[Delivery induction with slow-release dinoprostone in clinical practice: results of a clinical protocol]. / L'induzione del parto con prostaglandine a lento rilascio nella pratica clinica: risultati di un protocollo clinico.

AIM: The aim of this paper was to evaluate the feasibility of a protocol for the induction of delivery with slow-release dinoprostone in women with unfavourable cervix. METHODS: Indications for the induction were: pregnancy beyond 40 weeks, amniotic fluid index (AFI) <5, premature rupture of membranes, intrauterine growth retardation, or adverse maternal conditions. Eligibility criteria were: single pregnancy, cephalic presentation, Bishop Score <4, no previous uterine scar. Slow-release vaginal insert containing dinoprostone 10 mg was used to induce delivery according to a dedicated protocol agreed between clinicians and midwifes. Dinoprostone induction failure was defined as no cervical dilation >3 cm at the removal of the insert. RESULTS: One-hundred-nineteen patients were enrolled. The onset of labour was obtained in 102 (85.7%) patients, 98 (82.3%) with the insert only, and in 4 (3.3%) after the sequential administration of prostaglandins and oxitocin. The mean interval between insert application and delivery was 16.85±11.48 hours. Vaginal delivery was reported in 87 (73.1%) women, whereas Cesarean was necessary in 32 (26.9%) patients [29 nulliparous]. Cesarean section was also required in 15/98 (15.3%) women who responded to prostaglandins and in 17/21 (80.9) non-responders. Protocol violations occurred in 11 (9.2%) patients. Uterine hyperstimulation occurred in 4 (3.3%) patients. CONCLUSION: Induction of delivery with slow-release dinoprostone seems a feasible option, characterized by high efficacy, good adherence to protocol, low incidence of adverse events and easy management. In our opinion the high compliance of the gynecologists and midwifes is based on the insert handiness.

Liver resection for hemoperitoneum caused by spontaneous rupture of unrecognized hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an increasingly common form of cancer. Although its spontaneous rupture is rare in Western countries, it constitutes a surgical emergency and is associated with high mortality. There is a lack of consensus as to the best approach and what parameters to use in choosing it. The three main approaches are conservative, endovascular and resection - the treatment of choice for acute abdominal bleeding. We report a case of hemoperitoneum following the spontaneous rupture of an unrecognized HCV-related HCC in a patient with no history of liver disease. The patient was successfully treated by emergency surgery, with resection of two segments of the left liver.

Cholecystectomy by single incision laparoscopic surgery (SILS): early experience and technique standardization.

Single Incision Laparoscopic Surgery (SILS) is a recent surgical technique, first described in the 1990s. Its aim is to optimize the esthetic result offered by laparoscopy by minimizing the number of abdominal incisions. Various preliminary studies have been carried out on the application of SILS, especially in cholecystectomy and appendectomy. This study evaluates the preliminary results of cholecystectomy by SILS (SILS™ Port) conducted between October 2009 and February 2011 on 21 patients (4 men and 17 women) with a mean age of 49.9 years and a mean Body Mass Index (BMI) of 22.8. All patients were treated by the same team, which had previously undergone six months' simulator training. There were two main selection criteria, both evaluated intraoperatively: absence of adhesions and of significant inflammatory sequelae from previous cholecystitis; and suitable distance between gallbladder and SILS access port. Conversion to traditional laparoscopy was necessary in just two cases, while an accessory trocar was introduced in another two cases. Conversion to open surgery was not necessary in any case. One case of SILS cholecystectomy was complicated by postoperative bile leakage, which was treated conservatively, as the fistula had a low output. The mean duration of hospitalization was 3.6 days. This preliminary experience led us to conclude that SILS is safe and highly satisfactory in the postoperative phase, thanks to the reduced need for painkillers and the improved esthetic result.

Nitrite modulates contractility of teleost (Anguilla anguilla and Chionodraco hamatus, i.e. the Antarctic hemoglobinless icefish) and frog (Rana esculenta) hearts.

Being the largest form of intravascular and tissue storage of nitric oxide (NO) and a signalling molecule itself, the nitrite anion (NO(2)(-)) has emerged as a key player in many biological processes. Since the heart is under an important NO-mediated autocrine-paracrine control, in mammals the cardiac effects of nitrite are under intensive investigation. In contrast, nothing is known in non-mammalian vertebrates. We evaluated nitrite influence on cardiac performance in the perfused beating heart of three different cold-blooded vertebrates, i.e. two teleost fishes, the temperate red-blooded Anguilla anguilla, the Antarctic stenotherm, hemoglobinless Chionodraco hamatus (icefish), and the frog Rana esculenta. We showed that, under basal conditions, in all animals nitrite influences cardiac mechanical performance, inducing negative inotropism in eel and frog, while being a positive inotrope in C. hamatus. In all species, these responses parallel the inotropic effects of authentic NO. We also demonstrated that the nitrite-dependent inotropic effects are i) dependent from NO synthase (NOS) activity in fish; ii) sensitive to NO scavenging in frog; iii) cGMP/PKG-dependent in both eel and frog. Results suggest that nitrite is an integral physiological source of NO and acts as a signalling molecule in lower vertebrate hearts, exerting relevant inotropic actions through different species-specific mechanisms.

Phospholamban S-nitrosylation modulates Starling response in fish heart.

The Frank-Starling mechanism is a fundamental property of the vertebrate heart, which allows the myocardium to respond to increased filling pressure with a more vigorous contraction of its lengthened fibres. In mammals, myocardial stretch increases cardiac nitric oxide (NO) release from both vascular endothelium and cardiomyocytes. This facilitates myocardial relaxation and ventricular diastolic distensibility, thus influencing the Frank-Starling mechanism. In the in vitro working heart of the eel Anguilla anguilla, we previously showed that an endogenous NO release affects the Frank-Starling response making the heart more sensitive to preload. Using the same bioassay, we now demonstrate that this effect is confirmed in the presence of the exogenous NO donor S-nitroso-N-acetyl penicillamine, is independent from endocardial endothelium and guanylate cyclase/cGMP/protein kinase G and cAMP/protein kinase A pathways, involves a PI(3)kinase-mediated activation of endothelial NO synthase and a modulation of the SR-CA(2+)ATPase (SERCA2a) pumps. Furthermore, we show that NO influences cardiac response to preload through S-nitrosylation of phospholamban and consequent activation of SERCA2a. This suggests that in the fish heart NO modulates the Frank-Starling response through a beat-to-beat regulation of calcium reuptake and thus of myocardial relaxation. We propose that this mechanism represents an important evolutionary step for the stretch-induced intrinsic regulation of the vertebrate heart, providing, at the same time, a stimulus for mammalian-oriented studies.

Clinical indications to the use of (99m)Tc-EDDA/HYNIC-TOC to detect somatostatin receptor-positive neuroendocrine tumors.

The aim of this study was to define, retrospectively, the utility to perform (99m)Tc-EDDA/HYNIC-Tyr3-octreotide ((99m)Tc-EDDA/HYNIC-TOC) scan in patients with NET. We studied 50 consecutive patients affected by different types of NET and divided in two groups. Group 1: 34 patients with known lesions in which (99m)Tc-EDDA/HYNIC-TOC was performed for staging, characterisation or to choose the appropriate treatment. Group 2: 16 patients suspected of having NET or in follow up after surgery. Patients were injected with 370 MBq of (99m)Tc-EDDA/HYNIC-Tyr3-octreotide and whole-body and SPET images acquired 2-3 hours after injection. Overall, 29 patients (58%) had a positive scan, with a sensitivity, specificity and accuracy of 70.3%, 76.9% and 72%, respectively (78.1%, 50% and 76.5%, in group 1 and 20%, 81.2%, 62.5% in group 2). In patients from group 1 (99m)Tc-HYNIC-TOC scintigraphy showed a concordance of 68% with another imaging procedure and in 9 patients revealed a greater number of lesions. In the second group, false negative results were especially found in patients with medullary thyroid cancer with negative radiological findings and elevated calcitonin. In conclusion, (99m)Tc-EDDA/HYNIC-TOC is highly indicated for in vivo histological characterization of known NET lesions, previously identified by other imaging modalities or biopsy, to plan appropriate therapy especially for patients with inoperable disease. In patients with only biochemical suspicion of NET and in those with negative markers, this scintigraphy does not significantly modify the clinical management.

Pancreatic scintigraphy with 99mTc-interleukin-2 at diagnosis of type 1 diabetes and after 1 year of nicotinamide therapy.

BACKGROUND: To evaluate the clinical utility of pancreatic scintigraphy with 99mTc-interleukin-2 to identify Type 1 diabetic patients with pancreatic inflammation at diagnosis. METHODS: 99mTc-interleukin-2 scintigraphy was performed on 42 newly diagnosed Type 1 diabetic patients, before and after 1 year of treatment with nicotinamide (25 or 50 mg/kg/day) in addition to intensive insulin therapy. Metabolic status was monitored every 3 months for 1 year. Sixteen normal subjects were studied as control. RESULTS: Significant pancreatic accumulation of 99mTc-interleukin-2 was found in 31% of the patients at the time of diagnosis. Patients positive or negative for pancreatic accumulation of interleukin-2 scintigraphy did not show any difference in metabolic or immunologic parameters at diagnosis. Positive patients, however, showed higher C-peptide values at 3 months and lower insulin requirement at 1 year, compared to negative patients (insulin requirement (IR): 0.33+/-0.11 vs 0.67+/-0.24 IU/kg/day, positive vs negative patients; p=0.0001); patients positive to IL2 scintigraphy treated with nicotinamide at 25 mg/kg were the only group showing a significant reduction in IR 1 year after diagnosis (IRt0: 0.53+/-0.30 vs IRt12: 0.28+/-0.07 IU/kg/day; p=0.013). After 1 year, all the positive patients showed a significant decrease in pancreatic uptake of 99mTc-interleukin-2 (P/B: 7.87+/-2.28 at diagnosis vs 5.00+/-1.23 after 1 year; p<0.0001 paired t-test). CONCLUSION: 99mTc-interleukin-2 scintigraphy at diagnosis of Type 1 diabetes may identify patients with pancreatic inflammation. In such patients, treated with nicotinamide at 25 mg/kg, insulin requirement and pancreatic inflammation after 1 year were significantly reduced suggesting that IL2 scintigraphy may be of potential use for assessing the autoimmune phenomena in endocrine pancreas.

The developing role of peptide radiopharmaceuticals in the study of chronic inflammation: new techniques for novel therapeutic options.

Chronic inflammatory diseases usually lead to fibrosis of the target organ and consequent hypo function. They are often relapsing, invalidating and require life-long treatment. In this class of patients it is very important to try and achieve specific immune suppression to extinguish the immune process with the aim of preventing the disease, preventing or delaying complications and avoiding disease relapse, often requiring surgical intervention. It is important that, while attempting to improve the quality of life of these patients by means of anti-inflammatory drugs, side effects are reduced to a minimum via the use of specific immune therapies that block as selectively as possible the pathologic mechanism responsible for the disease. New therapeutic options are being developed for specific targeted therapies. Several trials are being performed to assess the efficacy and safety of this approach. All of them, however, rely on the clinical assessment of the patients to evaluate the effect of treatment. It would be important to use an objective and reliable method to highlight directly the immune process underlying the individual disease. This manuscript reviews the radiopharmaceuticals available or recently developed for imaging chronic inflammatory diseases and their use for therapy decision making and follow-up.