Computer-aided assessment of the extra-cellular matrix during pancreatic carcinogenesis: a pilot study.

BACKGROUND: A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process. METHODS: A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method. RESULTS: We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal. CONCLUSION: These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies.

Matricellular proteins and survival in patients with pancreatic cancer: A systematic review.

Extracellular matrix (ECM) plays a fundamental role in tissue architecture and homeostasis and modulates cell functions through a complex interaction between cell surface receptors, hormones, several bioeffector molecules, and structural proteins like collagen. These components are secreted into ECM and all together contribute to regulate several cellular activities including differentiation, apoptosis, proliferation, and migration. The so-called "matricellular" proteins (MPs) have recently emerged as important regulators of ECM functions. The aim of our review is to consider all different types of MPs family assessing the potential relationship between MPs and survival in patients with pancreatic ductal adenocarcinoma (PDAC). A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement issued in 2009 was conducted through Ovid interface, and literature review was performed in May 2017. The search text words were identified by means of controlled vocabulary, such as the National Library of Medicine's MESH (Medical Subject Headings) and Keywords. Collected data showed an important role of MPs in carcinogenesis and in PDAC prognosis even though the underlying mechanisms are still largely unknown and data are not univocal. Therefore, a better understanding of MPs role in regulation of ECM homeostasis and remodeling of specific organ niches may suggest potential novel extracellular targets for the development of efficacious therapeutic strategies.

Gastrointestinal Ultrasound in Emergency Setting.

Acute bowel diseases are responsible for more than one third of subjects who were referred to the emergency department for acute abdominal pain and gastrointestinal evaluation. Gastrointestinal ultrasound (GIUS) is often employed as the first imaging method, with a good diagnostic accuracy in the setting of acute abdomen, and it can be an optimal diagnostic strategy in young females due to the radiation exposure related to X-ray and computed tomography methods. The physician can examine the gastrointestinal system in the area with the greatest tenderness by ultrasound, thus obtaining more information and data on the pathology than the standard physical examination. In this comprehensive review, we have reported the most relevant indications and advantages to using ultrasound in the investigation of abdominal acute pain.

Ultrasound evaluation of bowel vasculopathy in systemic sclerosis.

BACKGROUND: Gastrointestinal (GI) manifestations are frequent in systemic sclerosis (SSc) with an impact on quality of life and morbidity. Bowel vasculopathy is a key pathogenetic factor responsible for GI involvement. OBJECTIVES: To compare abdominal ultrasound (US) and Color Doppler Ultrasonography (CDU) features of splanchnic vessels of SSc patients with healthy controls. METHODS: The charts of SSc patients who underwent an abdominal US and CDU study were retrospectively analyzed. For Superior Mesenteric Artery (SMA) and Inferior Mesenteric Artery (IMA) caliber, Peak Systolic Velocity (PSV), Reverse Velocity (RV), End-Diastolic Velocity (EDV), Mean Velocity (mV), Blood-flow, Resistive Index (RI) and Pulsatility Index (PI) were recorded. RESULTS: 28 SSc patients and 28 controls were enrolled. In SSc, caliber of SMA was significantly smaller than in controls (5.75 ± 0.62 mm vs. 6.45 ± 0.60 mm, p < 0.0001 - p adj =0.0002). The flow study of SMA and IMA showed a significant reduction of RV (SMA: 7.25 ± 6.37 cm/s vs. 18.52 ± 6.16 cm/s, p < 0.0001 - p adj <0.0001; IMA: 2.69 ± 6.10 cm/s vs. 17.06 ± 5.75 cm/s, p < 0.0001 - p adj <0.0001) and PI (SMA: 3.33 ± 0.75 vs. 4.53 ± 1.03, p < 0.0001 - p adj =0.0002; IMA: 3.54 ± 0.95 vs. 6.08 ± 1.53, p < 0.0001 - p adj <0.0001) in SSc patients than controls. CONCLUSION: involvement of splanchnic vessels in SSc may be non-invasively investigated with abdominal US and CDU. Morphological and functional changes of Doppler parameters observed in SMA and IMA clearly demonstrate that these vessels are affected by SSc vasculopathy.

Lung Ultrasound (LUS) in COVID-19 Pneumonia: Usefulness in Two Atypical Cases.

Clinical experience and scientific articles have shown that patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be paucisymptomatic or asymptomatic at the time of diagnosis. In this paper, we will discuss two paucisymptomatic patients with blood tests suggestive for SARS-CoV-2 infection but with repeated negative nasopharyngeal swabs and without typical features of COVID-19 pneumonia on chest high-resolution computed tomography. In these cases, lung ultrasound helped to raise clinical suspicion of COVID-19 pneumonia and facilitate diagnosis. LEARNING POINTS: During the current COVID-19 pandemic, lung ultrasound (LUS) is being used extensively to evaluate and monitor lung damage in infected patients.Several patients have been described with negative PCR swabs who tested positive for SARS-CoV-2 in bronchoalveolar lavage fluid.Typical signs of interstitial pneumonia on LUS strongly indicate COVID-19 pneumonia, thus suggesting further investigation and invasive tests to confirm the diagnosis.

Thoracic ultrasound and SARS-COVID-19: a pictorial essay.

Thoracic ultrasound seems to adapt to the screening for lung involvement of patients with suspected or ascertained SARS-COVID-19 infection due to its characteristics of easy applicability. It can be also a relevant method in monitoring patients. B lines are early finding of COVID-19, even in mild-symptomatic subjects; in the most serious cases such as pre-ARDS or ARDS, the B lines end up filling the ultrasound image almost completely, until it merges, so as to create a single hyperechoic image named as "white lung", with distortion and irregularity of the pleural line. In advanced stage, lung consolidations are present, representing pulmonary pathological areas that are no longer normally ventilated.

Update on bedside ultrasound (US) diagnosis of acute cholecystitis (AC).

Acute cholecystitis (AC) represents a principal cause of morbidity worldwide and is one of the most frequent reasons for hospitalization due to gastroenteric tract diseases. AC should be suspected in presence of clinical signs and of gallstones on an imaging study. Upper abdominal US represents the first diagnostic imaging step in the case of suspected AC. Computed tomography (CT) with intravenous contrast (IV) or magnetic resonance imaging (MRI) with gadolinium contrast and technetium hepatobiliary iminodiacetic acid (Tc-HIDA) can be employed to exclude complications. US examination should be performed with right subcostal oblique, with longitudinal and intercostal scans. Normal gallbladder US findings and AC major and minor US signs are described. Polyps, sludge and gallbladder wall thickening represent the more frequent pitfalls and they must be differentiated from stones, duodenal artifacts and many other non-inflammatory conditions that cause wall thickening, respectively. By means of bedside ultrasound, the finding of gallstones in combination with acute pain, when the clinician presses the gallbladder with the US probe (the sonographic Murphy's sign), has a 92.2 % positive predictive value for AC. In our preliminary experience, bedside US-performed by echoscopy (ES) and/or point-of-care US (POCUS) demonstrated good reliability in detecting signs of AC, and was always integrated with physical examination and performed by a skilled operator.

Percutaneous real-time sonoelastography as a non-invasive tool for the characterization of solid focal liver lesions: A prospective study.

BACKGROUND: Real-time sonoelastography is currently used for the characterization of superficial solid lesions such as thyroid and breast masses. This study evaluates the usefulness of percutaneous sonoelastography for the characterization of solid focal liver lesions. METHODS: 30 out of 43 patients with 38 known liver lesions were included in a prospective, diagnostic study. Qualitative analysis (pattern of deformation, elasticity type of liver tumour) and semi-quantitative measurements (strain ratio, hardness percentage, histogram) were evaluated. Sensitivity, specificity, positive and negative predictive values were calculated and the area under the receiver operating characteristics curve was constructed. RESULTS: Patterns A and C-D are specific of benign lesions and metastases respectively. The patterns for haemangiomas, focal nodular hyperplasia and metastases were significantly different to each other in terms of strain ratio, hardness percentage and histogram (p<0.05). A statistically significant difference (p<0.001) was observed between the median values of the 3 measured parameters for benign (1.02; 12%; 47) and malignant lesions (1.66; 65%; 20.5) respectively. The area under the receiver operating characteristics curve values for strain ratio, hardness percentage and histogram were 0.88, 0.89, and 0.86 respectively for cut-off values of 1.2, 45, and 30. CONCLUSIONS: By percutaneous sonoelastography it is possible to differentiate benign versus malignant focal liver lesions, metastases in particular, with good diagnostic performance.

Interferon plus ribavirin and interferon alone in preventing hepatocellular carcinoma: a prospective study on patients with HCV related cirrhosis.

AIM: To determine the role of interferon (IFN) with or without ribavirin in preventing or delaying hepatocellular carcinoma (HCC) development in patients with hepatitis C virus (HCV) related cirrhosis. Data on the preventive effect of IFN plus ribavirin treatment are lacking. METHODS: A total of 101 patients (62 males and 39 females, mean age 55.1+/-1.4 years) with histologically proven HCV related liver cirrhosis plus compatible biochemistry and ultrasonography were enrolled in the study. Biochemistry and ultrasonography were performed every 6 mo. Ultrasound guided liver biopsy was performed on all detected focal lesions. Follow-up lasted for 5 years. Cellular proliferation, evaluated by measuring Ag-NOR proteins in hepatocytes nuclei, was expressed as AgNOR-Proliferative index (AgNOR-PI) (cut-off = 2.5). Forty-one patients (27 males, 14 females) were only followed up after the end of an yearly treatment with IFN-alpha2b (old treatment control group = OTCG). Sixty naive patients were stratified according to sex and AgNOR-PI and then randomized in two groups: 30 were treated with IFN-alpha2b + ribavirin (treatment group = TG), the remaining were not treated (control group = CG). Nonresponders (NR) or relapsers in the TG received further IFN/ribavirin treatments after a 6 mo of withdrawal. RESULTS: AgNOR-PI was significantly lowered by IFN (P<0.001). HCC incidence was higher in patients with AgNOR-PI>2.5 (26% vs 3%, P<0.01). Two NR in the OTCG, none in the TG and 9 patients in the CG developed HCC during follow-up. The Kaplan-Mayer survival curves showed statistically significant differences both between OTCG and CG (P<0.004) and between TG and CG (P<0.003). CONCLUSION: IFN/ribavirin treatment associated with re-treatment courses of NR seems to produce the best results in terms of HCC prevention. AgNOR-PI is a useful marker of possible HCC development.

Gastric autoimmune disorders in patients with chronic hepatitis C before, during and after interferon-alpha therapy.

AIM: To explore the prevalence of autoimmune gastritis in chronic hepatitis C virus (HCV) patients and the influence of alpha-interferon (IFN) treatment on autoimmune gastritis. METHODS: We performed a prospective study on 189 patients with positive anti-HCV and viral RNA enrolled in a 12-month IFN protocol. We evaluated: a) the baseline prevalence of autoimmune gastritis, b) the impact of IFN treatment on development of biochemical signs of autoimmune gastritis (at 3, 6 and 12 months), c) the evolution after IFN withdrawal (12 months) in terms of anti-gastric-parietal-cell antibodies (APCA), gastrin, anti-thyroid, and anti-non-organ-specific antibodies. RESULTS: APCA positivity and 3-fold gastrin levels were detected in 3 (1.6 %) and 9 (5 %) patients, respectively, at baseline, in 25 (13 %) and 31 (16 %) patients at the end of treatment (both P<0.001, vs baseline), and in 7 (4 %) and 14 (7 %) patients 12 months after withdrawal (P=0.002 and P=0.01 respectively, vs baseline; P=not significant vs end of treatment). The development of autoimmune gastritis was strictly associated with the presence of autoimmune thyroiditis (P =0.0001), no relationship was found with other markers of autoimmunity. CONCLUSION: In HCV patients, IFN frequently precipitates latent autoimmune gastritis, particularly in females. Following our 12-month protocol, the phenomenon generally regressed. Since APCA positivity and high gastrin levels are associated with the presence of antithyroid antibodies, development of autoimmune thyroiditis during IFN treatment may provide a surrogate preliminary indicator of possible autoimmune gastritis to limit the need for invasive examinations.

Bedside ultrasonography (US), Echoscopy and US point of care as a new kind of stethoscope for Internal Medicine Departments: the training program of the Italian Internal Medicine Society (SIMI).

In recent years, thanks to the development of miniaturized ultrasound devices, comparable to personal computers, tablets and even to smart phones, we have seen an increasing use of bedside ultrasound in internal medicine departments as a novel kind of ultrasound stethoscope. The clinical ultrasound-assisted approach has proved to be particularly useful in assessing patients with nodules of the neck, dyspnoea, abdominal pain, and with limb edema. In several cases, it has allowed a simple, rapid and precise diagnosis. Since 2005, the Italian Society of Internal Medicine and its Ultrasound Study Group has been holding a Summer School and training courses in ultrasound for residents in internal medicine. A national network of schools in bedside ultrasound was then organized for internal medicine specialists who want to learn this technique. Because bedside ultrasound is a user-dependent diagnostic method, it is important to define the limits and advantages of different new ultrasound devices, to classify them (i.e. Echoscopy and Point of Care Ultrasound), to establish appropriate different levels of competence and to ensure their specific training. In this review, we describe the point of view of the Italian Internal Medicine Society on these topics.

Ultrasonography (US) and non-invasive diagnostic methods for non-alcoholic fatty liver disease (NAFLD) and early vascular damage. Possible application in a population study on the metabolic syndrome (MS).

Abdominal ultrasonography (US) represents the first-line imaging examination in chronic liver diseases; in most cases, US, laboratory findings and the clinical context are generally sufficient to guide the diagnosis. Thanks to the considerable diffusion of US, we have seen an increased diagnosis of NAFLD in recent years, although this condition is generally silent from a clinical point of view. We have to identify the metabolic syndrome in the general population and to promptly recognize NAFLD to prevent its development into non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. Among the non-invasive diagnostic techniques for NAFLD and for early vascular damage, ultrasonography represents the method of choice. In fact, besides the traditional semiotics of fundamental US of the liver, new US techniques have recently been proposed (contrast enhancement US, acoustic structure characterization), with respect to serum biomarkers and Fibroscan, for the study of liver fibrosis. Similarly, also as concerns the US measurement of carotid intima-media thickness, new automated methods with sophisticated software and radio-frequency signal have recently been introduced. Finally, we report the preliminary results of a personal experience on liver and carotid US in the epidemiology of the metabolic syndrome.