months, the median OS was 6.2 months, and the one-year survival rate was 0%. Grade 3 hematologic toxicity was observed in three cases (23%), but all of them recovered upon drug withdrawal, and there was no treatment-related death., Conclusion: Although gemcitabine plus cisplatin has a high DCR (92.3%) and relatively low toxicity, the RR is less than 10%, and development of new therapies is desired for the treatment of unresectable GBC.

Endoscopic ultrasound (EUS) has recently played an increasing role in the diagnosis of gallbladder diseases. This review aims to summarize the role of EUS in the diagnosis of gallbladder lesions. EUS provides high-resolution images that can improve the diagnosis of gallbladder polypoid lesions and microlithiasis, in addition to evaluating gallbladder thickness and staging of gallbladder carcinoma. Contrast-enhancing agents may be useful for the differential diagnosis of gallbladder lesions, but the evidence of their effectiveness is still limited and further studies are required in this area to establish its usefulness. Endoscopic ultrasound combined with fine needle aspiration has played an increasing role in providing histological diagnosis of gallbladder tumors in addition to gallbladder thickening.

Pancreatic changes in aging have been described for many decades. They involve not only pancreatic parenchyma but also pancreatic ductal, microscopic, and exocrine functional changes. There have been many studies of these changes based on pathology and various imaging modalities, as well as functional studies. The pancreatic volume was found to decrease with advancing age, with a higher incidence of pancreatic steatosis, as demonstrated in autopsy and imaging studies. The pancreatic ductal structure has been described with wide ranges of normal variation, but many studies have shown a tendency toward enlargement with advancing age. By endoscopic ultrasound imaging, the aging pancreas may exhibit abnormal findings similar to chronic pancreatitis. Microscopically, there has been evidence of patchy lobular fibrosis and papillary hyperplasia and demonstrable k-ras mutation in both normal and dysplastic ductal mucosa. The evidence of pancreatic exocrine insufficiency has yielded conflicting results, but most studies have shown a tendency toward decreased pancreatic exocrine function in the elderly. Differentiating pancreatic change in the elderly from early chronic pancreatitis may be difficult as there are limited studies to compare these two conditions in terms of structural and functional changes.

We used contrast-enhanced endoscopic ultrasonography (CE-EUS) to diagnose a case of solid-pseudopapillary neoplasm (SPN) in an adult man. A 58-year-old man was referred to our hospital because of a pancreatic mass found by positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) during a medical checkup in 2009. Trans-abdominal ultrasonography revealed a 24-mm hypoechoic mass at the pancreatic tail with calcification inside. Multiphasic computed tomography (CT) showed a solid mass with delayed enhancement. EUS revealed a hypoechoic mass without lateral shadowing, and neither a septum nor cystic component was detected. CE-EUS using Sonazoid(®) showed a hypovascular mass compared with the surrounding pancreatic parenchyma, and the inside of the mass was enhanced like an alveolus nest, suggesting pseudopapillary change. Diagnosis of a solid-pseudopapillary neoplasm and a concomitant small neuroendocrine tumor was made by distal pancreatectomy.

Purpose: S-1 is one of the second-line candidate agents for gemcitabine-refractory unresectable pancreatic cancer. Two phase II studies have been reported for second-line chemotherapy with S-1, but these studies did not investigate introduction rate and suitable dose of second-line S-1. Therefore, we conducted a prospective multicenter study in which chemo-naïve patients were enrolled and had two levels of S-1 dose., Methods: Chemo-naïve patients with unresectable pancreatic cancer were enrolled. This study started with 80 mg/m(2)/day dose of S-1 as second-line chemotherapy and tolerability was checked. When tolerability was not confirmed in initial patients, the dose of S-1 was shifted to 60 mg/m(2)/day. When tolerability was confirmed at 80 or 60 mg/m(2)/day, the study continued, and up to 20 patients were accumulated with the dose. In addition, the introduction rate of second-line S-1 was examined., Results: Six of the initial 7 patients with 80 mg/m(2)/day dose of S-1 completed one course of second-line chemotherapy. Twenty patients were accumulated with an 80 mg/m(2)/day dose of S-1. With the exception of one patient continued gemcitabine chemotherapy, two of the remaining 19 patients withdrew from this study because of toxicity during the period of gemcitabine chemotherapy. Fifteen of the remaining 17 gemcitabine-refractory patients could complete one course of S-1 as second-line chemotherapy with acceptable toxicity., Conclusions: This prospective multicenter study showed that 15 (78.9%) out of 19 chemo-naïve unresectable pancreatic cancer patients could complete one course of 80 mg/m(2)/day dose of S-1 as second-line chemotherapy after first-line gemcitabine chemotherapy failure with tolerable toxicity.