D Novero

Azienda Ospedaliero-Universitaria San Giovanni Battista di Torino, Torino, Piedmont, Italy

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Publications (49)151.07 Total impact

  • Article: Hepatocellular carcinoma complicating primary sclerosing cholangitis in Crohn's disease. A case report.
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    ABSTRACT: The prevalence of primary sclerosing cholangitis (PSC) in Crohn's disease (CD) patients is up to 8.5%. Although cholangiocarcinoma may complicate long-standing PSC in one third of the cases if follow-up is extended long enough, hepatocellular carcinoma (HCC) is a rare complication of PSC. The concomitant presence of PSC, HCC and CD have been reported sporadically. We discuss here a case of association of these three conditions.
    Minerva gastroenterologica e dietologica 10/2007; 53(3):279-83.
  • Article: Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi).
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    ABSTRACT: A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged <65 years (74 score 2, 38 score 3) entered the study protocol. There were five early and two late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at a median 48 months follow-up, 87 (78%) patients are alive, 82 (73%) in continuous CR, with 4 year overall survival (OS) and event-free survival (EFS) projections of 76% (CI 68-85%) and 73% (CI 64-81%), respectively. There were no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL is improved with the early administration of rituximab-supplemented intensive chemotherapy compared with the poor outcome following conventional chemotherapy.
    Leukemia 08/2007; 21(8):1802-11. · 9.56 Impact Factor
  • Article: Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients.
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    ABSTRACT: Myeloid sarcoma (MS) is a rare neoplasm whose knowledge is largely based on case reports and/or technically dated contributions. Ninety-two MSs in adulthood with clinical data available were evaluated both morphologically and immunohistochemically. Seventy-four cases were also studied by fluorescent in situ hybridization on tissue sections and/or conventional karyotyping on bone marrow or peripheral blood. Histologically, 50% of the tumors were of the blastic type, 43.5% either monoblastic or myelomonocytic and 6.5% corresponded to different histotypes. CD68/KP1 was the most commonly expressed marker (100%), followed by myeloperoxidase (83.6%), CD117 (80.4%), CD99 (54.3%), CD68/PG-M1 (51%), CD34 (43.4%), terminal-deoxy-nucleotidyl-transferase (31.5%), CD56 (13%), CD61/linker for activation of T cells (2.2%), CD30 (2.2%) and CD4 (1.1%). Foci of plasmacytoid monocyte differentiation were observed in intestinal cases carrying inv16. Chromosomal aberrations were detected in about 54% of cases: monosomy 7(10.8%), trisomy 8(10.4%) and mixed lineage leukemia-splitting (8.5%) were the commonest abnormalities, whereas t(8;21) was rare (2.2%). The behavior was dramatic irrespective of presentation, age, sex, phenotype and cytogenetics. Most if not all, long survivors received bone-marrow transplantation. The present report expands the spectrum of our knowledge showing that MS has frequent monoblastic/myelomonocytic differentiation, displays distinctive phenotypic profile, carries chromosomal aberrations other than t(8;21), and requires supra-maximal therapy.
    Leukemia 03/2007; 21(2):340-50. · 9.56 Impact Factor
  • Article: [The Haemolymphopathology Italian Group (H.I.G.): an essential resource for the new technical and organization problems troubling modern haemolymphopathology diagnostics].
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    ABSTRACT: Recently, many progresses have been recorded in the molecular and histogenetic characterization of the haematopoietic and lymphoid tumours, resulting in important classifying changes. As a consequence, the exact definition of lymphoma subtype requires an integration between traditional morphologic "expertise" and several bio-functional data obtained from advanced and complex ancillary techniques (immunohistochemistry, molecular biology and cytogenetics). At the same time, the data provided by gene expression profiling studies are going to deeply modify the therapies in haematological cancers. These studies are expected to allow the achievement of single-patient-tailored genic therapy; for this reason it is necessary to get biological samples of good quality. Indeed, while these progresses contribute to highlight the pathologist's diagnostic role, they should make us reflect on the state of the art of the Italian haemolymphopathology diagnostics and on its ability to cope up with the new challanges. The aim of this article is to outline a realistic picture of the present condition, and to explain the reasons for setting up, inside SIAPEC-IAP, the Haemolymphopathology Italian Group (H.I.G.). The purpose of H.I.G. will be twofold: first of all, scheduling of a series of projects so as to the haemolymphopathological diagnostic standardization; secondly, building a national network among all the pathologists involved in this exciting and complex field of the anatomic pathology.
    Pathologica 03/2006; 98(1):37-40.
  • Article: A case of ulcerative jejunoileitis treated with anti tumor necrosis factor-alpha antibodies.
    Panminerva medica 01/2006; 47(4):269-72. · 1.11 Impact Factor
  • Article: Disseminated Kaposi's sarcoma associated with idiopathic CD4+ lymphocytopenia and low dose steroid therapy.
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    ABSTRACT: A case of disseminated Kaposi sarcoma in a 76-year-old woman treated with low-dose steroids for a seronegative polyarthritis is described. HIV serology was negative, whereas PCR for HHV-8 was positive. The patient presented with a profound reduction in the peripheral blood CD4+ cell count and a decrease in serum immunoglobulins and was diagnosed as having idiopathic CD4+ lymphocytopenia. The clinical picture was characterized by limited cutaneous lesions with typical features of KS associated with widespread visceral involvement and unusually aggressive behaviour.
    Clinical and Experimental Dermatology 08/2005; 30(4):395-7. · 1.20 Impact Factor
  • Article: Association between Crohn's disease and Conn's syndrome. A report of two cases.
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    ABSTRACT: The natural history of Crohn's disease (CD) is characterised by periods of remission followed by phases of flares. Persistent or intractable diarrhoea may be associated with ileal disease or arise following ileal resection, resulting in potassium depletion. Medical therapy with steroids presents troublesome side-effects (e.g. hypertension). Conn's syndrome, caused by unilateral aldosterone-producing adenoma, is characterised by clinical features including hypokalaemia and hypertension. Thus, CD and Conn's syndrome may have an overlap of manifestations, and up to now, the simultaneous occurrence of these conditions has not been described. We report here 2 cases of association between CD and Conn's syndrome.
    Panminerva medica 04/2005; 47(1):61-4. · 1.11 Impact Factor
  • Article: Eosinophilic gastroenteritis with ascites: a case report and review of the literature.
    Digestive Diseases and Sciences 06/2003; 48(5):1013-20. · 2.12 Impact Factor
  • Article: CASE REPORT: Eosinophilic Gastroenteritis with Ascites: A Case Report and Review of the Literature
    Digestive Diseases and Sciences 04/2003; 48(5):1013-1020. · 2.12 Impact Factor
  • Article: Point mutations of the BCL-6 gene: clinical and prognostic correlation in B-diffuse large cell lymphoma.
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    ABSTRACT: Although point mutations of the 5' noncoding regions of the BCL-6 proto-oncogene are frequently detected in B-diffuse large cell lymphoma (B-DLCL), a thorough analysis of the clinical correlation of these mutations has not been performed to date. In this study, BCL-6 mutations were examined by DNA direct sequencing in 103 patients with B-DLCL. BCL-6 mutations were found in 53/103 patients, including 38/76 treated with standard chemotherapy and 15/27 treated with autologous stem cell transplantation (ASCT) up front. The presence of BCL-6 mutations was correlated with clinical features at diagnosis and outcome. Mutated patients had a significantly higher LDH level (66% vs 38%, P < 0.05), and bulky disease (51% vs 32%, P = 0.05). In the whole series of patients BCL-6 mutations did not affect CR and OS. Patients with BCL-6 mutations tended to have a prolonged 5-years DFS and FFS compared to those without mutations (DFS 82% vs 63%, FFS 63% vs 49%). Among B-DLCL treated with standard chemotherapy, mutated patients showed a significantly improved 5-year DFS (85% vs 61%, P < 0.05) and, notably, the only four relapses observed among mutated patients occurred in less than 8 months. The multivariate regression analysis (P < 0.01) with DFS as endpoint confirmed the independent prognostic value of BCL-6 mutations. There was a trend for 5-year failure-free survival to be better for patients with BCL-6 mutations (63% vs 43%, P = 0.09). In the 27 patients treated with ASCT, BCL-6 mutations did not correlate with outcome. These results suggest that BCL-6 mutations may predict a higher chance of being free of disease in B-DLCL treated with standard chemotherapy. Larger series of patients need to be analyzed to evaluate the clinical relevance of BCL-6 mutations properly.
    Leukemia 03/2002; 16(2):268-75. · 9.56 Impact Factor
  • Article: Overweight as an adverse prognostic factor for non-Hodgkin's lymphoma patients receiving high-dose chemotherapy and autograft.
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    ABSTRACT: Despite detailed evaluation of disease-associated prognostic factors, little is known about the impact of overweight in autograft programs for non-Hodgkin's lymphoma (NHL) patients. In order to address this issue, 121 NHL patients were retrospectively evaluated. They had been upfront (92 patients) or in relapse (29 patients) and received high-dose sequential (HDS) chemotherapy including peripheral blood progenitor cell (PBPC) autograft. Body mass index (BMI) was calculated as weight in kilograms divided by the square of the height in meters; overweight was defined as BMI > or = 28. Univariate and multivariate analyses were used to determine the prognostic implication of overweight and other known prognostic indicators on overall (OS) and event-free (EFS) survival for the entire group and overweight and non-overweight (reference) subgroups. With a median follow-up of 3 years, the estimated 5-year OS and EFS for the entire group were 58% and 49%, respectively. Twenty-eight patients (23%) had BMI > or = 28. Their median OS and EFS were 2.2 and 1.4 years, respectively, whereas median OS and EFS for the reference group have not been reached, with a 5-year projection of 65 and 55%, respectively (P < 0.002). On multivariate analysis, the risk of death among overweight patients was 2.9 (CI, 1.3-6.2) times that of the reference group; using EFS as the end point, a similar association between overweight and survival was observed. In conclusion, in high-risk NHL patients undergoing intensive chemotherapy and PBPC autografting overweight is associated with a poorer outcome.
    Bone Marrow Transplantation 12/2000; 26(11):1185-91. · 3.75 Impact Factor
  • Article: Long-term follow-up of advanced-stage low-grade lymphoma patients treated upfront with high-dose sequential chemotherapy and autograft.
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    ABSTRACT: Long-term outcome, after first line intensified high-dose sequential (i-HDS) chemotherapy, was evaluated in 46 patients, aged < or =65 years, with advanced low-grade lymphoma. Seventeen patients had small lymphocytic lymphoma (SLL), 29 had follicular lymphoma (FL), 10 of them with histologic transformation. I-HDS included: (1) tumor debulking, by 2 APO+2 DHAP courses; (2) sequential administration of high-dose (hd) etoposide, methotrexate, and cyclophosphamide, followed by peripheral blood progenitor cell (PBPC) harvest; (3) hd-mitoxantrone + melphalan with PBPC autograft. Ten FL patients had their PBPC immunologically purged ex vivo. There were two treatment-related deaths; five FL patients had short-lasting response followed by disease progression, five SLL reached a stable PR; overall, 34 patients (74%) reached CR. At a median follow-up of 4.3 years, the estimated 9-year OS and EFS were 84% and 45%, respectively. No significant differences were observed in the OS among patients at low, intermediate or high IPI score, with an estimated OS projection of 95%, 78%, and 75%, respectively. FL had longer survival without evidence of residual disease (9-year EFS: 59%) as compared to SLL patients (8.8-year EFS: 17%); however, both groups had prolonged survival and no need of salvage treatment, as shown by the time to disease progression curve, projected to 66% and 62% for SLL and FL, respectively. The results indicate that hd-approach in low-grade lymphoma: (1) is associated with longer progression-free survival as compared to conventional therapies; (2) may imply higher tumor mass reduction in FL as compared to SLL patients; (3) offers long life expectancy, with potential survival benefits at least for patients at intermediate/high IPI score.
    Leukemia 04/2000; 14(4):740-7. · 9.56 Impact Factor
  • Article: Idiotype vaccination in human myeloma: generation of tumor-specific immune responses after high-dose chemotherapy.
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    ABSTRACT: Igs contain unique portions, collectively termed idiotypes (Id), that can be recognized by the immune system. Id expressed by tumor cells in B-cell malignancies can be regarded as tumor-specific antigens and a target for vaccine immunotherapy. We have started a vaccination trial in multiple myeloma (MM) using Id-specific proteins conjugated to keyhole limpet hemocyanin (KLH) as immunogens and low doses of subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) as immunoadjuvants. Twelve patients who had previously been treated with high-dose chemotherapy followed by peripheral blood progenitor cell (PBPC) transplantation entered this study from August 1995 to January 1998. All patients were in first remission at the time of vaccination. They received subcutaneous injections of Id vaccines and immunoadjuvants in an outpatient setting. The generation of Id-specific T-cell proliferative responses was documented in 2 patients, whereas a positive Id-specific delayed-type hypersensitivity (DTH) reaction was observed in 8 of the 10 patients studied. DTH specificity was confirmed in 1 patient by investigating the reactivity to synthetic peptides derived from the VDJ sequence of the tumor-specific Ig heavy chain. None of the patients generated soluble immune responses to Id, whereas the generation of soluble and cellular immune responses to KLH was observed in 100% and 80%, respectively. Eleven patients completed the treatment, whereas 1 patient failed to finish owing to progression of disease. Freedom from disease progression (FFDP), measured from the date of first Id/KLH injection to the date of first treatment after vaccination or last follow-up, ranged from 9 to 36 months. These data indicate that the immune competence status of MM patients is still susceptible to specific immunization after high-dose chemotherapy and PBPC transplantation. It remains to be determined whether generation of Id-specific immune responses can reduce the relapse rate of patients with minimal residual disease.
    Blood 08/1999; 94(2):673-83. · 9.90 Impact Factor
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    Article: Mantle cell lymphoma: a retrospective study on 27 patients. Clinical features and natural history.
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    ABSTRACT: Mantle cell lymphoma (MCL) is a separate histological and clinical entity recently recognized in the new revised European-American Lymphoma Classification. Little information exists regarding its therapy. We report the results of a retrospective study of 27 patients affected by MCL evaluating the clinical characteristics and the results of different therapeutical options used during the period of observation. From 1983 to 1993, we observed 27 patients affected by MCL according to the criteria proposed by European Lymphoma Task Force in a revision of 55 cases classified as NHL E according to Working Formulation (WF) criteria. We analyzed the clinical characteristics, the prognostic factors and the O.S. of these patients. The clinical characteristics of our patients (pts) are similar to those observed in other series: male prevalence, median age 62 years, B symptoms in 9 cases, P.S. > 2 in 11 cases, 3 pts were in stage I and II, 4 in stage III, 20 in stage IV; 18 pts had a bone marrow involvement, 13 pts had spleen enlargement and 14 had extranodal localization; 8 pts had bulky tumor and 5 had LDH above normal. The CR rate was 51.8%, the median O.S. was 43 months, and DFS was 18 months; the pts without bulky disease and with localized disease had a better CR rate. The inclusion of an anthracycline in the regimen did not affect the results. Our results were not divergent from those present in literature. The mantle cell lymphoma is an incurable and highly aggressive disease. Autologous bone marrow transplantation as support of high dose chemotherapy or allogenic bone marrow transplantation may be a chance for some patients, but not for the majority of patients, which are older than 65 years. Studies of a larger series and different therapeutical approaches, i.e. using biological modifiers in association or as maintenance after chemotherapy are essential.
    Haematologica 04/1998; 83(4):312-6. · 6.42 Impact Factor
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    Article: Rearrangements of bcl-6, bcl-2, c-myc and 6q deletion in B-diffuse large-cell lymphoma: clinical relevance in 71 patients.
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    ABSTRACT: B-diffuse large-cell lymphomas (DLCL) have been associated with some molecular lesions, but the role of such lesions as prognostic markers is still controversial. This report concerns an investigation of the frequency and clinical correlation of bcl-6, bcl-2, c-myc rearrangements and 6(q) deletions in B-DLCL. The presence of these genetic lesions was analyzed in samples of lymph nodes or bone marrow collected at diagnosis in 71 patients with B-DLCL, all treated with an anthracycline-containing chemotherapy regimen. Rearrangement of bcl-6 was found in 11 patients (15%), rearranged bcl-2 in 12 (17%), 6(q) deletions in 10 patients (14%) and c-myc rearrangement in four (6%). Patients with rearranged bcl-6 tended to have a more aggressive disease than patients with germ-line bcl-6 (intermediate-high/high risk according to IPI criteria: 73% vs. 43%), but there were no differences in three-year survival rates (62% vs. 42%) between the two groups. The numbers of involved extranodal sites were similar in patients with rearranged and those with germ-line bcl-6. Patients with bcl-2 rearrangement appeared to have a less aggressive disease than those with germ-line bcl-2 (low/ low-intermediate risk 75% vs. 47%) and a slightly better three-year survival rate (70% vs. 41%) but again the difference was not significant. Both groups with or without 6(q) deletion had similar clinical characteristics and outcomes. The four patients with c-myc rearrangement had aggressive disease and did poorly. The analysis of molecular lesions in B-DLCL may be useful for a better diagnostic definition; however, in this study we were unable to show that the evaluated genetic lesions had a significant impact on clinical outcome.
    Annals of Oncology 01/1998; 9(1):55-61. · 6.43 Impact Factor
  • Article: [Lymphadenopathy caused by Toxoplasma in an intramammary lymph node: role of molecular biology in the diagnosis].
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    ABSTRACT: We describe a case of Toxoplasma gondii lymphoadenopathy in an intramammary lymph node in a 22 year old woman. Clinical evidence and ultrasound were suggestive for fibroadenoma, while cytology on fine needle aspiration suspected a lymphomatous lesion. The pathological examination demonstrated a lymph node with granulomatous foci with epithelioid histiocytes, consistent with Toxoplasma gondii lymphadenopathy. The pathological finding was confirmed by serological tests and by PCR (Polymerase Chain Reaction) using specific primers designed on ribosomal 18s DNA sequence of Toxoplasma gondii. The aim of this work is to emphasize the role of molecular biology techniques as an aid to pathological diagnosis in parasite diseases.
    Pathologica 09/1997; 89(4):446-8.
  • Article: Cell proliferation, bcl-2, c-myc, p53 and apoptosis as indicators of different aggressiveness in small lymphocytic lymphoma (SLL).
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    ABSTRACT: Cell proliferation activity, by MIB1 mAb, expression of bcl-2, c-myc and p53 gene proteins and apoptotic index (AI) were assessed in 54 cases of SLL and compared to the morphological subtypes of this disorder, defined by Lennert on the basis of amount and distribution of small and larger activated lymphocytes as diffuse, tumor-forming and pseudofollicular subtypes (DS, TFS, PFS). MIB1 scores showed significant differences between DS, PFS and TFS (5.5%, 16.61% and 24.14%, respectively; p < 0.0001). Worth noting, the MIB1 score did not differ significantly when comparing DS with the diffuse areas of PFS, or TFS with the pseudofollicles of PFS. The mean bcl-2 gene protein score was displayed to a high extent in all subtypes, but less extensively by larger activated lymphocytes that, conversely, expressed c-myc. MIB1 score correlated negatively with bcl-2 and positively with c-myc protein scores. These findings suggest that lymphocytes protected from apoptosis by bcl-2 would be exponed to cell activation and growth acceleration provided by c-myc. This condition would account for a different aggressiveness of morphologically activated subtypes, such as TFS and PFS with larger pseudofollicles. The survival analysis, performed in 23 cases, showed a trend of association of cell proliferation and c-myc expression with a more aggressive progression of the disease. Overexpression of p53 and apoptosis were found only in a minority of cases, unrelated to the subtypes. In conclusion, cell growth fraction, bcl-2 and c-myc assessment may be of help in predicting the aggressiveness of different subtypes of SLL. This approach should be most conveniently applied to PFS, which represents a continuum between DS and TFS, in order to distinguish, in this heterogeneous subtype, more indolent from more aggressive disorders.
    European Journal Of Haematology 09/1997; 59(3):148-54. · 2.61 Impact Factor
  • Article: Analysis of the immunoglobulin heavy-chain gene rearrangement providing molecular evidence of second lymphoma in a patient in apparent relapse after autotransplantation.
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    ABSTRACT: Development of a second lymphoma after autotransplantation is an unusual event. Its real incidence, however, could be underestimated, since histologic and immunophenotyping techniques are often unable to distinguish it from a relapse. We report a lymphoma patient in apparent relapse after 42 months of molecular remission achieved by autotransplantation. Sequencing analysis of the immunoglobulin heavy-chain genes showed that the rearrangement of variable, diversity and joining segments had changed between diagnosis and relapse and suggested that a second lymphoma had developed.
    Bone Marrow Transplantation 09/1997; 20(4):341-3. · 3.75 Impact Factor
  • Article: Recurrent necroinflammatory disease of multiple organs and colon. Systemic presentation of inflammatory bowel disease or gut involvement during systemic disorder.
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    ABSTRACT: A 30-year-old man with a recurrent febrile illness resembling infection is described. Because he presented with an acute abdomen, he underwent a laparotomy, which showed the paraaortic and mesenteric lymph nodes to be changed into an abscess-like granulomatous tissue made up of necrotized granulocytes. During further flare-ups, the disease affected the spleen, skin, colon, peripheral nerve, and muscle. Histology on the biopsy materials of both the skin and colon, and on the surgically removed spleen showed the same invading pathologic tissue. Exhaustive investigation disclosed no pathogen, and the flare-ups responded repeatedly to high-dose steroids. This patient's picture has recently been defined as a syndrome of chronic granulomatosis based on several published cases. As a distinctive feature, in our patient the granulomas affected also the colon. For the present, and for another previously described similar case we analyzed the factors that might permit the differential diagnosis between the above-mentioned granulomatous syndrome and Crohn's colitis.
    Digestive Diseases and Sciences 11/1996; 41(10):2100-5. · 2.12 Impact Factor
  • Article: Recurrent necroinflammatory disease of multiple organs and colon
    Digestive Diseases and Sciences 09/1996; 41(10):2100-2105. · 2.12 Impact Factor

Institutions

  • 1997–2000
    • Azienda Ospedaliero-Universitaria San Giovanni Battista di Torino
      Torino, Piedmont, Italy
  • 1993–1994
    • Università degli Studi di Torino
      • Dipartimento di Biotecnologie Molecolari e Scienze per la Salute
      Torino, Piedmont, Italy