Precancerous lesions of the pancreas

Pancreatic cancer has a very poor prognosis, with a five year survival of only 5%. New studies have shown that it takes over 11 years for cells to develop invasive capability. This provides an opportunity to intervene if precursor lesions can be detected. This paper reviews the molecular, pathological, clinical findings and management of pancreatic intraepithelial neoplasia (PanIN), intraductal pancreatic mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN), three precursor lesions which can give rise to invasive carcinoma of the pancreas.     

Advanced precancerous lesions in the liver

We will focus on precursors of the most common liver cancer, i.e. hepatocellular carcinoma (HCC), which takes place in 90% of cases in a hepatitis/cirrhotic setting. High grade dysplastic nodules (HG-DN) are small sizable nodules and the most advanced precancerous lesions of the liver, with a risk of malignant transformation of about 30–40% at 24 months. We will survey the diagnostic distinction between them and early HCC from a clinical, radiological and pathological point of view. The use of a diagnostic algorithm supported by international guidelines is the best practice to manage HG-DN and early HCC. There is no typical imaging for HG-DN, needing all of them to be biopsied for characterization. The natural history of HG-DN is not predictable in individual cases and additional markers should be validated to increase the diagnostic accuracy and predict the behaviour. The treatment of HG-DN is under investigation.     

MUC2 expression and prevalence of high-grade dysplasia and invasive carcinoma in mixed-type intraductal papillary mucinous neoplasm of the pancreas

Background/objectivesMorphological types and mucin protein expressions classify intraductal papillary mucinous neoplasms (IPMNs). Main duct (MD)-IPMN mostly consists of intestinal type (I-type), which expresses MUC2. Branch duct (BD)-IPMN mostly consists of gastric type (G-type), which does not express MUC2. However, the definition of mixed-type IPMN has yet to be clarified and it contains various histological types. The aim of this study was to investigate the relationship between MUC2 expression and the presence of high-grade dysplasia (HGD) and invasive carcinoma, especially in mixed-type IPMN.MethodsThis retrospective study included 101 consecutive patients with surgically resected IPMNs between April 2001 and October 2012. All patients were morphologically classified into four distinct types (I-type, G-type, PB-type: pancreatobilliary, O-type: oncocytic) and immunohistochemical reactivity of various anti-mucin antibodies were investigated.ResultsAccording to the classification of the 2012 international guidelines, the numbers (and histomorphological types: I/G/PB/O) of MD, mixed-type, and BD-IPMNs were 16 (12/4/0/0), 45 (16/28/1/0), and 40 (0/38/1/1). Prevalence of MUC2 expression in MD, mixed-type, and BD-IPMNs were 75% (12/16), 36% (16/45), and 0% (0/40). In mixed-type IPMN, the prevalence of HGD and/or invasive carcinoma in MUC2-positive IPMN was significantly higher than that of MUC2-negative IPMN (HGD + invasive carcinoma: 88% vs. 38%, p = 0.0017; invasive carcinoma: 50% vs. 21%, p = 0.042). Multivariate analysis showed that MUC2 expression is an independent predictive factor of HGD and invasive carcinoma in mixed IPMN (odds ratio 14.6, 95% CI 2.5–87.4, p = 0.003).ConclusionsIn mixed-type IPMN, MUC2 expression clearly identified HGD and invasive carcinoma and may provide most appropriate surgical indication.     

Baru almond improves lipid profile in mildly hypercholesterolemic subjects: A randomized,controlled, crossover study

Backgroud and aimThe usual consumption of nuts reduces cardiovascular diseases (CVD) risk by improving serum lipids and oxidation status. Baru almonds (Dipteryxalata Vog.), a native species of Brazilian Savannah, have considerable contents of monounsaturated fatty acids (MUFA), dietary fiber, vitamin E and zinc, which could exert positive effects in serum lipids and markers of oxidation. However, there is no study about the effect of their consumption on human health. Thus, the aim of this study was to evaluate the effect of baru almonds supplementation on lipid profile and oxidation of mildly hypercholesterolemic subjects.Methods and ResultsA randomized, crossover, placebo controlled study was performed with 20 mildly hypercholesterolemic subjects (total cholesterol (TC) mean ±SEM = 5.8 ± 0.2 mmol/L). The assay had 2 periods of 6 weeks each and a 4-week washout period between the treatments. Subjects were randomly allocated in alternated periods receiving the following treatments per period: supplementation with 20 g/day of baru almonds or placebo (1 corn starch capsule/day). Compared to placebo, supplementation of baru almonds reduced TC (−8.1 ± 2.4%, P = 0.007), low-density lipoprotein cholesterol (LDL-c) (−9.4 ± 2.4%, P = 0.006) and non-high-density lipoprotein cholesterol (non-HDL-c) (−8.1 ± 3.0%, P = 0.013). There were no significant changes on the oxidation biomarkers evaluated.ConclusionDietary supplementation of mildly hypercholesterolemic subjects with baru almonds improved serum lipid parameters, so that this food might be included in diets for reducing the CVD risk.Clinical Trial registryBrazilian Registry of Clinical Trials (ReBEC) (website: http://www.ensaiosclinicos.gov.br). Register number: RBR-4zdy9p.     

Improved survival of Korean patients with idiopathic pulmonary arterial hypertension after the introduction of targeted therapies

ObjectivesWe compared the survival of patients with idiopathic pulmonary arterial hypertension (IPAH), receiving conventional and targeted therapies.BackgroundIPAH is an incurable disease with high mortality. To manage IPAH, several targeted therapies have been used in Korea.MethodsWe performed a retrospective study of 71 patients diagnosed with IPAH in a tertiary hospital between January 1994 and February 2013. Patients were classified into “conventional therapy group” (treated with conventional therapies and/or beraprost) and “targeted therapy group” (treated with targeted therapies other than beraprost).ResultsThe median age of the patients was 33 years and 50 patients were female. The survival rate at 1, 3, 5, and 10 years was 80.1% 62.0%, 51.5%, and 26.8%, respectively. The survival rate in the targeted therapy group was greater than in the conventional therapy group (p-value = 0.026).ConclusionsWe believe targeted therapies would improve survival benefits in IPAH patients.     

Persistence of Iatrogenic Atrial Septal Defect After Interventional Mitral Valve Repair With the MitraClip System: A Note of Caution

ObjectivesThe purpose of this study was to investigate the persistence rates of iatrogenic atrial septal defect (iASD) after interventional edge-to-edge repair with serial transesophageal echocardiography examinations and close clinical follow-up (FU).BackgroundTranscatheter mitral valve repair (TMVR) with the MitraClip system (Abbott Vascular, Abbott Park, Illinois) is a therapeutic alternative to surgery in selected high-risk patients. Clip placement requires interatrial transseptal puncture and meticulous manipulation of the steerable sheath. The persistence of iASD after MitraClip procedures and its clinical relevance is unknown.MethodsA total of 66 patients (76.7% male, mean age 77.1 ± 7.9 years) with symptomatic mitral regurgitation (MR) at prohibitive surgical risk (EuroSCORE II 10.1 ± 6.1%) underwent MitraClip procedures and completed 6 months of FU.ResultsTransesophageal echocardiography after FU showed persistent iASD in 50% of cases. Patients with iASD did not significantly differ from patients without ASD concerning baseline characteristics, New York Heart Association functional class, severity of MR, and acute procedural success rates (p > 0.05). When comparing procedural details and hemodynamic measures between groups, MitraClip procedures took longer in patients without iASD (82.4 ± 39.7 min vs. 68.9 ± 45.5 min; p = 0.05), and echocardiography after FU showed less decrease of systolic pulmonary artery pressures in the iASD group (−1.6 ± 14.1 mm Hg vs. 9.3 ± 17.4 mm Hg; p = 0.02). Clinically, patients with iASD presented more often with New York Heart Association functional classes >II after FU (57% vs. 30%; p = 0.04), showed higher levels of N-terminal pro-brain natriuretic peptide (6,667.3 ± 7,363.9 ng/dl vs. 4,835.9 ± 6,681.7 ng/dl; p = 0.05), and had less improvement in 6-min walking distances (20.8 ± 107.4 m vs. 114.6 ± 116.4 m; p = 0.001). Patients with iASD showed higher death rates during 6 months (16.6% vs. 3.3%; p = 0.05). Cox regression analysis found that only persistence of iASD (p = 0.04) was associated with 6-month survival.ConclusionsThe persistence rate of 50% iASD after MitraClip procedures is considerably high. Persistent interatrial shunting was associated with worse clinical outcomes and increased mortality. Further studies are warranted to investigate if persistent interatrial shunting is the mediator or marker of advanced disease in these patients.     

Noninvasive Imaging of Cardiovascular Injury Related to the Treatment of Cancer

The introduction of multiple treatments for cancer, including chemotherapeutic agents and radiation therapy, has significantly reduced cancer-related morbidity and mortality. However, these therapies can promote a variety of toxicities, among the most severe being the ones involving the cardiovascular system. Currently, for many surviving cancer patients, cardiovascular (CV) events represent the primary cause of morbidity and mortality. Recent data suggest that CV injury occurs early during cancer treatment, creating a substrate for subsequent cardiovascular events. Researchers have investigated the utility of noninvasive imaging strategies to detect the presence of CV injury during and after completion of cancer treatment because it starts early during cancer therapy, often preceding the development of chemotherapy or cancer therapeutics related cardiac dysfunction. In this State-of-the-Art Paper, we review the utility of current clinical and investigative CV noninvasive modalities for the identification and characterization of cancer treatment-related CV toxicity.     

Obstructive jaundice in autoimmune pancreatitis can be safely treated with corticosteroids alone without biliary stenting

ObjectiveAutoimmune pancreatitis (AIP) responds dramatically to corticosteroids treatment. We reviewed our experience to determine the safety and effectiveness of treating obstructive jaundice in definitive AIP with corticosteroids alone without biliary stenting.MethodsFrom our AIP database, we retrospectively identified type 1 AIP subjects whose jaundice was treated with corticosteroids alone without biliary stenting. Their medical records were reviewed and clinical data were evaluated to determine the outcomes.ResultsFifteen AIP subjects (87% male, mean age 68.4 years) were treated with corticosteroids at initial presentation (n = 8), first (n = 5) or subsequent (n = 2) relapse. Mean values (upper limit of normal, ULN) of liver tests prior to corticosteroids were aspartate aminotransferase (AST) 203.5u/l (4 × ULN), alanine aminotransferase (ALT) 325.8u/l (6 × ULN), alkaline phosphatase (ALP) 567.4u/l (5 × ULN), and total bilirubin (TB) 5.9 mg/dl (5.9 × ULN). At first follow-up (mean 4 days) the decrease was 54.9% for AST, 51.6% for ALT, 33% for ALP and 47.2% for TB (all p < 0.05). After 15–45 days, all patients had normal AST, 3/15 had ALT > 1.5 × ULN, 1/15 had ALP > 1.5 × ULN, 1/15 had TB > 1.5 × ULN. No patient required biliary stent placement, or developed cholangitis or other infectious complications during steroid treatment.ConclusionUnder the supervision of an experienced pancreatologist and with close monitoring of patients, obstructive jaundice secondary to definitive AIP can be safely and effectively managed with corticosteroids alone, without the need for biliary stenting.     

Real-Time Assessment of Myocardial Viability in the Catheterization Laboratory Using the Intracoronary Electrograms Recorded by the PTCA Guidewire in Patients With Left Ventricular Dysfunction: Comparison With Delayed-Enhancement Magnetic Resonance Imaging

ObjectivesThis study aimed to determine whether the intracoronary electrograms (IC-EGMs) recorded using a standard percutaneous coronary intervention guidewire could provide myocardial viability information.BackgroundThe revascularization of dysfunctional but viable myocardium may confer prognostic benefits compared with medical therapy in patients with post-ischemic heart failure. However, knowledge of myocardial viability is often unavailable at the time of the procedure.MethodsThe peak-to-peak voltage of 317 IC-EGMs recordings from 25 patients with a previous myocardial infarction and systolic dysfunction were matched with corresponding delayed-enhancement magnetic resonance imaging sites using a 17-segment model of the left ventricle.ResultsSixty-seven recordings were obtained from segments classified as complete scar on delayed-enhancement magnetic resonance imaging (group A), 162 from partially viable segments (group B), and 88 from fully viable segments (group C). Three high-pass (HP) filters (0.5, 30, and 100 Hz) were applied to the signals to modulate their spatial resolution. For all filters, the peak-to-peak voltage significantly decreased from group C to group B to group A (p < 0.001 for all comparisons). When receiver-operating characteristic analysis was used to compare nonviable (group A) with viable (group B + C) segments, the optimal discriminating voltages were 4.6, 2.2, and 0.78 mV for, respectively, HP-0.5, HP-30, and HP-100 filters, with a sensitivity of 92%, 94%, and 99% and a specificity of 70%, 79%, and 69%.ConclusionsThe amplitude of the IC-EGMs discriminates viable from nonviable left ventricular segments. Because this technique is simple and inexpensive and provides real-time results, it is potentially useful to aid decision making in the catheterization laboratory.