S. Vavassori

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

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.

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

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. (Hepatology 2015;62:784–791)

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.

Colo-rectal endoscopic full-thickness resection (EFTR) with the over-the-scope device (FTRD®): A multicenter Italian experience

BACKGROUND AND AIM Endoscopic full-thickness resection(EFTR) with FTRD® in colo-rectum may be useful for several indications.The aim was to assess its efficacy and safety. MATERIAL AND METHODS In this retrospective multicenter study 114 patients were screened; 110 (61M/49F, mean age 68 ± 11 years, range 20-90) underwent EFTR using FTRD®. Indications were:residual/recurrent adenoma (39), incomplete resection at histology (R1 resection) (26), non-lifting lesion (12), adenoma involving the appendix (2) or diverticulum (2), subepithelial lesions(10), suspected T1 carcinoma (16), diagnostic resection (3). Technical success (TS: lesion reached and resected), R0 resection (negative lateral and deep margins),EFTR rate(all layers documented in the specimen) and safety have been evaluated. RESULTS TS was achieved in 94.4% of cases. EFTR was achieved in 91% with lateral and deep R0 resection in 90% and 92%. Mean size of specimens was 20 mm (range 6-42). In residual/recurrent adenomas, final analysis revealed: low-risk T1 (11), adenoma with low-grade dysplasia (LGD) (24) and high-grade dysplasia (HGD) (3), scar tissue (1). Histology reports of R1 resections were: adenoma with LGD (6), with HGD (1), low-risk (6) and high-risk (1) T1, scar tissue (12). Non-lifting lesions were diagnosed as: adenoma with HGD (3), low-risk (7) and high risk (2) T1. Adverse clinical events occurred in 12 patients (11%),while adverse technical events in11%. Three-months follow-up was available in 100 cases and residual disease was evident in only seven patients. CONCLUSIONS EFTR using FTRD® seems to be a feasible, effective and safe technique for treating selected colo-rectal lesions. Comparative prospective studies are needed to confirm these promising results.

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.

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.

718 CONTRAST-ENHANCED CT SCAN DIFFERENTIATES HEPATOCELLULAR CARCINOMA AND INTRAHEPATIC CHOLANGIOCARCINOMA IN CIRRHOSIS

716 PROGNOSTIC GENE-EXPRESSION SIGNATURE FOR HEPATITIS C-RELATED EARLY-STAGE LIVER CIRRHOSIS Y. Hoshida, A. Villanueva, A. Sangiovanni, M. Sole, C. Hur, K.L. Andersson, R.T. Chung, J. Gould, K. Kojima, S. Gupta, B. Taylor, A. Crenshaw, S. Gabriel, B. Minguez, M. Iavarone, S.L. Friedman, M. Colombo, J.M. Llovet, T. Golub. Broad Institute of Harvard and MIT, Dana-Farber Cancer Institute, Boston, MA, USA; Laboratori de Reserca Translacional d’Oncoloǵia Hepatica, IDIBAPS, Ciberehd, Hospital Clinic, Barcelona, Spain; Division of Gastroenterology, Fondazione Ca Granda IRCCS Ospedale Maggiore Policlinico, Universita degli Studi di Milano, Milan, Italy; Dept. of Pathology, Hospital Cĺinic, Barcelona, Spain; Massachusetts General Hospital-Harvard Medical School, Boston, MA, USA; Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Barcelona, Spain; Department of Liver Diseases, Mount Sinai School of Medicine, New York, NY, USA E-mail: hoshida@broadinstitute.org

T-16 Contrast-enhanced CT scan differentiates hepatocellular carcinoma and intrahepatic cholangiocarcinoma in cirrhosis

716 PROGNOSTIC GENE-EXPRESSION SIGNATURE FOR HEPATITIS C-RELATED EARLY-STAGE LIVER CIRRHOSIS Y. Hoshida, A. Villanueva, A. Sangiovanni, M. Sole, C. Hur, K.L. Andersson, R.T. Chung, J. Gould, K. Kojima, S. Gupta, B. Taylor, A. Crenshaw, S. Gabriel, B. Minguez, M. Iavarone, S.L. Friedman, M. Colombo, J.M. Llovet, T. Golub. Broad Institute of Harvard and MIT, Dana-Farber Cancer Institute, Boston, MA, USA; Laboratori de Reserca Translacional d’Oncoloǵia Hepatica, IDIBAPS, Ciberehd, Hospital Clinic, Barcelona, Spain; Division of Gastroenterology, Fondazione Ca Granda IRCCS Ospedale Maggiore Policlinico, Universita degli Studi di Milano, Milan, Italy; Dept. of Pathology, Hospital Cĺinic, Barcelona, Spain; Massachusetts General Hospital-Harvard Medical School, Boston, MA, USA; Liver Unit, Department of Medicine, Hospital Universitari Vall d’Hebron, Barcelona, Spain; Department of Liver Diseases, Mount Sinai School of Medicine, New York, NY, USA E-mail: hoshida@broadinstitute.org