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Biomedical subjects

M G Bernengo

Publications and source records attributed to M G Bernengo.

At least 37 records · Page 2Linked to original sources

Prognostic factors in Sézary syndrome: a multivariate analysis of clinical, haematological and immunological features.

BACKGROUND: Sézary syndrome (SS) prognostic factors are not well defined because of the rarity of this disease. The specific goal of this prospective study was to assess by multivariate analysis the predictive value with respect to survival of a series of clinical, haematological and immunological parameters taken at SS diagnosis. PATIENTS AND METHODS: A cohort of 62 SS patients diagnosed and followed since 1975 was examined, and 51 were included in the multivariate analysis model. RESULTS: The median survival time was 31 months (range: 1 month-15.7+ years), and the five-year survival rate 33.5%. The following variables were found by univariate analysis to be associated with a poor prognosis at the time of SS diagnosis: previous history of mycosis fungoides (P = 0.013), high number of circulating leukocytes (P = 0.001), Sézary cells (SC) (P < 0.001) and CD4+ cells (P < 0.001), presence of large circulating SC (P < 0.001), above normal range LDH serum levels (P = 0.015), presence of PAS-positive inclusions in the cytoplasm of circulating SC (P < 0.001), high CD4/CD8 ratio (P = 0.004) and a CD7 negative circulating SC phenotype (P < 0.001). Among them, the stepwise multivariate analysis selected as adverse independent prognostic factors: PAS-positive cytoplasmic inclusions (P = 0.001), CD7 negative phenotype (P = 0.018) and presence of large circulating SC (P = 0.045). CONCLUSIONS: Two low-/high-risk groups have been singled out on the basis of the risk index. Patients with no or one adverse prognostic feature(s) (risk index < or = 1; n = 31) share a slow disease course and a relatively favorable prognosis (five-year survival: 58%); on the other hand, patients with 2 or 3 adverse prognostic feature (risk index > 1; n = 20) are characterized by an aggressive disease course not modifiable by traditional therapies (five-year survival: 5%).

Adult↗

Immunohistologic findings and adhesion molecule pattern in primary pure cutaneous Rosai-Dorfman disease with xanthomatous features.

Skin involvement is common in sinus histiocytosis with massive lymphadenopathy (SH, Rosai-Dorfman disease), but pure cutaneous cases are rare. A 70-year-old woman presented with a 10-year history of large red-orange nodules and plaques on her upper arms, face, and buttocks, without evidence of lymphadenopathy or internal involvement. Distinctive histopathologic differences were observed according to the duration of the lesions. In recent lesions, the dermal infiltrate was mostly composed of sheets of characteristic SH cells; on the other hand, in long-lasting lesions, the presence of xanthomatous changes and prominent fibrosis, in keeping with the self-limited nature of this disease, raises problems of differential diagnosis with other xanthohistiocytic disorders. Immunophenotypic studies showed that the SH cells are S-100+ CD1a negative-activated macrophages, capable of lysosomal activity. The adhesion molecule pattern of SH cells (CD11b+, CD11c+, CD18+, CD62L+, and CD103+) was similar to that of circulating monocytes, suggesting their recent migration from the bloodstream.

Aged↗

Multiple primary melanomas: analysis of 49 cases.

Development of multiple primary melanomas is a rare but well recognized disease, with an estimated incidence ranging from 1.75% to 8.5% in several series. The clinical, histological and epidemiological characteristics of 49 patients, identified from 2470 with histologically confirmed melanoma, are described in this study. Thirty-five of these patients had two primary melanomas, 11 had three melanomas and three had four, five and six melanomas, respectively. Diagnosis was concurrent in 22 patients (45%); in the remaining cases the median time interval between the first and second melanoma was 22.6 months and the longest interval was 21.5 years. The mean Breslow's thickness decreased significantly (P < 0.001) from the first melanoma to the second and third lesion. The multiple melanoma patients had a higher percentage of subjects over 70 years of age or with lentigo maligna melanoma than single melanoma patients. The mean follow-up time was 12 years (range 4 23 years). The 5-year survival rate from first melanoma excision (83%) does not differ from that of patients with a single melanoma. In conclusion, the presence of multiple primary melanomas does not appear to be a negative prognostic factor; our data show the importance of close follow-up in melanoma patients in order to detect not only metastases, but also subsequent primaries in their earliest phases.

Aged↗

Effects of topical calcipotriol on the expression of adhesion molecules in psoriasis.

Seven patients with chronic plaque psoriasis were treated with topical calcipotriol for 8 to 24 weeks; the lesions improved in 5 patients. Immunohistochemistry was performed on frozen sections, to evaluate the expression of adhesion molecules and extracellular matrix components before and after therapy. Changes in expression and topography of beta1 and beta4 integrins were found on psoriatic lesions before therapy and a reduction in the expression of tenascin was detected as well. Moreover, several activation markers such as ICAM-1, HLA-DR, CD26 were focally positive, with a diffuse cytoplasmic reactivity, in basal and suprabasal layers in untreated lesions. In the 5 patients in whom lesions regressed after topical calcipotriol treatment, we observed a histological normalization of the epidermis and the inflammatory infiltrate was reduced. Moreover, not only was there a normalization in the expression and topography of adhesion molecules, but also the integrin pattern observed after therapy was superimposable to that of normal skin.

Administration, Topical↗

Multiple pyogenic granuloma of the penis.

A case of multiple pyogenic granuloma affecting the penis of a 28 year old man is reported. The lesions were arranged in a floret-like fashion around the inner aspect of the prepuce and developed after circumcision for congenital phimosis. Histopathological examination of sections from a biopsy specimen of the papillomatous growths revealed the findings of pyogenic granuloma. In this patient, the pathogenesis of the lesions is probably related to the failure in surgical wound repair that followed circumcision. Problems of clinical and histopathological differential diagnosis are discussed.

Electrocoagulation↗

Systemic polychemotherapy in the treatment of primary cutaneous lymphomas: a clinical follow-up study of 81 patients treated with COP or CHOP.

The efficacy of systemic polychemotherapy in the treatment of primary cutaneous B-cell lymphomas (CBCL) or T-cell lymphomas (CTCL) is still controversial. A series of 81 patients (46 primary CBCL and 35 CTCL) were treated with COP or CHOP regimens. In primary CBCL, the overall objective response rate (RR) was 98%, with an 89% CR rate and a 33% relapse-rate. Five-year disease-free survival was 70%, 5-year survival 97%. Patients with leg or widespread lesions showed a higher relapse-rate (55% vs 26%) than those with trunk or head lesions. The overall objective RR was 40% in CTCL patients, with a 23% CR rate; median response duration was 5.7 months, median survival 19 months. The results confirm both the good prognosis of primary CBCL and the efficacy of polychemotherapy. CHOP regimen is to be preferred to COP in as much as it reduces relapse rates. Conversely, there are no indications for the use of COP/CHOP regimens as first-line chemotherapy in CTCL patients.

Adult↗

Combination of etoposide, idarubicin, cyclophosphamide, vincristine, prednisone and bleomycin (VICOP-B) in the treatment of advanced cutaneous T-cell lymphoma.

BACKGROUND: Response of cutaneous T-cell lymphoma (CTCL) to systemic chemotherapy is unsatisfactory: despite an initially high response rate (RR), duration is always short-lived. OBJECTIVE: To investigate the capability of a third-generation regimen including idarubicin in improving RR and response duration in CTCL patients. METHODS: Twenty-five patients with advanced CTCL (stages IIB and IV) were treated with a 12-week polychemotherapeutic regimen (VICOP-B), which foresees the use of idarubicin in association with etoposide, cyclophosphamide, vincristine, prednisone and bleomycin. RESULTS: The overall objective RR was 80% (36% complete response). The mycosis fungoides (MF) RR was 84%, with a median duration of 8.7 months. The pleomorphic-lymphoma RR was higher (100%), but the corresponding response duration was shorter (median: 3 months). No responses were documented in Sézary syndrome. CONCLUSION: VICOP-B regimen is effective and feasible as first-line chemotherapy in advanced MF, with or without extracutaneous involvement.

Adult↗

Detection of HIV p24 from antigen presenting monocytes for early diagnosis of HIV-1 infection.

The monocytic/macrophagic lineage has an antigen presenting cell function also towards HIV. On the basis of this fact, a new method, indirect immunofluorescence (IIF) for measurement of p24 from monocytes was used. The results were compared to an amplified enzymatic test for serum dissociated p24 detection in 14 HIV negative individuals at risk for HIV and 12 HIV positive patients. Only one seronegative, who had a symptomatic primary HIV infection, had a positive IIF and also an elevated level of p24 in serum. The others had a negative IIF and, 6 months after the specimen, were not positive to the routine methods for detection of anti-HIV antibodies. Seronegative subjects not at risk for HIV were consistently negative to IIF. Among the HIV positive patients 4 were positive to IIF and the remaining 5 were positive to routine methods. Divergent results could be explained by the fact that one test measures cell derived antigen and the other serum antigen and that monocytes can loose APC function in the advanced stages of the illness. The test proved to be cheap and simple, and it is possible to hypothesize an application of it as a support test for the early diagnosis of HIV infection in laboratories not endowed with high levels of technology. Moreover, the results of the amplified p24 ELISA test in 44 seronegative at risk test are reported herein.

Enzyme-Linked Immunosorbent Assay↗

CD56-positive cutaneous lymphoma: a poorly recognized entity in the spectrum of primary cutaneous disease.

CD56-positive (CD56+) lymphomas, characterized by the expression of the neural cell adhesion molecule on pathological lymphocytes, share a frequent extranodal involvement and a generally aggressive course. Five CD3- CD56+ lymphoma patients presenting with nodular lesions were identified among 180 immunophenotyped cutaneous lymphomas. All the patients were men, with ages ranging from 55 to 78 years. After staging, two patients were diagnosed as having primary cutaneous lymphomas; the remaining three had the secondary cutaneous type. The clinical course was aggressive and four patients died within 8 months from diagnosis. The remaining patient is still alive after a 17-month follow-up. The histological diagnosis was immunoblastic lymphoma in two patients, and medium and large cell pleomorphic lymphoma in three. The angiocentric infiltrate was located mainly in the dermis; azurophilic granules were present in three of the five patients. Immunogenotypic analyses suggested the natural killer cell origin of these neoplasias: all cases exhibited a CD56+ CD3- CD5- T-cell receptor (TCR) silent phenotype, and Southern blot analysis showed a germline configuration of the TCR beta-chain gene.

Aged↗

Low-dose integrated chemoimmuno-hormonotherapy with cisplatin, subcutaneous interleukin-2, alpha-interferon and tamoxifen for advanced metastatic melanoma--a pilot study.

Recently, Khayat et al. reported that high-dose recombinant interleukin-2 (rIL-2) i.v. may induce tumour regressions in metastatic melanoma patients through an association with cisplatin (CDDP) and alpha-interferon (alpha-IFN). Treatment-related toxicities are, however, important. Previous studies have demonstrated that rIL-2 toxicity may be reduced through a subcutaneous injection. In order to evaluate the effectiveness of low subcutaneous rIL-2 doses in a chemoimmuno-hormonotherapeutic combination, 36 metastatic melanoma patients were treated with CDDP, rIL-2, alpha-IFN and tamoxifen (TAM). The overall response rate was 47.2%: five patients had complete response (14%), 12 partial response (33%) and 13 stable disease (36%). Median response duration was 6.4 months (range: 2-29+). Median overall survival was 10 months (range: 3-36+). The CDDP/rIL-2/alpha-IFN/TAM regimen was effective both on soft tissue and visceral metastases. Toxicity was low and patient management did not require an intensive care unit. A statistically significant increase in both percentage and absolute values of lymphocytes, eosinophils, CD3+/CD4+, CD25+, CD16/56+ and HLA-DR+ cells was found in all patients after two treatment courses. This study shows that lower doses of subcutaneous rIL-2, as well as CDDP and alpha-IFN, associated with TAM, may have similar anticancer efficacy with respect to Khayat's schedule but lower toxicity.

Adult↗

Keratinocytes express dipeptidyl-peptidase IV (CD26) in benign and malignant skin diseases.

CD26 expression on keratinocytes, in both normal and pathological skin, was investigated using immunohistochemical techniques. A sporadic focal CD26 positivity was found in normal skin, whereas increased expression of CD26 was observed both in cutaneous T-cell lymphomas and in inflammatory skin diseases, e.g. psoriasis, lichen planus and spongiotic dermatitis, in the basal and spinous layers. CD26 keratinocyte staining was not specific for a single disease, but seems to be associated with the presence of a reactive or neoplastic infiltrate in the epidermis. We propose that the CD26 molecule may function as a keratinocyte activation antigen.

Adult↗

Adjuvant therapy of stage IIIb melanoma with interferon alfa-2b: clinical and immunological relevance.

BACKGROUND: The poor prognosis of stage IIIb melanoma (5-year survival: 36%) shows the need for effective adjuvant therapy to prolong disease-free survival. OBJECTIVE: The feasibility and efficacy of interferon alfa-2b (IFN-alpha) therapy in stage IIIb melanoma patients was investigated. METHODS: alpha-IFN was given at a dose of 3 MU i.m. three times a week to 50 patients. Clinical and immunological controls were carried out. RESULTS: The median follow-up was 43 months (range 5-84). Median survival was 43 months and median disease-free survival 39 months. Overall 5-year survival (62%) was higher than that reported in the literature to date. A significant increase of circulating CD56+ and DR+ lymphocytes after therapy was more evident in disease-free patients than in those with progressing disease. CONCLUSIONS: Adjuvant IFN-alpha therapy in stage IIIb melanoma patients is well tolerated and seems to increase survival. However, multicenter randomized trials are needed to confirm these preliminary findings.

Adult↗

Mantle zone lymphoma: an immunohistologic study of skin lesions.

BACKGROUND: Mantle zone lymphoma (MZL) is a B-cell proliferation regarded as the follicular variant of intermediate lymphocytic lymphoma (ILL). Neoplastic small lymphoid cells proliferate as wide mantles around atrophic centers of benign appearance. OBJECTIVE: The clinical, histologic, and immunohistochemical features of four cases of MZL, heralded by cutaneous lesions, are described and correlated with the lymph node pattern. RESULTS: All specimens showed extensive nodules in the reticular dermis invading the subcutaneous tissue. They were mainly composed of a proliferation of small lymphocytes with slightly irregular nuclear contours and clumped chromatin, forming wide mantles around small atrophic germinal centers. Serial biopsy specimens in case 1 revealed evolution of the skin lesions from pseudolymphoma into MZL. Their immunohistochemistry was similar to that of lymph nodes and showed that the neoplastic cells were CD5+, CD20+, CD22+, CD25+, CD74+, Leu-8+, HLA-DR+, IgM+, IgD+ with restriction for the lambda light chain, CD10-, and CD71-, whereas the germinal center cells were polyclonal. In three cases many CD38+, PCA-1+ plasma cells were present both in the grenz zone and in bordering neoplastic nodules. The clinical course was chronic. The only death occurred from unrelated causes; one patient is still alive 17 years after onset. CONCLUSION: Skin lesions may be the only manifestation of MZL for an extended period. The differentiation between pseudolymphoma and other lymphoma subtypes is based not only on the histologic and cytologic features but also on the architecture, followed by immunohistochemical confirmation.

Adult↗

Adhesion molecules in lymphomatoid granulomatosis.

The expression of some adhesion molecules of the integrin family and their ligands was investigated in skin biopsies from a patient with lymphomatoid granulomatosis (LG), who at onset presented cutaneous lesions followed by lung and brain involvement. The angiocentric and angiodestructive skin infiltrate consisted mainly of T helper 'memory' cells (CD2+, CD3+, CD4+, CD5+, CD7+, CD45RO+) with a variable expression of activation antigens (CD25-, CD38+, CD71+, HLA-DR+) and 20% Ki67+ (nearly all atypical cells). T cells highly expressed alpha 3 beta 1 and alpha 5 beta 1 integrins, along with integrins of the beta 2 family. A modification of the expression pattern in laminin and collagen IV and an increased expression of tenascin and fibronectin were also observed.

Cell Adhesion Molecules↗

Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma.

PURPOSE: Some phase II studies have suggested that the combination of interferons (IFNs) with dacarbazine (DTIC) in the treatment of malignant melanoma (MM) increases the antitumor activity of DTIC alone. In an attempt to confirm this hypothesis, a randomized study was performed with the further intent of observing whether low doses of recombinant interferon alfa-2a (rIFN alpha 2a) could be as effective as intermediate doses. PATIENTS AND METHODS: Two hundred sixty-six patients were randomized onto three different treatment arms: DTIC 800 mg/m2 intravenously (IV) days 1 and 21; DTIC plus rIFN alpha 2a 9 mIU intramuscularly (IM) daily; and DTIC plus rIFN alpha 2a 3 mIU IM three times per week. Major prognostic factors were well balanced among the three arms. Chemotherapy was administered for a maximum of eight cycles. After 6 months of therapy, rIFN alpha 2a was continued until disease progression at 3 mIU three times per week in responding patients who had received the combined treatment. RESULTS: The percentage of objective responses did not differ among the three groups (20%, 28%, and 23%, respectively), although a significant prolongation of response duration was observed when rIFN alpha 2a was added to DTIC (2.6 v 8.4 v 5.5 months, respectively). However, this improvement in response duration did not translate into an amelioration of overall survival. The addition of rIFN alpha 2a led to the onset of flu-like syndrome, but in no case was it necessary to withdraw the treatment program and no toxic deaths or life-threatening toxicities were reported. CONCLUSION: In this study, rIFN alpha 2a significantly prolonged response duration, whereas no effects on response rate and survival were observed; rIFN alpha 2a 3 mIU appeared to be equally effective and better tolerated than 9 mIU.

Adult↗

Soluble interleukin-2 receptor in Sézary syndrome: its origin and clinical application.

Soluble interleukin-2 receptor (sIL-2R) serum levels were evaluated in Sézary syndrome (SS), mycosis fungoides, non-epidermotropic T-cell lymphomas, inflammatory skin diseases (eczema, psoriasis and lichen planus) and benign erythroderma. All groups displayed mean values significantly higher than controls, and values in SS were also significantly higher than those in the other diseases investigated. Follow-up of 17 SS patients showed that serum sIL-2R correlated with the clinical course of the disease and with other haematological parameters (absolute number of circulating Sézary cells, lactic dehydrogenase). Culture experiments demonstrated that, in contrast with other haematological disorders, highly enriched resting Sézary cells were unable to release sIL-2R, and failed to release normal amounts even after mitogen stimulation. Nevertheless, the leukaemic burden, together with the activation and consequent CD25 expression of leukaemic lymphocytes infiltrating the skin, may justify the hypothesis of a neoplastic sIL-2R source. To further support this hypothesis, the highest sIL-2R values were found in patients with advanced disease, in which normal reactive lymphocytes were dramatically reduced.

Adult↗