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Biomedical subjects

A Zaccaria

Publications and source records attributed to A Zaccaria.

At least 19 recordsLinked to original sources

Prediction of response to imatinib by prospective quantitation of BCR-ABL transcript in late chronic phase chronic myeloid leukemia patients.

Imatinib mesylate (STI571), a specific Bcr-Abl inhibitor, has shown a potent antileukemic activity in clinical studies of chronic myeloid leukemia (CML) patients. Early prediction of response to imatinib cannot be anticipated. We used a standardized quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR) for BCR-ABL transcripts on 191 out of 200 late-chronic phase CML patients enrolled in a phase II clinical trial with imatinib 400 mg/day. Bone marrow samples were collected before treatment, after 12, 20 and at the end of study treatment (52 weeks) while peripheral blood samples were obtained after 2, 3, 6, 10, 14, 20 and 52 weeks of therapy. The amount of BCR-ABL transcript was expressed as the ratio of BCR-ABL to beta2-microglobulin (beta2M). We show that, following initiation of imatinib, the early BCR-ABL level trends in both bone marrow and peripheral blood samples made it possible to predict the subsequent cytogenetic outcome and response. We propose this method as the method of choice for monitoring patients on imatinib therapy. QRT-PCR studies may be able to identify degrees of molecular response that predict both complete cytogenetic response and long term stability, as well as patterns of response that provide an early indication of relapse and imatinib resistance.

Antineoplastic Agents↗

CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma.

Thirty untreated patients, median age 69 years (range 60 - 75 years), with diffuse large B-cell lymphoma (B-DLCL) were treated with a pegylated liposomal doxorubicin (PL-doxorubicin) modified CHOP-rituximab regimen. PL-doxorubicin 30 mg/m2, was given in combination with standard dosage of prednisone, vincristine, cyclophosphamide, rituximab (according to CHOP-R regimen) every 21 days for six courses. Cardiac toxicity was evaluated by mean of echocardiography for left ventricular ejection fraction (LVEF) evaluations and serum troponin-I levels. Overall response and complete response rates were 76% and 59%. Projected two year event free survival and overall survival are 65.5% and 68.5%. No treatment-related mortality was documented. WHO grade III-IV neutropenia and thrombocytopenia were 86% and 3%. Extra-hematological III-IV toxicity was represented, respectively, by a single case of infection, mucositis, and bleeding. LVEF evaluations and the troponin levels did not show significant changes over the course of the treatment. One patient with a previous history of atrial fibrillation experienced a single episode of arrhythmia. None of the patients developed palmar-plantar erythrodysesthesia. This regimen appears an active regimen for the treatment of elderly patients with B-DLCL. The replacement of conventional doxorubicin with PL-doxorubicin seems to be associated with a negligible incidence of extra-hematological toxicity, in particular cardiac and infectious complications.

Aged↗

Management of acute lower limb ischemia following percutaneous arterial closure device application: our experience.

INTRODUCTION: The Authors report their experience in the management of acute lower limb ischemia following percutaneous arterial closure device application. PATIENT AND METHODS: Five patients required an emergency vascular operations for acute lower limb ischemia. The symptoms onset was < 1 hour in 1 case, 4-12 hours in 2 cases and > 24-36 hours in 2 cases. A preoperative angiography was performed in all the cases. A transfemoral embolectomy was carried out. Direct suture repair were performed in three cases, vein patch angioplasty was carried out in two cases. In one case, a common femoral artery endarterectomy was performed. RESULTS: No post-operative mortality and limb loss occurred. CONCLUSIONS: Acute lower limb ischemia due to closure devices required an extensive approach with reconstruction in high risk septic area. Angiography is mandatory for surgical strategies. We prefer direct suture repair and vein path angioplasty for vascular reconstruction.

Acute Disease↗

Indications and results of endovenous laser tratment (EVLT) for greater saphenous vein incompetentce. Our experience.

AIM: Endovenous laser treatment (EVLT) seems to be a safe and less invasive method for the treatment of the great saphenous vein (GSV) incompetence. The aim of our study was to evaluate the indications and results of EVLT. METHODS: Between January 2003 and October 2004, 77 patients (55 C3 and 22 C4) underwent EVLT. In 23 cases phlebectomy was performed, in 16 patients a subfascial perforator vein ligations occurred. In 62 patients we used a percutaneous access to the distal GSV, in 15 cases a surgical isolation was performed. In all cases a 600 nm with 1 mm diameter laser was used. RESULTS: Follow-up was performed for a period of 6 months and showed GSV recanalization in 2 cases; 18 patients (23.3%) developed a transient postoperative pain along GSV, in 4 (5.1%) of them the pain persisted for 3 months. In 6 cases a reversible paresthesia due to a lesion of the saphenous nerve were recorded (7.7%) and in 1 case (1.2%) a skin burn occurred. No deep vein thromboses were observed. CONCLUSIONS: EVLT is a safe technique, with low incidence of recanalizations and postoperative complications. Our opinion is to extend the indication in selected cases of GSV incompetence.

Female↗

Vascular Thoracic Outlet Syndrome staging and treatment.

Thoracic Outlet Syndrome (TOS) is a well known lesion. Sophisticated imaging techniques can clearly highlight any anatomical damage and a wide range of therapeutic choices are available. It would seem obvious that any given patient should obtain the same treatment irrespective of the medical institution he contacts, but this is not the case. Instead each specialist may recommend different treatments: physiatrist, neurologist, surgeons (thoracic, vascular, neuro, orthopedic). Everyone preserves his specific language and there is no univocal treatment plan consensus for this complex syndrome. Evidently, the correct staging of TOS is still an unresolved question. In order to solve this problem, we collected all clinical and instrumental aspects of the syndrome into a clear, precise classification. Similar to TNM staging of malignant diseases, we used a grouping model based on the three mainly involved anatomical structures: N (= Nerves; brachial plexus and sympathetic fibers), A (= Artery; subclavian-axillary), V (= Vein; subclavian-axillary). We named it the NAV staging of TOS. A retrospective examination of our case records confirmed a valid and useful correlation between the proposed NAV staging and the therapeutic procedures that were actually applied. It is now essential to perform a multi-centre study to extend the validity of our staging.

Decompression, Surgical↗

Rupture of an isolated true superficial femoral artery aneurysm: case report.

True isolated atherosclerotic aneurysm of the superficial femoral artery is a rare pathology. We report a case of ruptured superficial femoral artery aneurysms (SFAA) not associated with aortic, common femoral or popliteal artery aneurysms. An emergency surgical procedure was performed and, after endoaneurysmal branches ligation, a ePTFE graft interposition was performed. The literature review shows a prevalence of rupture as compared with ischemic complications and the need for surgical repair in case of SFAA with diameter twice the normal vessel size. Early diagnosis and management are recommended because of the lower morbility and mortality rates associated with elective surgery by comparison with emergency procedures.

Aneurysm, Ruptured↗

Suprarenal artery stenosis may be mistaken for renal artery stenosis in Doppler studies.

There are several limitations in using colour-flow-Doppler (CFD) to diagnose renal artery stenosis. This report describes a case of "false positive" stenosis of the renal artery diagnosed using CFD. A patient affected by arterial hypertension and with a suspected stenosis of the renal artery was examined using CFD. However, the patient was in fact suffering from suprarenal artery stenosis.

Aged↗

Atherosclerotic ischemic renal disease.

AIM: Atherosclerotic ischemic renal disease is a frequent cause of end-stage renal failure leading to dialysis among the elderly; its prevalence is inferred from autopsy or retrospective arteriographic studies. Screening investigation for ischemic nephropathy on large cohorts, based on non invasive diagnostic techniques, have not so far been published. This study has been conducted on 269 subjects over 50 with hypertension and/or chronic renal failure, unrelated to other known causes of renal disease. METHODS: All 269 patients were studied either by color-flow duplex sonography (n=238) or by renal scintigraphy (n=224), and 199 of the 269 patients were evaluated using both of these techniques. Forty patients, found to have renal artery stenosis, were subjected to 3D-contrast enhancement magnetic resonance angiography (MRA) and/or digital selective angiography (DSA). An additional 23 cases, negative both to scintigraphy and to ultrasound study, underwent renal angiography (MRA and/or DSA). RESULTS: Color-duplex sonography, carried out in 238 patients, revealed 49 cases of renal artery stenosis. MR or DSA was carried out in 35 of these 49 patients, and confirmed the diagnosis in 33. Color-duplex sonography was 91.7% sensitive and 90.9% specific, with positive predictive value of 94.2% and negative predictive value of 86.9%. Specificity and sensitivity of renal scintigraphy, carried out in 224 patients, was significantly lower. Patients with renal artery stenosis showed a higher degree of renal insufficiency compared to non stenotic patients while there were no differences in the extent of proteinuria between the two groups. Renal artery stenosis, based on color-duplex sonography studies, was present in 11% of patients in the age group 50-59, 18% in the 60-69 and 23% at age 70 and above. CONCLUSION: A relatively large percentage of the elderly population with renal insufficiency and/or hypertension is affected by renal artery stenosis and is at risk of developing end-stage renal failure. Color-duplex ultrasonography is a valid routine method of investigation of population at risk for renal artery stenosis.

Aged↗

Randomized trial of 8-week versus 12-week VNCOP-B plus G-CSF regimens as front-line treatment in elderly aggressive non-Hodgkin's lymphoma patients.

BACKGROUND: Among the third-generation chemotherapy regimens specifically adapted in the last decade for elderly aggressive non-Hodgkin's lymphoma (NHL) patients, we designed an 8-week cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin and prednisone (VNCOP-B) plus granulocyte colony-stimulating factor (G-CSF) regimen which, in a national multicenter trial, induced good complete response (CR) and relapse-free survival rates with only moderate toxic effects. Here we report a prospective, multicenter, randomized trial comparing the efficacy and toxicity of 8- and 12-week regimens of VNCOP-B plus G-CSF. PATIENTS AND METHODS: From February 1996 to June 2001, 306 consecutive previously untreated stage II-IV aggressive NHL patients > or =60 years of age were enrolled from 12 Italian cooperative institutions. Of the 297 evaluable patients, 149 and 148 received 8- and 12-week regimens, respectively, of VNCOP-B. RESULTS: The CR rates were 63% and 56% in the 8- and 12-week groups; at a median of 32 months (range 3-62 months), relapse-free survival rates were 59% and 55%, respectively. Hematological and non-hematological toxicities were similar in both treatment groups. CONCLUSIONS: Our data show that extending induction treatment with the VNCOP-B plus G-CSF regimen from 8 to 12 weeks does not raise the CR rate or provide a more durable remission.

Aged↗

Fludarabine, arabinosyl cytosine and idarubicin (FLAI) for remission induction in poor-risk acute myeloid leukemia.

Progress in treatment of acute myeloid leukemia (AML) is slow and treatment intensification alone has limited effects, particularly in poor-risk cases. Poor-risk cases, that are identified mainly by prior history, leukemic cell mass and cytogenetic abnormalities, share multiple mechanisms of drug resistance that are responsible for treatment failure. Since Pgp-mediated resistance to anthracycline can be reduced with Idarubicin (IDA) and resistance to arabinosyl cytosine (AC) can be reduced with Fludarabine (FLUDA), we tested a combination of high dose AC (2000 mg/sqm, 5 doses), FLUDA (30 mg/sqm, 5 doses) and IDA (12 mg/sqm, 3 doses) for remission induction and consolidation in 45 consecutive cases of poor-risk AML. The complete remission (CR) rate was 71% after the first course and 82% overall, with a projected 2-year survival and relapse-free survival of 44% and 50% respectively. Non-hematologic toxicity was very mild, that is very important in elderly patients, but hemopoietic toxicity was substantial, with a time to hematologic recovery of 3 to 4 weeks and two cases of death in CR. Peripheral blood stem cells (PBSC) could be mobilized and collected successfully only in 11 cases. This three-drug combination is effective and has a limited non-hematologic toxicity, but FLUDA may increase the difficulty of obtaining PBSC early after remission induction.

Acute Disease↗

Primary mediastinal large B-cell lymphoma with sclerosis: a clinical study of 89 patients treated with MACOP-B chemotherapy and radiation therapy.

BACKGROUND AND OBJECTIVES: Primary mediastinal large B-cell lymphoma (PMLBCL) with sclerosis has recently been recognized as a specific clinical and pathologic entity for which the best therapeutic approach seems to be a combination of chemotherapy and radiotherapy. DESIGN AND METHODS: Between 1989 and 1998, 89 previously untreated patients with PMLBCL with sclerosis were treated with a combination of a third-generation chemotherapy regimen (MACOP-B) and mediastinal radiation therapy. The response evaluations were examined after chemotherapy and at the end of radiotherapy. RESULTS: Twenty-three (26%) patients achieved a complete response (CR) and 59 (66%) obtained a partial response (PR) after the MACOP-B regimen. After radiation therapy, 55/59 (93%) of the patients in PR achieved CR. The CR rate at the end of the treatment was 88% (78/89). Only 7 (8%) patients were non-responders. Among the 78 patients who obtained a CR there were 7 (9%) relapses in a median follow-up of 5 months (all relapses occurred within 9 months); the other 71 patients are currently in continuous CR with a median follow-upof 45 months (range, 4-110 months). Projected overall survival was 86% at 9 years; the relapse-free survival curve of the 78 patients who achieved CR was 91% at 9 years. INTERPRETATION AND CONCLUSIONS: In patients with PMLBCL with sclerosis, combined modality treatment using the MACOP-B chemotherapy regimen and radiation therapy induces a good remission rate with the patients having a greater than 90% chance of surviving disease-free at 9 years. Radiotherapy often plays a pivotal role in obtaining CR status.

Adolescent↗

Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma.

PURPOSE: A first comparative trial of fludarabine (FLU) alone versus FLU plus idarubicin (FLU-ID) for indolent or mantle-cell lymphomas. PATIENTS AND METHODS: From September 1995 to July 1998, 199 patients aged 25 to 65 years (median, 54 years) with newly diagnosed stages II to IV indolent or mantle-cell lymphomas (standard risk according to the International Prognostic Index) were enrolled onto a multicenter, 1:1 randomized study. Of the 199 patients who were able to be assessed, 101 were assigned to the FLU group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 5) and 98 to the FLU-ID group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 3 and idarubicin 12 mg/m(2) on day 1). RESULTS: In the FLU group, complete response (CR) and partial response rates were 47% and 37%, respectively, whereas in the FLU-ID group, they were 39% and 42%, respectively. In-depth analysis of the CR rate with respect to histologic type showed that FLU seemed to be superior to FLU-ID in treating follicular lymphomas (60% v 40%, respectively), whereas FLU-ID seemed to be more effective than FLU in treating nonfollicular lymphomas (small lymphocytic, 43% v 29%, respectively; immunocytoma, 38% v 23%, respectively; P = not significant), excluding the mantle-cell subset (in which there was no difference between the two groups). No striking differences were observed between the two protocols in terms of overall response or toxicity, which was generally mild. However, with a median follow-up of 19 months, only 29 patients (62%) who received FLU alone have maintained their initial CR, compared with 32 (84%) of those who received FLU-ID therapy (P =.021). CONCLUSION: Although the FLU-ID regimen may not significantly improve the induction of CR in most indolent-lymphoma patients, our preliminary data do suggest that, with respect to FLU alone, it may be capable of conferring a longer-lasting CR and that it might be superior in terms of CR rate in small lymphocytic and immunocytoma subtypes.

Adult↗

The lung as a target organ in patients with hematologic disorders.

The lung is one of the organs most severely affected by complications during the course of hematologic disorders. In the last years an impressive amount of progress has been made in clarifying the pathogenesis of lung diseases, particularly those occurring in conditions of severe immunosuppression such as bone marrow transplantion, acquired immunodeficiency syndrome or leukemia. Peculiar anatomical characteristics render the lung parenchyma highly susceptible to infections, but the clinical outcome is due not only to the injury induced by the pathogens but also to their interactions with inflammatory cells and particularly to the effects of a wide network of secreted cytokines. Polymorphonuclear cells, macrophages, lymphocytes and structural pulmonary cells (epithelial cells, interstitial cells) generate a variety of cytokines and growth factors which, in turn, may be responsible for the majority of the clinical effects in response to infections, such as those of Pneumocystis carinii and cytomegalovirus, but also to certain drugs or to radiation. The pathogenesis of graft-versus-host disease (GVHD) is still poorly understood, but animal models seem to demonstrate the involvement of a number of cytokines and growth factors, together with toxic effects induced by conditioning regimens.

Chemotaxis, Leukocyte↗

Elderly aggressive-histology non-Hodgkin's lymphoma: first-line VNCOP-B regimen experience on 350 patients.

Age is a risk factor and a prognostic parameter in elderly aggressive-histology non-Hodgkin's lymphoma (NHL) patients. Several adapted chemotherapeutic regimens have recently been designed and tested on elderly patients. Several of these trials have shown that older aggressive-histology NHL patients can benefit from specific and adequate treatment capable of curing a percentage of these patients. Between January 1992 and September 1997, 350 previously untreated aggressive-histology NHL patients greater than 60 years of age were treated with a combination therapy including cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone (VNCOP-B). Complete remission (CR) was achieved by 202 (58%) patients and partial remission (PR) by 87 (25%), whereas the remaining 61 (17%) patients were nonresponders. The overall response rate (CR + PR) was 83%. Clinical and hematologic toxicities were modest, because 71% of the patients received granulocyte colony-stimulating factor (G-CSF). The CR rates for the three age groups (60 to 69, 70 to 79, and >/=80 years) were similar: 61%, 59%, and 56%, respectively. At 5 years, the relapse-free survival rate was 65%, the overall survival rate was 49%, and the failure-free survival rate was 33%. In the multivariate analysis, prognostic factors associated with longer survival or longer relapse-free survival turned out to be localized disease stage (P =.001) and good performance status (P =.0002). Application of the International Prognostic Factor Index was significantly associated with outcome (P =.001). These data confirm on a large cohort of patients that the VNCOP-B regimen is effective in inducing good CR and relapse-free survival rates with only moderate toxic effects in elderly aggressive-histology NHL.

Aged↗

Ultrasound echo-enhancers in the evaluation of endovascular prostheses.

Whereas conventional vascular surgical procedures are routinely monitored by ultrasound imaging, endovascular prostheses are usually monitored by radiographical imaging techniques. The aim of this study was to determine the safety, patient acceptance and role of ultrasound echo-enhancers (SHU 508 A) in the evaluation of endovascular devices. Nine patients were studied: six had stents (four in the internal carotid artery and two in the renal artery) and three had endoluminal prostheses (one in the abdominal aorta, one in the subclavian and one in the iliac artery). Endovascular patency and correct placement were studied with contrast angiography and ultrasound examination with and without contrast enhancement. Patients underwent angiography at the end of the endovascular procedure, and ultrasound examinations on the first postoperative day. Ultrasound contrast media (SHU 508 A) was injected through an antecubital vein at a rate of 1 ml/s. A total of 13 injections were given in nine patients. Ultrasonograms were obtained with 7.5 and 3.5 MHz transducers (Acuson 128 XP) and recorded on videotape for off-line visual inspection. Baseline and echo-enhanced sequences were assessed by two independent observers. None of the patients reported side-effects during or after the injection of the ultrasound echo-enhancer. Postoperative angiography showed endovascular patency and correct placement in all patients. The baseline ultrasound examination confirmed endoprosthesis patency in seven of nine patients: none revealed endoprosthesis malplacement. Contrast-enhanced ultrasound examination confirmed endoprosthesis patency. In two cases, the echo-contrast examination revealed persisting flow within the aneurysmal sac: in another patient it showed the incomplete adhesion of the distal portion of the endoprosthesis to the arterial wall. The preliminary findings suggest that ultrasound echo-enhancers are safe to use and induce no side-effects. Echo-enhanced sequences often provide additional information on the technical success of endovascular procedures. They promise to be useful in follow-up studies for assessing the functioning of endoprostheses.

Aged↗

Nongastrointestinal low-grade mucosa-associated lymphoid tissue lymphoma: analysis of 75 patients.

PURPOSE: Nongastrointestinal locations represent about 30% to 40% of all low-grade mucosa-associated lymphoid tissue (MALT) lymphomas. We report a retrospective analysis of 75 patients with nongastrointestinal low-grade MALT lymphoma, presenting their clinical, therapeutic, and follow-up data with respect to the initial location of the lymphoma. PATIENTS AND METHODS: From January 1988 to October 1997, 75 patients with untreated nongastrointestinal low-grade MALT lymphoma were subjected to treatments ranging from local radiotherapy and local interferon alfa administration to chemotherapy. The lymphomas were located in the lung (19 patients), orbital soft tissue (16 patients), skin (seven patients), thyroid (seven patients), lachrymal gland (six patients), conjunctiva (six patients), salivary gland (six patients), breast (three patients), eyelid (two patients), larynx (one patient), bone marrow (one patient), and trachea (one patient). RESULTS: Complete and partial remissions were achieved in 59 (79%) and 16 (21%) of the 75 patients, respectively, with an overall response rate of 100%. All but two of the patients are still alive, with a median follow-up of 47 months; these two patients died from other causes. The estimated time to treatment failure rate is 30% at 5 years. In the thyroid and lachrymal gland sites, no relapses were reported. CONCLUSION: Our data regarding the largest reported series of nongastrointestinal MALT lymphomas confirm the good prognosis of this particular clinicopathologic entity and the significant efficacy of different therapeutic approaches to specific sites.

Adult↗