Cinzia Boemo

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.

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.

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.

Mucin expression pattern in pancreatic diseases: findings from EUS-guided fine-needle aspiration biopsies.

OBJECTIVES:Alterations in mucin (MUC) glycosylation and expression have been described in cancer. Endoscopic ultrasound-guided fine-needle aspiration (EUS–FNA) can provide material for molecular biology analysis. This study assessed the feasibility of evaluating MUC expression from material obtained by EUS–FNA and studied the profile of MUC expression in benign and malignant pancreatic lesions.METHODS:A total of 90 patients with solid or cystic pancreatic lesions underwent FNA. The aspirated material was used for cytological analysis and RNA extraction to assess the expression pattern of MUCs by reverse transcription-PCR with primers specific for the MUC1, MUC2, MUC3, MUC4, MUC5A, MUC5B, MUC6, and MUC7 genes.RESULTS:RNA extraction was successful in 81% of the biopsies. The prevalences of MUC1, MUC2, MUC4, and MUC7 in ductal adenocarcinoma were 57.7, 51.4, 18.9, and 73.0%, respectively. Fifty percent of benign lesions and neuroendocrine tumors (NETs), and 63% of intraductal papillary mucinous neoplasms (IPMNs) were positive for MUC1. Twenty-five percent of benign lesions, 86% of NETs, and 47% of IPMNs were positive for MUC2. Of NETs, 50% were positive for MUC1, and 14% were positive for MUC7. None of the benign lesions or NETs expressed MUC4. MUC7 expression was highly significant for adenocarcinoma (P=0.007) and borderline for IPMN (P=0.05). MUC7 was expressed in 37.5% of chronic pancreatitis cases.CONCLUSIONS:RNA can be extracted from samples obtained under EUS–FNA. MUC7 could serve as a potential biological marker to identify malignant lesions, especially pancreatic adenocarcinoma.

Chronic Pancreatitis-Like Changes Detected by Endoscopic Ultrasound in Subjects without Signs of Pancreatic Disease: Do These Indicate Age-Related Changes, Effects of Xenobiotics, or Early Chronic Pancreatitis?

Background/Aims: The threshold number of endoscopic ultrasound (EUS) criteria for diagnosing chronic pancreatitis (CP) is variable. The presence of more than three abnormal ductular or parenchymal features is typically used, but the diagnostic significance of fewer EUS criteria is currently unclear. The aim of this study was to determine the prevalence of EUS features of CP in patients without pancreaticobiliary disease and to analyze the association with specific factors of interest. Methods: Over a 24-month period, 2,614 patients underwent EUS for an indication unrelated to pancreaticobiliary disease. Main outcome measurements wereunivariate and multivariate analysis between any EUS abnormality and demographic data and habits. Results: 82 patients (16.8%) showed at least one ductular or parenchymal abnormality. 38 patients presented with only one abnormal feature, 26 patients with two, 12 patients with three, 4 patients with four, and 2 patients with five. Low-level alcohol consumption significantly increased the risk of hyperechoic parenchymal foci, main pancreatic duct (MPD) dilatation and wall hyperechogenicity. Smoking was associated with an increased risk of hyperechoic parenchymal foci. Male gender and advanced age were significantly associated with an increased risk of MPD dilatation. Conclusions: Long-term smoking and alcohol consumption, although at a low dose, induces CP-like changes. These abnormalities might represent either a clinically silent CP or a toxic effect of smoking and alcohol. Conversely, MPD dilation might represent a normal age-related variant or, alternatively, an effect of chronic low-level alcohol consumption.

Endoscopic ultrasound-guided application of a new internally gas-cooled radiofrequency ablation probe in the liver and spleen of an animal model: a preliminary study

BACKGROUND AND STUDY AIMS In a previous study, a new flexible bipolar hybrid cryotherm probe was applied with success to the pancreas of a living pig. Here we evaluated feasibility, efficacy, and safety of its application to the porcine liver and spleen. MATERIAL AND METHODS Ten applications to the liver and nine to the spleen were performed in 19 pigs. Power input (16-18 W) and simultaneous cooling with CO(2) (standardized pressure: 675 psi) as the cryogenic agent were investigated. Application time varied from 120 seconds to 900 seconds. The ablation area was measured by endoscopic ultrasound (EUS) after ablation (T0), and before euthanasia (T1). Gross pathology (T2) and histology after necropsy represented the gold standard. The interval from treatment to euthanasia was 1 or 2 weeks. RESULTS For both organs the correlation between EUS and gross pathology was good (correlation coefficient R(liver) = 0.71; R(spleen) = 0.73). EUS tended to overestimate the area of the ablated zone. EUS observed a time-dependent ablation area: we demonstrated a positive trend of lesion size (T1) over time in liver tissue (R = 0.51 (P = 0.1)). In the spleen we found a clear correlation of lesion area T2 and application time (R = 0.75, P = 0.01). There were no complications. CONCLUSIONS Selective EUS-guided transgastric cryotherm ablation of the liver and spleen in a pig model is feasible and safe. The new bipolar probe creates a time-dependent ablation area without any complications, and opens a field of new potential indications of RF-ablative therapies.

Improved 5-year survival of patients with immunochemical faecal blood test-screen-detected colorectal cancer versus non-screening cancers in northern Italy

BACKGROUND Colorectal cancer screening may reduce disease-related mortality by early-stage detection of cancers. AIMS To study the effect of a single immunochemical faecal occult blood test (i-FOBt) screening round on reduction in colorectal cancer-related-mortality among average risk subjects. METHODS Comparison of 5-year mortality rates in 3 cohorts from a Northern Italian province: (1) colorectal cancers detected at the 1st biennial round of a mass-screening programme targeting 50-69 years old subjects, (2) non-screening cancers symptomatically diagnosed during the same time period, and (3) cancers detected in the pre-screening biennium. Multivariate analyses were performed with the Cox regression model including tumour node metastasis (TNM) stage at diagnosis, anatomical distribution of cancers, age at diagnosis, gender and patient group. Kaplan-Meyer survival estimates and log-rank test for equality of survivor functions were calculated. RESULTS Stage distribution significantly differed between screening and non-screening colorectal cancers: 73% of screen-detected colorectal cancers were stages I and II versus 43% and 40% of non-screening and pre-screening colorectal cancers. Cumulative 5-year mortality rate was significantly lower in screening compared to non-screening or pre-screening colorectal cancers patients (19% versus 37% and 41%, p < 0.001). CONCLUSIONS Colorectal cancers were detected at earlier stages in i-FOBT-positive subjects in comparison with non-screening patients; colorectal cancers found at screening had a significantly improved 5-year survival.

US-guided application of a new hybrid probe in human pancreatic adenocarcinoma: an ex vivo study

BACKGROUND Ablative therapies such as radiofrequency and cryotechnology are widely used in oncological intervention but not in the pancreatic field because of their high operative risks. A new flexible bipolar ablation device (Cryotherm probe [CTP]) was developed combining radiofrequency and cryotechnology. OBJECTIVE To evaluate the efficacy of the CTP in destroying neoplastic tissue of explanted pancreatic tumors of patients with pancreatic adenocarcinoma. DESIGN Ex vivo clinical study. SETTING Inpatient hospital setting. PATIENTS This study involved 16 explanted pancreatic tumors from 16 patients. INTERVENTIONS CTP application was performed on explanted pancreatic tumors. Anatomic specimens were divided into 4 groups; each group received a predefined application time of 120 to 600 seconds. MAIN OUTCOME MEASUREMENTS The coagulation diameter (short axis) perpendicular to the devices longitudinal axis was used as the primary outcome measure. RESULTS All pancreatic specimens showed histological signs of coagulative necrosis. There was a positive correlation between the short axis of the obtained necrosis and duration of application (r = 0.74). LIMITATIONS This study was an ex vivo study with all limitations typical of this kind of study. CONCLUSIONS The CTP is effective in destroying neoplastic pancreatic tissue, creating an ablation zone, the extent of which is related to the duration of application.

Operative Endoscopic Ultrasonography for Pancreatic Diseases

Endoscopic ultrasonography (EUS) is a highly accurate method for staging gastrointestinal diseases, especially benign and malignant pancreatic lesions. As the probe can be placed so close to the pancreas (in the stomach and duodenum), EUS provides high-resolution images of the pancreas, with precise visualization of the biliary and pancreatic ducts and peripancreatic vessels.

S1302 Synchronous Intraductal Papillary Mucinous Neoplasm and Autoimmune Pancreatitis: An Original Association

tertiary care referral centers experience with EUS-FNA of pancreatic cysts. Medical records of patients who had more than one EUS-FNA from 2003 to 2007 were reviewed. Cyst size, location, CEA level, cytopathology and interval between EUS-FNA examinations were recorded. For each patient, cyst diagnosis was determined by surgical pathology (when available) or via established criteria for diagnosis of mucinous cystic neoplasms by cyst fluid chemistry (CEA >192 ng/mL) and/or cytopathologic analysis. Results: 197 patients underwent EUS-FNA for the evaluation of a pancreatic cyst, of which 31 (16%) had more than one examination. A total of 71 exams were performed in these patients. Repeat EUS-FNA led to a new diagnosis in 9 patients (29%). Two were found to have a malignancy, 4 patients had a pseudocyst, 2 patients had a mucinous cystic neoplasm and 1 patient had a serous cystadenoma. The average interval between exams among patients in which a repeat EUSFNA made a diagnostic difference was 20.6 vs. 13.0 months in those in which it did not (p=0.15). Pancreatic cysts increased in size by, on average, 0.53cm/yr +/0.82 cm among patients in which repeat EUS-FNA made a definitive diagnosis. In patients where the initial EUS-FNA was non-diagnostic, insufficient cyst fluid aspiration was noted in comparison to those in whom a definitive diagnosis was made (33% vs.72%p=0.056). Conclusion: This is the first study, to our knowledge, to evaluate the role of repeat EUS-FNA for the definitive diagnosis of indeterminant pancreatic cysts. In our small sample, repeat EUS-FNA led to a clear diagnosis in 29% of patients. Although the statistical power of this study is limited, it appears that repeat EUS-FNA should be considered in patients who have a cyst increasing in size or if insufficient cyst fluid was aspirated initially to quantify a CEA level.