Giampiero Palmieri

Malignant renal neoplasms: correlation between ADC values and cellularity in diffusion weighted magnetic resonance imaging at 3 T

PurposeThis study aimed at exploring the feasibility of high-field diffusion-weighted magnetic resonance imaging (DW-MRI) (3 T) and to correlate apparent diffusion coefficient (ADC) values with tumour cellularity in renal malignancies.Materials and methodsThirty-seven patients (ten healthy volunteers and 27 patients with suspected renal malignancy) underwent T1-, T2-weighted and T1-weighted contrast-enhanced magnetic resonance imaging (MRI). Diffusion-weighted images were obtained with a single-shot spin-echo echo-planar imaging (SE-EPI) sequence with a b value of 500 s/mm2. All lesions were surgically resected, and mean tumour cellularity was calculated. Comparison between tumour cellularity and mean ADC value was performed using simple linear regression analysis.ResultsThe mean ADC value in normal renal parenchyma was 2.35±0.31×10−3 mm2/s, whereas mean ADC value in renal malignancies was 1.72±0.21×10−3 mm2/s. In our population, there were no statistically significant differences between ADC values of different histological types. The analysis of mean ADC values showed an inverse linear correlation with cellularity in renal malignancies (r=−0.73, p<0.01).ConclusionsDW-MRI is able to differentiate between normal and neoplastic renal parenchyma on the basis of tissue cellularity.RiassuntoObiettivoValutare l’utilità dell’imaging RM ad alto campo (3T) con sequenze pesate in diffusione (DWI) nello studio delle neoplasie renali e correlare i valori del coefficiente apparente di diffusione (ADC) con la cellularità delle neoplasie.Materiali e metodiTrentasette pazienti (10 volontari sani e 27 con lesioni renali sospette) sono stati studiati con imaging RM e sequenze T1, T2 pesate e T1 pesate dopo somministrazione di bolo di contrasto paramagnetico. Le immagini pesate in diffusione (DWI) sono state acquisite con sequenza sSH SE-EPI e fattore b di 500 s/mm2. Per ogni lesione chirurgicamente asportata è stata valutata la cellularità media. L’analisi di regressione lineare semplice è stata utilizzata per valutare la correlazione fra cellularità tumorale e valore ADC.RisultatiL’ADC medio nel parenchima dei pazienti sani è stato 2,35±0,31×10−3 mm2/s. Il valore medio nei tumori renali maligni era di 1,72±0,21×10−3 mm2/s. Non è stata riscontrata una differenza statisticamente significativa tra i valori medi di ADC dei differenti istotipi neoplastici. È stata documentata una correlazione inversa fra il valore medio di ADC e la cellularità media nei tumori renali maligni (r=−0,73, p<0,01).ConclusioniL’imaging in diffusione consente una distinzione significativa tra parenchima renale normale e neoplastico. È possibile differenziare i tessuti neoplastici sulla base della cellularità.

Multicentric inflammation in epicardial coronary arteries of patients dying of acute myocardial infarction

OBJECTIVES We sought to test the hypothesis of whether inflammatory cell infiltration in patients dying of an acute myocardial infarction (MI) is a multifocal event involving multiple coronary branches. BACKGROUND Coronary instability is thought to reflect local disruption of a single vulnerable plaque. However, previous postmortem studies have not addressed the question of whether activation of inflammatory cells, particularly T lymphocytes, is limited to the culprit lesion only or rather diffuse in the coronary circulation. METHODS We performed a systematic flow cytometric study in three groups of autopsied patients (group 1 = acute MI; group 2 = old MI; group 3 = no ischemic heart disease). Cell suspensions of enzymatically digested coronary arteries were stained for flow cytometry with CD3, CD68, alpha-smooth muscle actin, and human leukocyte antigen (HLA)-DR antibodies. RESULTS The coronary plaques showed: 1) a higher proportion of inflammatory cells in groups 1 and 2 than in group 3; 2) a higher percentage of T lymphocytes in group 1 than in group 2 (11.67 +/- 0.70% vs. 5.67 +/- 0.74%, p = 0.001) and in group 2 than in group 3 (p = 0.008); and 3) diffuse cell activation in the whole coronary tree of group 1, but not of group 2 subjects. CONCLUSIONS Our study suggests that lymphocytes may play a key role in coronary instability by determining activation of various cellular types throughout the coronary circulation. Activated T lymphocytes and their products may well represent a new target in both the treatment and prevention of acute coronary syndromes.

Wireless capsule endoscopy and small intestine contrast ultrasonography in recurrence of Crohn's disease

Background: The best available tool to assess recurrence of Crohns disease (CD) is ileocolonoscopy (CC). Small intestine contrast ultrasonography (SICUS) and wireless capsule endoscopy (WCE) are noninvasive techniques able to detect small bowel lesions. In a prospective longitudinal study, we aimed to investigate the usefulness of SICUS and WCE for assessing postoperative recurrence of CD 1 year after surgery, using CC as the gold standard. Methods: Twenty‐two patients (11 men, median age 33 years, range 22–67 years) undergoing ileocolonic resection for CD were prospectively followed from July 2003 to May 2006, with the Crohns Disease Activity Index (CDAI) used for clinical assessment every 3 months for 1 year. At 1 year, recurrence was assessed by SICUS and CC, followed by WCE. CD recurrence was assessed by CC (Rutgeerts score). SICUS was performed after ingestion of polyethylene glycol, and WCE was performed with Given M2A equipment. Results: At 1 year, all 22 patients had inactive CD (CDAI < 150). In 5 patients, WCE was not performed because of luminal narrowing or stenosis. Seventeen of the 22 patients had all 3 techniques performed. CC detected recurrence in 21 of 22 patients. Lesions compatible with recurrence were detected by SICUS in all 22 patients (1 false positive). When considering only the 17 patients studied by all 3 techniques, recurrence was detected by CC in 16 of 17 patients, whereas lesions compatible with recurrence were detected by SICUS in all 17 patients (16 true positives [TPs], 1 FP) and by WCE in 16 of 17 patients (16 TPs, 1 true negative). Conclusions: The present findings suggest that SICUS and WCE may be used as noninvasive techniques for the assessment of recurrence of CD in patients being regularly followed up after ileocolonic resection. (Inflamm Bowel Dis 2007)

Hyperfibrinogenemia Is Associated With Specific Histocytological Composition and Complications of Atherosclerotic Carotid Plaques in Patients Affected by Transient Ischemic Attacks

BACKGROUND Epidemiological studies have demonstrated that hyperfibrinogenemia is an independent risk factor for cerebrovascular atherosclerosis. However, the underlying mechanisms are poorly understood. We studied whether hyperfibrinogenemia could modify the histological composition of atherosclerotic plaque and precipitate carotid thrombosis resulting from rupture of the plaque. METHODS AND RESULTS We studied the histological composition of 71 carotid atherosclerotic plaques from patients who had undergone surgical endarterectomy after a first episode of transient ischemic attack. Patients were divided into 3 groups corresponding to the tertiles of plasma fibrinogen values. Hypercholesterolemia, hypertriglyceridemia, hypertension, diabetes, and smoking habit were also assessed. At the histological analysis, plaques of patients in the highest tertile of fibrinogen (>407 mg/dL) were characterized by a high incidence of thrombosis (66.7% of cases) compared with plaques of subjects in the lower (21.7%) (P=0.002) and middle (29. 2%) (P=0.009) tertiles. Plaque rupture was significantly associated with high fibrinogen levels (54.2%, P=0.003). Multivariate logistic regression indicated that hyperfibrinogenemia was an independent risk factor for a decrease in cap thickness (P=0.0005), macrophage foam cell infiltration of the cap (P=0.003), and thrombosis (P=0. 003). When the presence of other risk factors was accounted for, hyperfibrinogenemia remained an independent predictor of carotid thrombosis with an odds ratio of 5.83, compared with other risk factors. CONCLUSIONS The results of the present study add to the evidence that hyperfibrinogenemia, independently of other risk factors, is associated with a specific histological composition of carotid atherosclerotic plaques that predisposes them to rupture and thrombosis.

Plasma and Muscle Carnitine Levels in Haemodialysis Patients with Morphological-Ultrastructural Examination of Muscle Samples

The present study investigates 14 patients on intermittent haemodialysis. Pre-dialysis blood and muscle samples taken for determining plasma free- and acetylcarnitine levels. The tissue fragments were used for light and electron microscopy studies. Our results support the findings of other investigators that patients on haemodialysis generally display decreased free- and acetylcarnitine levels both in plasma and skeletal muscle when compared with control values. Muscle carnitine deficiency was apparently more severe in the longer-term haemodialysis patients. Moreover, a significant correlation (p less than 0.05) between plasma and muscle free-carnitine values was found. Morphologically no pathological alterations were observed in the muscle fibres in 13 of the patients. Light and electron microscopic studies of the muscle fibre of the 14th patient showed a typical nemaline myopathy with rod bodies in the cytoplasm. The muscle free-carnitine concentration in this patient was among the lowest of the group.

Morphometric evidence of the trophic effect of L-carnitine on human skeletal muscle.

We investigated the effect of long-term i.v. administration of L-carnitine on human muscle fibers using morphometric parameters. We administered 2g/day L-carnitine to patients undergoing hemodialysis for at least 12 months. At the end of this period a marked increase in serum and muscle carnitine levels was observed in all patients, together with hypertrophy and predominance of type 1 fibers. L-carnitine was withheld for 4 months, during which time serum and muscle levels gradually decreased and no changes were observed in muscle fibers. Subsequent addition of L-carnitine to dialysis fluid for another 4 months stabilized lower levels. At the end of this period reduction of diameter of type 1 fibers was observed. Type 2 fibers remained unchanged. Moreover, type 1 fibers remained predominant in all cases. Hence, we suggest that carnitine has a specific trophic effect on type 1 fibers which are characterized by an oxidative metabolism.

Relationships between risk factors and morphological patterns of human carotid atherosclerotic plaques. A multivariate discriminant analysis

The histological characterization of the fibroatheromatous plaques and their histogenesis are still to be defined. Factors responsible for the evolution of intimal components and the mechanisms and stages of fibroatheromatous plaque formation are still largely obscure. Focusing on symptomatic plaques, the aim of this study is to determine whether plaque heterogeneity is the result of a haphazard clustering of various components or an organized pattern in response to risk factors. To this end, 180 carotid plaques from patients affected by transient ischemic attacks (TIA) or by stroke, with angiographic stenosis greater than 50%, were studied after endoarterectomy. Clinical and morphological data were collected by means of a pre-defined protocol, quantified and correlated, by using the discriminant analysis, with age, sex, hypertension, diabetes, hypercholesterolemia and smoking habit. Our results show that the relationships between plaque components are non-random and consistent with the knowledge derived from studies on human and experimental plaques. Moreover, some plaque patterns can be significantly correlated with single risk factors. The fibrous plaque was correlated with aging and diabetes; the granulomatous plaque, rich in giant cells, with the female sex and hypertension; the xanthomatous plaque, rich in foam cells and with extensive alcianophilia, with hypercholesterolemia. In the smokers, finally, the plaques were frequently complicated by mural thrombosis.

Tropomyosin expression in the ileal pouch: a relationship with the development of pouchitis in ulcerative colitis.

OBJECTIVE:Human tropomyosin isoform 5 (hTM5) is a cytoskeletal protein expressed in normal epithelial cells, predominantly in the colon. An autoimmune response toward hTM5 has been reported in ulcerative colitis (UC). Whether hTM5 expression in the ileum is involved in pouchitis is unknown. We assessed hTM5 expression on ileal epithelial cells at surgery and subsequently on development of pouchitis in UC.METHODS:In a prospective longitudinal study, 28 UC patients undergoing ileal pouch procedures were included. Biopsy samples were taken from the rectum at surgery, as well as from the ileal pouch at surgery and at 6 months. The specimens were stained by immunoperoxidase using the anti-hTM5 monoclonal antibody CG3. Pouchitis was assessed by the Pouchitis Disease Activity Index and hTM5 expression on a scale of 0–3.RESULTS:At surgery, in rectal samples, hTM5 expression was strong in all epithelial cells including the luminal surface, whereas in ileal samples hTM5 was not expressed or focally expressed only in the goblet cells. At 6 months, the ileum was found to have undergone morphological changes, becoming similar to the colon and showing shortening or reduced number of villi. These changes were associated with a diffuse hTM5 staining in the goblet cells and in the nongoblet epithelial cells lining the crypts and the lumen. The hTM5 score was related to the Pouchitis Disease Activity Index at 6 months (r = 0.82; p = 0.01).CONCLUSIONS:Expression of hTM5 shows a different pattern in the ileal pouch in UC after surgery. This event is associated with morphological changes of the ileum toward colonic epithelium, related to the development of pouchitis.

Histological, Immunohistochemical, and Ultrastructural Findings in Human Corneas After Photorefractive Keratectomy

BACKGROUND Four human corneas that had undergone photorefractive keratectomy (PRK) and subsequent penetrating keratoplasty were examined by means of light and electron microscopy in an attempt to detect possible causes for complications after PRK. METHODS Four eyes with a central corneal leukoma resulting from a previous PRK treatment underwent penetrating keratoplasty respectively 3 days, 3 months, 5 months, and 13 months after the refractive procedure. Different excimer laser instruments (Meditec MEL 50, Summit UV200, and VISX 20/20) had been used. The corneal buttons removed were submitted for light microscopy, electron microscopy and immunohistochemistry. RESULTS An immature (one to two layers, basement membrane anomalies) but continuous epithelium was present even in the 3-day specimen; between six and eight epithelial layers could be seen in the 13-month specimen, which still presented an undulated aspect of the otherwise normal basement membrane. A continuous acellular collagen layer underlying the epithelium of the ablated area was detected in the superficial stroma of all examined corneas. No Descemets membrane or endothelial alterations could be seen. CONCLUSIONS Despite recovery of a continuous epithelial layer as early as 3 days after PRK, abnormalities of both epithelium and superficial stroma could be detected in all specimens, including the one obtained 13 months after the refractive procedure.

Protective role of tauroursodeoxycholate during harvesting and cold storage of human liver: a pilot study in transplant recipients.

Background. Ischemia-reperfusion injury is a major cause of early graft dysfunction after liver transplantation. Tauroursodeoxycholic acid (TUDCA), a natural amidated hydrophilic bile salt, protects from cholestasis and hepatocellular damage in a variety of experimental models, as well as from ischemia-reperfusion injury. We investigated in the human liver transplantation setting the effect of the addition of TUDCA at time of liver harvesting and cold storage on the intra- and postoperative enzyme release and liver histopathology at the end of cold storage, at reperfusion, and 7 days after transplantation. Methods. Eighteen patients undergoing elective liver transplantation were studied, including 6 serving as controls. In six patients, TUDCA was added to the University of Wisconsin solution used during harvesting and cold storage, to reach final concentrations of 2 mM. In three of these patients, TUDCA (3 g) was infused in the portal vein of the donor before organ explantation; in the other three cases, TUDCA was given through both routes. Results. The use of TUDCA did not cause adverse events. The release of aspartate aminotransferase in the inferior vena cava blood during liver flushing was significantly lower (P =0.05) in TUDCA-treated than in control grafts, as were cytolytic enzyme levels in peripheral blood during the first postoperative week (P <0.02). At electron microscopy, an overt endothelial damage (cytoplasmic vacuolization, cell leakage, and destruction with exposure of hepatocytes to the sinusoidal lumen) was invariably found in control grafts, both at reperfusion and at day 7 after transplant. These features were significantly ameliorated by TUDCA (P <0.001). Several ultrastructural cytoplasmic abnormalities of hepatocytes were seen. Among these, damage to mitochondria matrix and crystae was significantly reduced in TUDCA-treated versus control grafts (P <0.01). Mild to severe damage of bile canaliculi was a constant feature in control biopsies, with dilatation of canalicular lumen and loss of microvilli. Both these abnormalities were markedly ameliorated (P <0.001 by TUDCA). The best preservation was observed when TUDCA was given through both routes. Conclusions. The use of TUDCA during harvesting and cold storage of human liver is associated with significant protection from ischemia-reperfusion injury. The clinical significance of this findings must be studied.