Multiparametric ultrasound evaluation with CEUS and shear wave elastography for carotid plaque risk stratification.

PURPOSE: To assess the diagnostic effectiveness of Multiparametric ultrasound (MPUS), which includes color Doppler ultrasound (CDUS), CEUS and Shear wave elastography (SWE), for evaluating carotid plaque as compared with CT-angiography (CTA) and histology. MATERIALS AND METHODS: Forty-three consecutive patients scheduled to undergo carotid endarterectomy underwent MPUS. Then, after periods ranging from 2 days to 2 weeks, all underwent CTA. Each plaque was classified by means of dedicated scores for CEUS and SWE as compared with CTA features. At surgery, each plaque was removed in a single fragment to facilitate histological analysis, which evaluated 4 features: extension of the lipid core, thickness of the fibrous cap, inflammatory infiltrate (CD68 + and CD3 + markers) and the presence of intraplaque microvessels. For the CEUS, SWE and CTA, the following values for identifying plaque vulnerability were evaluated: sensitivity, specificity, accuracy, negative predictive value (NPV), positive predictive value (PPV) and Area under the curve (AUC). Cohen's kappa was used to evaluate the concordance between measurements in the different imaging methods. A p < 0.05 was considered statistically significant. RESULTS: At histology, 31 out of 43 plaques were identified as vulnerable because of the presence of at least one of the following criteria: fibrous cap < 200 µm, lipid core, intraplaque hemorrhage, inflammatory infiltrate or intraplaque neovascularization. CTA showed a sensitivity of 87.1%, a specificity of 100%, a PPV of 100%, an NPV of 75% and an AUC of 93.5%. SWE showed a sensitivity of 87.1%, a specificity of 66.7%, a PPV of 87.1%, an NPV of 66.7% and an AUC of 76.9%. CEUS showed a sensitivity of 87.1%, a specificity of 58.3%, a PPV of 84.4%, an NPV of 63.6% and an AUC of 72.7%. CONCLUSIONS: Multiparametric ultrasound is an effective modality to obtain comprehensive information on carotid plaques. Further studies are needed to determine whether it can be considered a diagnostic standard.

Pilot study on circulating miRNA signature in children with obesity born small for gestational age and appropriate for gestational age.

BACKGROUND: Children born small for gestational age (SGA) are at increased risk of metabolic dysfunction. Dysregulation of specific microRNAs (miRNAs) contributes to aberrant gene expression patterns underlying metabolic dysfunction. OBJECTIVE: We aimed to determine and compare circulating miRNA (c-miRNA) profile of SGA and appropriate for gestational age (AGA) children with obesity and with normal weight, in order to identify biomarkers for early detection of increased risk of developing metabolic dysfunction in SGA and AGA children with obesity. METHODS: Small non-coding RNAs from serum of 15 SGA children with obesity (OB-SGA), 10 SGA children with normal weight (NW-SGA), 17 AGA children with obesity (OB-AGA) and 12 AGA children with normal weight (NW-AGA) (mean age 11.2 ± 2.6) have been extracted and sequenced in order to detect and quantify miRNA expression profiles. RESULTS: RNA-seq analyses showed 28 miRNAs dysregulated in OB-SGA vs. NW-SGA and 19 miRNAs dysregulated in OB-AGA vs. NW-AGA. Among these, miR-92a-3p, miR-122-5p, miR-423-5p, miR-484, miR-486-3p and miR-532-5p were up regulated, and miR-181b-5p was down regulated in both OB-SGA and OB-AGA compared with normal weight counterparts. Pathway analysis and miRNA target prediction suggested that these miRNAs were particularly involved in insulin signalling, glucose transport, insulin resistance, cholesterol and lipid metabolism. CONCLUSION: We identified a specific profile of c-miRNAs in SGA and AGA children with obesity compared with SGA and AGA children with normal weight. These c-miRNAs could represent specific biomarkers for early detection of increased risk of developing metabolic dysfunction in SGA and AGA children with obesity.

Gamma rays induce a p53-independent mitochondrial biogenesis that is counter-regulated by HIF1α.

Mitochondrial biogenesis is an orchestrated process that presides to the regulation of the organelles homeostasis within a cell. We show that γ-rays, at doses commonly used in the radiation therapy for cancer treatment, induce an increase in mitochondrial mass and function, in response to a genotoxic stress that pushes cells into senescence, in the presence of a functional p53. Although the main effector of the response to γ-rays is the p53-p21 axis, we demonstrated that mitochondrial biogenesis is only indirectly regulated by p53, whose activation triggers a murine double minute 2 (MDM2)-mediated hypoxia-inducible factor 1α (HIF1α) degradation, leading to the release of peroxisome-proliferator activated receptor gamma co-activator 1ß inhibition by HIF1α, thus promoting mitochondrial biogenesis. Mimicking hypoxia by HIF1α stabilization, in fact, blunts the mitochondrial response to γ-rays as well as the induction of p21-mediated cell senescence, indicating prevalence of the hypoxic over the genotoxic response. Finally, we also show in vivo that post-radiotherapy mitochondrial DNA copy number increase well correlates with lack of HIF1α increase in the tissue, concluding this may be a useful molecular tool to infer the trigger of a hypoxic response during radiotherapy, which may lead to failure of activation of cell senescence.

Regulation of IGFBP3 gene expression in short children born small for gestational age.

OBJECTIVE: Approximately 6% of newborns at term are small for gestational age (SGA) and present a birth weight and/or length less than -2SD from the mean. SGA infants are at increased risk for perinatal morbidity, associated psychological and/or mental problems, persistent short stature (about 15% of subjects) and metabolic alterations. Insulin-like growth factors (IGFs), their common receptor (IGF1R) and their binding proteins (IGFBPs) play a critical role in fetal and postnatal growth. In these genes common polymorphisms, such as single nucleotide polymorphisms and variable number of tandem repeats, have been investigated with conflicting results with respect to SGA-related outcomes, and the functional role of these gene variants remains to be elucidated. DESIGN: The study group consisted of 100 pre-pubertal short children born SGA and 94 healthy controls, matched for sex and age, recruited at the Department of Biomedicine of Development Age of the Bari University and at the Paediatric Department of the Messina Hospital. In the present study we analyzed the allelic frequency of the polymorphisms -795 G/A, -667 G/A, -396 C/T in the IGFBP3 in SGA children and their influence on the basal and insulin-stimulated transcriptional activity of the gene. RESULTS: We found that the polymorphisms -667 G/A and -396 C/T in the IGFBP3 promoter region are capable of having an effect on the transcriptional activity of the gene, although with opposing effects. Interestingly, the -667 G/A polymorphism has a negative impact on the IGFBP3 transcription, while the -396 C/T polymorphism determines an increase of the transcriptional activity of the IGFBP3 gene promoter. Interestingly, we found that the -396 C/T polymorphism correlates with lower birth length in SGA children. Most importantly, while the diminished IGFBP3 transcriptional activity induced by the -667A polymorphism was significantly recovered after insulin administration (p-value<0.05), the increased transcriptional activity caused by the -396T polymorphism was not restored to baseline levels by insulin. CONCLUSIONS: Altogether our results demonstrated that the -667 G/A and the -396 C/T polymorphisms in IGFBP3 promoter region influence the basal transcriptional activity of the gene.

Actinomycosis of submandibular gland: an unusual presentation.

An unusual presentation of oro-facial actinomycosis, mimicking the clinical appearance of a malignant lesion is reported. The patient, a 74-year-old female, presented with a right submandibular mass, which slowly grew in size over a period of about 2 months, and a modest dysphagia. A painless cervical mass was palpable over the submandibular region. The rhino-pharyngo-laryngeal region, explored by flexible fiberoptic examination, was normal. At ultrasonography, a 2x2 cm infiltrating dyshomogeneous mass, involving the right submandibular gland, was visible. No connection with adjacent organs was found. There was no associated cervical lymphoadenopathy. Ultrasound-guided fine-needle aspiration cytology, performed on lesion, revealed no evidence of malignancy. The presence of characteristic colonies of actinomyces infection was found. The patient was treated initially with tetracycline chloridrate 100 mg: 1 tablet every 12 hours for 7 weeks, but a repeat ultrasonography showed no resolution. A further fine-needle aspiration cytology showed no actinomyces infection in the specimen. The patient was treated with methylprednisolone, 20 mg every 24 hours, for 5 days. After steroid treatment, the patient has been well and, upon repeat ultrasonography, total resolution of the submandibular lesion was confirmed. In conclusion, the clinical presentation of cervicofacial actinomycosis is variable and may mimic a malignant lesion or chronic granulomatous infections. Diagnostic and therapeutic findings are discussed.

Prevalence and genomic variability of transfusion transmitted virus in Italian cryptogenic chronic liver disease and healthy blood donors.

BACKGROUND: Infection with transfusion transmitted virus, a new member of the Parvoviridae family, has been found in patients both with chronic and fulminant post-transfusion cryptogenic hepatitis. AIM: To evaluate the prevalence and clinical impact of transfusion transmitted virus infection in Italy. PATIENTS AND METHODS: Studies were carried out on 256 patients and control subjects from three centres from Northern, Central and Southern Italy (92 nonA-nonC chronic hepatitis, 10 acute non fulminant cryptogenic hepatitis, 41 hepatitis C virus-related chronic hepatitis and 113 blood donors). Serum transfusion transmitted virus was detected by nested polymerase chain reaction using two overlapping sets of primers. RESULTS: A total of 52 of the 92 patients (54.3%) with chronic cryptogenic liver disease and 17 of the 41 hepatitis C virus chronic hepatitis patients (41.4%) were transfusion transmitted virus-DNA positive. Transfusion transmitted virus co-infection in hepatitis C virus patients was not associated with either a higher severity of liver histology or higher alanine transaminase levels or signs of cholestasis, transfusion transmitted virus was found in 48 out of 113 (42.4%) blood donors. In the majority of samples, transfusion transmitted virus DNA was detected with only one of the two sets of primers used. Genotyping and phylogenetic analysis performed on 21 randomly selected viral isolates showed the presence of both type 1 and type 2 transfusion transmitted virus and allowed identification of two isolates with high homology to genotype 6, described, so far, mostly in Japan. CONCLUSIONS: Transfusion transmitted virus type 1 and 2 infection is common among blood donors and patients with liver disease in Italy. The pathogenic potential of transfusion transmitted virus type 1 and 2 in nonA-nonC hepatitis patients is unlikely but further studies are needed to evaluate the epidemiological and clinical impact of other transfusion transmitted virus subtypes.

Long-term octreotide treatment of metastatic carcinoid tumor.

The optimal dosage of somatostatin analogs for the long-term control of carcinoid tumors has not yet been established. Receptor alterations induced during long term treatment with somatostatin analogs have lead to consecutive drug dosage increases in order to control carcinoid disease. In this report, we describe the rapid and effective control of tumor in a patient with metastatic carcinoid treated for nine years with a single daily dose of octreotide based on tumor marker levels. Tumoral somatostatin receptor (sst) subtype analysis by RT-PCR amplification showed the expression of sst2 subtype only. We suggest that a single daily dose of octreotide strictly related to tumor marker secretion, could have played a role in the effective long-term therapy by avoiding the phenomenon of somatostatin receptor desensitisation. Furthermore, the exclusive presence of sst2 subtype supports the high affinity of octreotide to tumoral cells.

[Intraoperative echography: the state of the art]. / L'ecografia intraoperatoria: stato dell'arte.

The intraoperative ultrasound (IOUS) is a diagnostic technique, of not recent introduction in the clinical practice, that nevertheless has not yet achieved the capillary and extensive diffusion that would deserve for his elevated sensitivity and specificity in the study of parenchymas (particularly liver and pancreas) as well as in the study alterations of ducts (for example the biliary tree) or of vessels. The authors, in the present article, describes the present uses and the actual diagnostical potentialities of the IOUS in the varied fields of more frequent uses in surgery and particularly in the liver surgery, in the surgery of the common bile duct and in the pancreatic surgery; and in addiction pointing out the possible advantages that the introduction of more recent technologies (for example the color and the power Doppler) n the routine of operating room will bring in the correct surgical management and particularly in oncologic surgery.

Dynamics of intra-hepatic lymphocytes in chronic hepatitis C: enrichment for Valpha24+ T cells and rapid elimination of effector cells by apoptosis.

Chronic viral hepatitis is characterized by a dramatic lymphocyte infiltrate in the liver. Although it is one of the most common chronic inflammatory diseases in humans, little information is available on the functional state of these intra-hepatic lymphocytes (IHL). To address this issue, we have optimized cytofluorimetric techniques to assess directly ex vivo the functions, dynamics and repertoires of IHL isolated from biopsies of patients with chronic hepatitis C. We estimate that 1% of the total body lymphocytes infiltrate the inflamed liver and find that, at variance with peripheral blood lymphocytes (PBL) isolated from the same patients, most IHL display an activated phenotype and produce Th1 type lymphokines when stimulated in vitro. Virtually all IHL are found in the G0/G1 state of the cell cycle, while a sizeable percentage of them is undergoing programmed cell death in vivo, as detected by the TUNEL assay performed on freshly isolated cells. In contrast again to PBL from the same patients, IHL show a preferential compartmentalization of NK and TCRgamma/delta+ cells, and a remarkable (up to 20-fold) enrichment for Valpha24+ T cells. Together our data suggest that in a liver injured by chronic hepatitis C, most IHL are pro-inflammatory activated cells which are highly enriched for effectors of innate resistance. These IHL do not undergo clonal expansion in the liver but rather display effector function and die in situ at a high rate, suggesting that maintenance of the IHL pool is dependent on continuous migration from extra-hepatic sites.

Expression of co-stimulatory molecules by Kupffer cells in chronic hepatitis of hepatitis C virus etiology.

In this paper we show that in viral hepatitis most Kupffer cells (KCs) are activated and express high levels of CD80, CD40, and class-II MHC molecules, thus acquiring the phenotype of professional antigen presenting cells (APCs). Activated KCs display a close contact with CD4+ T lymphocytes and form KCs-T lymphocyte clusters. Clusters are found within the sinusoids, across the sinusoid wall, and within the liver parenchyma as well, as a consequence of transendothelial migration (TEM). The positivity of activated KCs for hepatitis C virus (HCV) antigens, which likely reflects phagocytosis of infected hepatocytes, suggests that KCs-T cell clusters represent the morphological expression of the functional interaction between KCs acting as professional APCs and antigen-experienced CD4+ T lymphocytes within the liver. These phenotypic and morphological changes are distinct features of livers in chronic hepatitis patients compared with controls.

[Non visible carcinoma of the gallbladder. A strategic problem after video laparoscopic cholecystectomy]. / Il carcinoma non visibile della cistifellea. Un problema strategico dopo videolaparocolecistectomia.

A formal contraindication to laparoscopic cholecystectomy is gallbladder cancer. Sometimes its first appearance is intraoperative finding or microscopic examination of gallbladder removed for presumed benign disease. These patients with "inapparent carcinoma" may be long-term survivors if definitive and curative therapy is performed. We present the case of 56 y. woman which presented a T2 unsuspected carcinoma that was reoperated and cured by wedge liver resection, extended lymph node dissection and large excision of tissue of trocar wounds.

Endocaval suture of aortocaval fistula.

A case of aortocaval fistula complicating a ruptured infrarenal aortic aneurysm is reported. As the length of the defect and the thickness of the aortic wall made repair from within the aorta unsafe, the defect was repaired from within the vena cava. The details of the technique are reported. It can be a useful alternative to inferior vena cava ligation, when standard repair of aortocaval fistulae from within the aorta is risky or difficult to attempt.

Ultrasound-guided alcoholization of celiac plexus for pain control in oncology.

BACKGROUND: Treatment of inoperable pancreatic cancer pain is of paramount importance. The ineffectiveness of pharmacological agents has led many investigators to recommend chemical neurolysis of the celiac ganglions for pain control. This procedure may be performed under either fluoroscopic or computed tomography (CT) guidance, or it may accompany laparotomy. The authors describe a modified sonographically (ultrasound-US)-guided technique for alcoholization of the celiac ganglions. METHODS: Twelve patients underwent the neurolytic procedure. Nine of 12 suffered from pancreatic cancer. The remaining three were affected by inoperable hepatic, gastric, or colon cancer, respectively, with multiple hepatic metastases. US-guided alcohol neurolysis was performed by an anterior approach. In the last four patients, PIA (percutaneous injection alcohol) needles, modified by the authors, replaced the spinal needles employed in the first eight patients to inject the alcohol. Pain and pain relief were rated according to a Simple Descriptive Scale (SDS), and treatment success was gauged by declining opiate doses and need for pharmacological therapy. Results after treatment performed using different needles were compared. RESULTS: Procedure-related mortality was zero. Complications of the neurolytic procedure included left pleural effusion in one patient and mild diarrhea in two other patients. Positive, negative, and indeterminant results were noted in nine (75%, p < 0.001), two, and one patient(s), respectively. CONCLUSIONS: The neurolytic technique, although far from being considered a routine procedure, appears to provide patients with safe and effective pain relief for pain unresponsive to conventional medical treatment.

Transcutaneous ethanol injection in hepatocarcinoma: problems in analgesia and sedation.

Therapeutic ethanol injection into primitive or secondary hepatic tumours if performed in "one shot" causes a great deal of pain. For this reason an analgesic/sedation protocol was devised. This relies on the administration of ketorolac-propofol-nitrogen oxide mixture that has been used to treat patients with neoplastic hepatic diseases. A 20 patient series is described. Analgesic protocol was very effective and the only drawbacks were a residual sleepiness than in part is probably dependent on ethanol emigration into the bloodstream and consequently to the central nervous system depression.

[Bilateral aneurysm of the popliteal vein. A case report and review of the literature]. / L'aneurisma bilaterale della vena poplitea. Caso clinico e revisione della letteratura.

We report a case of a 86-year-old woman, with a 1-year history of pain during walking and standing; a duplex scanning of the popliteal fossa was performed bilaterally. We pointed out the presence of a bilateral popliteal vein aneurysm, partially thrombosed. She was treated only with oral anticoaugulant therapy, because of her age. Venous aneurysms are quite rare and are considered to be true when all three cell layers are present in the vessel wall; bilateral popliteal venous aneurysm is very rare and only one case was previously described. This report describes, moreover, with a large review of the world literature, histologic features and diagnostics and therapeutic choices.

[A case of nodular pseudosarcomatous fasciitis treated with "presuture" technique]. / Su di un caso di fascite nodulare pseudosarcomatosa trattato con tecnica di "presutura".

This paper reviews a case of nodular (pseudosarcomatous) fasciitis. It consists of a rare benign lesion of the soft tissues. The rapidity of its growth and the cellular features represent a diagnostic challenge when compared with that of a sarcoma. The patient, a 36 year old female, 20 days before surgical treatment, noticed the growth of a nodular lesion on the left forearm skin. After echotomography and ultrasound guided needle biopsy diagnosis of nodular pseudosarcomatous fasciitis was established and the patient underwent surgical treatment. The nodular lesion, noncapsulated, (diameter 2.5 x 1.2 cm) greyish-white colored, with slimy consistency, and myxoid character, was microscopically composed by atypical fibroblasts, with myxoid ground substance. The nodular lesion was removed using the "pressure" technique by Serge Baux of Rothschild Hospital in Paris using two Kirschner threads pulling the skin surrounding the biopsy wound. By this technique was possible to achieve a rapid skin expansion. The nodular pseudosarcomatous fasciitis remains a very difficult lesion to recognise unless the aid of a biopsy.

[Role of ultrasonography-guided fine-needle biopsy in the selection for surgical treatment in thyroid diseases. Multicenter retrospective study of 5,109 patients]. / Analisi del ruolo della citologia agoaspirativa ecoguidata quale criterio di selezione nella terapia chirurgica delle malattie tiroidee. Studio retrospettivo multicentrico su 5109 pazienti.

FNAB cytology is a very specific diagnostic tool for distinguishing benign from malignant lesions. It allows the histologic type to be diagnosed too. FNAB findings also help select the type of surgery. The value of FNAB cytology was investigated in 5,109 patients examined from 1987 through March 1993. 607 patients has surgical confirmation. 444 patients underwent cytology before surgery, while 163 patients were not submitted to FNAB. Histology diagnosed 116 malignant tumors (19.2%): 83 of them were papillary carcinomas (71.5%), 26 follicular carcinomas (2.6%), 1 primary thyroid lymphoma (0.9%) and 3 medullary carcinoma (2.6%). Seventy-nine of 116 cases had been diagnosed by FNAB cytology, while 37 of 116 were diagnosed at surgery. Aspiration biopsy under US guidance reduced the rate of thyroidectomies from 19.2% to 8.5% because true-positive cases were assessed before surgery. FNAB cytology should be used as a preliminary diagnostic tool, thanks to its high accuracy and to its capabilities of distinguishing benign from malignant lesions for proper medical or surgical treatment. Moreover, FNAB cytology allows potentially malignant lesions to be surgically explored.

Laparoscopic ultrasonography: limits and potential of present technologies.

During recent years, laparoscopic contact sonography has been introduced into clinical practice to remedy the limitations of minimal invasive surgery. The technology of laparoscopic ultrasound probes is described in this paper as well as the technique of US contact scanning via the laparoscopic approach. This method is a tool which allows the examination of tissues and non-palpable parenchymal organs in endoscopic surgery, thus permitting correct assessment of both anatomy and the spreading of neoplasms, with consequent impact upon surgical decision making.

[Images of hepatic parasitic cysts: echotomography, computed tomography and magnetic resonance compared]. / Immagini delle cisti parassitarie epatiche: ecotomografia, tomografia computerizzata e risonanaza magnetica a confronto.

Hepatic hydatic cysts are a very common finding in the endemic areas like Australia, the Middle East, New Zealand, South Africa and in some countries bordering the Mediterranean. Immigration has increased the finding of this pathology in some European and North American areas. Our purpose is to show possibilities and limits using US, TC and RM to demonstrate the presence of parasitic hepatic localizations and their evolution after therapy.