Silvia Carrara

A predictive model identifies patients most likely to have inadequate bowel preparation for colonoscopy.

BACKGROUND & AIMS An inadequate level of bowel preparation can affect the efficacy and safety of colonoscopy. Although some factors have been associated with outcome, there is no strategy to identify patients at high risk for inadequate preparation. We searched for factors associated with an inadequate level of preparation and tested the validity of a predictive clinical rule based on these factors. METHODS We performed a prospective study of 2811 consecutive patients who underwent colonoscopy examinations at 18 medical centers; clinical and demographic data were collected before the colonoscopy. Bowel preparation was classified as adequate or inadequate; 925 patients (33%) were found to have inadequate preparation. Multivariate analysis was used to identify factors associated with inadequate preparation, which were expressed as odds ratio (OR) and used to build a predictive model. RESULTS Factors associated with inadequate bowel preparation included being overweight (OR, 1.5), male sex (OR, 1.2), a high body mass index (OR, 1.1), older age (OR, 1.01), previous colorectal surgery (OR, 1.6), cirrhosis (OR, 5), Parkinson disease (OR, 3.2), diabetes (OR, 1.8), and positive results in a fecal occult test (OR, 0.6). These factors predicted which patients would have inadequate cleansing with 60% sensitivity, 59% specificity, 41% positive predictive value, and 76% negative predictive value; they had an under the receiver operating characteristic curve value of 0.63. Assuming 100% efficacy of a hypothetical regimen to address patients predicted to be at risk of inadequate preparation, the rate would decrease from 33% to 13%. CONCLUSIONS We identified factors associated with inadequate bowel preparation for colonoscopy and used these to build an accurate predictive model.

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.

Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline – Updated January 2017

For pancreatic solid lesions, ESGE recommends performing endoscopic ultrasound (EUS)-guided sampling as first-line procedure when a pathological diagnosis is required. Alternatively, percutaneous sampling may be considered in metastatic disease.Strong recommendation, moderate quality evidence.In the case of negative or inconclusive results and a high degree of suspicion of malignant disease, ESGE suggests re-evaluating the pathology slides, repeating EUS-guided sampling, or surgery.Weak recommendation, low quality evidence.In patients with chronic pancreatitis associated with a pancreatic mass, EUS-guided sampling results that do not confirm cancer should be interpreted with caution.Strong recommendation, low quality evidence.For pancreatic cystic lesions (PCLs), ESGE recommends EUS-guided sampling for biochemical analyses plus cytopathological examination if a precise diagnosis may change patient management, except for lesions ≤ 10 mm in diameter with no high risk stigmata. If the volume of PCL aspirate is small, it is recommended that carcinoembryonic antigen (CEA) level determination be done as the first analysis.Strong recommendation, low quality evidence.For esophageal cancer, ESGE suggests performing EUS-guided sampling for the assessment of regional lymph nodes (LNs) in T1 (and, depending on local treatment policy, T2) adenocarcinoma and of lesions suspicious for metastasis such as distant LNs, left liver lobe lesions, and suspected peritoneal carcinomatosis.Weak recommendation, low quality evidence.For lymphadenopathy of unknown origin, ESGE recommends performing EUS-guided (or alternatively endobronchial ultrasound [EBUS]-guided) sampling if the pathological result is likely to affect patient management and no superficial lymphadenopathy is easily accessible.Strong recommendation, moderate quality evidence.In the case of solid liver masses suspicious for metastasis, ESGE suggests performing EUS-guided sampling if the pathological result is likely to affect patient management, and (i) the lesion is poorly accessible/not detected at percutaneous imaging, or (ii) a sample obtained via the percutaneous route repeatedly yielded an inconclusive result.Weak recommendation, low quality evidence.

Consensus guidelines on severe acute pancreatitis

This Position Paper contains clinically oriented guidelines by the Italian Association for the Study of the Pancreas (AISP) for the diagnosis and treatment of severe acute pancreatitis. The statements were formulated by three working groups of experts who searched and analysed the most recent literature; a consensus process was then performed using a modified Delphi procedure. The statements provide recommendations on the most appropriate definition of the complications of severe acute pancreatitis, the diagnostic approach and the timing of conservative as well as interventional endoscopic, radiological and surgical treatments.

Does cytotechnician training influence the accuracy of EUS-guided fine-needle aspiration of pancreatic masses?

BACKGROUND/AIM The presence of on-site cytopathologists improves the diagnostic yield of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic masses; however, on-site cytopathologists are not available to all endoscopic units. We hypothesized that experienced cytotechnicians can accurately assess whether an on-site pancreatic mass fine needle aspiration specimen is adequate. The aim of this study was to evaluate the effect of formal cytotechnician training on the diagnostic accuracy of EUS-FNA of pancreatic masses. METHODS Single-centre, prospective study. The cytotechnician made an on-site assessment of specimen adequacy with immediate evaluation of smears over a 12-month period (pre-training period) then over another 12-month period (post-training period), with a years intermediate training when the cytopathologist and the cytotechnician worked together in the room. The gold standard used to establish the final diagnosis was based on a non-equivocal fine needle aspiration biopsy reviewed by the same expert cytopathologist. The main outcome measurements were the cytotechnician diagnostic accuracy before and after the training period. RESULTS A total of 107 patients were enrolled in the pre-training period. Cytotechnician in-room adequacy was 68.2% (73/107). The diagnostic accuracy was 74.8%. The adequacy for the blind-review pathologist was 93.4% (100/107), significantly higher (p=0.008) than the cytotechnicians results. During the post-training period, 95 EUS-FNA were performed and reviewed. Cytotechnician in-room adequacy was 87.4% (83/95). The diagnostic accuracy was 90.5%. The adequacy for the blinded pathologist was 95.8% (91/95), not significantly different from the cytotechnician (p=0.23). CONCLUSIONS An adequate training period with an expert pathologist significantly improves the cytotechnician skill in terms of judging adequacy and diagnostic accuracy.