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Biomedical subjects

Vito Franco

Publications and source records attributed to Vito Franco.

18 recordsLinked to original sources

Splenic marginal zone lymphoma: a prognostic model for clinical use.

The Integruppo Italiano Linfomi (IIL) carried out a study to assess the outcomes of splenic marginal zone lymphoma and to identify prognostic factors in 309 patients. The 5-year cause-specific survival (CSS) rate was 76%. In univariate analysis, the parameters predictive of shorter CSS were hemoglobin levels below 12 g/dL (P < .001), albumin levels below 3.5 g/dL (P = .001), International Prognostic Index (IPI) scores of 2 to 3 (P < .001), lactate dehydrogenase (LDH) levels above normal (P < .001), age older than 60 years (P = .01), platelet counts below 100,000/microL (P = .04), HbsAg-positivity (P = .01), and no splenectomy at diagnosis (P = .006). Values that maintained a negative influence on CSS in multivariate analysis were hemoglobin level less than 12 g/dL, LDH level greater than normal, and albumin level less than 3.5 g/dL. Using these 3 variables, we grouped patients into 3 prognostic categories: low-risk group (41%) with no adverse factors, intermediate-risk group (34%) with one adverse factor, and high-risk group (25%) with 2 or 3 adverse factors. The 5-year CSS rate was 88% for the low-risk group, 73% for the intermediate-risk group, and 50% for the high-risk group. The cause-specific mortality rate (x 1000 person-years) was 20 for the low-risk group, 47 for the intermediate-risk group, and 174 for the high-risk group. This latter group accounted for 54% of all lymphoma-related deaths. In conclusion, with the use of readily available factors, this prognostic index may be an effective tool for evaluating the need for treatment and the intensity of therapy in an individual patient.

Adult↗

Essential thrombocythemia or chronic idiopathic myelofibrosis? A single-center study based on hematopoietic bone marrow histology.

We reviewed a large series of patients with essential thrombocythemia diagnosed on the basis of the Polycythemia Vera Study Group criteria, and reclassified them by evaluating their major morphologic features and clinical course using the World Health Organization classification. The morphologic review of the bone marrow biopsies of 116 patients (44 males and 72 females; aged 19 - 83 years, median 55 years; median follow-up 121 months) led to 22 cases (19%) being classified as essential thrombocythemia (ET), 24 (21%) as chronic idiopathic myelofibrosis (CIMF)-0, 44 (37%) as CIMF-1, 13 (12%) as CIMF-2, 9 (8%) as latent phase polycythemia vera, and four (3%) as chronic myeloproliferative disorder, unclassifiable. There was a significant difference in the median age of the ET and fibrotic CIMF patients (54.7 +/- 13.55 vs. 59.13 +/- 15.05 years; P = 0.03). Histologic analysis showed that the simultaneous presence of loose clusters of large/giant megakaryocytes and nuclear hyperlobulation was significantly different between the ET and the prefibrotic CIMF (P<0.01) and fibrotic CIMF patients (P<0.01), and that the association of dense clusters of megakaryocytes with maturation defects and bulbous nuclei also distinguished the prefibrotic CIMF (P<0.05) and fibrotic CIMF patients (P<0.001) from those with ET. The association of cellularity, granulocytic proliferation and reticulin fibers was helpful in distinguishing prefibrotic from fibrotic CIMF (P<0.001).

Adult↗

Assessment of the frequency of additional cancers in patients with splenic marginal zone lymphoma.

OBJECTIVES: Solid second primary cancers (SPC) have become an issue of extensive research. The purpose of the present study was to estimate the standardised incidence ratio (SIR) and the absolute excess risk (AER) of SPC in patients with splenic marginal zone lymphoma (SMZL). METHODS: We investigated the incidence of additional cancers in 129 patients consecutively diagnosed with SMZL in three Italian haematological centres, asking the cooperating doctors for additional information on initial and subsequent therapies and on the onset and type of second cancers. RESULTS: Twelve SPC were recorded (9.3%); the 3- and 5-yr cumulative incidence rates were 5.5% and 18.3% respectively, with an SIR of 2.03 [95% confidence interval (CI): 1.05-3.56; P < 0.05; AER = 145.81]. Of 12 SPC observed, four were urinary tract neoplasms (SIR, 3.70; 95% CI: 1.01-9.48; P < 0.05; AER = 70.06), four were lung cancers (SIR, 9.16; 95% CI: 1.41-13.25; P < 0.05; AER = 85.50) and the other four were hepatic carcinoma, endometrial cancer, breast cancer and colorectal cancer. CONCLUSIONS: Our findings evidence a high frequency of additional cancers in patients with SMZL and suggest that the incidence rate of SPC is significantly different from that expected in the general population. The frequency of cases with urinary tract and lung malignancies in our series is higher than expected. Although confirmatory data are needed, it is our opinion that SMZL patients are at risk of second cancer and should be carefully investigated on diagnosis and monitored during the follow-up.

Aged↗

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: use of fuzzy neural networks.

Our aim was to evaluate in oral squamous cell carcinoma (OSCC) the relationship between some cell cycle markers and HPV infection, conditionally to age, gender and certain habits of patients, and to assess the ability of fuzzy neural networks (FNNs) in building up an adequate predictive model based on logic inference rules. Eighteen cases of OSCC were examined by immunohistochemistry for MIB-1, PCNA and survivin expression; presence of HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR, MY09-MY11/GP5-GP6), and HPV genotype was determined by direct DNA sequencing. Data were analyzed by traditional statistics (TS) and FNNs. HPV DNA was found in 9/18 OSCCs (50.0 %) without any significant higher risk of HPV infection with respect to the sociodemographic variables considered (p > 0.2), apart from tobacco smoking, reported in 44.4% of OSCC HPV-positive vs. 100% HPV-negative subjects (p = 0.029). Regarding cell cycle markers, TS and FNN revealed that survivin was expressed significantly more in HPV-negative than in HPV-positive OSCC [root mean-square error (RMSE) = 5.89 x 10(-6), % predicted 100.0]; furthermore, smoking played a protective role for survivin expression in HPV-positive cases (OR = 0.019, 95%CI 0.001-0.723, RMSE = 0.20, % of prevision 94.4). FNN, although on a small sample size, allowed us to confirm data by TS and to hypothesize a different cell cycle pattern for HPV-positive vs. HPV-negative OSCC. In the latter cases, the relevance of apoptotic vs. proliferative markers suggested that they may be related to the different supposed outcome of HPV-negative OSCC and that HPV may have a protective role in the expression level of survivin, especially in tobacco smokers.

Adult↗

European consensus on grading bone marrow fibrosis and assessment of cellularity.

Quantification of characteristic bone marrow biopsy features includes basic parameters such as cellularity and fiber content. These are important to assess the dynamics of disease processes with a significant impact on risk stratification, survival patterns and, especially, therapy-related changes. A panel of experienced European pathologists and a foreign expert evaluated, at a multi-headed microscope, a large number of representative slides of trephine biopsies from patients with myelofibrosis in an attempt to reach a consensus on how to grade cellularity and fibrosis. This included a critical evaluation of previously described scoring systems. During the microscopic analysis and subsequent discussion and voting, the importance of age-dependent decrease in cellularity was recognized. Grading of myelofibrosis was simplified by using four easily reproducible categories including differentiation between reticulin and collagen. A consensus was reached that the density of fibers must be assessed in relation to the hematopoietic tissue. This feature is especially important in order to avoid a false impression of a reduced fiber content in fatty and/or edematous bone marrow samples after treatment. The consensus for measuring myelofibrosis by clear and reproducible guidelines achieved by our group should allow for precise grading during the disease process and after therapy.

Bone Marrow↗

Splenic marginal zone lymphoma with or without villous lymphocytes. Hematologic findings and outcomes in a series of 57 patients.

BACKGROUND: Splenic marginal zone lymphoma (SMZL) is a well defined pathologic entity. However, questions regarding the bone marrow infiltration rate, the minimal diagnostic data set, and therapy remain unanswered. METHODS: Clinical-pathologic features and outcomes of 57 consecutive patients who had splenomegaly with no clinically significant lymphadenomegaly and who were diagnosed with SMZL with or without (+/-) villous lymphocytes (VL) were reviewed. RESULTS: SMVL +/- VL occurred mostly in elderly males (median age, 62 years +/- 10 years; male-to-female ratio, (1.85). Anemia was recorded in 49% of patients, and 30% of patients had moderate thrombocytopenia. Leukocytosis and leukopenia were found in 33% and 14% of patients, respectively, and typical VL were found in 84% of patients. Serology for hepatitis C virus infection was positive in 16% of patients, and a small monoclonal component was detected in 36% of patients. The bone marrow was infiltrated with an intrasinusoidal component in all patients. Thirteen patients were monitored using a watch-and-see policy, and they remained alive 1-5 years after diagnosis. Overall, 21 patients (36%) underwent splenectomy; and, in all patients, the diagnosis of SMZL was confirmed histologically in the surgical specimens. Twenty-five patients received single-agent therapy, which included either alkylators or pentostatine, and they achieved an overall response rate (ORR) of 65% and 87%, respectively: Polychemotherapy was administered to 6 patients (ORR, 83%). The median survival for all patients in the series was not reached, and it is expected that 70% of patients will be alive at 5 years. CONCLUSIONS: Up to 20% of patients who had SMZL +/- VL could be monitored using a watch-and-wait policy. The bone marrow intrasinusoidal infiltration pattern may be a valuable diagnostic hallmark, thus obviating diagnostic splenectomy. The issues regarding prognostic stratification and the best therapeutic strategy need to be addressed in properly designed, prospective trials.

Adult↗

Long-lasting remission of primary hepatic lymphoma and hepatitis C virus infection achieved by the alpha-interferon treatment.

Primary hepatic lymphoma is a rare but well-defined lymphoma entity that often pursues an aggressive clinical course. Most cases have been described in hepatitis C virus (HCV)-related chronic liver disease patients. Although anthracycline-based chemotherapy has been reported to be highly effective, the best therapeutic strategy has not been defined yet. The prognosis is dismal especially in patients treated with chemotherapy alone or when an advanced liver disease is present. Herein, we describe a case of primary hepatic large B-cell non-Hodgkin's lymphoma, in a patient with HCV chronic infection. After a minor response with eight cycles of CHOP chemotherapy, a complete and sustained remission was obtained with alpha-interferon at the daily dose of 3 MU. HCV-RNA clearance pace from the blood almost paralleled the response of the lymphoma and both diseases went in remission within 1 year of therapy. The possible place of alpha-Interferon in the treatment of primary hepatic lymphoma is discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Bone marrow biopsy in Hodgkin's lymphoma.

In the study of patients with Hodgkin's lymphoma (HL) the evaluation of bone marrow biopsy (BMB) can be difficult. In this review we analyze the main diagnostic features and the clinical risk factors of BM involvement. Although the role of BMB is criticized by some authors, its value is irreplaceable in the staging of HL and in the diagnosis of primary medullary HL. The Ann Arbor staging committee criteria should be revised and updated in the light of the current immunohistochemical studies that give a fundamental help in the diagnostic process. A single BMB should be adequate for diagnosis in most instances. In cases of suspicious involvement a controlateral BMB could be performed.

Bone Marrow Examination↗

Value of bone marrow biopsy in the diagnosis of essential thrombocythemia.

BACKGROUND AND OBJECTIVES: Essential thrombocythemia (ET) is a Philadelphia chromosome-negative chronic myeloproliferative disorder (CMPD) whose diagnosis, according to the Polycythemia Vera Study Group (PVSG) criteria, does not include histopathological data. The new WHO classification of CMPD has supplied new diagnostic guidelines which highlight the value of histopathology and facilitate a more precise differentiation of ET from reactive conditions and other CMPDs. DESIGN AND METHODS: Bone marrow biopsies from 142 adult patients diagnosed with ET according to PVSG criteria were evaluated using the new WHO classification. Megakaryocyte morphology and arrangement, amount of fibrosis and a clustering index were studied along with determination of microvessel density (MVD), amount of CD34+ cells and percentage of MIB-1+ cells and megakaryocytes. The last value, indicated as megakaryocyte proliferation index (MPI), was determined and expressed as a percentage of the counted cells. RESULTS: According to WHO criteria the 142 biopsies were classified as follows: ET (21%); Idiopathic myelofibrosis (IMF) grade 0 (30%); IMF-1 (34%); IMF-2 (10%) ET/IMF-0 (5%). A significant difference (p<0.001) was observed between clustering index values in ET and IMF cases. A peculiar proliferative feature of megakaryocytes, defined coupling, was detected in all ET cases. MVD was more pronounced and the number of CD34+ cells higher in cases of IMF than in cases of ET (p <0.005; p = 0.001, respectively) and MVD significantly correlated with the extent of fibrosis (r=0.861). ET cases showed the lowest values of proliferation; IMF-0 and IMF-1 showed higher values while a decrease of MPI was observed in IMF-2 in accordance with the increase of fibrosis. INTERPRETATION AND CONCLUSIONS: In the diagnosis of thrombocythemic disorders, a multidisciplinary approach must include the evaluation of bone marrow biopsies. Some histopathological criteria, along with the use of markers related to activity and proliferation such as CD34 and MIB-1, underline the biological differences between ET and prefibrotic states of IMF.

Adult↗

Circulating intercellular adhesion molecule-1 in chronic hepatitis C patients with normal or elevated aminotransferase before and after alpha-interferon treatment.

OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1) plays a fundamental role during liver inflammation. In fact, weak ICAM-1 expression is physiologically restricted to the endothelium of portal vessels and to sinusoidal lining cells, but it becomes markedly evident on sinusoidal lining cells and at the surface of hepatocytes during inflammatory liver diseases. The aim of this study was to evaluate the behaviour of soluble ICAM-1 (sICAM-1) in chronic hepatitis C (CH-C) patients with persistently normal aminotransferase in comparison with patients with CH-C and elevated aminotransferase, and its changes during alpha-interferon (IFN) therapy. Immunohistochemical localization of ICAM-1 was also performed on liver tissue specimens of both groups. METHODS: Sixty subjects were divided into 3 groups: group A included 19 patients with CH-C and persistently normal aminotransferase; group B included 21 patients with CH-C and persistently elevated aminotransferase levels, and group C included 20 healthy subjects representing the control group. The first two groups were treated with recombinant alpha-IFN 2b at a dose of 6 MU 3 times a week for 3 months and followed up with 3 MU 3 times a week for another 3 months. RESULTS: Baseline values of serum ICAM-1 in groups A and B were significantly higher than those in group C (p < 0.0001). The median baseline value of sICAM-1 in group A (525.0 ng/ml) was lower than that of group B (561.0 ng/ml), but the difference was not statistically significant. Furthermore, there was a trend toward higher ICAM-1 values as histological severity increased (Mantel-Haenszel chi(2) 8.8, p < 0.003). Post-treatment sICAM-1 serum values showed a marked decrease in both groups, but only among responder patients, while ICAM-1 levels were unchanged in non-responders. Immunohistochemical localization showed no staining for ICAM-1 in normal liver specimens, while there was a quite similar staining for ICAM-1 in the two groups of patients, consistent with an inflammatory process. CONCLUSIONS: This study shows that circulating ICAM-1 levels in most patients with CH-C and persistently normal aminotransferase are higher than those in a control group and the fact that ICAM-1 molecules are also expressed on the hepatocyte membrane suggests that they could play an important role, in association with other molecules, in the intercellular adhesion processes during the induction and maintenance phases of the immune response. In both groups, only patients responding to alpha-IFN therapy showed a marked decrease in serum ICAM-1 below baseline values.

Adult↗

Splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a specific low-grade small B-cell lymphoma that is incorporated in the World Health Organization classification. Characteristic features are splenomegaly, moderate lymphocytosis with villous morphology, intrasinusoidal pattern of involvement of various organs, especially bone marrow, and relative indolent course. Tumor progression with increase of blastic forms and aggressive behavior are observed in a minority of patients. Molecular and cytogenetic studies have shown heterogeneous results probably because of the lack of standardized diagnostic criteria. To date, no definitive therapy has been established. Therapeutic options include treatment abstention, splenectomy, splenic irradiation, and chemotherapy.

Animals↗

Bone marrow biopsy in hemophagocytic syndrome.

AIMS: Hemophagocytic syndrome (HPS) is a severe and acute clinical event occurring with fever, hepatosplenomegaly, and pancytopenia due to uncontrolled phagocytosis of blood cells and precursors. Although HPS represents a secondary phenomenon, it can mask the underlying condition, generally a neoplastic or infective disease, thus making the patient management rather difficult. The aims of this study were to point out the main pathological features useful to highlight the primary disease and show the eventual discrepancies among the different cases. METHODS AND RESULTS: Bone-marrow biopsies (BMBs) of 26 patients with HPS were morphologically and immunophenotypically evaluated; the patients were 12 females and 14 males with mean age of 45.8 years (range 18-80 years). Fifteen patients had a hematological neoplasia either at onset (13 cases) or relapse (2 cases); 5 patients had evidence of active infection immediately prior to HPS development, whereas in 6 patients no definite etiology was established. Cases were therefore divided into neoplasia related, infection related, and "idiopathic". In all cases BMB showed marked histiocyte hyperplasia with hemophagocytosis. In cases of bone-marrow lymphoma or leukemia involvement, immunohistochemistry allowed diagnosis of the underlying disease to be made; infection-related cases showed a reactive marrow with mature interstitial T-lymphoid infiltration, whereas in idiopathic cases T-cells were mainly aggregated in small clusters. In no cases were significant percentages of natural-killer (NK) cells detected. INTERPRETATION AND CONCLUSIONS: Although no strict morphological or immunophenotypical criteria able to allow an immediate diagnosis of underlying disease were pointed out, in most cases BMB proved to be an essential and reliable diagnostic tool. According to our experience, when HPS occurs, the first diagnosis to investigate is a neoplastic disease which sometimes can be latent or hidden.

Adolescent↗