Paolo Giorgio Arcidiacono

Feasibility and yield of a new EUS histology needle: results from a multicenter, pooled, cohort study

BACKGROUND EUS-guided FNA is an efficacious technique for sampling intraintestinal and extraintestinal mass lesions. However, cytology has limitations to its final yield and accuracy, which may be overcome if histological specimens are provided to the pathologist. OBJECTIVE To evaluate feasibility, yield, and diagnostic accuracy of a newly developed 19-gauge, fine-needle biopsy (FNB) device. DESIGN Multicenter, pooled, cohort study. SETTING Five medical centers. PATIENTS This study involved 109 consecutive patients with 114 intraintestinal or extraintestinal mass lesions and/or peri-intestinal lymph nodes. INTERVENTION EUS-guided FNB (EUS-FNB) with a newly developed, 19-gauge, FNB device. MAIN OUTCOME MEASUREMENTS Percentage of cases in which pathologists classified the sample quality as optimal for histological evaluation and the overall diagnostic accuracy compared with a composite criterion-standard diagnosis. RESULTS We evaluated 114 lesions (mean [± standard deviation] size 35.1 ± 18.7 mm; 84 malignant [73.7%] and 30 [26.3%] benign). EUS-FNB was technically feasible in 112 lesions (98.24%). Sample quality was adequate for full histological assessment in 102 lesions (89.47%). In 98 cases (85.96%), diagnosis proved to be correct according to criterion-standard diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy for diagnosis of malignancy were 90.2%, 100%, 100%, 78.9%, and 92.9%, respectively. LIMITATIONS Use of a surrogate criterion-standard diagnosis, including clinical follow-up when no surgical specimens were available, mainly in benign diagnoses. CONCLUSION Performing an EUS-FNB with a new 19-gauge histology needle is feasible for histopathology diagnosis of intraintestinal and extraintestinal mass lesions, offering the possibility of obtaining a core sample for histological evaluation in the majority of cases, with an overall diagnostic accuracy of over 85%.

Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study.

BACKGROUND AND STUDY AIMS Endoscopic ultrasound (EUS) elastography represents a new imaging procedure that might characterize the differences of hardness and strain between diseased tissue and normal tissue. The aim of this study was to assess the efficiency of EUS elastography for the differentiation of focal masses in chronic pancreatitis and pancreatic cancer. PATIENTS AND METHODS The study group comprised 258 patients with focal pancreatic masses included prospectively at 13 participating centers. Qualitative analysis of the diagnoses made by two expert doctors using all recorded video clips was performed in order to test the interobserver variability. A post-processing software analysis was used to examine the EUS elastography videos by calculating average-hue histograms of individual elastography images. The quantitative information was used to calculate intra-observer variability and the accuracy of the method. RESULTS Qualitative analysis of the recorded videos revealed a kappa value of 0.72. Intra-observer variability analysis revealed that the single measure intraclass correlation ranged between 0.86 and 0.94. The average-hue histogram analysis of the data indicated a sensitivity of 93.4 %, a specificity of 66.0 %, a positive predictive value of 92.5 %, a negative predictive value of 68.9 %, and an overall accuracy of 85.4 %, based on a cut-off value of 175. Area under the receiver operating characteristic curve (AUROC) was 0.854 ( P < 0.0001) with a confidence interval of 0.804 - 0.894. CONCLUSION The value of quantitative analysis of EUS elastography recordings was proven by good reproducibility of the videos, as well as good parameters of the AUROC analysis. (Clinical Trials.gov identifier: CT00909103).

Efficacy of an Artificial Neural Network–Based Approach to Endoscopic Ultrasound Elastography in Diagnosis of Focal Pancreatic Masses

BACKGROUND & AIMS By using strain assessment, real-time endoscopic ultrasound (EUS) elastography provides additional information about a lesions characteristics in the pancreas. We assessed the accuracy of real-time EUS elastography in focal pancreatic lesions using computer-aided diagnosis by artificial neural network analysis. METHODS We performed a prospective, blinded, multicentric study at of 258 patients (774 recordings from EUS elastography) who were diagnosed with chronic pancreatitis (n = 47) or pancreatic adenocarcinoma (n = 211) from 13 tertiary academic medical centers in Europe (the European EUS Elastography Multicentric Study Group). We used postprocessing software analysis to compute individual frames of elastography movies recorded by retrieving hue histogram data from a dynamic sequence of EUS elastography into a numeric matrix. The data then were analyzed in an extended neural network analysis, to automatically differentiate benign from malignant patterns. RESULTS The neural computing approach had 91.14% training accuracy (95% confidence interval [CI], 89.87%-92.42%) and 84.27% testing accuracy (95% CI, 83.09%-85.44%). These results were obtained using the 10-fold cross-validation technique. The statistical analysis of the classification process showed a sensitivity of 87.59%, a specificity of 82.94%, a positive predictive value of 96.25%, and a negative predictive value of 57.22%. Moreover, the corresponding area under the receiver operating characteristic curve was 0.94 (95% CI, 0.91%-0.97%), which was significantly higher than the values obtained by simple mean hue histogram analysis, for which the area under the receiver operating characteristic was 0.85. CONCLUSIONS Use of the artificial intelligence methodology via artificial neural networks supports the medical decision process, providing fast and accurate diagnoses.

Endoscopic ultrasound-guided application of a new hybrid cryotherm probe in porcine pancreas: A preliminary study

BACKGROUND AND STUDY AIMS Open, laparoscopic, or percutaneous radiofrequency (RF) ablation of the pancreas is still dangerous, whereas endoscopic ultrasound (EUS)-guided ablation might reduce risk because it is less invasive and provides real-time monitoring. We aimed to demonstrate the feasibility of transluminal RF ablation and to evaluate the efficacy and safety of a new flexible bipolar ablation probe combining RF and cryotechnology. METHODS 14 ablations were performed in 14 pigs. Energy input (16 W) and simultaneous cryogenic cooling with carbon dioxide (650 psi) were standardized. Application time range was 120 - 900 seconds. Ablation area was measured by EUS immediately after ablation (area T0), and before euthanasia (area T1). Macroscopic findings (area T2) and histological findings after necropsy served as gold standard. The interval from application to euthanasia was either 1 or 2 weeks. RESULTS The correlation between EUS findings (area T1) and macroscopic appearance (area T2) was good ( R = 0.89). The correlation between the T2 ablation area and the application time showed a fitted ratio of 2.3 ( P < 0.0001) with a 1-week interval and 0.2 ( P = 0.01) with a 2-week interval. No pig died because of the procedure. Two pigs showed histochemical pancreatitis, which was clinically overt in one. Necropsy additionally revealed one burn to the gastric wall and four gut adhesions. CONCLUSIONS Selective transluminal RF ablation of the pancreas under EUS control in a living pig model is feasible. The new flexible bipolar probe creates an ablation area with extent related to the duration of application, and with fewer complications than conventional RF ablation techniques.

Risk factors for intraductal papillary mucinous neoplasm (ipmn) of the pancreas: A multicentre case-control study

OBJECTIVES:To investigate environmental, personal, and hereditary risk factors associated with the occurrence of intraductal papillary mucinous neoplasms of the pancreas (IPMNs).METHODS:Multicentre case–control study. Risk factors were identified from a questionnaire collecting data on family and medical history, and environmental factors. Cases were prevalent IPMNs seen at the participating units within an 18-month timeframe. Matched controls were enrolled alongside patients seen at outpatient clinics.RESULTS:Three-hundred and ninety patients with IPMN and 390 matched controls (166 males, mean age 65 in each group) were enrolled. Of the IPMNs, 310 had branch-duct involvement and 80 main-duct involvement. The only cancer with a 1st degree family history significantly higher in IPMN was pancreatic ductal adenocarcinoma (PDAC) (5.4% vs. 1.5%). Previous history of diabetes (13.6% vs. 7.5%), chronic pancreatitis (CP) (3.1% vs. 0.3%), peptic ulcer (7.2% vs. 4.3%), and insulin use (4.9% vs. 1.1%) were all more frequent with IPMNs. Logistic regression multivariate analysis revealed that history of diabetes (odds ratio (OR): 1.79, confidence interval (CI) 95%: 1.08–2.98), CP (OR: 10.10, CI 95%: 1.30–78.32), and family histories of PDAC (OR: 2.94, CI 95%: 1.17–7.39) were all independent risk factors. However, when analysis was restricted to diabetics who had taken insulin, risk of IPMN became stronger (OR: 6.03, CI 95%: 1.74–20.84). The association with all these risk factors seemed stronger for the subgroup with main duct involvement.CONCLUSIONS:A previous history of diabetes, especially with insulin use, CP, and family history of PDAC are all relevant risk factors for the development of IPMN. These results suggest an overlap between certain risk factors for PDAC and IPMN.

Feasibility and safety of EUS-guided cryothermal ablation in patients with locally advanced pancreatic cancer

BACKGROUND New therapies are needed for pancreatic cancer. OBJECTIVE To determine the feasibility and safety of a new endoscopic treatment. Secondary endpoints were to determine effects on tumor growth measured with CT scan and to find the overall survival. DESIGN A cohort study of patients with local progression of advanced pancreatic adenocarcinoma after neoadjuvant therapy. The cryotherm probe (CTP), a flexible bipolar device that combines radiofrequency with cryogenic cooling, was used under EUS guidance. SETTING San Raffaele Hospital, Milan, Italy; University Medical Center, Hamburg-Eppendorf, Germany. PATIENTS A total of 22 patients (male/female 11/11; mean age 61.9 years) were enrolled from September 2009 to May 2011. INTERVENTION Radiofrequency heating: 18 W; pressure for cooling: 650 psi (Pounds per Square Inch); application time: depending on tumor size. MAIN OUTCOME MEASUREMENTS Feasibility was evaluated during the procedure. A clinical and radiologic follow-up was planned. RESULTS The CTP was successfully applied in 16 patients (72.8%); in 6 it was not possible because of stiffness of the GI wall and of the tumor. Amylase arose in 3 of 16 patients; none had clinical signs of pancreatitis. Late complications arose in 4 cases: 3 were mostly related to tumor progression. Median postablation survival time was 6 months. A CT scan was performed in all patients, but only in 6 of 16 was it possible to clearly define the tumor margins after ablation. In these patients, the tumor appeared smaller compared with the initial mass (P = .07). LIMITATIONS Small sample of patients, difficulty of objectifying the size of the ablated zone by CT scan. CONCLUSION EUS-guided CTP ablation is feasible and safe. Further investigations are needed to demonstrate progression-free survival and local control.

Cytological Ki-67 in pancreatic endocrine tumours: An opportunity for pre-operative grading

The cytological Ki-67 expression measured on cytological samples collected by endoscopic ultrasonography-guided fine needle aspiration cytology (EUS-FNAC) may provide pre-operative indications for pancreatic endocrine tumours (PETs) management. The aim of our study was to assess reliability of Ki-67 expression measured on cytological samples obtained by EUS-FNAC in patients with PETs. Eighteen patients with PETs underwent EUS-FNAC before surgery. Ki-67 expression was measured on FNACs and on histological sections. Using a cut-off of 2%, percent agreement of Ki-67 expression on cytological and histological samples was 89% (k-statistic: 0.78, 95% confidence intervals (95% CI): 0.5, 1.0). Using cut-off values of 2 and 10%, percent agreement was 78% (k-statistic: 0.65, 95% CI: 0.3, 0.9). Ki-67 expression measured on cytological samples obtained by EUS-FNAC before surgery showed good agreement with that measured on histological samples.

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms.

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.

Pancreatic Endoscopic Ultrasound-guided Fine Needle Aspiration: Complication rate and clinical course in a single centre

BACKGROUND Endoscopic Ultrasound-guided Fine Needle Aspiration (EUS-FNA) is effective for obtaining biopsy specimens from pancreatic lesions. AIM To determine the frequency and severity of complications after EUS-FNA of solid and cystic pancreatic lesions in a single centre large series of patients. PATIENTS AND METHODS From January 2005 to December 2008, information on all patients referred to our unit for pancreatic EUS was systematically entered in a computer database including clinical and morphologic data. Records were reviewed to evaluate whether complications such as haemorrhage, acute pancreatitis, intestinal perforation, or others occurred after EUS-FNA of the pancreas. RESULTS A total of 3296 pancreatic EUS were done in four years. In the 1034 pancreatic EUS-FNA, we observed 10 (0.96%) haemorrhages (7 intracystic, 2 in the pancreatic duct, and 1 in a small carcinoma), 2 (0.19%) acute severe pancreatitis and 1 (0.09%) duodenal perforation followed by complicated post-surgical hospitalization and death. The haemorrhages were all self-limiting. Overall, major complications (pancreatitis and perforation) arose in 0.29% of these examinations. CONCLUSIONS EUS-FNA is safe, with a low risk of severe haemorrhage. Although rare, acute pancreatitis is generally mild or severe, requiring prolonged hospitalization. One fatal complication occurred after duodenal perforation in a patient with duodenal neuroendocrine tumour and pancreatic infiltration.

Intraductal optical coherence tomography for investigating main pancreatic duct strictures

BACKGROUND AND STUDY AIMS:Optical coherence tomography (OCT) permits high-resolution imaging of tissue microstructures using a probe that can be inserted into the main pancreatic duct (MPD) through a standard endoscopic retrograde cholangiopancreatography (ERCP) catheter. This prospective study was designed to assess the diagnostic capacity of OCT to differentiate between nonneoplastic and neoplastic lesions in patients with MPD segmental strictures.PATIENTS AND METHODS:Twelve consecutive patients with documented MPD segmental stricture were investigated by endoscopic ultrasonography (EUS), with fine-needle aspiration cytology if necessary, and ERCP, followed by brush cytology and OCT scanning.RESULTS:OCT recognized a differentiated three-layer architecture in all cases with normal MPD or chronic pancreatitis, while in all the neoplastic lesions the layer architecture appeared totally subverted, with heterogeneous backscattering of the signal. The accuracy of OCT for detection of neoplastic tissue was 100% compared with 66.7% for brush cytology. In one case, neither OCT scanning nor brush cytology was possible because of the severity of the stricture.CONCLUSIONS:This pilot study showed that OCT is feasible during ERCP, in cases of MPD segmental stricture, and was superior to brush cytology in distinguishing nonneoplastic from neoplastic lesions.