Search PubMed⌕ Search

Biomedical subjects

R Rosso

Publications and source records attributed to R Rosso.

At least 163 records · Page 9Linked to original sources

Locally advanced non-metastatic breast cancer: analysis of prognostic factors in 125 patients homogeneously treated with a combined modality approach.

125 stage III breast cancer patients, including 51 cases of inflammatory carcinoma, were treated with the following combined modality approach: three courses of primary 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) chemotherapy followed by locoregional treatment and subsequent adjuvant chemotherapy consisting of three courses of FAC alternating with three courses of cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Clinical response to primary FAC was 65% (complete 10%). Residual tumour mass in the mastectomy specimen was > 1 and < or = 1 cm in 82 and 18% of cases, respectively. Complete pathological response following primary chemotherapy was achieved in only 3.5% of cases. After primary FAC and local treatment, 97% of patients were disease-free. Overall survival (S) and progression-free survival (PFS) at 5 years were 56 and 34%, respectively. Univariate analysis showed that age, receptor status and clinical and pathological response to primary chemotherapy did not appear to influence treatment outcome significantly, whereas stage, presence of inflammatory disease and number of involved nodes had a significant impact on both S and PFS.

Adenocarcinoma↗

Hepatitis C virus infection in hypogammaglobulinemic patients receiving long-term replacement therapy with intravenous immunoglobulin.

BACKGROUND: Hepatitis C virus (HCV) seroconversion and viremia have been reported in patients treated with intravenous immunoglobulin (IVIG). STUDY DESIGN AND METHODS: A prevalence study was conducted to evaluate the rate of HCV infection in patients undergoing long-term treatment with IVIG. Fifty-four patients with congenital or acquired hypogammaglobulinemia treated with IVIG at 300 to 400 mg per kg every 14 to 21 days for a mean of 6.6 years were enrolled for clinical and biochemical examination. The type of IVIG preparation (type 1 only, type 2 only, or other products) administered to each patient was recorded. Antibodies to HCV were measured by enzyme-linked immunosorbent assay and immunoblotting; HCV RNA was detected by nested polymerase chain reaction. RESULTS: Anti-HCV was detected in 31 patients (57.4%) and HCV RNA was found in 5 patients (9.2%), all of whom were anti-HCV-positive. Abnormal alanine aminotransferase (ALT) levels were found in 10 patients (18.5%). Circulating HCV RNA (p = 0.01) and elevated ALT (p = 0.01) correlated significantly with anti-HCV positivity. Moreover, the rates of anti-HCV positivity and of ALT elevation were significantly higher among patients treated with type 1 IVIG and other products than among those receiving type 2 IVIG (p < 0.001 and p = 0.05, respectively). CONCLUSION: Anti-HCV positivity and viremia were frequently observed. The significant correlation between the detection of HCV RNA, the elevation of ALT, and positivity for anti-HCV suggests HCV infection. Exclusion of anti-HCV-positive donors and of anti-HCV-positive IVIG lots should improve the safety of IVIG.

Adolescent↗

Ambulatory 4-day continuous-infusion schedule of high-dose ifosfamide with mesna uroprotection and granulocyte colony-stimulating factor in advanced solid tumours: a phase I study.

BACKGROUND: There is evidence that continuous infusion allows the delivery of higher doses of a drug while reducing the incidence of neurologic and renal toxicity. To verify prior to phase II testing the feasibility of ambulatory treatment with high-dose ifosfamide/mesna by continuous infusion in adult solid tumours, the maximum tolerated dose (MTD) and the non-haematological dose-limiting toxicities for the achievement of 2 courses of therapy were determined. PATIENTS AND METHODS: Thirty-two patients with advanced solid tumours were given continuous-infusion ifosfamide, from 9 to 16 g/m2, over 4 consecutive days, with equidose mesna uroprotection and granulocyte colony-stimulating-factor support; courses were repeated every 3 weeks. Total dose/course was escalated by 1 g/m2, in cohorts of 3 to 5 patients until the MTD was determined. RESULTS: At 16 g/m2, the dose-limiting toxicity was renal, with 2 of the 5 patients treated developing renal failure. Haematological toxicity was dose-related and significant at higher dosages, but generally surmountable. Ifosfamide at 15 g/m2/course with mesna uroprotection was identified as the MTD. CONCLUSIONS: The present study shows that high-dose continuous-infusion ifosfamide, administered by portable infusion pumps, is feasible in an ambulatory regimen, with acceptable non-haematological toxicity and good patient compliance.

Adult↗

Littoral cell angiosarcoma of the spleen. Case report with immunohistochemical and ultrastructural analysis.

This report describes a case of a malignant vascular tumor of the spleen with the morphologic, immunologic, and ultrastructural features observed in splenic sinus-lining cells (littoral cells). Histological examination showed a well-differentiated neoplasm forming ectatic blood channels with intraluminal papillary fronds. Tumor cells displayed malignant nuclear features and hemophagocytosis. Solid neoplastic areas with mitotic figures were present. Ultrastructurally, the tumor cells showed the concomitant presence of lysosomes and Weibel-Palade bodies. Immunohistochemically, the tumor cells were positive for both endothelial (Factor VIII-AG, CD34) and histiocytic markers (cathepsin D, lysozyme, alpha-1-antichimotrypsin). Our results indicate that angiosarcoma may originate from all the vascular compartments of the spleen, including red-pulp sinuses, and may have morphologic and immunophenotypic similarities to littoral cell angioma, a recently described benign vascular tumor of the spleen.

Aged↗

Evidence for a polyclonal nature of the cell infiltrate in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease).

Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease, is rare histiocytic disorder of known origin which shares several cell markers with Langerhans' cell histiocytosis (LCH). Although Rosai-Dorfman cells exhibit an aberrant immunophenotype, the indolent clinical course of SHML suggests a reactive disorder rather than a neoplastic process. Until recently this was prevailing opinion concerning LCH also, but recent studies have detected clonal histiocytes in all forms of this latter condition, which is therefore considered a clonal neoplastic disorder with highly variable biological behaviour. To determine whether the histiocytic proliferation in SHML is polyclonal or clonal we used X-linked polymorphic loci to assess clonality in lesional tissues in two women. Polymorphic regions of the human androgen receptor (HUMARA) locus were amplified by polymerase chain reaction (PCR) analysis. The HUMARA locus was informative in both cases and, following digestion with methylation-sensitive enzymes, typical polyclonal X-inactivation patterns were observed. Since abnormal cells accounted for > 90% lesional tissue cells, we conclude that Rosai-Dorfman histiocytic proliferation was polyclonal in the women studied.

Base Sequence↗

HCV infection in patients with primary defects of immunoglobulin production.

We tested for infection with hepatitis C virus (HCV) in 58 patients affected by humoral immunodeficiencies: 43 common variable immunodeficiency (CVI), two hyper IgM syndrome (HIM), two IgG subclass deficiency, four ataxia-telangiectasia (AT), and seven X-linked agammaglobulinaemia (XLA). While the assessment of serum specific HCV antibodies in some of these patients was not informative because of the impairment in specific antibody production, the reverse transcriptase polymerase chain reaction (RT-PCR) assay used to detect serum HCV RNA was a useful method for diagnosing infection. We found that 38% of late onset hypogammaglobulinaemic patients (CVI, HIM or IgG subclass deficiency) had evidence of HCV infection. HCV infection was not detectable in patients with XLA or AT. The majority of our patients had persistent viraemia, and those who underwent liver biopsy showed histological findings of chronic hepatitis. Moreover, we could demonstrate in vitro that eight of 18 HCV-infected patients were actively producing anti-HCV antibodies, despite their impaired antibody production. The high rate of HCV infection in hypogammaglobulinaemic patients could be related to several nosocomial routes of transmission, including intravenous immune globulin administration. Despite the persistent viremia only two patients had cirrhosis and none had hepatocarcinoma.

Adolescent↗

Acquired progressive lymphangioma of the skin following radiotherapy for breast carcinoma.

A case of a vascular tumor clinically and pathologically consistent with acquired progressive lymphangioma (benign lymphangioendothelioma) in a 48-year-old woman is reported. The lesion appeared in the skin close to a mastectomy scar 3 years after surgery and radiotherapy for invasive ductal carcinoma. On histologic examination, it mimicked an aggressive vascular neoplasm because of its infiltrative pattern. However, follow-up studies confirmed the benign nature of the lesion, clinically and histologically. This case indicates that acquired progressive lymphangioma may follow radiotherapy and must be considered in the differential diagnosis of other vascular proliferations occurring in the skin of the breast, especially of low-grade postradiation angiosarcoma, a recently described neoplastic entity.

Breast Neoplasms↗

Topical dimethylsulfoxide for the prevention of soft tissue injury after extravasation of vesicant cytotoxic drugs: a prospective clinical study.

PURPOSE: To evaluate the activity and tolerability of dimethylsulfoxide (DMSO) in the prevention of soft tissue toxicity after extravasation of cytotoxic drugs. PATIENTS AND METHODS: From June 1991 to December 1994, all patients who had an extravasation during intravenous (IV) infusion of cytotoxic drugs in our institution were considered for an open, prospective study of preventive treatment with 99% DMSO, applied topically on the extravasation site every 8 hours for 7 days. Intermittent local cooling (for 1 hour three times daily) on the first 3 days was also used. RESULTS: One hundred forty-four patients with extravasations of doxorubicin (n = 11), epirubicin (n = 46), mitomycin (n = 5), mitoxantrone (n = 13), cisplatin (n = 44), carboplatin (n = 6), ifosfamide (n = 14), and fluorouracil (n = 5) entered the study; 127 were assessable. Only one patient suffered an ulceration. The treatment was well tolerated, with mild local burning and a characteristic breath odor being the only side effects of DMSO application, even in cases in which treatment continued for up to 6 weeks to obtain remission of the symptoms of extravasation. CONCLUSION: Topical DMSO is an effective and safe antidote that may be used with local cooling after extravasations of vesicant drugs other than those drugs for which standard interventions are defined.

Administration, Topical↗

CD30/Ki-1-positive lymphoproliferative disorders of the skin--clinicopathologic correlation and statistical analysis of 86 cases: a multicentric study from the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group.

PURPOSE: Recently, it has been shown that CD30 antigen expression is associated with a relatively favorable prognosis in primary cutaneous large-cell lymphomas (CLCLs). However, prognostic subsets within the CD30+ group have been difficult to identify due to lack of uniform clinicopathologic and immunophenotypic criteria, limited clinical information, and the inclusion of relatively few patients for statistical analysis in prior studies. To address these problems, we formed a multicentric study group of pathologists and dermatologists to classify and evaluate 92 cases of CD30+ cutaneous lymphoproliferative disorders. PATIENTS AND METHODS: An expert panel established consensus diagnoses for 86 CD30+ cutaneous lymphomas. Cases, clinically and histologically classified as lymphomatoid papulosis (LyP), anaplastic large-cell lymphoma (ALCL), nonanaplastic lymphoma, and borderline histology between LyP and ALCL, were then analyzed statistically by univariate, multivariate, and Cox regression model analysis of potential prognostic features. RESULTS: Spontaneous regression and age less than 60 years were associated with a favorable prognosis, while extracutaneous disease and age greater than 60 had a poor prognosis. Patients with LyP had the best prognosis, followed by those with primary CD30+ lymphomas, regardless of cytologic type (anaplastic or nonanaplastic). Borderline cases, morphologically indistinguishable from LyP and CD30+ ALCL, had a favorable prognosis, similar to LyP. CONCLUSION: Our findings indicate that CD30+ cutaneous lymphoproliferative disorders comprise a spectrum of closely related skin lesions, which can be assigned a relatively favorable or unfavorable prognosis by a combined clinical and pathologic analysis.

Adolescent↗

Adjuvant Treatment of Colorectal Cancer in the Elderly.

From March 1992 until January 1994, 1,014 patients radically resected for Dukes' B(2), B(3) or C colon cancer were randomized to receive FU plus levamisole or FU plus leucovorin (LV) plus levamisole. Only 41% of patients older than age 70 years, as compared to 53% of those younger, have completed the treatment as planned. This poorer compliance was not associated with a higher incidence or degree of toxicity. Only a small difference in percentages was detected between the age groups of patients requiring dose reductions or treatment delays, while the percentages of patients that had their treatment discontinued was markedly increased in the older age group, without a parallel increase in severe toxicity. Preliminary results suggest that adjuvant chemotherapy with FU plus levamisole or FU plus LV plus levamisole is well tolerated by elderly patients and is not associated with greater toxicity in patients over 70 years of age than in younger patients. The lower adherence to the treatment plans in older patients may be due to reluctance by physicians and families to administer chemotherapy due to the misconception that the elderly are more prone to adverse reactions.

Journal Article↗

Caring for the Older Cancer Patient: Comprehensive Geriatric Evaluation.

Elderly patients comprise almost half of daily adult oncology practice, but management guidelines based on data from clinical trials performed in the elderly are lacking. Comprehensive geriatric evaluation and the use of different outcome measures for trials of interventions in the elderly are needed to provide clinicians and patients the information required to make the best management decisions.

Journal Article↗

[Functional and morphological results of transplantation of vascularized knee joints in a dog model--a preliminary report].

Functional and morphological results of transplantation (n = 3) and replantation (n = 4) of vascularised total knee joints were compared in a canine model. Follow up time was 6 months. All vascular anastomoses remained patent and all osteotomies healed. Replanted animals displayed normal static weight bearing in contrast to the transplant recipients, which showed reduced weight bearing after 6 months compared to preoperative values. Mild to moderate signs of chronic allograft rejection were detected in all transplanted animals. Functional results were correlated with morphological outcome demonstrating the relevance of adequate control of rejection.

Animals↗

In vitro synergism between 5-fluorouracil and natural beta interferon in human colon carcinoma cells.

The combination of 5-fluorouracil (FUra) plus IFN-beta was studied in vitro using a human colon carcinoma cell line, HCT-8. Continuous exposure to high concentrations of IFN-beta is cytotoxic to these cells (ED50, 600 +/- 50 IU/ml). A strong synergism (P < 0.002) was observed when a short-term (1-h), high-concentration exposure to fluoropyrimidine (300 or 1000 microM) was followed by IFN-beta given continuously. In fact, the mean ratio between the expected (product of the survival of each agent alone) and the observed clonogenic cell survival rates of the combination was 3.4 (range, 2.4-4.9). Longer exposures to the fluoropyrimidine (24 h, 7 days) produced less than additive effects with IFN-beta, indicating strong schedule dependency for this synergism. The mechanism of interaction was studied at four levels. First, thymidylate synthase (TS) activity, inhibition, and recovery were measured by an in situ assay in cells treated with FUra, IFN-beta, and their combination. When the prolonged infusion of IFN-beta followed a 1-h exposure to FUra, the observed TS inhibition and recovery, at each time point, were very similar to the expected values, indicating that the interactions between these drugs at the level of TS are not the determinant of the synergism. Second, cell cycle analysis was done. During the continuous exposure to IFN-beta, a significant accumulation of HCT-8 cells in S-phase was observed at 24, 48, and 72 h compared to untreated controls (P = 0.003); however, under the same experimental conditions producing synergy in the clonogenic assay, no significant cell cycle perturbations were produced by the combination of FUra followed by IFN-beta compared to those caused by each agent alone. Third, using the alkaline elution test, we also demonstrated that the synergism is not due to enhanced FUra-induced DNA single-strand break frequency in high molecular weight DNA. Finally, nucleic acid incorporation experiments, using tritiated FUra, showed that the cytokine, given continuously (300 IU/ml), enhanced the amount of FUra incorporated into nucleic acids 24 h after a 1-h exposure to 300 and 1000 microM of FUra. The median percentage of enhancement values were 31.6 +/- 11.5%,m for the lower drug concentration and 18. 4 +/- 8.1% for the higher drug concentration tested. These results suggest that the mechanism of this synergism may be related to the ability of IFN-beta to promote the incorporation of intracellular FUra metabolites into nucleic acids and/or to inhibit the cleavage of FUra nucleotides from RNA/DNA.

Antineoplastic Combined Chemotherapy Protocols↗

Schedule-selective biochemical modulation of 5-fluorouracil: a phase II study in advanced colorectal cancer.

Based on experimental findings suggesting that 5-fluorouracil (FUra) may have different mechanisms of action depending on the schedule of administration, we generated the hypothesis that biochemical modulation of this fluoropyrimidine should be schedule specific. We thus tested the activity of a hybrid regimen consisting of two biweekly cycles of FUra bolus (600 mg/m2) modulated by pretreatment (24-h interval) with methotrexate (200 mg/m2), alternating with a 3-week continuous infusion of FUra (200 mg/m2/day) modulated by low-dose (6S)leucovorin (20 mg/m2 bolus weekly). Thirty-three consecutive patients with advanced measurable colorectal cancer and no prior therapy for metastatic disease entered the study from February 1992 to August 1993. They were treated with two biweekly cycles of FUra bolus (600 mg/m2) preceded by (24-h interval) methotrexate (200 mg/m2), alternating with a 3-week continuous infusion of FUra (200 mg/m2/day) modulated by low-dose (6S)leucovorin (20 mg/m2 bolus weekly). The median Eastern Cooperative Oncology Group performance status was 1; the liver was the only metastatic site in 17 patients. Treatment outcome was evaluated by computed tomographic scan in all patients, except for two. Three complete and 13 partial responses were obtained among these 33 patients (response rate, 48%; 95% confidence limits, 31-66%). Performance status (Eastern Cooperative Oncology Group) influenced clinical response. The combined complete response and partial response rate was 69%, 33%, and 25% in patients with an Eastern Cooperative Oncology Group performance status of 0, 1, and 2, respectively (chi2, 4.6, P = 0.032, two-tailed Mantel test for trend). After a median follow-up time of 26 months, 10 patients are still alive. The median progression-free survival and overall survival were 9.5 and 20.2 months, respectively. No toxic deaths or grade 4 toxicity occurred. The incidence of grade 3 toxicity per patient in any cycle was: mucositis 6%, diarrhea 3%, and vomiting 3% for the bolus part and 21%, 3%, and 6%, respectively, for the continuous infusion part of the regimen. Hand-foot syndrome occurred in 27% of the patients treated with the continuous infusion regimen.

Adult↗

Release of peripheral blood progenitor cells during standard dose cyclophosphamide, epidoxorubicin, 5-fluorouracil regimen plus granulocyte colony stimulating factor for breast cancer therapy.

BACKGROUND: High dose chemotherapy with the support of peripheral blood progenitor cells (PBPC) is increasingly used in the treatment of solid tumors. Although the best method of PBPC mobilization is still under investigation, it should be optimized for different tumor types to obtain antitumor effect and mobilizing activity. The authors report these results in terms of the number of PBPC released and the time of maximum mobilization induced by standard dose cyclophosphamide, epidoxorubicin, 5-fluorouracil (CEF) (cyclophosphamide 600 mg/m2, epidoxorubicin 60 mg/m2, 5-fluorouracil 600 mg/m2) plus granulocyte colony stimulating factor (G-CSF) in patients with breast cancer. METHODS: Peripheral blood progenitor cells were studied by clonogenic assay of granulocyte macrophage colony-forming units (CFU-GM), megakaryocyte colony-forming unit (CFU-Meg) and erythrocyte burst-forming unit (BFU-E) and by flow cytometric analysis of CD34+ cells in 12 patients with early breast cancer throughout three cycles of CEF chemotherapy plus G-CSF. RESULTS: Colony assays and CD34+ cell determination were performed on 111 and 151 blood samples, respectively. The peak of CFU-GM and CD34+ cells occurred consistently at day 11 throughout all three cycles. At day 11 of the first cycle, the median peak values were 2223 CFU-GM/mL and 256 CD34+ cells/microL. A progressive decrease in peak value from the first to the third cycle was observed. CONCLUSIONS: Standard dose CEF chemotherapy plus G-CSF is a disease specific regimen allowing PBPC mobilization without any relevant toxicity. Maximum mobilization was recorded at day 11 of the first cycle.

Adult↗

Primary gastric CD30 (Ki-1)-positive large cell non-Hodgkin's lymphomas. A clinicopathologic analysis of six cases.

BACKGROUND: The CD30/Ki-1 antigen characterizes a series of non-Hodgkin's lymphomas (NHL) predominantly showing anaplastic large cell (ALCL) morphology and frequently involving the skin and other extranodal sites. In cutaneous large cell lymphomas, the CD30 expression was indicated as a favorable prognostic marker independently from cytology, anaplastic versus nonanaplastic. The stomach is the most common site of extranodal lymphomas in the adult population, but primary gastric CD30+ lymphomas have been reported rarely. METHODS: The clinical, morphologic, and immunohistochemical features of six cases with primary CD30/Ki-1+ gastric large cell lymphomas were analyzed. RESULTS: The mean age of patients was 64 years with a prevalence of women (M:F ration = 1:2). Patients were assigned to Stage IE or IIE. Three of them died of disease, whereas the others are still alive (mean follow-up, 18 months). Three of six cases had ALCL morphology, whereas other cases had centroblastic, immunoblastic, and high-grade mucosa-associated lymphoid tissue lymphoma. Immunohistochemistry revealed a B-cell phenotype in three of six cases; a T-cell phenotype in one of six cases; and a null, non-B, non-T phenotype in two of six cases. CONCLUSIONS: Within CD30+ primary gastric large cell lymphomas, cytology, anaplastic versus nonanaplastic, did not affect clinical presentation and/or prognosis. The survival rate of the patients studied is in keeping with literature reports regarding prognosis of primary high-grade gastric NHL. The findings suggest that clinical behavior of this extranodal lymphoma is more closely related to clinical symptoms and initial stage of disease than to CD30 expression.

Adult↗