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Whether donor graft steatosis affects liver function and influences survival after liver transplantation is still open to debate. The aim of this study was to assess the impact of donor graft steatosis on long-term liver histology after liver transplantation. One hundred sixteen consecutive liver transplants were performed in 56 hepatitis C virus-positive (HCV+) patients and 60 HCV- patients who had protocol liver biopsies at 6, 12, 24, and 36 months after liver transplantation. Liver biopsies were obtained from all grafts. No steatosis was seen in 50.9% of the biopsies taken at the back table before implantation, whereas steatosis was mild in 39.6% of the samples and moderate/severe in 9.5% of the samples. In the 56 HCV+ recipients, fibrosis stage 3 was seen in 22.2% and stage 4 was seen in 2.2% of 45 biopsies at 36 months after liver transplantation. There was no correlation between donor graft steatosis and fibrosis after liver transplantation, regardless of the etiology of liver disease. No difference in 36-month survival after liver transplantation was seen, regardless of whether the etiology of the patient's liver disease was HCV-related or non-HCV-related (80.3% versus 75%; P = 0.4) and whether the steatosis in the graft was reportedly absent, mild, or moderate/severe (79.7% versus 73.9% versus 81.1%; P = 0.7). In conclusion, nearly one-quarter of HCV+ recipients have precirrhosis/cirrhosis 3 years after liver transplantation. Steatotic grafts do not seem to exacerbate the progression of fibrosis in HCV+ recipients, nor do they seem to negatively affect 3-year patient survival.

Aim To evaluate the accuracy of magnetic resonance imaging in assessing tumor response following neoadjuvant chemotherapy in patients with locally advanced breast cancer. Materials and Methods Twenty-six patients entered a phase II study of neoadjuvant chemotherapy, undergoing bilateral breast magnetic resonance imaging before therapy and before surgery. Tumor response was classified using RECIST criteria, using tumor size at magnetic resonance imaging. The latter was then compared to residue found at histopathological examination. Results Magnetic resonance imaging showed 6 (23%) complete responses, 17 (65%) partial responses, 3 (11.5%) disease stabilizations and no disease progressions. Twenty-three tumors (88.5%) were considered responsive and 3 (11.5%) unresponsive. Pathological tumor response was: 6 complete responses (23%), 17 partial responses (65%), 2 stable disease (8%), 1 progression (4%). When results of the preoperative magnetic resonance imaging were compared to pathological tumor response, magnetic resonance imaging overestimated tumor size in 12 cases (46%) and underestimated it in 9 (35%). However, preoperative magnetic resonance imaging failed to detect invasive tumor in 2 false-negative cases (8%), 1 of which was multifocal. Mastectomy was performed in 12 cases: 1 case of disease progression even though the neoplasm appeared smaller at magnetic resonance imaging, 3 cases with stable disease, and 4 cases with T3 or T4 disease. The 9th patient was T2N2 with initial retroareolar disease and negative magnetic resonance imaging after chemotherapy. The 10th patient, affected by lobular cancer, was in partial remission but was T3N1. The 11th patient was 57 years old but was not interested in conservative surgery. The 12th patient requested bilateral prophylactic mastectomy due to her positive family history of breast cancer. Conclusions Magnetic resonance imaging of the breast allowed conservative surgery in 54% of the patients. This low value is primarily due to overestimation of tumor size, with a negative predictive value of 67% in our population. However, surgeons were able to choose conservative surgery with relative safety in cases of small residual disease.

The histologic subtyping of the 2 major histotypes of nonsmall-cell lung cancer, that is, adenocarcinoma (AdC) and squamous cell carcinoma (SCC), is crucial to therapeutic decision making, but making this distinction can be a challenge. Querying the Oncomine database pinpointed anterior gradient 2 (AGR2) as being upregulated in lung AdC. On applying both quantitative real-time polymerase chain reaction and immunohistochemistry, this study tested the reliability of AGR2 status as a histotype-specific marker of lung AdC. AGR2 immunohistochemistry expression was semiquantitatively assessed in 120 cases of lung cancer (60 AdCs, 60 SCCs); 35 additional tissue samples from non-neoplastic lungs were considered as normal controls. To further support our findings, the expression of AGR2 mRNA was tested by quantitative real-time polymerase chain reaction in 30 of the considered cases (10 AdCs, 10 SCCs, and 10 normal lungs). AGR2 was consistently expressed in normal bronchial/bronchiolar columnar cells. Cases of AdC always expressed the protein (staining moderately in 30% and strongly in 70%), whereas none of the SCC cases strongly expressed AGR2 (staining was negative in 55%, weak in 33%, and moderate in 12%). AGR2 mRNA was significantly overexpressed in AdCs by comparison with SCCs (P=0.003) or normal lung tissue (P=0.002). AGR2 is upregulated in lung AdC (by comparison with either SCC or normal bronchial/bronchiolar columnar cells). AGR2 protein expression may support the histologic subtyping of nonsmall-cell lung cancer and be of clinical value in differentiating lung AdC from SCC.

The association of lymphoma and human immunodeficiency virus (HIV) seropositivity in a patient with a rare congenital clotting disorder (Factor X Friuli) is reported. The propositus was a previously asymptomatic HIV-positive 46-year-old man who suddenly presented a rapidly evolving right exophthalmos due to a centroblastic lymphoma, as the presenting symptom of full-blown AIDS. The clinical picture was characterized by unusual site of presentation, advanced stage and fatal course over a short period of time, despite therapy. Bone marrow, but not lymph node or parenchymal involvement, was present. Central nervous system involvement, with an unusual diffuse and massive pattern, and the B-cell origin of the lesion were demonstrated at autopsy. Few reports exist so far about the association of malignancy and HIV in patients with congenital coagulation disorders and this is the first report about a defect other than classic hemophilia.

Localized fibrous tumours of the pleura (LFTP) represent clinical entities rarely encountered, especially in giant forms. We report of three cases of giant localized fibrous tumours of the pleura found last year in a short time. The patients underwent surgery by thoracotomy. All tumours arose from visceral pleura and were radically excised by a wedge resection of the lung. The patients discharged from the hospital after a short postoperative period without complications. Two of three giant localized fibrous tumours were classified as benign forms; in one case a malignant characteristic was found.

Objective: The aim of this study is to analyze long-term survival and the prognostic significance of some factors after surgical resection of thymic epithelial tumours. Methods: We performed a retrospective analysis of clinical and histopatological data on 132 patients operated on for thymic tumours, from 1970 and 2001. Histologic diagnosis based on the new WHO classification system was made by a single patologist. A univariate and multivariate analysis of prognostic factors predicting survival was carried out. Results: There were: 108 complete resections (81.8%), 12 partial resections (9.1%) and 12 biopsies (9.1%). Overall 5, 10 and 15-year survival rate was 72, 61 and 52.5%, respectively. The Masaoka staging system showed 44 stage I, 18 stage II, 52 stage III and 18 stage IV. Histologic results were: 14 subtype A, 31 AB, 20 B1, 28 B2, 29 B3 and 10 C; the respective proportions of invasive tumour (stage II‐ IV) was 28.6, 58.1, 50, 75, 86.2 and 100%. There were 16 tumour recurrences (14.8%) of 108 radically resected thymomas, 10 were treated with radical re-resection. In univariate analysis, four prognostic factors were statistically significant: radical resection, Masaoka clinical staging, WHO histologic subtype and resectable tumour recurrence. In multivariate analysis, the independent factors predicting long-term survival were WHO histology and Masaoka stage. Conclusions: The WHO histologic classification seems to be the most significant prognostic factor reflecting the invasiveness of the thymic tumour. Completeness of resection and Masaoka stage I and II assure a better survival. Unresectable recurrence of thymic tumour predicted a worse prognosis. q 2004 Elsevier B.V. All rights reserved.

The host immune system acts to the transplanted liver with a predominantly cell mediated alloimmune effector mechanism defined as acute cellular rejection in 24–80% of patients. Liver biopsy remains the gold standard in the diagnosis of rejection.

Several biochemical events accompany and mediate the development of chronic liver disease and its evolution into cancer. Low plasma zinc and high copper levels have been observed in various liver diseases, such as liver cirrhosis and viral hepatitis, while increased oestradiol levels have been documented in chronic liver damage and hepatocellular carcinoma. We administered CCL4 intragastrically to 10 female Sprague Dawley rats for 30 weeks. All animals developed cirrhosis and four also developed hepatocellular carcinoma. Plasma levels of zinc, copper and oestradiol were significantly higher in the latter group than in animals with simple cirrhosis. Progesterone, AST and bilirubin showed a trend toward significant differences whereas testosterone and ALP levels were unchanged. These findings add to the evidence that sex hormones and trace elements are involved in the process of the development of chronic liver damage and carcinogenesis.

The origin, mechanism, and significance of the bile duct proliferation (BDP) associated with cholestasis remain unexplained. This study examined the effect of oral administration of ursodeoxycholic acid (UDCA) on both BDP and cholestasis in the rat. After bile duct ligation, male Sprague-Dawley rats were treated for 30 days with either UDCA (5 mg/day) (group A) or saline solution (group B). Animals were sacrificed at day 30. The serum activity of aminotransferase (ALT, AST), alkaline phosphatase, and gamma-glutamyltransferase (GGT) was significantly lower (P < 0.01) in the UDCA-treated rats. Total serum bilirubin and total serum bile acids were lower (P < 0.001) in group A. Moreover, the control of BA in bile was reduced also (P < 0.02). Conversely, serum cholesterol levels were not different between the two groups. Histological examination showed that the number of ductular cells in the portal areas was significantly (P < 0.001) reduced in UDCA-treated as compared to saline-treated rats. The replication activity, assessed as the number of bromodeoxyuridine-positive cells, was also significantly lower in treated animals (33 +/- 11 vs 64 +/- 22 per 1000 cells; P < 0.001). Lobular bile ductules were three times larger in group B, and extrahepatic duct measurements confirmed this increase in size of the larger biliary ducts (P < 0.001). These findings demonstrate that UDCA reduces BDP in response to BD ligation. Although the mechanism(s) of this effect is still hypothetical, UDCA may reduce the level of irritating bile salts such as chenodeoxycholic acid and lithocolate and increase periductular bile acid recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytologic examination of fine-needle aspiration (FNA) sometimes fails to diagnose the malignant nature of B-cell proliferations. In this study we analyzed the Ig gene rearrangement of 49 FNA samples by polymerase chain reaction (PCR) in order to evaluate whether molecular analyses can improve the accuracy of FNA. Twenty-six patients had non-Hodgkin's lymphoma, 11 had reactive lymphoid diseases, 5 had chronic inflammation and 7 had carcinoma. A semi-nested PCR was performed using an oligoprimer specific for consensus sequences of the V regions (FR3A) and two oligoprimers derived from conserved sequences of the J regions (LJH and VLJH). Histologic examination always followed the molecular and cytologic analysis. The sensitivity of PCR and FNA morphological examination in detecting a neoplastic pattern was 92% and 78%, respectively. When samples were considered inadequate for cytologic examination, PCR always reached a diagnosis consistent with the histologic features. Our results demonstrate that PCR analysis of FNA specimens is a reliable and sensitive method capable of enhancing the diagnostic accuracy of cytologic examination.