Adrian Săftoiu

Neural network analysis of dynamic sequences of EUS elastography used for the differential diagnosis of chronic pancreatitis and pancreatic cancer

BACKGROUND EUS elastography is a newly developed imaging procedure that characterizes the differences of hardness and strain between diseased and normal tissue. OBJECTIVE To assess the accuracy of real-time EUS elastography in pancreatic lesions. DESIGN Cross-sectional feasibility study. PATIENTS The study group included, in total, 68 patients with normal pancreas (N = 22), chronic pancreatitis (N = 11), pancreatic adenocarcinoma (N = 32), and pancreatic neuroendocrine tumors (N = 3). A subgroup analysis of 43 cases with focal pancreatic masses was also performed. INTERVENTIONS A postprocessing software analysis was used to examine the EUS elastography movies by calculating hue histograms of each individual image, data that were further subjected to an extended neural network analysis to differentiate benign from malignant patterns. MAIN OUTCOME MEASUREMENTS To differentiate normal pancreas, chronic pancreatitis, pancreatic cancer, and neuroendocrine tumors. RESULTS Based on a cutoff of 175 for the mean hue histogram values recorded on the region of interest, the sensitivity, specificity, and accuracy of differentiation of benign and malignant masses were 91.4%, 87.9%, and 89.7%, respectively. The positive and negative predictive values were 88.9% and 90.6%, respectively. Multilayer perceptron neural networks with both one and two hidden layers of neurons (3-layer perceptron and 4-layer perceptron) were trained to learn how to classify cases as benign or malignant, and yielded an excellent testing performance of 95% on average, together with a high training performance that equaled 97% on average. LIMITATION A lack of the surgical standard in all cases. CONCLUSIONS EUS elastography is a promising method that allows characterization and differentiation of normal pancreas, chronic pancreatitis, and pancreatic cancer. The currently developed methodology, based on artificial neural network processing of EUS elastography digitalized movies, enabled an optimal prediction of the types of pancreatic lesions. Future multicentric, randomized studies with adequate power will have to establish the clinical impact of this procedure for the differential diagnosis of focal pancreatic masses.

Randomized controlled trial of endoscopic ultrasound-guided fine-needle sampling with or without suction for better cytological diagnosis.

Objective. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a highly accurate method to obtain specific diagnosis in various diseases. The optimal method of EUS-guided sampling of material for pathologic diagnosis has not been clearly established. The aim of our study was to compare two different techniques of EUS-guided sampling of solid masses, using either non-suction or suction with a 10-ml syringe. Material and methods. Patients assessed during a 6-month period were randomized to three passes of EUS-guided sampling with suction (26 patients) or non-suction (26 patients). The samples were characterized for cellularity and bloodiness, with a final cytology diagnosis established blindly. The final diagnosis was reached either by EUS-FNA if malignancy was definite, or by surgery and/or clinical follow-up of a minimum of 6 months in the cases of non-specific benign lesions. Results. EUS-guided fine-needle sampling with suction of solid masses increased the number of pathology slides (17.8±7.1 slides for suction as compared with 10.2±5.5 for non-suction, p=0.0001), without increasing the overall bloodiness of each sample. Sensitivity and the negative predictive values were higher when suction was applied, as compared to the non-suction group (85.7% as compared with 66.7%, p=0.05). Conclusions. This prospective randomized study showed that EUS-guided fine-needle sampling of solid masses using suction yields a higher number of slides without increasing bloodiness. Although, the proportion of target cells was relatively similar between the suction and non-suction sampling techniques, the sensitivity and negative predictive values of the procedure were significantly higher when suction was added.

Combined contrast-enhanced power Doppler and real-time sonoelastography performed during EUS, used in the differential diagnosis of focal pancreatic masses (with videos).

BACKGROUND Contrast-enhanced power Doppler (CEPD) and real-time sonoelastography (RTSE) performed during EUS were previously described to be useful for the differential diagnosis between chronic pseudotumoral pancreatitis and pancreatic cancer. OBJECTIVE To prospectively assess the accuracy of the combination of CEPD and RTSE to differentiate pancreatic focal masses. DESIGN Cross-sectional feasibility study. SETTING A tertiary-care academic referral center. PATIENTS The study group included 54 patients with chronic pancreatitis (n = 21) and pancreatic adenocarcinoma (n = 33). INTERVENTIONS Both imaging methods (CEPD and RTSE) were performed sequentially during the same EUS examination. Power Doppler mode examination was performed after intravenous injection of a second-generation contrast agent (2.4 mL of SonoVue), and the data were digitally recorded, comprising both the early arterial phase and venous/late phase. Three 10-second sonoelastographic videos were also digitally recorded that included the focal mass and the surrounding pancreatic parenchyma. Postprocessing analyses based on specially designed software were used to analyze the CEPD and RTSE videos. A power Doppler vascularity index was used to characterize CEPD videos, the values being averaged during a 10-second video in the venous phase. Hue histogram analysis was used to characterize RTSE videos, with the mean hue histogram values being also averaged during a 10-second video. MAIN OUTCOME MEASUREMENTS To differentiate chronic pancreatitis and pancreatic cancer. RESULTS The sensitivity, specificity, and accuracy of combined information provided by CEPD and RTSE to differentiate hypovascular hard masses suggestive of pancreatic carcinoma were 75.8%, 95.2%, and 83.3%, respectively, with a positive predictive value and negative predictive value of 96.2% and 71.4%, respectively. LIMITATION A single-center, average size of study population. CONCLUSIONS A combination of CEPD and RTSE performed during EUS seems to be a promising method that allows characterization and differentiation of focal pancreatic masses.

Role of Endoscopic Ultrasound in the Diagnosis and Staging of Pancreatic Cancer

Early diagnosis of pancreatic cancer remains a difficult task, and multiple imaging tests have been proposed over the years. The aim of this review is to describe the current role of endoscopic ultrasound (EUS) for the diagnosis and staging of patients with pancreatic cancer. A detailed search of MEDLINE between 1980 and 2007 was performed using the following keywords: pancreatic cancer, endoscopic ultrasound, diagnosis, and staging. References of the selected articles were also browsed and consulted. Despite progress made with other imaging methods, EUS is still considered to be superior for the detection of clinically suspected lesions, especially if the results of other cross‐sectional imaging modalities are equivocal. The major advantage of EUS is the high negative predictive value that approaches 100%, indicating that the absence of a focal mass reliably excludes pancreatic cancer. The introduction of EUS‐guided fine needle aspiration allows a preoperative diagnosis in patients with resectable cancer, as well as a confirmation of diagnosis before chemoradiotherapy for those that are not. This comprehensive review highlighted the diagnostic capabilities of EUS including the newest refinements such as contrast‐enhanced EUS, EUS elastography, and 3‐dimensional EUS. The place of EUS‐guided biopsy is also emphasized, including the addition of molecular marker techniques.

Endoscopic ultrasound (EUS)-guided Trucut biopsy adds significant information to EUS-guided fine-needle aspiration in selected patients: a prospective study.

Objective. Endoscopic ultrasound (EUS)-guided Trucut biopsy (EUS-TCB) has recently emerged as a method that seeks to overcome the limitations of EUS-guided fine needle aspiration (EUS-FNA) by providing a core-tissue specimen needed to increase the yield and accuracy of the diagnosis. The aim of our study was to evaluate whether EUS-TCB adds any information to EUS-FNA in selected patients and to assess the diagnostic yield, overall accuracy and complications of EUS-TCB as compared with EUS-FNA. Material and methods. The study prospectively included 30 patients who had undergone both procedures. Results. The yield of adequate tissue harvesting was similar for EUS-FNA and EUS-TCB (96.4% versus 89.3%, p=NS), with the same number of passes done. The diagnostic accuracy of EUS-FNA was also similar to that of EUS-TCB for the diagnosis of malignant mediastinal masses (73.7% versus 68.4%, p=NS). However, the accuracy for obtaining a specific diagnosis was significantly lower for EUS-FNA compared with EUS-TCB (5.3% and 68.4%, p<0.005). EUS-TCB did not appear to help as a rescue procedure in mediastinal tumours, after a false negative result of EUS-FNA. All cases of submucosal tumours were correctly classified by EUS-TCB as gastrointestinal stromal cell tumours (GISTs) or leiomyomas, while EUS-FNA raised only a suspicion of mesenchymal tumour. Conclusions. EUS-TCB was certainly useful when immunohistochemistry was needed, for example in submucosal tumours and lymphoma, as well as to confirm and characterize the primary or metastatic origin of mediastinal masses. The information provided by EUS-FNA and EUS-TCB is complementary, especially in selected cases where a complete histological diagnosis has an important impact on the clinical management.

Endoscopic ultrasound-guided fine needle aspiration biopsy: Equipment and technique

Endoscopic ultrasound‐guided fine needle aspiration biopsy (EUS‐FNA) is currently performed on a routine basis at many endoscopic centers and it is evident that this procedure has a major impact on the therapeutic management of patients by obtaining a definite tissue diagnosis from lesions outlined by endosonography. The reported yield of EUS‐FNA is about 90–95%, with an overall sensitivity and specificity of 90% and 100%, respectively. Moreover, even minute lesions down to a size of 5 mm may be imaged and consequently biopsied. This Review describes the technique of EUS‐FNA in detail, based on a literature review and the authors’ extensive experience with this method. The endoscopes and needle systems available on the market are presented in detail. The biopsy procedure is carefully explained, as well as the preparation of the cytology smears. Finally, the limitations and complications of the procedure are reviewed in brief, stressing the low rate of complications (below 1–2%), most of them being minor and self‐limiting. Currently endosonography has strengthened its position as a diagnostic and staging method, especially after establishing the method of FNA biopsy. Thus, EUS‐FNA is very useful to establish an initial tissue diagnosis of malignancy, but also to accurately stage the patients preoperatively, influencing the decision‐making process and reducing the morbidity and mortality that accompanies inappropriate surgical interventions in patients with advanced cancer.

Real-Time Image Fusion Involving Diagnostic Ultrasound

OBJECTIVE The aim of our article is to give an overview of the current and future possibilities of real-time image fusion involving ultrasound. We present a review of the existing English-language peer-reviewed literature assessing this technique, which covers technical solutions (for ultrasound and endoscopic ultrasound), image fusion in several anatomic regions, and electromagnetic needle tracking. CONCLUSION The recent progress of real-time ultrasound in image fusion may provide several new possibilities, including diagnosis, treatment, and follow-up of oncologic patients.

Contrast-enhanced harmonic endoscopic ultrasound.

Second-generation intravenous blood-pool ultrasound contrast agents are increasingly used in endoscopic ultrasound (EUS) for characterization of microvascularization, differential diagnosis of benign and malignant focal lesions, and improving staging and guidance of therapeutic procedures. Although initially used as Doppler signal enhancers, second-generation microbubble contrast agents are now used with specific contrast harmonic imaging techniques, which benefit from the highly nonlinear behavior of the microbubbles. Contrast-specific modes based on multi-pulse technology are used to perform contrast-enhanced harmonic EUS based on a very low mechanical index (0.08 - 0.12). Quantification techniques based on dynamic contrast-enhanced ultrasound have been recommended for perfusion imaging and monitoring of anti-angiogenic treatment, mainly based on time-intensity curve analysis. Most of the clinical applications include the differential diagnosis of focal pancreatic masses, with adenocarcinoma having a distinct hypovascular (hypo-enhanced) appearance compared with neuroendocrine tumors, which are hypervascular (with strong arterial hyper-enhancement). However, pseudotumoral chronic pancreatitis and autoimmune pancreatitis also have an iso- or hypervascular appearance, making the differential diagnosis difficult. Even more promising is the use of dynamic contrast-enhanced harmonic EUS for the longitudinal monitoring of the effects of chemotherapy and/or anti-angiogenic therapy in advanced digestive cancers, which are difficult to examine by conventional cross-sectional imaging techniques.

Contrast-enhanced ultrasound (CEUS) for the evaluation of focal liver lesions - a prospective multicenter study of its usefulness in clinical practice.

PURPOSE To assess the value of contrast-enhanced ultrasound (CEUS) for differentiating malignant from benign focal liver lesions (FLLs) and for diagnosing different FLL types. MATERIAL AND METHODS CEUS performed in 14 Romanian centers was prospectively collected between February 2011 and June 2012. The inclusion criteria were: age > 18 years; patients diagnosed with 1 - 3 de novo FLLs on B-mode ultrasound; reference method (computed tomography (CT), magnetic resonance imaging (MRI) or biopsy) available; patients informed consent. FLL lesions were characterized during CEUS according to the European Federation of Societies for Ultrasound in Medicine and Biology guidelines. For statistical analysis, indeterminate FLLs at CEUS were rated as false classifications. RESULTS A total number of 536 cases were included in the final analysis, 344 malignant lesions (64.2 %) and 192 benign lesions (35.8 %). The reference method was: CT/MRI - 379 cases (70.7 %), pathological exam - 150 cases (27.9 %) and aspiration of liver abscesses - 7 cases (1.4 %). CEUS was conclusive in 89.3 % and inconclusive in 10.7 % of cases. To differentiate between malignant and benign FLLs, CEUS had 85.7 % sensitivity, 85.9 % specificity, 91.6 % positive predictive value, 77.1 % negative predictive value and 85.8 % accuracy. The CEUS accuracy for differentiation between malignant and benign liver lesions was similar in tumors with diameter ≤ 2 cm and those with diameter > 2 cm. CONCLUSION CEUS represents a useful method in clinical practice for differentiating between malignant and benign FLLs detected on standard ultrasonography, and the results of this study are in concordance with previous multicenter studies: DEGUM (Germany) and STIC (France).

Power Doppler endoscopic ultrasonography for the differential diagnosis between pancreatic cancer and pseudotumoral chronic pancreatitis.

Objective. The accuracy of endoscopic ultrasonography (EUS) and EUS‐guided fine‐needle aspiration for the differential diagnosis of pancreatic masses is variable in the literature, being as low as 75% in some studies. The aim of the study was to assess the accuracy of power Doppler EUS for the differential diagnosis between pancreatic cancer and pseudotumoral chronic pancreatitis. Methods. We included 42 consecutive patients with pancreatic tumor masses (27 men and 15 women) examined by EUS between January 2002 and August 2004. Endoscopic ultrasonographic procedures included power Doppler EUS as well as EUS‐guided fine‐needle aspiration in all patients. Final diagnosis of pancreatic cancer was confirmed in 29 patients on the basis of a combination of information provided by imaging tests, follow‐up of at least 6 months, and laparotomy in 18 patients for diagnostic or palliative reasons. Results. Sensitivity and specificity of the absence of power Doppler signals inside the suggestive pancreatic mass were 93% and 77%, respectively, with accuracy of 88%. Moreover, the addition of the information provided by the presence of peripancreatic collaterals improved the sensitivity and specificity to 97% and 92%, with accuracy of 95%. Conclusions. Power Doppler EUS provides useful information for the differential diagnosis of pancreatic masses. The results were in concordance with previous studies that showed a hypovascular pattern of pancreatic carcinoma, as well as the formation of collaterals in advanced cases due to the invasion of the splenic or portal veins. Further studies of dynamic EUS with contrast agents are necessary to better characterize pancreatic masses.