Rosa Liotta

Exogenous glucagon-like peptide 1 reduces contractions in human colon circular muscle.

Glucagon-like peptide 1 (GLP1) is a naturally occurring peptide secreted by intestinal L-cells. Though its primary function is to serve as an incretin, GLP1 reduces gastrointestinal motility. However, only a handful of animal studies have specifically evaluated the influence of GLP1 on colonic motility. Consequently, the aims of this study were to investigate the effects induced by exogenous GLP1, to analyze the mechanism of action, and to verify the presence of GLP1 receptors (GLP1Rs) in human colon circular muscular strips. Organ bath technique, RT-PCR, western blotting, and immunofluorescence were used. In human colon, exogenous GLP1 reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions without affecting the frequency and the resting basal tone. This inhibitory effect was significantly reduced by exendin (9-39), a GLP1R antagonist, which per se significantly increased the spontaneous mechanical activity. Moreover, it was abolished by tetrodotoxin, a neural blocker, or Nω-nitro-l-arginine - a blocker of neuronal nitric oxide synthase (nNOS). The biomolecular analysis revealed a genic and protein expression of the GLP1R in the human colon. The double-labeling experiments with anti-neurofilament or anti-nNOS showed, for the first time, that immunoreactivity for the GLP1R was expressed in nitrergic neurons of the myenteric plexus. In conclusion, the results of this study suggest that GLP1R is expressed in the human colon and, once activated by exogenous GLP1, mediates an inhibitory effect on large intestine motility through NO neural release.

Effects of menthol on circular smooth muscle of human colon: Analysis of the mechanism of action

Menthol is the major constituent of peppermint oil, an herbal preparation commonly used to treat nausea, spasms during colonoscopy and irritable bowel disease. The mechanism responsible for its spasmolytic action remains unclear. The aims of this study were to investigate the effects induced by menthol on the human distal colon mechanical activity in vitro and to analyze the mechanism of action. The spontaneous or evoked-contractions of the circular smooth muscle were recorded using vertical organ bath. Menthol (0.1 mM-30 mM) reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions without affecting the frequency and the resting basal tone. The inhibitory effect was not affected by 5-benzyloxytryptamine (1 μM), a transient receptor potential-melastatin8 channel antagonist, or tetrodotoxin (1 μM), a neural blocker, or 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (10 µM), inhibitor of nitric oxide (NO)-sensitive soluble guanylyl cyclase, or tetraethylammonium (10 mM), a blocker of potassium (K+)-channels. On the contrary, nifedipine (3 nM), a voltage-activated L-type Ca2+ channel blocker, significantly reduced the inhibitory menthol actions. Menthol also reduced in a concentration-dependent manner the contractile responses caused by exogenous application of Ca2+ (75-375 μM) in a Ca2+-free solution, or induced by potassium chloride (KCl; 40 mM). Moreover menthol (1-3 mM) strongly reduced the electrical field stimulation (EFS)-evoked atropine-sensitive contractions and the carbachol-contractile responses. The present results suggest that menthol induces spasmolytic effects in human colon circular muscle inhibiting directly the gastrointestinal smooth muscle contractility, through the block of Ca2+ influx through sarcolemma L-type Ca2+ channels.

Intraductal aspiration: a promising new tissue-sampling technique for the diagnosis of suspected malignant biliary strictures

BACKGROUND Brushing is the most commonly used technique for biliary sampling at ERCP, despite its limited sensitivity. OBJECTIVE To evaluate intraductal aspiration (IDA) as a new combined endoscopic technique for cytodiagnosis, its cellular adequacy, diagnostic accuracy for cancer detection, feasibility, and safety. DESIGN Prospective, observational study. SETTING Single tertiary referral center. MAIN OUTCOME MEASUREMENTS IDA cellular adequacy, diagnostic accuracy for cancer detection, feasibility, and safety. PATIENTS AND METHODS From April 2009 to September 2010, 42 consecutive patients with suspected malignant biliary stricture underwent ERCP, with tissue sampling obtained with IDA. IDA included performance of standard brushing in all patients. After standard brushing, to perform IDA, we removed the brush from its catheter and used the tip of the catheter as a scraping device. The tip was scraped back and forth across the stricture at least 10 times. The catheter and a suction line were connected to a specimen trap to obtain intraductal aspiration of fluids and samplings. RESULTS Our cytopathologists found adequate cellular yield in 39 of the 42 IDA samples (92.8%) versus 15 of the 42 brushing samples (35.7%) (P < .001). IDA showed a significantly higher sensitivity than brushing (89% vs 78% for adequate samples and 89% vs 37% for all samples) and provided significantly superior cellular adequacy (92.8% vs 35.7%). LIMITATIONS Observational study, small number of patients. CONCLUSIONS IDA significantly improves brushing cellular adequacy and has high sensitivity for cancer detection. It was also safe, simple, rapid, and applicable during routine diagnostic ERCP, with no additional costs.

Endoscopic ultrasound-guided fine needle aspiration and biopsy using a 22-gauge needle with side fenestration in pancreatic cystic lesions

BACKGROUND Cytologic diagnosis by endoscopic ultrasound-guided fine needle aspiration is associated with low sensitivity and adequacy. A newly designed endoscopic ultrasound-guided fine needle biopsy device, endowed with a side fenestration, is now available. AIMS We carried out a study with the aim of evaluating the feasibility, safety, and diagnostic yield of the 22-gauge needle with side fenestration for endoscopic ultrasound fine needle aspiration and biopsy of pancreatic cystic lesions. METHODS 58 patients with 60 pancreatic cystic lesions consecutively referred for endoscopic ultrasound guided-fine needle aspiration were enrolled in a prospective, dual centre study, and underwent fine needle aspiration and biopsy with the 22-gauge needle with side fenestration. RESULTS Fine needle aspiration and biopsy was technically feasible in all cases. In 39/60 (65%) pancreatic cystic lesions, the specimens were adequate for cyto-histologic assessment. In lesions with solid components, and in malignant lesions, adequacy was 94.4% (p = 0.0149) and 100% (p = 0.0069), respectively. Samples were adequate for histologic evaluation in 18/39 (46.1%) cases. There were only 2 (3.3%) mild complications. CONCLUSIONS Fine needle aspiration and biopsy with the 22-gauge needle with side fenestration is feasible, and superior to conventional endoscopic ultrasound-guided fine needle aspiration cytology from cystic fluid, particularly in pancreatic cystic lesions with solid component or malignancy, with a higher diagnostic yield and with no increase in complication rate.

A Fatal Case of a Paint Thinner Ingestion: Comparison Between Toxicological and Histological Findings

Toluene and xylene are aromatic hydrocarbons commonly used as an industrial solvent for the manufacturing of pharmaceuticals, paints, and chemicals. The Occupational Safety and Health Administration has determined that toluene levels of 2000 parts per million (ppm) are considered dangerous to life and health. Several studies have examined the absorption of toluene and xylene following inhalation and oral ingestion in humans. Volatile organic compounds that are absorbed into the blood are distributed throughout the body; in particular, distribution of absorbed toluene and xylene in humans and rodents is characterized by preferential uptake in well-perfused and lipophil tissues such as the brain, liver, lungs, and body fat and also in central nervous system. The available studies indicate that xylenes are rapidly absorbed independently from the kind of exposition. We illustrate a fatal case of self-poisoning by ingestion of varnishes diluting solvents, reporting the identification and quantification of volatile organic compounds (toluene, o-m-p xylene) from human biologic liquids and viscera samples using the Solid–Phase Microextraction-Headspace-Gas Chromatography/Mass Spectrometry to toxicological analysis, and the histopathological findings evaluated in liver, kidney, and lungs.

Post-traumatic lethal carotid-cavernous fistula

The authors report about an unexpected death by traumatic lesion of the internal carotid artery in a 30-year-old man who had fallen two metres. The man suffered a fracture of the left maxillary sinus and a fracture of the right orbit with bilateral haemorrhage of the maxillary sinus. Surgical treatment was performed with favorable outcome. Clinically, there were no neurological symptoms but about 60 days after his accident, the man died from uncontrolled epistaxis. He was submitted to the autopsy that show a linear fracture in the left side of the turcic sella and lesion of the left internal carotid artery with carotid-cavernous fistula.

Sudden death in adolescence caused by cardiac haemangioma

Primary tumors of the heart in infants and children are rare. The types of heart tumors in pediatric age groups are generally different from those in adults. Cardiac myxoma is by far the most common tumor in adults, but in infants and adolescents the prevalent tumor of the heart is rhabdomyoma. Among benign cardiac tumors, cardiac hemangiomas are rare and often diagnosed post-mortem due to the lack of specific clinical symptoms and signs. We report a case of sudden death due to cardiac hemangioma in an apparently healthy 15-year-old adolescent. The autopsy revealed a cardiac hemangioma located at the apex of the heart; the histopathological examination showed the tumor was a mixed capillary and arteriolar hemangioma, a very rare type of primary tumor in adolescents.

Mini-Invasive Approach Contributes to Expand the Indication for Liver Resection for Hepatocellular Carcinoma Without Increasing the Incidence of Posthepatectomy Liver Failure and Other Perioperative Complications: A Single-Center Analysis.

BACKGROUND Liver resection (LR) for hepatocellular carcinoma (HCC) is the best alternative option for increasing the survival of many patients with intermediate or advanced stages of the Barcelona Clinic Liver Cancer staging classification. Mini-invasive approach may play a positive role in treating a tumor rising almost exclusively in a diseased liver. METHODS A prospectively collected database was retrospectively reviewed for 167 consecutive patients who underwent LR between 1999 and 2015. RESULTS A total of 38 LRs were performed from 1999 to 2009 (Period I), and 129 between 2010 and 2015 (Period II). Laparoscopic procedures increased from 5.3% to 38.1%. Not undergoing laparoscopic LR increased length of stay, and Clavien Grade II or worse complications. Ninety-day mortality decreased from 5.2% to 0%, and morbidity did not differ significantly, despite the fact that the most complex patients were in Period II. CONCLUSIONS Mini-invasive approaches allow to safely expand limits of LR for HCC; in particular, laparoscopic approach favors surgical option even in more complex patients without increase the risk of posthepatic liver failure or other postsurgical complications.

Activation of angiotensin II type 1 receptors and contractile activity in human sigmoid colon in vitro

To analyse the effects of angiotensin II (Ang II) on the contractility of human sigmoid colon, and to characterize the subtype(s) of receptor(s) involved and the related action mechanism.

US-Guided Percutaneous Liver Biopsy in Pediatric Liver Transplant Recipients

Objectives: The present study assesses the safety of ultrasound (US)-guided percutaneous liver biopsies (PLBs) within pediatric liver allograft recipients, describes the pathological results according to early (⩽12 months) and late (>12 months) posttransplantation periods, and analyzes the value of liver function tests (LFTs) and Doppler US variables in determining these results. Methods: A total of 219 US-guided PLBs in 85 pediatric patients with liver transplant (mean age 7 ± 5 years, range: 6 months to 18 years) performed between March 2005 and May 2012 were retrospectively evaluated at a single institution. Doppler US and LFT evaluation (including total bilirubin, alanine aminotransferase, aspartate aminotransferase, &ggr;-glutamyl transferase, alkaline phosphatase) occurred within 1 day of early (n = 92, 42%) and late term (n = 127, 58%) posttransplantation biopsies. Results: The rate of major complications (hemorrhage requiring blood transfusion) was 0.91% (n = 2). The early versus late term biopsy results, respectively, included: cholestasis at 36% versus 18% (P = 0.003), minimal changes 16% versus 24% (not significant [NS]), acute rejection 13% versus 5% (P = 0.027), inflammatory diseases 15% versus 15% (NS), indeterminate acute rejection 11% versus 7% (NS), chronic rejection 4% versus 14% (P = 0.017), fibrotic diseases 4% versus 12% (NS), and other 0% versus 5% (NS). Neither LFT nor US variables were correlated with pathological outcomes. Conclusions: The rate of complications in pediatric patients after US-guided liver biopsy is low. A range of pathological results exists between early and late posttransplantation liver biopsies. LFT and Doppler US findings are not predictors of pathological results.