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F Milone,
C Pivonello,
F Cariati,
M Sarnataro,
V Ramundo,
V Marotta,
H Jann,
U-F Pape,
B Wiedenmann,
A Colao,
M Pavel,
A Faggiano
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ABSTRACT: Abstract Introduction: The impact on the survival of bone metastases (BM) in patients with neuroendocrine tumor (NET) is a matter of debate. BM have a key role in causing symptoms and in decreasing patients' quality of life. Although the mechanisms of the development of BM are not completely clear, it is now well understood that the Receptor Activator of Nuclear factor Kappa-B-/Ligand (RANK/RANKL)/osteoprotegerin (OPG) pathway plays a relevant role. Aim: To characterize the RANK/RANKL/OPG pathway in patients affected with NET. Patients and methods: Two cohorts of 15 patients each were enrolled in the study; one cohort was affected with NET without BM and the second cohort was affected with NET with BM. The serum RANK/RANKL/OPG pathway was assessed in both the groups. Results: Serum OPG levels and RANKL/OPG ratio were lower and higher, respectively, in NET patients harboring BM than in those without BM. During the ROC analysis, a cut-off value of 1071 pg/ml for OPG and 0.62 for RANKL/OPG ratio were able to significantly distinguish between the two groups. Conclusions: This study indicates that RANK/RANKL/OPG pathway is imbalanced in patients with NET harboring BM. Specific alterations of this pathway could predict an early development of BM.
Biomarkers 01/2013; · 2.21 Impact Factor
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ABSTRACT: BACKGROUND: The aim of this prospective randomized study was to determine the utility of transversus abdominis plane (TAP) block to improve the efficacy of conventional local anaesthesia for hernia repair in order to achieve an adequate anaesthesia and to evaluate its post-operative analgesic effectiveness. METHOD: Hundred and fifty consecutive male patients undergoing outpatient hernia repair (Lichtenstein technique) were enrolled in this study. Patients were randomly allocated to undergo a combined TAP block and local anaesthesia (case group) or single conventional local anaesthesia (control group). The study was designed to obtain a 1:2 case-control ratio. The primary outcome was the evaluation of the proportion of patients achieving an adequate anaesthesia. The secondary outcome was the evaluation of pain on movement, pain at rest, rescue analgesia need, nausea and satisfaction. RESULTS: An adequate anaesthesia was achieved in 8 % case and in 36 % control subjects (p = 0.001). At the 6 and 12 h post-operative evaluations, patients enrolled in the case group reported significantly less pain (evaluated by VAS score) both at rest and on movement (p always = 0.001). Moreover, the need of rescue analgesia resulted significantly higher in the control group (14 vs. 32 %, p = 0.01). CONCLUSION: Our results demonstrated that, as compared with conventional local anaesthesia, the combination of TAP block with local anaesthesia showed a higher efficacy in the obtainment of an adequate anaesthesia and in the post-operative pain control for hernia repair.
Hernia 11/2012; · 1.84 Impact Factor
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ABSTRACT: Peripheral arterial disease (PAD) predicts cardiovascular and cerebrovascular ischemic events. PAD treatment is aimed at reducing clinical symptoms, local tissue loss and at preventing complications. Aims:To evaluated the effect of peridural analgesia on peripheral perfusion and pain control.In 280 diabetic subjects with severe limb ischemia (65.7% males and 34.3% females, mean age 59.3±14.4 years) with a failure of medical treatment and contraindications to endovascular and/or surgical reperfusion, we performed a 30-day long peridural ropivacaine infusion, monitoring blood pressure, VAS and ABI periodically.During ropivacaine infusion VAS significantly decreased (from 4.06±0.343 to 1.96±0.413, p<0.001). Furthermore, in the 261 (93.2%) subjects achieving a VAS value≤2 during infusion, the effect was maintained after infusion withdrawing. ABI significantly improved both during infusion (from 0.30±0.04 at baseline to 0.65±0.05 at T30, p<0.001) and after infusion withdrawing as compared with baseline values.30-day peridural analgesia with ropivacaine is a valuable therapeutic option in severe peripheral limb ischemia subjects with contraindication to surgery and with pharmacological therapy failure.
Experimental and Clinical Endocrinology & Diabetes 11/2012; · 1.69 Impact Factor
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European journal of clinical nutrition 06/2012; 66(8):971. · 3.07 Impact Factor
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V Scarano,
M Milone,
M N D Di Minno,
G Panariello,
S Bertogliatti,
M Terracciano,
V Orlando,
C Florio,
M Leongito,
R Lupoli, F Milone,
M Musella
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ABSTRACT: Although the micronutrient deficiencies and the related neurological manifestations are widely reported after malabsorbitive weight loss surgery, little is known about cerebral dysfunction secondary to micronutrient impairment in subjects undergoing restrictive interventions (that is, sleeve gastrectomy). We describe a case of a 27-year-old woman with a late development of a Wernicke's encephalopathy (WE) and of severe polyneuropathy following a sleeve gastrectomy without any sleeve stenosis. The impact of WE after bariatric surgery is significantly underestimated. Such a risk should be taken into consideration also after restrictive weight loss surgery. Thus, surgeon/clinicians involved in bariatric patients management must be aware of neurological sequelae related to this intervention.
European journal of clinical nutrition 02/2012; 66(5):645-7. · 3.07 Impact Factor
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ABSTRACT: Neuroendocrine tumors (NETs) can be sporadic or they can arise in complex hereditary syndromes. Patients with hereditary NETs can be identified before the development of tumors by performing genetic screenings. The aim of the study was to evaluate the clinical and prognostic impact of a preclinical genetic screening in subjects with hereditary NET syndromes. 46 subjects referred for hereditary NET syndrome [22 MEN1, 12 MEN2, 12 Familial Paragangliomatosis (FPGL)] were enrolled and divided in 2 groups (group A, 20 subjects with clinical appearance of NET before the genetic diagnosis; group B, 26 subjects with genetic diagnosis of hereditary NET syndromes before the clinical appearance of NETs). The main outcome measures were severity of disease, prognosis, and survival. The rate of surgery for MEN1-, MEN2-, FPGL4-related tumors was 90% in group A and 35% in group B (p<0.01). Both symptoms related to tumors and symptoms related to therapies were significantly less frequent in group B than in group A (p<0.05). Tumor stage was locally advanced or metastatic in 50% of group A and in no one of group B (p<0.01). The mortality rate was 25% in group A and 0% in group B (p<0.05). An early genetic screening for hereditary NET syndromes results in an improvement in clinical presentation and morbidity. A potential impact of the genetic screening on the mortality rate of these subjects is suggested and needs to be investigated in further and more appropriate studies.
Hormone and Metabolic Research 10/2011; 43(11):794-800. · 2.19 Impact Factor
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ABSTRACT: The authors compared multidetector-row computed tomography (MDCT) and endoscopic ultrasound (EUS) in the identification of pancreaticoduodenal endocrine tumours (PETs) in patients with multiple endocrine neoplasia type 1 (MEN 1).
Fourteen consecutive patients (eight men and six women, aged 26-54 years) with MEN 1 underwent MDCT performed with a 4- (n=5) or 64- (n=9) detector-row system and EUS done with a radial transducer (7.5-20 MHz) within 7-28 days of each other. Prior to MDCT examination, patients were given 750 cc of water and asked to lie down in the right lateral decubitus for 15 min. Multiphase MDCT images were acquired both before and after the injection of nonionic iodinated contrast material (2 cc/kg) at an injection rate of 4 ml/s, with technical parameters and scan delay varying in relation to the system used. Images were all reconstructed at 3-mm intervals for the three phases (arterial, pancreatic and portal) and evaluated on a dedicated workstation.
MDCT detected a total of 25 PETs (3-18 mm) in nine patients. Of these lesions, nine were situated within the duodenal wall and 16 in either the pancreatic head (n=3), body (n=7), or tail (n=6). Three additional lesions were detected retrospectively after EUS imaging. Most (18/22, 81%) were hypervascular nodules, and four appeared as either hypoattenuating or cystic lesions. EUS detected a total of 32 PETs (2-18 mm) in 11 patients. Most lesions (29/32, 90%) appeared hypoechoic and were situated in the duodenal wall (n=15) or in either the pancreatic head (n=10), body (n=6) or tail (n=1).
Our preliminary data indicate that MDCT is complementary to EUS in the identification of PETs in MEN-1 patients.
La radiologia medica 02/2011; 116(4):595-606. · 1.44 Impact Factor
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Thrombosis Research 10/2010; 126(4):295-8. · 2.44 Impact Factor
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ABSTRACT: The prognosis of medullary thyroid carcinoma (MTC) depends on the completeness of the first surgical treatment. To date, it is not possible to predict whether the tumor has been completely removed after surgery. The aim of this study was to evaluate the reliability of an intraoperative calcitonin monitoring as a predictor of the final outcome after surgery in patients with MTC.
Twenty patients underwent total thyroidectomy and central lymph node dissection on the basis of a positive pentagastrin test. In six cases a preoperative diagnosis of MTC was achieved at the cytological examination. During the surgical intervention, calcitonin was measured at the time of anesthesia, at the time of manipulation, and 10 and 30 min after surgical excision. At the histological examination, 10 patients had MTC and 10 had C cell hyperplasia.
As compared with calcitonin levels before thyroidectomy, a decrease of calcitonin greater than 50% 30 min after surgery was able to significantly distinguish patients who were cured from those who experienced persistence of disease. It was not possible to find a similar result when the decrease of calcitonin 10 min after surgery was considered.
A rate of calcitonin decrease less than 50% 30 min after thyroidectomy plus central neck lymph node dissection suggests the persistence of tumor tissue in patients operated for MTC. These results indicate that intraoperative calcitonin monitoring may be a useful tool to predict the completeness of surgery in patients with MTC.
The Journal of clinical endocrinology and metabolism 09/2010; 95(9):E32-6. · 6.50 Impact Factor
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ABSTRACT: Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-secreting neuroendocrine tumour originating from thyroid C cells. Serum CT concentrations are helpful in the early detection of MTC, while it is still unclear whether they can be used also for the differential diagnosis between MTC and C-cell hyperplasia (CCH), a precancerous condition in familial MTCs but with unclear clinical significance in sporadic MTCs. Nowadays, surgery is recommended in all patients with basal or pentagastrin (PG)-stimulated CT value of 100 pg/ml or more, without discriminating if they are affected with MTC or CCH only. The objective of this study was to investigate the utility of the PG test for CT in distinguishing CCH from MTC before surgery.
Sixteen of 20 patients with thyroid nodules and basal CT levels between 15 and 100 ng/l had a positive PG test (>100 ng/l PG CT peak) and form the basis of the data analysis. A diagnosis of MTC was histologically proved on surgical samples in seven patients and of CCH in nine other patients. Four patients with neither FNAB nor PG test consistent with a diagnosis of MTC did not undergo thyroidectomy.
A peak of CT of 275 ng/l after PG was able to significantly distinguish patients with MTC from patients with CCH, with 100% sensitivity and 89% specificity (P = 0.002). PG-stimulated calcitonin levels >275 ng/l had a positive predictive value (PPV) value for diagnosis of MTC of 100%, and PG-stimulated calcitonin levels <275 had a PPV for the diagnosis of CCH of 89%.
A CT cut-off after PG of 275 ng/l is suggested to be highly predictive in distinguishing CCH from MTC before surgery, and this may be helpful in selecting patients for thyroid surgery.
Clinical Endocrinology 07/2010; 73(1):85-8. · 3.17 Impact Factor
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ABSTRACT: Neuroendocrine differentiation of tumors is often difficult to establish. In the same manner, the evaluation of the prognostic role of neuroendocrine differentiation may constitute a relevant clinical problem. Although different classifications are used for neuroendocrine tumors (NET) of different origin, the last World Health Organization (WHO) classification of NET, originally proposed for gastroenteropancreatic tumors, has proved to be a practical tool to allow pathologists to uniform the diagnoses and re-classify these tumors into 3 main categories.
The present study was carried out in order to evaluate diagnostic and prognostic implications of NET reclassification according to the last WHO classification of NET.
Thirty-one tumors with an initial diagnosis referable to a NET achieved before 1999 were independently evaluated by 3 pathologists on the basis of the 2000 WHO classification of NET. Immunohistochemistry for panneuroendocrine markers and Ki-67 was also performed in all cases.
Twelve, 14, and 4 tumors were respectively reclassified as well-differentiated NET, well-differentiated neuroendocrine carcinoma and poorly differentiated neuroendocrine carcinoma; 1 tumor was reclassified as mixed endocrine-exocrine tumor. Two or more neuroendocrine markers were expressed in all NET regardless of histotype, differentiation degree, and site of primary tumor. After revision, 10 of the 31 tumors under study (32%) changed histo-prognostic category when compared to the initial diagnosis. Ki-67 score was the best predictor of survival at the multivariate analysis.
The WHO classification is suitable to accurately reclassify tumors with an initial diagnosis referable to a NET and to separate these tumors in 3 well-distinct histo-prognostic categories with relevant clinical implications. Ki-67 score seems to be a better predictor of survival than the degree of differentiation.
Journal of endocrinological investigation 04/2008; 31(3):216-23. · 1.57 Impact Factor
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P Ferolla,
A Faggiano,
G Mansueto,
N Avenia,
M G Cantelmi,
P Giovenali,
M L Del Basso De Caro, F Milone,
G Scarpelli,
S Masone,
F Santeusanio,
G Lombardi,
G Angeletti,
A Colao
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ABSTRACT: Neuroendocrine tumors (NET) may originate in different organs, from cells embryologically different but expressing common phenotypic characteristics, such as: the immuno-reactivity for markers of neuroendocrine differentiation (defined as "pan-neuroendocrine"), the capacity to secrete specific or aspecific peptide and hormones and the expression of some receptors, that are at the basis of the current diagnostic and therapeutical approach, peculiar to these tumors. NET have been conventionally distinguished in functioning, when associated with a recognized clinical endocrine syndrome, and non-functioning. However, this terminology may be misleading, since the great majority of NET may secrete neuroendocrine peptides, which can be employed as clinical markers for both diagnosis and follow-up. On the other hand, tissue immuno-reactivity for specific hormones does not always reflect secretory activity of the tumor cells. Finally, receptors and genetic markers are acquiring a relevant role in the characterization of NET, both improving knowledge of biology and physiopathology of NET, as well as in developing specific strategies to establish an early diagnosis and targeted therapies, to adopt prophylactic strategies in familial forms, and to identify more efficacious targets for therapy in the future.
Journal of endocrinological investigation 04/2008; 31(3):277-86. · 1.57 Impact Factor
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Stefano Spiezia,
Roberto Garberoglio,
Carolina Di Somma,
Maurilio Deandrea,
Edoardo Basso,
Paolo P Limone, F Milone,
V Ramundo,
Paolo E Macchia,
Bernadette Biondi,
Gaetano Lombardi,
Annamaria Colao,
Antongiulio Faggiano
Journal of the American Geriatrics Society 10/2007; 55(9):1478-9. · 3.74 Impact Factor
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P Ferolla,
A Faggiano,
N Avenia, F Milone,
S Masone,
F Giampaglia,
F Puma,
G Daddi,
G Angeletti,
G Lombardi,
F Santeusanio,
A Colao
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ABSTRACT: The widespread availability and reliability of immunohistochemical techniques in the last three decades have allowed researchers to identify cells with common neuroendocrine markers in virtually every organ. As a whole, these neuroendocrine cells form the so-called diffuse neuroendocrine system. Tumours arising from the cells of the diffuse neuroendocrine system are defined as (neuro)endocrine tumours (NETs). NETs have been increasingly described in recent years. However, despite the increase in the number of published papers focused on NET, we still lack adequate epidemiological data, particularly for non-gastroenteropancreatic (GEP) NETs. Furthermore, the real incidence of neuroendocrine differentiation for most sites is not completely known and is probably underestimated. As a consequence, data on the clinical features of many NET subgroups are not well known or confusing. For all of these reasons, we have attempted to evaluate the epidemiology of non-GEP NETs, reviewing the limited data available in the literature.
Clinical Endocrinology 02/2007; 66(1):1-6. · 3.17 Impact Factor
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A Faggiano,
A Pisani, F Milone,
M Gaccione,
M Filippella,
A Santoro,
G Vallone,
F Tortora,
M Sabbatini,
L Spinelli,
G Lombardi,
B Cianciaruso,
A Colao
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ABSTRACT: Fabry disease (FD) is a genetic disorder caused by lysosomal alpha-galactosidase-A deficiency and is characterized by the systemic accumulation of globotriaosylceramide. All endocrine glands are susceptible to globotriaosylceramide accumulation because of their high vascularization and low cellular proliferation rate. Nevertheless, this endocrine system has never been investigated in detail.
We aimed to investigate the function and morphology of the endocrine glands in FD.
The thyroid, gonadal, adrenal, and GH/IGF-I axes were evaluated in 18 FD patients (nine females and nine males, aged 21-64 yr) and 18 sex- and age-matched healthy subjects.
We conducted an observational, analytical, open, prospective study.
Ten of the 18 patients received enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase-A (agalsidase beta) at a dose of 1 mg/kg body weight every 2 wk.
FD patients had higher baseline TSH levels than controls (P < 0.01). Three subjects were diagnosed with an early stage of subclinical primary hypothyroidism associated with negative antithyroid antibodies. A history of menses abnormalities, miscarriage, or assisted delivery was found in 89% of FD women. Asthenozoospermia, oligozoospermia, or both were found in all FD men through seminal fluid analysis. FD patients had significantly higher circulating ACTH and lower cortisol levels than controls (P < 0.05). In patients under ERT, a suboptimal cortisol response to the 250-microg ACTH test was found in 10%, and the ACTH-stimulated cortisol peak was significantly correlated to the health status profile (P < 0.05).
A variety of latent endocrine dysfunctions, including life-threatening conditions, occur in patients with FD. Endocrine dysfunctions are also present in patients already receiving ERT and are in part related to their persistent poor quality of life. An endocrine work-up should be recommended in all FD patients. Adequate monitoring and hormonal therapy, when required, have to be performed in cases of subclinical endocrine dysfunction to avoid life-threatening events.
Journal of Clinical Endocrinology & Metabolism 11/2006; 91(11):4319-25. · 6.50 Impact Factor
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S Savastano,
A Belfiore,
B Guida,
L Angrisani,
F Orio,
T Cascella, F Milone,
F Micanti,
G Saldalamacchia,
G Lombardi,
A Colao
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ABSTRACT: In humans, dehydroepiandrosterone (DHEAS) has been postulated to have anabolic and lipolytic properties that could potentially counteract the catabolic effect of cortisol. DHEAS secretion is reduced in morbid obesity, likely due to hyperinsulinemia, and laparoscopic adjustable gastric banding (LASGB), by inducing considerable and rapid weight loss, reduces insulin levels. To investigate the role of decreased insulin levels after LASGB-induced weight loss on DHEAS levels and on body composition changes, we studied 30 pre-menopausal morbidly obese women (BMI ranging 37-62 kg/m2) before, 6, 12 and 24 months after LASGB. Total body water (TBW), fat-free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance analysis; tissue hydration was also assessed by impedance vector analysis. At study ending, the subjects had a total weight loss of 28% of baseline body weight (15% after 6 months). After LASGB, weight loss was mainly due to decreased FM, and TBW, FFM, and body hydration were not significantly reduced. Weight loss was associated with an 82% rise in serum DHEAS already after 6 months while cortisol, cortisol/DHEAS molar ratio, and insulin levels fell by 5.5, 62 and 50%, respectively, after 6, 12 and 24 months (p<0.05). CONCLUSIONS: LASGB associated with a well balanced low-calorie diet permits a satisfactory 2-yr weight loss, sparing FFM and without body fluid alterations. As the result of a stable weight reduction program weight loss is associated to decrease in cortisol, cortisol/DHEAS molar ratio, and insulin plasma levels with marked rise in DHEAS. Higher cortisol/DHEAS molar ratio values at baseline are also associated to lower weight loss after LASGB, with lower decrease in FM and higher reduction in FFM and body cell mass, in spite of no differences in dietary regimes. Cortisol/DHEAS molar ratio is likely to represent a reliable marker of favourable modifications in body composition.
Journal of endocrinological investigation 07/2005; 28(6):509-15. · 1.57 Impact Factor
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ABSTRACT: Currently available medical treatment of acromegaly includes dopamine agonists, slow release formulation of somatostatin analogues and pegvisomant, a GH-receptor antagonist. Dopamine agonists are well tolerated, not expensive but poorly effective. Somatostatin analogues are highly effective in 60-70% of patients based on the receptor profile of individual tumors. Pegvisomant is reported to normalize IGF-I levels in nearly the totality of the patients, but is devoted of tumor shrinking effect. In a preliminary study in patients with acromegaly, a new somatostatin analogue with affinity to four of the five somatostatin receptors (SOM230) was shown to be similarly effective as octreotide in some patients and more effective than octreotide in other patients. Moreover, new molecules with selective activity on the somatostatin receptor type 2, or 5, or 1 have been reported in vitro to strongly suppress GH secretion. Other new promising alternatives are the chimeric compounds with both somatostatin receptor and dopamine receptor binding. These drugs have been also shown to possess strong GH-inhibitory activity in primary cultures from GH-secreting adenomas. These drugs are the future perspectives in the treatment of patients with GH-secreting or GH/PRL-secreting tumors.
Journal of endocrinological investigation 02/2005; 28(11 Suppl International):58-66. · 1.57 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the incidence of abdominal wall hernias (AWH) in patients operated on for abdominal aortic aneurysm (AAA) compared with patients treated for aortoiliac occlusive disease. The efficacy of MRI in early diagnosis of AWH also was studied.
One hundred fourteen patients operated for either AAA (51 patients, group A) or aortoiliac occlusive disease (63 patients, group B) constitute the study. The presence of AWH onset was evaluated by clinical observation followed by ultrasonography. Data acquired by ultrasonography were compared with those obtained by MRI to determine the efficacy of this diagnostic tool in all 114 patients. The prevalence of inguinal hernias in both groups also was determined.
A significant difference was found in the incidence of AWH. AWH developed in 31.7% (16 of 51) of group A patients and 17.4% (11 of 63) of group B patients (p < 0.03). A significant prevalence ofinguinal hernias was detected in group A (p < 0.01). The Cox hazard regression analysis revealed as independent predictors of postoperative AWH only the presence of AAA and a history of laparotomy.
Ours and other studies recall collagen synthesis disorders to explain the statistical association observed among AAA, inguinal hernias, and AWH. MRI, especially in patients at risk, appears to be an effective diagnostic approach to early detection of AWH.
Journal of the American College of Surgeons 11/2001; 193(4):392-5. · 4.55 Impact Factor
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ABSTRACT: The authors discuss the problems in the diagnosis and treatment of pancreatic pseudocysts; they emphasize the risk of complication. The authors discuss their personal experience in the treatment of 31 pancreatic pseudocysts using the different techniques, and the very good results they observed in their own series.
Hepato-gastroenterology 07/1990; 37(3):324-6. · 0.66 Impact Factor
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Minerva cardioangiologica 06/1985; 33(5):301-4.
