Lipid metabolism impairment in human gliomas: expression of peroxisomal proteins in human gliomas at different grades of malignancy.

Gliomas are histologically graded by cellularity, cytological atypia, necrosis, mitotic figures, and vascular proliferation, features associated with biologically aggressive behaviour. However, abundant evidence suggests the presence of unrecognized, clinically relevant subclasses of the diffuse gliomas, both in respect to their underlying molecular phenotype and their clinical response to therapy. It is well-known that patient prognosis and therapeutic decisions rely on accurate pathological grading. Recently, it was reported that human gliomas accumulate lipid droplets during progression, suggesting a lipid metabolism impairment. Considering the crucial role of peroxisomes in lipid metabolism, in the present work we studied the expression profiles of proteins either exclusively localized to peroxisomes, such as peroxin14 (PEX14), peroxisomal membrane protein 70Kda (PMP70), acyl-CoA oxidase, thiolase, or partially associated to peroxisomes such as Hydroxymethylglutaryl-CoA reductase (HMGCoA-red) and peroxisomal-related proteins, namely PPARalpha, in human glioma specimens at different grades of malignancy. Moreover, Nile red staining of lipid droplets, thin layer chromatography (TLC) and proton nuclear magnetic resonance spectroscopy (NMR) were carried out in order to correlate the biochemical results with the lipid content of tumor tissues. The results obtained indicate that correlating the malignancy grade with the expression of peroxisomal genes and proteins, may constitute a sensitive tool to highlight possible subtypes not recognized by the classical histological techniques.

p16INK4a and low-grade cervical intraepithelial neoplasia. Diagnostic and therapeutic implications.

The objectives of this study were to evaluate the evolution of a LSIL associated with p16INK4a overexpression and on the basis of this association, identify patients who would benefit from immediate treatment rather than a later follow-up. Two hundred and forty-five cervical biopsies were studied: 199 (81.2%) were classified CIN 1, 18 (7.4%) CIN 2/3 while 28 (11.4%) were not pathological. Immunohistochemistry revealed that 22 of the 217 CIN samples (11%) were positive for the p16INK4a antigen. The results of the PCR-ELISA for the research and typing of the HPV in these 22 cases were: 14 (63.6%) HPV 16; three (13.6%) HPV 31; 2 (9%) HPV 33; one (4.6%) HPV 43; one (4.6%) HPV 45; one (4.6%) HPV 18. Colposcopic and histological tests performed at four- and eight-month follow-ups in these patients revealed worsening of the initial lesion. Hence, we conclude that immediate therapy would be of benefit in these patients.

Uterine tumors resembling ovarian sex cord tumors. A case report.

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are rare, usually benign, polypoid or nodular neoplasms which generally arise in the fourth to sixth decade of life. We report a case of a 74-year-old woman who presented with vaginal bleeding and remarkable uterine enlargement. Abdominal hysterectomy with bilateral salpingo-oophorectomy was performed and a diagnosis of UTROSCT was made. Immunohistochemistry is mandatory for a correct diagnosis and a panel of at least two markers of sex cord differentiation is recommended. Differential diagnoses include leiomyosarcoma, UTROSCT and ESTSCLE, mixed müllerian tumor and metastatic ovarian sex cord tumor.

Very large Ameloblastic Fibroma with Calcifying Odontogenic Cyst in an 8-year-old child. Histological and immunohistochemical characterisation.

BACKGROUND: Ameloblastic fibroma (AF) is an uncommon odontogenic tumour that may present an aggressive behaviour and may have potential for malignant transformation. Ghost cell (GC) differentiation within AF is extremely rare. There are only seven cases in the international literature in which ghost cells are found in AF. CASE REPORT: In this study, we report a case of a 8-year-old female child with a cystic-solid mass, measuring 3 x 1.7 x 1.2 cm, characterised by mixed odontogenic tumour, with AF in most of the lesion, with areas characterised by GC, while ameloblastic and ameloblastic fibrodontoma areas were also detected. Other histological sections showed only AF tissue, with areas of Calcifying Odontogenic Cyst. The immunohistochemical characterisation of the lesion was also performed. A comparative table of the immunoistochemical staining of the AF and COC areas revealed some differences in the expression of markers.

A case report of three synchronous tumors in the same pancreatic specimen.

It is known that Duodenal adenocarcinoma (DA) is a rare malignant solid tumor that cause occlusion symptoms with orthodox dysphagia when locally advanced. Pancreatic neuroendocrine tumors (PanNETs) account for about 2% of all pancreatic neoplasms. The combination of these two lesions, with the synchronous presence of ectopic pancreatic tissue (EPT) of the duodenum, has never been described in literature, to our knowledge. Here we report a case of combined DA, EPT and PanNET affecting a 71-year-old woman.

Cervical-vaginal disease in HIV immunosuppressed patients: management and present screening programme.

The aim of this study was to evaluate the rate of the cervical intraepithelial neoplasia (L-SIL and H-SIL) in HIV-positive patients using cytological, colposcopic and histological examinations. The correlations between these cervical lesions, the role of HPV and the clinical and immunological aspects of HIV infection and inflammatory cervical-vaginal disease were studied. We believe that HPV infection and preneoplastic and/or neoplastic lesions occur more often in immunodepressed HIV-positive patients, and that on the grounds of the high risk of precancerous lesions in this population and the low sensibility of the Pap test, it is advisable to perform a colposcopic examination to discover early lesions that must undergo a specific biopsy.

Detection of antigens recognized by a novel monoclonal antibody in tissue and serum from patients with breast cancer.

Monoclonal antibodies were produced in mice immunized with proteins released into tissue culture fluid of human breast cancer cells maintained in vitro. One monoclonal antibody (SP-2) identified a Mr 90,000 antigen which appears to be a proteolipid. In immunoperoxidase assays, SP-2 reacted with 81 of 90 specimens of human breast cancer. It also reacted with 12 of 23 cancers of nonbreast origin but was unreactive with all normal tissues tested. The Mr 90,000 antigen, purified by immunoaffinity chromatography using SP-2, was used in an indirect binding inhibition assay for the detection of antigen in human serum. With this assay, 35 of 69 patients with breast cancer and 11 of 37 patients with benign breast lesions showed serum antigen levels above 6 units/ml. Patients with nonbreast cancers also demonstrated elevated levels of antigen in 32% of cases. The SP-2 defined Mr 90,000 antigen appeared to be distinct from carcinoembryonic antigen and other monoclonal antibody-defined breast cancer antigens of similar molecular weight. SP-2 may prove useful as a serum and/or tissue marker in breast pathology.

Treatment of giant aortic aneurysm with tracheal compression and sternal erosion without circulatory arrest.

Treatment of huge aneurysms involving the ascending aorta and the aortic arch with compression of the surrounding structures represents a surgical challenge. The case of a patient affected by respiratory insufficiency and sternal erosion caused by chronic giant aortic aneurysm is reported. The use of a stepwise approach and selective cerebral arterial perfusion ensured successful operative management, avoiding circulatory arrest and enabling an expeditious postoperative recovery.

Right latissimus dorsi cardiomyoplasty in diaphragm eventration and cardiac malposition.

Cardiomyoplasty recently has been introduced as a surgical therapy for long-lasting cardiac dysfunction in selected patients. We report the case of a patient affected by chronic heart failure, unresponsive to maximal medical therapy, with concomitant posttraumatic injury of the left phrenic nerve, left diaphragm eventration, and cardiac malposition (right displacement). In view of the progressive deterioration of the cardiac function, cardiomyoplasty was recommended, and the right latissimus dorsi muscle was used to perform the wrapping procedure. A 6-month follow-up showed significant functional, as well as hemodynamic, improvements in addition to a reduction in medical therapy.

Continuous versus intermittent warm blood cardioplegia: functional and energetics changes.

BACKGROUND: The aim of this study was to compare the protective effects of continuous warm blood cardioplegia (CWBC) and intermittent warm blood cardioplegia (IWBC) in an experimental model of blood-perfused, isolated rabbit heart. METHODS: In the CWBC group, cardiac arrest was induced by continuous infusion of blood cardioplegia (10 mEq/L KCl) followed by 30 minutes of reperfusion with blood. In the IWBC group, after 5 minutes of perfusion with blood cardioplegia (10 mEq/L KCl), coronary flow was abolished for 10 minutes, followed by reperfusion with blood cardioplegia for 5 minutes. This sequence was repeated three times for a total period of 45 minutes. Finally the hearts were reperfused for 30 minutes with blood. RESULTS: Infusion of potassium induced a marked increase in coronary perfusion pressure (from 50 +/- 3 to 98 +/- 1 mm Hg; p < 0.01), which remained elevated throughout in the CWBC group, whereas in the IWBC group, it dropped to 0 during each no-flow period. In both groups, cardioplegia resulted in a significant reduction in oxygen consumption (from 5.5 +/- 0.2 to 0.6 +/- 0.03 mL O2.min-1.100 g-1 wet wt; p < 0.01). During CWBC, glucose extraction was significantly reduced (from 152 +/- 10 to 64 +/- 18 micrograms.min-1.g-1 wet wt; p < 0.01). Free fatty acid uptake and creatine kinase and lactate release were not affected. During IWBC, in contrast, a transient but significant release of creatine kinase (from 643 +/- 254 to 2,234 +/- 296 mU.min-1.g-1 wet wt; p < 0.01) and lactate (from 63 +/- 22 to 374 +/- 32 micrograms.min-1.g-1 wet wt; p < 0.01) occurred after each period of ischemia. Despite these metabolic differences, both cardioplegic procedures allowed a prompt and complete recovery of mechanical function and tissue content of high-energy phosphates. CONCLUSIONS: Both CWBC and IWBC exert optimal protection in the isolated blood perfused rabbit heart. Thus, IWBC can be safely used to improve visualization of the surgical field.

Valve repair for traumatic tricuspid regurgitation.

OBJECTIVE: The review of six cases of valve repair for traumatic tricuspid regurgitation in our institution and 74 in the literature in order to assess effective methods of treating this lesion. METHODS: Tricuspid valve regurgitation is a rare complication of blunt chest trauma. Optimal treatment for this condition is still controversial ranging from long-term medical therapy to early surgical correction. We followed the cases of six consecutive patients with post-traumatic tricuspid incompetence who were successfully treated with reparative techniques. All patients were male and their ages ranged from 18 years to 42 years. Valve regurgitation was always secondary to blunt chest trauma due to motor vehicle accident. The mechanism of valve insufficiency was invariably anterior leaflet prolapse due to chordal or papillary muscle rupture associated with annular dilatation. Surgical procedures included Carpentier ring implant (5 patients), Bex posterior annuloplasty (1 patient), implant of artificial chordae (4 patients), papillary muscle reinsertion (2 patients), commissuroplasty (1 patient) and "artificial double orifice" technique (1 patient). RESULTS: Tricuspid insufficiency improved in all patients after the correction. No complications were recorded and all patients were asymptomatic at the follow-up. CONCLUSIONS: Since post-traumatic tricuspid regurgitation is effectively correctable with reparative techniques, early operation is recommended to relieve symptoms and to prevent right ventricular dysfunction.

Biological versus prosthetic ring in mitral-valve repair: enhancement of mitral annulus dynamics and left-ventricular function with pericardial annuloplasty at long term.

OBJECTIVE: The effects of different annuloplasty rings on mitral annulus dynamics and left-ventricular (LV) function after mitral-valve repair (MVR) are still controversial. This study sought to compare biological versus prosthetic rigid rings for annular remodelling in MVR at long term. METHODS: Forty-four consecutive patients were retrospectively enrolled. All patients had isolated posterior-leaflet prolapse and underwent identical surgical mitral-valve reconstruction (quadrangular resection of the posterior leaflet associated with annuloplasty). Twenty-three patients underwent mitral annuloplasty with an autologous pericardial ring (group I), whereas 21 patients had MVR with a Carpentier-Edwards rigid ring (group II). No differences existed between the groups in terms of pre-operative patient profile. Post-operative LV systolic indices have been assessed by two-dimensional echocardiography at rest and during supine bicycle exercise. Mitral annular motion has been examined by means of the extent of mitral annulus systolic excursion (MASE), as measured in four longitudinal LV segments (anterior, inferior, septal and lateral). Mean and peak trans-mitral flow velocities (TMFV) have been also evaluated by continuous-wave Doppler. RESULTS: The mean follow-up did not differ between the groups, those being 41+/-12 months in group I (range17-65 months) and 46+/-15 months in group II (range 23-83 months), respectively. Post-operative echocardiographic study did not show significant mitral regurgitation at rest or at peak exercise in any patient. ANOVA analysis for repeated measures showed a significant interaction in peak TMFV (F((1,42))=5.23; P=0.03), and in left-ventricular ejection fraction (LVEF; F((1,42))=7.61, P=0.01). The analysis of contrasts showed a significant increase in TMFV in both groups (group I from 1.22+/-0.22 to 1.79+/-0.32 m/s, t=-8.8, P<0.0001; and group II from 1.19+/-0.17 to 1.96+/-0.33 m/s, t=-12.8, P<0.0001). Recruitment of LVEF reserve during exercise was observed only in group I (from 59.5+/-6 to 65.8+/-6%, t=-3.95, P<0.005), whereas no substantial change occurred in LV performance in group II. A trend towards better MASE at all the studied longitudinal segments at rest and during exercise was observed in group I. No minor or major calcifications have been observed on pericardial rings. CONCLUSIONS: The autologous pericardium seems to be superior to rigid prosthetic rings for annuloplasty in MVR since it provides more favourable mitral annulus dynamics and preserves LV function during stress conditions. Effective and durable annular remodelling with the autologous pericardium is achieved up to 6 years from surgery, with no echocardiographic sign of degeneration in the long term. Further studies are required to compare biological versus flexible prosthetic rings in MVR.

The double-orifice technique for mitral valve reconstruction: predictors of postoperative outcome.

OBJECTIVE: The 'double-orifice' (DO) technique has been recently proposed as an additional option in mitral valve repair (MVR). However, little is known regarding the long-term postoperative outcome and the predictors of DO results. Therefore, the aim of this study was to evaluate our clinical series and to identify prognostic factors of DO repair. METHODS: From 1992, 75 patients underwent DO procedure because of severe mitral regurgitation. The study population consisted of 48 male and 27 female patients with a mean age of 58+/-13 years (range 16-80 years). The aetiology of mitral incompetence was Barlow disease in 30 cases, rheumatic disease in 18 cases, acute or healed endocarditis in 16 cases and other causes in 11 cases. Carpentier rigid ring was used in 38 patients, whereas autologous pericardium was used in 24 patients. Thirteen patients had no annuloplasty procedure. Statistical analysis included univariate and multivariate Cox proportional models to evaluate the predictors of the DO failure. RESULTS: There were four hospital and three late deaths with a survival rate of 92% at 8 years. Mean follow-up was 42+/-24 months (range 1-93 months). Twelve patients underwent reoperation (five cases of early failure) and had valve replacement, leading to 80% freedom from reoperation at 8 years. At follow-up, 13 patients had no mitral regurgitation, 36 patients had trivial or mild mitral incompetence, whereas eight patients had moderate or severe mitral insufficiency at transthoracic echocardiography. Preoperative low left ventricular ejection faction, pulmonary arterial hypertension and marked left atrial enlargement were predictors (P<0.05) of DO failure at univariate analysis. Pericardial annuloplasty was also a risk factor (P<0.05) for unsuccessful DO repair at long term. Cox proportional multivariate analysis confirmed left atrial dilatation, pulmonary hypertension and pericardial annuloplasty as independent predictors of unfavourable postoperative results. CONCLUSIONS: This study suggests that preoperative factors, like pulmonary hypertension and severe left atrial dilatation, may predict late DO failure. Our findings also indicate that pericardial annuloplasty may negatively influence mitral valve reconstruction at long term when DO is employed in MVR.

Mitral valve repair for isolated prolapse of the anterior leaflet: an 11-year follow-up.

OBJECTIVE: Mitral valve insufficiency (MVI) because of involvement of the anterior mitral leaflet may pose additional risks for late outcome after mitral valve repair, because of more complex techniques. We retrospectively reviewed our experience in patients operated on for isolated anterior mitral leaflet prolapse approached by various techniques. METHODS: Between 1986 and 1997, 616 patients underwent mitral valve repair at our Institution. Isolated pathology of the anterior mitral leaflet was the cause of MVI in 84 patients (13.6%). Age ranged from 23 to 74 years (mean 50 +/- 14). Etiology of MVI was predominantly degenerative (57 patients, 67.8%), and the mechanism of the regurgitation was mainly due to a chordal rupture (58 patients, 69%). Annular dilatation was present in 75 patients (89.5%). A variety of surgical techniques were applied including chordal shortening (five patients, 5.9%), chordal transposition (three patients, 3.5%), artificial chordae (11 patients, 13%). Since 1992, however, the majority of procedures was performed using the 'edge to edge' technique (52 patients, 51.9%). Annular dilatation was treated mainly by means of a prosthetic ring (46 patients, 61.3%) whereas 18 patients (24%) underwent posterior annuloplasty using gluteraldehyde-treated native pericardium. RESULTS: Follow-up ranged from 3 to 122 months (mean 46 +/- 24 months). There were three hospital deaths (3.5%) and five late deaths (5.9%) for a Kaplan-Meier estimated survival of 87.6% at 8 years. Three patients underwent early reoperation within 30 days (3.5%), and six patients underwent late reoperation (7.1%), for a cumulative freedom from reoperation of 85.4% at 8 years. Seventy-four percent of the survivors (50 patients) are still in New York Heart Association Class I, and 92% of survivors (62 patients) have no or trivial (1+) residual mitral regurgitation at echocardiographic follow-up. CONCLUSION: In spite of the greater complexity, conservative surgery to correct anterior mitral valve prolapse pertains high success rate of long term. Recent technical modifications ('edge-to-edge' technique) may allow more expeditious and reproducible procedures with expected favorable influence of mitral valve repair applicability.

Long-term results of coronary artery bypass grafting procedure in the presence of left ventricular dysfunction and hibernating myocardium.

OBJECTIVE: Long-term left ventricular (LV) performance and patient outcome after coronary artery bypass grafting (CABG) procedure in the presence of depressed LV function and hibernating myocardium (HM) have been poorly determined. Therefore, we prospectively evaluated patients undergoing CABG with severe LV dysfunction and HM to elucidate postoperative prognosis. METHODS: We enrolled 120 consecutive patients undergoing CABG with severe LV dysfunction and HM as assessed by dobutamine echocardiography and by rest-redistribution radionuclide (Thallium-201) study. Mean patient age was 60+/-9 years (range 31-77 years). Mean preoperative LVEF was 28%+/-9 (range 10-40%). All patients underwent echocardiographic study to assess LV recovery of function intraoperatively, prior to hospital discharge, at 3 months, at 1 year, and yearly during the follow-up. Univariate and multivariate analysis were performed to to evaluate predictors of postoperative survival. RESULTS: There were 2 hospital (1.6%) and 15 late (12.5%) deaths, mainly for heart failure, leading to an actuarial survival of 80+/-6% and 60+/-9% at 5 and 8 years, respectively. LVEF significantly improved perioperatively (from 28+/-9% to 40+/-2%, P<0.01). Increase in LVEF, however, was gradually offset over the time (EF of 33+/-9%, 32+/-8%, and 30+/-9% at 3 months, and 12 months, and 8 years after surgery, respectively). Furthermore, patients who experienced limited LV functional recovery perioperatively had a more remarkable decline of LVEF thereafter, and suffered from recurrence of heart failure symptoms (freedom from heart failure 82+/-5% and 60+/-8% at 4 and 8 years respectively). Advanced preoperative NYHA Class, and age were independent risks factors for reduced postoperative survival. Preoperative angina and use of arterial conduits apparently did not influence patient morbidity and mortality at long term. CONCLUSION: CABG procedure in the presence of HM enhances LV recovery of function and has a favourable prognosis. Functional benefit of the left ventricle, however, appears to be time-limited, despite remarkable improvement in patient functional capacity. Advanced preoperative heart failure, minimal perioperative improvement of LVEF, and age account for a poor long-term prognosis.

Müllerian adenosarcoma of the uterus.

A case of adenosarcoma of the uterus in a 59-year-old woman is here reported. Adenosarcoma is a low malignant potential tumor with a benign glandular and a malignant stromal component. The treatment is usually hysterectomy with bilateral salpingo-oophorectomy. Debated is the usefulness of adjuvant chemotherapy, while radiation treatment is not beneficial. Long term follow-up is necessary for these patients because of high recurrence risk, mostly in cases with myometrial invasion.

Epididymal lymphoma. A case report.

Primary epididymal lymphoma is an unusual observation. Only 2 cases of non-Hodgkin's lymphoma of the epididymis have been previously reported. We describe the clinical and pathologic features and management of a primary high-grade malignant lymphoma of the epididymis in which a tentative diagnosis of lymphoma was made on the basis of cytologic examination and immunochemical staining of the material obtained from an aspiration needle biopsy.

Light microscopic, immunocytochemical and ultrastructural study of a case of Sertoli cell tumor of the testis.

A case of testicular specialized gonadal stroma tumor was evaluated by histologic, ultrastructural and immunohistochemical techniques in a young adult male patient. The neoplastic cells were organized in cords or tubular structures delimited by a basement membrane. The ultrastructural findings suggested a diagnosis of a partially differentiated Sertoli cell tumor. This was also supported by the presence of a vimentin rich cytoskeleton, which is normally present in Sertoli and Leydig cells. The tumor cells did not secrete steroid hormones, as suggested by clinical findings, as well as by hormonal, immunohistochemical, and ultrastructural observations.

Benign granular cell tumor of the breast: a misleading disease.

Granular cell tumor (GCT) is a relatively rare neoplasm, and almost always benign in its prognostic behavior. Location of this tumor in the breast presents serious problems for differential diagnosis, both from a clinical point of view and at gross pathological examination, because of its resemblance to carcinoma. Fine needle aspiration biopsy and intraoperative frozen section examination may not be of any further help. The histogenesis of these lesions has been widely debated in the past, but no universally accepted conclusion has been reached. Most GCTs appear to be derived from Schwann cells, but many different neoplastic and non-neoplastic lesions show granular cell changes. Therefore, GCT should not be considered as a single entity but as the result of a cytoplasmic change due to still unknown metabolic alterations that may occur in various cell types. No firm conclusions can be drawn regarding the suspected hormonal influence on the development of breast GCT. The authors describe three typical cases of breast GCT that occurred in patients of different ages, and discuss the most important questions concerning this lesion.

Malignant conjunctival epibulbar fibrous histiocytoma with orbital invasion.

The Authors report on a rare case of malignant conjunctival epibulbar fibrous histiocytoma with orbital invasion. Fibrous histiocytoma is a tumour of mesenchymal origin, which, although among the most common adult age soft tumours, appears very rarely at the conjunctival level. In fact the most frequent site is the orbit. So far only 15 cases concerning conjunctiva have been described in the Literature only 4 of those have been reported as malignant. We observed a male patient, who 6 years ago, at the age of 53, noticed a neoformation on the temporal portion of the bulbar conjunctiva. In June 1988, after three successive operations, with a histological diagnosis of inflammatory granuloma, he came to our Clinic, where, because of the characteristics of the orbit infiltrations, only a partial excision was carried out for a biopsy. The histological examination, associated with immunohistochemical techniques, gave the result of malignant fibrous histiocytoma. Consequently in, July 1988, the patient underwent an exenteratio orbitae. To date, the patient enjoys good health without a trace of recurrence. Besides the clinical presentation of the case, histopathological and immunohistochemical findings concerning this type of lesion are presented and discussed, with a comparison of our findings with those reported in the literature.