Implementation of the European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) sedation training course in a regular endoscopy unit.

BACKGROUND: Several scientific societies have endorsed non-anesthesiologist sedation (NAS) during gastrointestinal endoscopy, considering it a safe procedure when administered by adequately trained personnel. This study aimed to evaluate the occurrence of adverse events after implementation of the European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) sedation training program. METHODS: From January 2017 to August 2018, data from all consecutive endoscopic procedures in adults (≥ 18 years) performed at our endoscopy unit were collected using an electronic reporting system. RESULTS: All staff (physicians and nurses) completed the ESGE-ESGENA sedation course. In total, 12 132 patients underwent endoscopic procedures, 10 755 (88.6 %) of which were performed in a non-anesthesiological setting. Of these, about 20 % used moderate sedation with midazolam + fentanyl and 80 % used deep sedation with additional propofol. No sentinel, 5 (0.05 %) moderate risk, and 18 (0.17 %) minor risk adverse events occurred, all during moderate or deep sedation, and all managed by endoscopy staff without the need for anesthesiologist assistance. CONCLUSIONS: After completing the ESGE-ESGENA sedation training program, the rate of adverse events was very low in our institution. The findings support implementation of the program in all digestive endoscopy units and inclusion in the curriculum for physicians and nurses to ensure safe endoscopic procedures.

Predictors of survival in patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib.

UNLABELLED: Treatment with sorafenib of patients with advanced hepatocellular carcinoma is challenged by anticipated discontinuation due to tumor progression, liver decompensation, or adverse effects. While postprogression survival is clearly determined by the pattern of tumor progression, understanding the factors that drive prognosis in patients who discontinued sorafenib for any reason may help to improve patient management and second-line trial design. Patients consecutively admitted to three referral centers who were receiving best supportive care following permanent discontinuation of sorafenib for any reason were included. Postsorafenib survival (PSS) was calculated from the last day of treatment to death or last visit available. Two hundred and sixty patients were included in this prospective study, aged 67 years, 60% with hepatitis C, 51% Child-Pugh A, 83% performance status (PS) ≥1, 41% with macroscopic vascular invasion, and 38% with extrahepatic tumor spread. Overall, median PSS was 4.1 (3.3-4.9) months, resulting from 4.6 (3.3-5.7) months for 123 progressors, 7.3 (6.0-10.0) months in 77 with adverse effects, and 1.8 (1.6-2.4) months in 60 decompensated patients (P < 0.001). Postsorafenib survival was independently predicted by PS, prothrombin time, extrahepatic tumor spread, macrovascular invasion, and reason for discontinuation. Two hundred patients potentially eligible for second-line therapy had a PSS of 5.3 (4.6-7.1) months, which was dependent on reasons of discontinuation (P = 0.004), PS (P < 0.001), macrovascular invasion (P < 0.001), and extrahepatic metastases (P < 0.002). CONCLUSION: Discontinuation due to adverse effects in the absence of macrovascular invasion, extrahepatic metastases, and deteriorated PS predicts the best PSS in compensated patients, thereby setting the stage for both improved patient counseling and selection for second-line therapy.

Cholangiocarcinoma in Cirrhosis: Value of Hepatocyte Specific Magnetic Resonance Imaging.

BACKGROUND: The diagnosis of intrahepatic cholangiocellular carcinoma (ICC) remains elusive at imaging, which is a critical issue in cirrhotic patients in whom a diagnosis of hepatocellular carcinoma (HCC) can be established only by imaging. AIM: The aim of the study was to evaluate the potential of MRI in the diagnosis of ICC in cirrhosis using 'hepatocyte-specific' Gadolinium (Gd)-based contrast agents. METHODS: Sixteen histologically proven and retrospectively identified ICCs on cirrhosis were investigated with hepatocyte-specific magnetic resonance contrast agents (6 in Bologna with Gd-EOB-DTPA and 10 in Milan with Gd-BOPTA). The control group consisted of 41 consecutively and prospectively collected nodules (31 HCCs) imaged with Gd-EOB-DTPA. RESULTS: Fifteen ICC nodules (94%) displayed hypointensity in the hepatobiliary phase, suggesting malignancy. Thirteen cholangiocarcinomas (81%) showed hyperenhancement in the venous phase. Only 2 cholangiocarcinoma nodules showed hypoenhancement in the venous phase, corresponding to washout, in both cases preceded by rim enhancement in arterial phase. All the hepatocarcinomas showed hypointensity in hepatobiliary phase, but was always preceded by hypointensity in the venous phase; arterial rim enhancement was never observed in any hepatocarcinoma or regenerative nodule. CONCLUSIONS: MRI with hepatocyte-specific Gd-based contrast agents showed a pattern of malignancy in almost all the ICCs, concurrently avoiding misdiagnosis with hepatocarcinoma. These findings suggest a greater diagnostic capacity for this technique compared with the results of MRI with conventional contrast agents reported in the literature in this setting.

VEGF and VEGFR genotyping in the prediction of clinical outcome for HCC patients receiving sorafenib: the ALICE-1 study.

Although new treatment modalities changed the global approach to hepatocellular carcinoma (HCC), this disease still represents a medical challenge. Currently, the therapeutic stronghold is sorafenib, a tyrosine kinase inhibitor (TKI) directed against the vascular endothelial growth factor (VEGF) family. Previous observations suggested that polymorphisms of VEGF and its receptor (VEGFR) genes may regulate angiogenesis and lymphangiogenesis and thus tumour growth control. The aim of our study was to evaluate the role of VEGF and VEGFR polymorphisms in determining the clinical outcome of HCC patients receiving sorafenib. From a multicentre experience 148 samples (tumour or blood samples) of HCC patients receiving sorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients' progression-free survival (PFS) and overall survival (OS) were analysed. At univariate analysis VEGF-A alleles C of rs25648, T of rs833061, C of rs699947, C of rs2010963, VEGF-C alleles T of rs4604006, G of rs664393, VEGFR-2 alleles C of rs2071559, C of rs2305948 were significant predictors of PFS and OS. At multivariate analysis rs2010963, rs4604006 and BCLC (Barcelona Clinic Liver Cancer) stage resulted to be independent factors influencing PFS and OS. Once prospectively validated, the analysis of VEGF and VEGFR SNPs may represent a clinical tool to better identify HCC patients more likely to benefit from sorafenib. On the other hand, the availability of more accurate predictive factors could help avoiding unnecessary toxicities to potentially resistant patients who may be optimal candidates for different treatments interfering with other tumour molecular pathways.

Contrast enhanced CT-scan to diagnose intrahepatic cholangiocarcinoma in patients with cirrhosis.

BACKGROUND & AIMS: Contrast enhanced computed tomography (CT-scan) is a standard of care for the radiological diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. This technique, however, is not validated to exclude intrahepatic cholangiocarcinoma (ICC) which may develop in patients with cirrhosis, as well. METHODS: To assess the features of contrast CT-scan in the diagnosis of ICC, we reviewed all CT-scan films obtained in cirrhotic patients with a histologically documented ICC, taking in consideration the pattern and dynamics of the arterial, portal venous and delayed phases of contrast uptake. RESULTS: Thirty-two patients had 40 nodules of ICC (22 male; median age 62years; 13 hepatitis C) that were identified either during surveillance with abdominal ultrasound (21 patients, 66%) or incidentally (11 patients, 34%). ICC was either multifocal or ≥ 30 mm in 11 of the former and 10 of the latter group (52% vs. 91%, p<0.05). Two nodules (5%) escaped detection by CT-scan, while the remaining 38 showed a heterogeneous contrast enhancement pattern, being the arterial peripheral-rim enhancement present in 19 (50%) cases and a progressive homogeneous contrast uptake in 16 (42%) cases during the three vascular phases, with no relation to tumor size. Importantly, all nodules lacked the radiological hallmark of HCC, the only ICC nodule showing a homogeneous wash-in during the arterial phase followed by a wash-out in the delayed venous phase, however showing a homogeneous wash-in during the portal phase too. CONCLUSIONS: ICC in cirrhotic patients displays distinct vascular patterns at CT-scan that allow for differentiation from HCC.

Patterns of appearance and risk of misdiagnosis of intrahepatic cholangiocarcinoma in cirrhosis at contrast enhanced ultrasound.

AIM: Primary aim was to validate the percentage of intrahepatic cholangiocarcinomas (ICC) which have a contrast vascular pattern at contrast enhanced ultrasound (CEUS) at risk of misdiagnosis with hepatocellular carcinoma (HCC) and, secondary aim, to verify if any characteristics in the CEUS pattern helps to identify ICC. METHODS: All ICC on cirrhosis seen in three Italian centres (Bologna, Milan and Pavia) between 2003 and 2011, in which CEUS and at least another imaging technique (CT or MRI) had been performed, were retrospectively identified. Those patients with ICC size comparable to the early HCC stage (Milan criteria, considered as small ICC) were enrolled for this study. The enhancement pattern at CEUS was analysed and compared with CT or MRI. RESULTS: A total of 25 small ICC made this study group. CEUS was at risk of misdiagnosis of ICC for HCC in a significantly higher number of cases than in CT (performed in 24 ICC) (52% vs. 4.2%, P = 0.009) and MRI (11 ICC) (52% vs. 9.1%, P = 0.02). A different contrast pattern among all techniques was found in 6 of 10 ICC lesions submitted to the three imaging methods. In the arterial phase, ICC lacked global hyperenhacement in approximately 50% of cases at CEUS and the degree of intensity of wash-out in the late phase was marked in 24% of nodules. CONCLUSIONS: CEUS misdiagnosed as HCC a significantly higher number of ICC lesions in cirrhotic patients than CT and MRI. However, some CEUS contrast features can help suspect ICC, especially in some cases with inconclusive CT or MRI.

Risk factors for inadequate bowel preparation in patients using high- and low-volume cleansing products.

INTRODUCTION: Bowel preparation is crucial for colonoscopy completeness and lesions detection. Today, several cleansing products are equally recommended by guidelines, irrespective of patients' characteristics. Identification of preparation-specific risk factors for inadequate bowel preparation may lead to a personalized prescription of cleansing products to refine patients' tolerance and improve endoscopic outcomes. METHODS: We prospectively enrolled consecutive outpatients referred for colonoscopy using either a high-volume [HV: 4 l polyethylene glycol (PEG)] or a low-volume (LV: 2 l PEG + bisacodyl) preparation. Day-before regimen or split-dose regimen was used for morning or afternoon colonoscopies, respectively. Univariate and multivariate analyses were conducted to identify risk factors related to inadequate bowel preparation, according to the Boston bowel preparation scale for HV and LV preparations. RESULTS: We enrolled 2040 patients, of which 1815 were included in the final analysis (average age 60.6 years, 50.2% men). Half of them (52%) used LV preparation. Adequate preparation was achieved by 87.6% without differences between the HV and LV groups (89.2% vs. 86.6%; P = 0.098). The use of day-before regimen and incomplete assumption of PEG were independent predictors of poor visibility for either HV or LV preparation. However, different specific risk factors for HV [diabetes: odds ratio (OR), 3.81; 95% confidence interval (CI), 1.91-7.58; low level of instruction: OR, 1.95; 95% CI, 1.11-3.44; and previous abdominal surgery: OR, 2.27; 95% CI, 1.20-4.30] and for LV (heart disease: OR, 2.06; 95% CI, 1.09-3.88; age > 65 years: OR, 1.51; 95% CI, 1.01-2.27) preparations were identified. CONCLUSION: Day-before preparation and incomplete assumption of the purgative agents affect bowel visibility irrespective of the preparation volume. LV should be preferred to HV preparations in patients with diabetes, low level of instruction, and previous abdominal surgery, whereas an HV preparation should be preferred in patients with heart disease and in older patients.

Efficacy and tolerability of high and low-volume bowel preparation compared: A real-life single-blinded large-population study.

BACKGROUND: Low-volume preparations for colonoscopy have shown similar efficacy compared to high-volume ones in randomized controlled trials (RCT). However, most RCTs do not provide data about clinical outcomes including lesions detection rate. Moreover, real-life comparisons are lacking. AIM: To compare efficacy (both in terms of adequate bowel preparation and detection of colorectal lesions) and tolerability of a high-volume (HV: 4 L polyethylene glycol, PEG) and a low-volume (LV: 2 L PEG plus bisacodyl) bowel preparation in a real-life setting. METHODS: Consecutive outpatients referred for colonoscopy were prospectively enrolled between 1 December 2014 and 31 December 2016. Patients could choose either LV or HV preparation, with a day-before schedule for morning colonoscopies and a split-dose for afternoon procedures. Adequate bowel preparation according to Boston Bowel Preparation Scale (BBPS), clinical outcomes including polyp detection rate (PDR), adenoma detection rate (ADR), advanced adenoma detection rate (AADR), sessile/serrated lesion detection rate (SDR) and cancer detection rate and self-reported tolerability of HV and LV were blindly assessed. RESULTS: Total 2040 patients were enrolled and 1815 (mean age 60.6 years, 50.2% men) finally included. LV was chosen by 52% of patients (50.8% of men, 54.9% of women). Split-dose schedule was more common with HV (44.7% vs 38.2%, P = 0.005). High-definition scopes were used in 33.4% of patients, without difference in the two groups (P = 0.605). HV and LV preparations showed similar adequate bowel preparation rates (89.2% vs 86.6%, P = 0.098), also considering the two different schedules (HV split-dose 93.8% vs LV split-dose 93.6%, P = 1; HV day-before 85.5% vs LV day-before 82.3%, P = 0.182). Mean global BBPS score was higher for HV preparations (7.1 ± 1.7 vs 6.8 ± 1.6, P < 0.001). After adjustment for sex, age and indications for colonoscopy, HV preparation resulted higher in PDR [Odds ratio (OR) 1.32, 95%CI: 1.07-1.63, P = 0.011] and ADR (OR 1.29, 95%CI 1.02-1.63, P = 0.038) and comparable to LV in AADR (OR 1.51, 95%CI 0.97-2.35, P = 0.069), SDR and cancer detection rate. The use of standard-definition colonoscopes was associated to lower PDR (adjusted OR 1.59, 95%CI: 1.22-2.08, P < 0.001), ADR (adjusted OR 1.71, 95%CI: 1.26-2.30, P < 0.001) and AADR (adjusted OR 1.97, 95%CI: 1.09-3.56, P = 0.025) in patients receiving LV preparation. Mean Visual Analogue Scale tolerability scored equally (7, P = 0.627) but a ≥ 75% dose intake was more frequent with LV (94.6% vs 92.1%, P = 0.003). CONCLUSION: In a real-life setting, PEG-based low-volume preparation with bisacodyl showed similar efficacy and tolerability compared to standard HV preparation. However, with higher PDR and ADR, HV should still be considered as the reference standard for clinical trials and the preferred option in screening colonoscopy, especially when colonoscopy is performed with standard resolution imaging.

Successful repair of wide traumatic rectal perforation using over-the-scope clip.

Background and study aims We report on a case of a traumatic rectal perforation that occurred in a 16-year-old girl, which was successfully treated using an over-the-scope clip, avoiding major surgery and stoma.

Imaging of combined hepatocellular-cholangiocarcinoma in cirrhosis and risk of false diagnosis of hepatocellular carcinoma.

Background: Diagnosis of hepatocellular carcinoma can be achieved by imaging in cirrhotic patients. Combined hepatocellular-cholangiocarcinoma is a primary liver tumor and its imaging patterns have been poorly investigated. Misdiagnosis for either hepatocellular carcinoma or benign lesions can occur. We aimed to evaluate the enhancement pattern of combined hepatocellular-cholangiocarcinoma in cirrhosis with imaging techniques and to estimate the risk of misdiagnosis for hepatocellular carcinoma. Methods: All histology-confirmed combined hepatocellular-cholangiocarcinoma in cirrhosis seen in two Italian centers between 2003 and 2016, in which at least one imaging technique had been performed, was retrospectively collected. The enhancement pattern was analyzed for all available imaging modalities. Results: A total of 37 combined hepatocellular-cholangiocarcinoma nodules were identified. Contrast-enhanced ultrasound, computed tomography, and magnetic resonance imaging had been performed in 27, 34, and 17 nodules, respectively. Contrast-enhanced ultrasound was at higher risk of misdiagnosis for pure hepatocellular carcinoma than computed tomography (p = 0.005) or magnetic resonance imaging (p = 0.040). Only six of 24 combined hepatocellular-cholangiocarcinoma lesions submitted to both contrast-enhanced ultrasound and computed tomography showed coincident patterns; contrast-enhanced ultrasound correctly suggested a condition of malignancy in a higher number of cases than computed tomography (p < 0.001) and magnetic resonance imaging (p = 0.002). Conclusions: Contrast-enhanced ultrasound misdiagnosed a higher number of combined hepatocellular-cholangiocarcinoma as hepatocellular carcinoma than computed tomography and magnetic resonance imaging. However, the latter techniques were able to identify features of malignancy less often.

Post-polypectomy bleeding after colonoscopy on uninterrupted aspirin/non steroideal antiflammatory drugs: Systematic review and meta-analysis.

BACKGROUND AND AIM: The aim of this systematic review and meta-analysis was to assess the risk of post-polypectomy bleeding (PPB) in patients that underwent colorectal polypectomy and exposed to ASA/NSAIDs. METHODS: Relevant publications were identified in MEDLINE/EMBASE for the period 1950-2016. Studies with specified ASA/NSAIDs exposure and bleeding rate were included. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was based on fixed or random effect models in relation to the heterogeneity. RESULTS: 11 studies (4 prospective and 7 retrospective) including 9307 patients were included in the analyses. Overall, 344 patients (OR 1.8; 95% CI 1.2-2.7; p-value 0.001, I2 52%) experienced rectal bleeding after procedure. While the rate of immediate PPB on aspirin and/or NSAIDs was not increased (OR 1.1; CI 95% 0.6-2.1; d.f.=1, p=0.64, I2 0%), the risk of delayed PPB was augmented (OR 1.7; 95% CI 1.2-2.2; d.f.=8, p=0.127, I2 36%). CONCLUSIONS: ASA/NSAIDs are not a risk factor for immediate PPB but the chance of delayed is increased.

Endoscopic full-thickness resection for T1 early rectal cancer: a case series and video report.

BACKGROUND AND STUDY AIMS: Endoscopic treatment of malignant colorectal polyps is often challenging, especially for early rectal cancer (ERC) localized close to the dentate line. Conversely, the surgical approach may result in temporary or definitive stoma and in frequent post-surgical complications. The Full-Thickness Resection Device (FTRD ® ) System (Ovesco Endoscopy, Tübingen, Germany) is a novel system that, besides having other indications, appears to be promising for wall-thickness excision of intestinal T1 carcinoma following incomplete endoscopic resection. However, follow-up data on patients treated with this device are scarce, particularly for ERC. PATIENTS AND METHODS: Six consecutive patients with incomplete endoscopic resection of T1-ERC were treated with the FTRD and their long-term outcomes were evaluated based on a detailed clinical and instrumental assessment. RESULTS: The endoscopic en bloc full-thickness resection was technically feasible in all patients. The histopathologic analysis showed a complete endoscopic resection in all cases, and a full-thickness excision in four. Neither complications, nor disease recurrence were observed during the 1-year follow-up period. CONCLUSIONS: The FTRD System is a promising tool for treating ERC featuring a residual risk of disease recurrence after incomplete endoscopic mucosal resection in patients unfit for surgery or refusing a surgical approach.

Ex vivo experimental study on the Thulium laser system: new horizons for interventional endoscopy (with videos).

BACKGROUND AND STUDY AIMS: The Thulium laser system (TLS) is an emerging interventional tool adopted in many surgical specialties. Its 2.0-µm wavelength allows precise coagulation (0.2 - 0.4 mm in depth) and cutting, limiting the possibilities of collateral injuries. We tested the impact of the TLS for gastric endoscopic submucosal dissection (ESD) and per oral endoscopic myotomy (POEM) ex vivo in pigs. MATERIALS AND METHODS: Ex vivo porcine stomach and esophagus models underwent 2 POEMs, and 3 ESDs (mean diameter 3.5 cm) with TLS using a 272-µm and a 365-µm thick optical fibers. Both continuous and pulsed laser emission were evaluated. Subsequent histopathological analysis was performed by an expert GI pathologist on the whole porcine models. RESULTS: Complete POEMs and gastric ESDs were successfully performed in all cases in 30 to 70 and 15 to 20 minutes. Both optical fibers were equally effective and precise. The best power output for mucosal incision was 25 to 30 W during ESD and 25 W for POEM using continuous laser emission. During submucosal dissection and tunneling the favorite power output was 20 W and 15 to 20 W, respectively, operating in continuous mode. No transmural perforation occurred throughout the operations and histopathology confirmed the absence of accidental muscular layer damage. CONCLUSIONS: The TLS stands out as a precise and manageable instrument in ex vivo models. This technique appears to be a promising tool for advanced interventional endoscopy.

Determinants of esophageal varices bleeding in patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND AND AIMS: Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC), yet treatment safety may be challenged by portal hypertension. We therefore assessed the prevalence, risk factors and clinical consequences of esophageal varices (EVs) in sorafenib-treated patients with HCC. METHODS: Starting in 2008, all compensated patients with advanced or intermediate HCC not eligible for other therapies were consecutively enrolled in a prospective evaluation of sorafenib therapy, all with pretreatment by upper-gastrointestinal endoscopy (UGE). RESULTS: A total of 150 patients received sorafenib for 4.6 (95% CI, 3.3-5.6) months. At baseline, 61 (41%) patients were EV free (group A), 78 (52%) had EVs (61 small EVs (group B), 17 medium/large EVs (group C)) and 11 (7%) previously endoscopically treated EVs (group D). Propranolol was given to all patients with medium/large EVs and those with previous bleeding. Twelve patients (8%) bled from EVs after 36 (18-260) days of sorafenib. During sorafenib, bleeding occurred in six of 26 group B patients with neoplastic portal vein thrombosis (nPVT), three of nine group C patients with nPVT, two of five group D patients with nPVT and one of six without nPVT (p < 0.0001), nPVT being the strongest independent predictor of bleeding by multivariate analysis (HR = 15.4, 95% CI 1.84-129.6). CONCLUSION: UGE screening is worthwhile in HCC patients allocated to sorafenib since it identifies patients with EVs at risk of bleeding during therapy, particularly those with nPVT.

Effect of proton pump inhibitors on magnesium balance: is there a link to cardiovascular risk?

Magnesium (Mg(2+)) is the second most copious element inside human cells and the fourth most abundant positively charged ion in the human body. It is of central importance for a broad variety of physiological processes, including intracellular signaling, neuronal excitability, muscle contraction, bone formation and enzyme activation. Its overall balance is tightly regulated by the concerted actions of the intestine, bones and kidneys. Disturbance of this balance can have serious consequences. Symptoms of hypomagnesaemia include tetany, seizures and cardiac arrhythmias, whereas hypermagnesaemia may cause cardiovascular and neuromuscular abnormalities. Drugs can interfere with Mg(2+) homoeostasis in several ways, and proton-pump inhibitors (PPIs) have been associated with hypomagnesaemia. A better understanding of the molecular mechanisms underlying the adverse effects of these medications on Mg(2+) balance will isuggest ideas for prevention and treatment, and might provide greater insight into Mg(2+) homoeostasis. This review gives an overview of the influence of PPIs on Mg(2+) homoeostasis and provides some understanding of the underlying physiological mechanisms. Moreover, we will discuss the potential link between PPI-induced changes in Mg(2+) homeostasis, and the reported cardiovascular risk observed in long-term PPI users.