Intracardiac metastasis originated from chondrosarcoma.

Primary cardiac tumors are extremely rare. By comparison, metastatic involvement of the heart is over 20 times more common and has been reported in autopsy series in up to one in five patients dying of cancer. Cardiac metastasis of chondrosarcoma is absolutely not frequent. In the recent literature, a cardiac metastasis from chondrosarcoma has never been described. We report the case of an 18-year-old man with a diagnosis of cardiac metastasis that originated from a left scapular chondrosarcoma. Chondrosarcoma is a skeletal tumor with various grades of malignancy, rapidly evolving, and with a strong tendency to metastasize, with low responsiveness to chemotherapy. The onset of characteristic systemic symptoms in the late stage of the disease led to the diagnosis of a mass localized in the right atrium. Management and differential diagnosis of infective heart lesions were also very complex in a rapidly evolving life-threatening condition.

Interstitial laser photocoagulation for benign thyroid nodules: time to treat large nodules.

BACKGROUND AND OBJECTIVE: Interstitial laser photocoagulation (ILP) is a new therapeutic option for the ablation of non-functioning and hyper-functioning benign thyroid nodules. Amelioration of the ablation procedure currently allows treating large nodules. Aim of this study was to evaluate the therapeutic efficacy of ILP, performed according to a modified protocol of ablation, in patients with large functioning and non-functioning thyroid nodules and to identify the best parameters for predicting successful outcome in hyperthyroid patients. MATERIALS AND METHODS: Fifty-one patients with non-functioning thyroid nodules (group 1) and 26 patients with hyperfunctioning thyroid nodules (group 2) were enrolled. All patients had a nodular volume ≥40 ml. Patients were addressed to 1-3 cycles of ILP. A cycle consisted of three ILP sessions, each lasting 5-10 minutes repeated at an interval of 1 month. After each cycle of ILP patients underwent thyroid evaluation. RESULTS: A nodule volume reduction, expressed as percentage of the basal volume, significantly occurred in both groups (F = 190.4; P < 0.0001 for group 1 and F = 100.2; P < 0.0001 for group 2). Receiver-operator-characteristic (ROC) curves were constructed for: (i) percentage of volume reduction; (ii) difference in nodule volume; (iii) total amount of energy delivered expressed in Joule. ROC curves identified the percentage of volume reduction as the best parameter predicting a normalized serum TSH (area under the curve 0.962; P < 0.0001). Intraoperative complications consisted in: (i) mild pain occurring in five (6.5%) patients, (ii) vasovagal reaction in two (2.6%) patients, (iii) fever within 24 hours from ILP in five (6.5%) patients. No major complications including persistent pain, laringeal nerve dysfunction, hypoparathyroidism, pseudocystic transformation, and/or neck fascitis were observed. CONCLUSIONS: ILP represents a valid alternative to surgery also for large benign thyroid nodules, both in terms of nodule size reduction and cure of hyperthyroidism (87% of cured patients after the last ILP cycle). ILP should not be limited to patients refusing or being ineligible for surgery and/or radioiodine.

Proteomic profiling of medial degeneration in human ascending aorta.

OBJECTIVE: The objective of this study was the construction of a reference map for aortic medial degeneration by a proteomic approach. DESIGN AND METHODS: A proteomic profiling of the media of human ascending aorta was performed by two-dimensional electrophoresis and MALDI-TOF mass spectrometry. RESULTS: A reliable protocol for two-dimensional electrophoresis analysis of human aortic media proteins was developed allowing the selection and identification of 52 spots. Protein identifications revealed that the predominant vascular smooth muscle cell proteins isolated from grade 1 aortic medial degeneration (MD) included proteins involved in muscle contraction, protein folding, cytoskeletal structure and metabolic processes, and those with antioxidant or transport functions. The most populated functional classes were those related to muscle contraction and cytoskeletal proteins, including actin, calmodulin, calponin, myosin light chain, tropomyosin, vimentin, profilin and transgelin. CONCLUSIONS: The obtained aortic MD proteomic profile provides a relevant background for future studies aimed to find further specific molecular changes potentially related to the aortic MD process.

Hypertension induces compensatory arterial remodeling following arteriotomy.

BACKGROUND: Hypertension has been traditionally considered a risk factor for restenosis following carotid arteriotomy. Genetic and morphological response to carotid arteriotomy in normotensive Wystar-Kyoto (WKY), spontaneously hypertensive (SHR), and Milan hypertensive (MHS) rats were analyzed. MATERIAL AND METHODS: C-myc, angiotensin II receptor-1 (AT1), angiotensin II receptor-2 (AT2), endothelin-1 receptor A (ET(A)), endothelin-1 receptor B (ET(B)), Bcl-2 family-members (Bcl-2/Bax, Bcl-X(L/S)) were analyzed in surgically injured as well as uninjured carotids of WKY and hypertensive strains (HS). Thirty-day histology and morphometry were accomplished on injured and uninjured carotids. RESULTS: C-myc mRNA is activated earlier and/or to a greater extent in hypertensive strains than in WKY. AT1 mRNA increases in WKY after injury, while it decreases in SHR and MHS. AT2 shows the opposite, decreasing in WKY and increasing in hypertensive strains. ET(A) mRNA decreases in all strains although with different timing and levels, associated with a replacement by ET(B) mRNA. Bcl-2/Bax ratio gradually decreases in WKY, while it shows only a transient decrease in SHR and MHS 4 h after the injury. Negative remodeling is observed in all injured carotids, although neointima was detected in WKY only. Thirty days following arteriotomy, morphometry demonstrated a significant decrease of luminal area, with consistent gain in the medial area in WKY, whereas hypertensive strains showed significant increase of the luminal area, consistent with a contemporary decrease of the medial area. CONCLUSIONS: Vaso-relaxant AT2 and ET(B) induced limited vasoconstriction in HS. Less apoptosis in hypertensive rats reduced cell proliferation, contrasting c-myc. These responses favorably modulated media/lumen area ratio following arteriotomy in HS.

Ascending aorta dilatation in aortic valve disease: morphological analysis of medial changes.

We investigated whether and how the severity of medial degeneration lesions varies along the circumference of the dilated intrapericardial aorta. Two groups of aortic wall specimens, respectively harvested in the convexity and concavity of ascending aorta in 72 patients undergoing surgery for dilatation of the intrapericardial aorta associated with aortic valve disease, were separately sent for pathology, morphometry, and ultrastructural examination. Cystic medial necrosis, fibrosis, and elastic fiber fragmentation were classified into three degrees of severity; their mean degree and morphometric findings in the convexity and in the concavity specimens were compared by paired t-test. Correlation between echocardiographic degree of aortic dilatation and severity of medial degeneration was assessed separately for each of the two groups of specimens. Morphologically, medial degeneration was found in all cases; a higher mean degree was found in the convexity group (2.39 +/- 0.58 vs 1.44 +/- 0.65 in the concavity group; P < 0.001). At morphometry normal smooth muscle cells in the convexity specimens were significantly reduced (P = 0.007); the length (P = 0.012) and number (P = 0.009) of elastic fibers reduced and increased, respectively. Moreover, in the convexity specimens a significantly smaller amount of smooth muscle cells and an increase of immunohistochemical labeling of apoptosis-associated proteins in the subintimal layer of the media was noticed. Correlation between aortic ratio and medial degeneration degree was significant in the convexity group (P < 0.001), but not in the concavity group (P = 0.249). Scanning electron microscopy analysis confirmed morphological results and allowed us to better distinguish the early pathological cavities from the microvessels, which were in the outer media in normal aorta and ubiquitous in aortitis or atherosclerosis. Electron transmission microscopy analysis showed changes in the extracellular matrix and smooth muscle cells, and these changes increased from the intima to the adventitial layer of the media. In dilated intrapericardial aorta, medial degeneration changes and expression of apoptosis-associated proteins are more marked in the ascending aorta convexity, likely due to hemodynamic stress asymmetry. Ultrastructural findings allow us to distinguish the early medial changes not yet evident on light microscopy.

Morphological and ultrastructural findings of prognostic impact in craniopharyngiomas.

Craniopharyngioma is a slow-growing epithelial tumor with an unpredictable tendency to recur. To verify the reliability in predicting the clinical outcome, some morphological and immunohistochemical findings were analyzed in 37 primitive tumors and in 6 recurrences (one recurred twice). All the tumors were surgically excised and all recurrences exhibited an adamantinomatous pattern; mitotic rate was low (< 5 x 10 HPF) in both recurrent and in nonrecurrent tumors. Primary tumors showed a mean positivity of 1.7% (range 0.3-2%) to PCNA vs. 4.1% (range 0.3-8%) in recurrences. The MIB-1 Labelling Index was: 22.12% in primary tumors, 27.5% in recurrences, 31.3% in adult nonrecurrent tumors, and 4.1% in the pediatric tumor. CD34 labeling vessels/field was 9.3 in primary tumors and 9.91 in the recurrences; VEGF expression was higher in recurrences than in primary tumors (40 vs. 25%). Ultrastructural analysis showed fenestrated endothelium with hydropic changes in VEGF-positive vessels. Lack of clear correlations between morphological or immuno-staining patterns and behavior suggests that these features have no prognostic value in adult as well as in pediatric craniopharyngiomas. In this study, the only results that may be related to the aggressiveness of tumor is the major vascularization in the recurrent tumors in which the vessels show also ultrastructural changes.

c-Myc antisense oligonucleotides preserve smooth muscle differentiation and reduce negative remodelling following rat carotid arteriotomy.

OBJECTIVES: The vascular biology of restenosis is complex and not fully understood, thus explaining the lack of effective therapy for its prevention in clinical settings. The role of c-Myc in arteriotomy-induced stenosis, smooth muscle cell (SMC) differentiation and apoptosis was investigated in rat carotids applying full phosphorothioate antisense (AS) oligonucleotides (ODNs). METHODS: Carotid arteries from WKY rats were submitted to arteriotomy and to local application of ODNs through pluronic gel. Apoptosis (deoxynucleotidyl transferase-mediated dUTP nick end-labelling), SMC differentiation (SM22 immunofluorescence) and vessel morphology and morphometry (image analysis) were determined 2, 5 and 30 days after injury, respectively. RESULTS: AS ODNs induced a 60% decrease of target c-Myc mRNA 4 h after surgery in comparison to control sense (S) and scrambled ODN-treated carotids (p < 0.05). A significant 37 and 50% decrease in SM22 protein in the media of S ODN-treated and untreated carotids was detected when compared to uninjured contralateral arteries (p < 0.05). This reduction in SM22 expression was prevented in AS ODN-treated carotids. Stenosis was mainly due to adventitial constrictive remodelling. Lumen area in AS ODN-treated carotids was 35% greater than in control arteries 30 days after surgery (p < 0.05). TUNEL assay revealed increased apoptosis in AS ODN-treated carotids (p < 0.05). CONCLUSIONS: c-Myc AS ODNs reduce arteriotomy-induced negative remodelling. This is accompanied by maintained SMC differentiation and greater apoptosis. The combination of reduced c-Myc-induced proliferation and increased apoptosis may thus underlie the less severe remodelling upon treatment with c-Myc mRNA AS ODN.

Intramedullary neurenteric cysts of the spine. Report of three cases.

Neurenteric spinal cysts are infrequently occurring dysraphic lesions that are caused by persistent or abnormal communication among neuroectoderm, notochord, and endoderm. They are generally located at the intradural, extramedullary compartment of the low cervical or upper spinal canal. They occur primarily in infants and in young adults in combination with other congenital abnormalities. The authors report on three cases of lower-thoracic and thoracolumbar intramedullary neurenteric cysts that atypically presented in adult patients in whom there was no concomitant malformation. These lesions appear notable for location, clinical presentation, intraoperative findings, and imaging features.

Scanning electron microscopy of aortic medial changes in aortic ascending dilatation.

The study of cystic cavities and collagen fibers fragmentation is useful to for a better knowledge of pathogenesis and surgical therapy of medial ascending aortic degeneration. Thus, the aim of this study was to describe by scanning electron microscopy the surfaces and shape of the cysts, measure their area, and identify microcystic spaces related to this degenerative disease. Scanning electron microscopy analysis was performed in 16 out of 36 patients who underwent surgery for ascending aorta dilatation with associated aortic valve disease. The aortic medial wall showed a cribrose appearance at low magnification (x50-100) and the intima was effuse. At high magnification (x500-2000), small cavities (clefts) lined by normal or fragmented elastic fibers and large cavities (pseudocystes) with anfractuous borders lined by fragmented elastic fibers and smooth muscle cells were observed. Furthermore, in the outer media wall microvessels lined by endothelium were also observed. These changes were lacking or less pronounced in normal aorta. SEM allows one to better identify the pathological cavities and to differentiate them from microvessels. These pathological cavities are more numerous and larger in the convexity than in the concavity of the aorta in according to our previous morphological and morphometric findings in asymmetrical aorta dilatation.

Extensive retroperitoneal fibrosis with duodenal and ureteral obstruction associated with giant inflammatory aneurysm of the abdominal aorta.

We report a case of abdominal aortic aneurysm complicated by retroperitoneal fibrosis with both duodenal and bilateral ureteral obstruction. The patient underwent successful bilateral transurethral ureteral stenting, and then he was referred for surgical treatment of the aneurysm. Massive retroperitoneal fibrosis was found at surgery, and the mass was removed along with the diseased aorta, which was replaced by a bifurcated Dacron prosthesis; duodenolysis and ureterolysis were concomitantly performed. Ureteral stents were removed on the 8th postoperative day. Follow-up assessment at 1 year showed normalization of the urinary tract structure at echography and good hemodynamic performance of the vascular prosthesis at Doppler examination. To our knowledge, no other case of duodenal and bilateral ureteral stenosis secondary to massive retroperitoneal reactive fibrosis in association with abdominal aortic aneurysm has been reported.

Stenosis progression after surgical injury in Milan hypertensive rat carotid arteries.

BACKGROUND: Milan hypertensive rats (MHS) are characterised by an increase in renal sodium reabsorption mainly related to adducin mutations. Interest in this model relies on the genetic link between adducin polymorphisms and primary hypertension, observed also in a subset of patients. OBJECTIVES: To investigate the molecular and morphological events involved in carotid stenosis and triggered by surgery in MHS model. METHODS: Stenosis was induced through arteriotomy. At different times after injury, the expression profiles of various gene families were investigated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), while histological techniques were used to follow morphometric and morphological changes. Apoptotic nuclei were revealed by terminal deoxynucleotidyl transferase-dUTP nick end labelling (TUNEL). RESULTS: mRNAs coding for transcription factors c-jun, c-fos and c-myc were rapidly induced by injury. Analysis of apoptosis-related genes revealed a decrease of the Bcl-2/Bax ratio 4 h after vascular trauma (P<0.05), followed by a recovery of antiapoptotic factors 24 and 48 h later. ET(A) and receptor mRNAs decreased after the injury and were replaced by ET(B) and AT2 mRNAs. Both ET(A) and AT1 turned to basal level 48 h after injury. Expression profiles of chatepsins B and D were also determined. A marked neoadventitia led to maximal 60+/-9% lumen reduction (P<0.05) 30 days after surgery. Media substitution by fibrotic and granulomatous tissue was also evident. Maximal 47+/-2% apoptotic nuclei were detected 48 h after the injury (P<0.05). CONCLUSIONS: The injury applied to MHS carotids induces negative remodelling and a limited apoptotic reaction. These findings could arise from the balancing among proliferative factors, apoptosis-related molecules and relaxant anti-proliferative receptors, all stimulated by the injury.

Aortic valve dysfunction and dilated ascending aorta. A complex and controversial association.

Several pathogenetic mechanisms account for the association of the ascending aorta dilation with aortic valve dysfunction. Functional aortic insufficiency can derive from medial degeneration of the aortic wall and annuloaortic ectasia; leaflet structural disease can determine root dilation by increasing aortic wall stress in case of both regurgitation and stenosis; aortic valve disease and aortic aneurysm can however coexist due to two different intrinsic etiologies. In the attempt to best tailor the surgical correction of such conditions to the underlying causative mechanism, several technical options have already been developed including composite or separate aortic valve and root replacement, valve-sparing operations, and aortoplasty techniques. The criteria for surgical indication cannot leave the underlying pathogenesis out of consideration as well. The newly acquired knowledge in the basic research on this topic is expected to affect the approach to the individual patient in the future.