Infusional CDE with rituximab for the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma: preliminary results of a phase I/II study.

Infusional CDE (cyclophosphamide, doxorubicin, etoposide; iCDE) is one of the most effective chemotherapeutic regimen for human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL), with a complete remission rate of 46% and a median overall survival of 8.2 months (Sparano JA, Blood 1993; 81:2810). Since the majority of HIV-associated NHL are CD20-positive we reasoned that the addition of rituximab to iCDE (R-iCDE) could also improve the poor outcome of these patients. As a first step we investigated the safety of R-iCDE in a phase I/II study. Thirty patients with aggressive HIV-associated NHL were enrolled between June 1998 and October 2000. Characteristics of 29 evaluable patients were: median age: 38 years (range 29-65 years); male sex 24/29; histology: DLCL 16 (55%), Burkitt 10 (35%), ALCL 2 (7%), unclassified 1 (3%); stage: I (35%), II (10%), III (10%), IV (45%); International Prognostic Index: 0, 1 (59%), 2 (24%), 3 (17%), 4, 5 (0); CD4 count: median 132/ mm3 (range 3-470/mm3). Patients received rituximab (375 mg/m2) in conjunction with iCDE (five or six cycles). All patients were treated with G-CSF and highly active antiretroviral therapy (HAART). Twenty-six of 29 patients received treatment as planned, while chemotherapy had to be discontinued in three patients (2 persistent thrombocytopenias, 1 cerebral hemorrhage). Grade 3 or 4 toxicity was observed as follows: neutropenia 79%, anemia 45%, thrombocytopenia 34%, bacterial infection 34%, opportunistic infection 7%, mucositis 17%. A dose reduction was necessary in 22%. Complete remission was achieved in 86% of the patients, partial remission in 4%. Ten percent had progressive disease. After a median follow-up of 9 months the median overall survival is not reached. The actuarial survival at 2 years is 80% and the actuarial progression-free survival is 79%. Four of 29 patients (14%) have died, three from NHL and one from cryptosporidiosis. These findings suggest that the combination of rituximab with iCDE in patients with HIV-associated NHL is safe and feasible and that the addition of the anti-CD20 antibody does not increase the risk for infections. The high complete remission rate also indicates a potential therapeutic benefit and warrants further randomized trials.

Low-dose leukocyte interferon-alpha therapy in dialysed patients with chronic hepatitis C.

Kidney failure is a contraindication to interferon therapy, and active chronic hepatitis is incompatible with kidney transplantation. Our study was aimed at investigating the activity and tolerability of leukocyte interferon-alpha in patients undergoing pre-transplant dialysis and suffering from chronic active hepatitis due to Hepatitis C virus infection. Ten patients, with persistently high ALT levels, were treated with leukocyte interferon-alpha, at a dose of 1 MU three times weekly for one year. Viraemia, ALT levels and other blood and urine tests, hepatitis stage and drug tolerance were all monitored throughout the study and the six-month follow-up period. After six months of treatment, two patients had continuing normalisation of ALT, negative HCV-RNA tests and normalisation of histological features ('long-term responders'). Four patients relapsed; three did not respond to treatment; and one patient discontinued it because of intolerance. The four relapsing patients received a second cycle with the same interferon, at a dose of 3 MU three times weekly, with attainment, in one patient, of complete remittance after six months of follow-up. Leukocyte interferon-alpha yielded an overall 30% therapeutic response in dialysed patients with chronic hepatitis C. Its use is helpful in enabling dialysed patients to undergo transplantation.

Ultrasound imaging in cystic echinococcosis. Proposal of a new sonographic classification.

The ultrasonography permits the study of the natural history of cystic echinococcosis (CE) and evaluation of stages of the parasitic pathology. The evolution of abdominal CE was studied in 54 patients suffering from 97 abdominal cysts treated with albendazole, in 20 patients suffering from 20 hepatic cysts treated with echoguided percutaneous ethanol injection and in 39 patients suffering from 42 abdominal cysts, but left untreated. A new sonographic classification is suggested. Type I: Simple CE; (a) overall echofree; (b) with fine echos. Type II: Multiple CE; (a) multiple contiguous; (b) multiseptated with rosette, honeycomb and wheel-like pattern. Type III: With detachment of endocyst CE; (a) with double layer image; (b) with water-lily sign. Type IV: Mixed type CE; with fluid and solid aspect. Type V: Heterogeneous CE; (a) with ball of wool pattern; (b) with hypoechogenic image. Type VI: Hyperechoic CE; (a) with snow-storm pattern; (b) with dyshomogeneous aspect. Type VII: Calcified CE; (a) with advanced calcification of the layer only; (b) with calcification of overall cyst. This classification appears more appropriate to the natural history of CE and permits a better differential diagnosis and more suitable treatment.

Sonographic management of mediastinal syndrome.

INTRODUCTION: Mediastinal syndrome is suspected on the basis of clinical symptoms and is generally confirmed by chest radiography or computed tomography (CT). However, also grey scale ultrasound (US) and contrast enhanced US (CEUS) are useful in this hematologic emergency as they provide the possibility to perform US-guided biopsy and histological diagnosis. MATERIALS AND METHODS: 15 Patients affected by mediastinal syndrome were prospectively studied using B-mode US and CEUS; 13 of these patients, who had no other lesions, were proposed for US-guided biopsy of the mediastinal mass, but only in 12 patients biopsy was technically possible. RESULTS: In this study, B-mode US reached an excellent sensitivity (100%) in evidencing the lesions but a low specificity which did not exceed 30-40%. CEUS reached an elevated specificity identifying neoplastic pathologies if both the early and the late phases are considered (90-86.6%). US-guided biopsy was possible in 92.3% of lesions showing a diagnostic adequacy of 91.66%. CONCLUSIONS: B-mode US associated with CEUS and US-guided biopsy reached an elevated accuracy in the diagnosis of mediastinal masses. If these results are confirmed by further studies, this diagnostic procedure could be included in the routine management of mediastinal syndrome.

Contrast enhanced ultrasonography (CEUS) in peripheral lung lesions: A study of 60 cases.

INTRODUCTION: The authors report their experience in 60 patients with infectious and neoplastic peripheral pulmonary lesions studied by conventional radiology, B-Mode ultrasound (US) and computed tomography (CT). In view of the particular pulmonary vascularization (consisting of both pulmonary and bronchial arteries) the patients underwent also contrast enhanced ultrasound (CEUS) using a II-generation contrast agent, SonoVue (sulphur hexafluoride microbubbles surrounded by a phospholipid shell). METHODS AND RESULTS: In this study, the sensitivity of CEUS reached 95% in the characterization of peripheral pulmonary lesions, which is similar to the sensitivity of CT (97%). The method used in this case-study was free of significant side effects. DISCUSSION: This preliminary clinical experience seems to confirm the possibility of using SonoVue enhanced US to make a differential diagnosis between infectious and neoplastic lesions based on a qualitative and quantitative assessment, by evaluating the enhancement pattern (homogeneous or inhomogeneous), arrival time of the contrast agent in the lesion, the possibility to identify the pulmonary arteries and time of contrast agent elimination.

Thrombocytopenia in patients with HCV-positive chronic hepatitis: efficacy of leucocyte interferon-alpha treatment.

Treating patients with HCV-associated thrombocytopenia is a problem, because the pathogenesis of thrombocytopenia is still unclear. We evaluated the clinical and haematological response to leucocyte interferon-alpha in 20 naive patients with chronic hepatitis C and thrombocytopenia (platelet count <140 x 10(9)/l for at least six months) without portal hypertension and/or hypersplenism. They were treated with leucocyte interferon-alpha (3 MU three times per week) for 12 months and followed up for 12 months. Biochemical (ALT) and virological (HCV-RNA) responses were determined. Two patients discontinued treatment because of hyperthyroidism. Of the 18 patients who completed treatment, 12 (66%) showed a biochemical response, 10 of whom (55.5%) also showed a virological response. At the end of follow-up, four patients (22%) showed a complete (biochemical and virological) response. During treatment, platelet counts decreased to less than 10-20% of pretreatment values in most patients. Three of the four patients with a complete response showed a platelet increase during treatment and throughout the follow-up period. In HCV-associated thrombocytopenia leucocyte interferon-alpha is well tolerated and in cases of sustained virological inhibition is able to ameliorate the disease by increasing the platelet count.

Inflammatory pseudotumour of the liver: diagnosis by fine needle biopsy in two cases and a review of the literature.

Inflammatory pseudotumours of the liver are rare: over 40 cases had been reported up to 1992, the majority of which are surgical or laparoscopic findings. In this paper we describe two additional cases in which diagnosis was acquired by fine needle biopsy under ultrasonographic guidance. This approach allowed sufficient sampling of tissue for diagnostic purposes.

Ecographic epidemiology of non-parasitic hepatic cysts.

An analysis of the epidemiology of non-parasitic hepatic cysts (NPHCs) has been carried out comparing these data with those of the current literature. This sample shows an incidence of 4.65%, which is greater than those reported by other authors. No difference between the two sexes was seen, but a very high incidence above 40 years of age was found.

Abdominal cystic hydatid disease (CHD): classification of sonographic appearance and response to treatment.

The natural history of cystic hydatid disease (CHD) can be divided into two stages. The first is characterized by the proliferation of the parasite; the second is marked by involution, ie, when the hydatid undergoes spontaneous distress or is subjected to pharmacological treatment. Echography makes it possible to study this evolution and to evaluate the stages of this parasitic pathology. This study of the evolution of abdominal CHD in 81 patients suffering from 127 cysts, with or without Albendazole treatment suggests a new sonographic classification: type I: simple CHD; type II: multiple CHD, type III: with detachment of membrane CHD; type IV: mixed CHD, type V: heterogeneous CHD; type VI: hyperechogenic CHD; type VII calcified CHD. Forty-seven patients suffering from 90 cysts of types I, II, III, IV, and V were treated with Albendazole; 31, suffering from 34 CHD of types VI and VII, were not treated, as they were considered involutional; 3 patients with 3 cysts refused therapy. Albendazole treatment resulted in the disappearance of 9 and in the solidification of 62 cysts. Of the remaining cases of CHD, 10 cysts showed sonographic alterations and 5 showed no modifications. Surgery was necessary for 2 patients (4 cysts). This new classification seems to be an aid in the recognition of the natural and therapy-induced involution of CHD and seems to improve the evaluation of the efficaciousness of the therapy.

[Alcohol consumption in a hospital population. Relationship of dose and liver damage]. / Studio sul consumo alcoolico in una popolazione ospedaliera. Rapporto dose-danno epatico.

We have performed a prospective study on 291 male non alcoholic-patients admitted in the General Hospital of Arezzo, drinkers of more than 100 ml of alcohol for day. We have evaluated the toxic effects on the liver and we found a direct correlation between dose and hepatic lesions. The factors body weight, period of drinking, way of drinking (during eating or not) seem to have no value to determinate the hepatic damage. The Authors think that this kind of investigation is important to elaborate preventive program not only for the "psichiatric" alcoholism, but for the danger of the excessive amount of wine normally consumed in the diet from high percentage of Italian people.

Decline of HBsAg antibodies after immunization with hepatitis B vaccines and after natural infection.

The long-term persistence of anti-HBsAg above 10 mUI is conventionally believed to protect against natural infection with hepatitis B virus, while it is not yet clear what is the clinical significance of the fall to below 10 mUI in antibody levels. In our opinion, an important method for evaluating the effectiveness of the vaccine lies in comparing the duration of vaccine-immunity with that following the disease, the later being held to provide life-long protection. In this view, we examined the sera samples of 69 subjects (56 healthy people, and 13 drug-addicts) previously affected from HBV infection looking for anti-HBsAg with an Elisa method. The subjects were aged between 4 months and 73 years and had all suffered from acute fully recovered icteric hepatitis in the previous 2 to 10 years. All the drug addicts (13 males) and 4 healthy children from the group had no or negligible levels of antibodies; 3 out of 8 old people (60 or more yrs old) showed no antibodies only 4-5 yrs after having been infected. In the remaining group of 44 healthy people 14 cases were observed which had antibody levels 10 mUI, regardless of age, sex or occupation; the greater the time between the infection and the test, the greater the probability of finding negligible antibody levels. We conclude that the reduction in antibody levels may not be indicative of a loss of immunity: many of our cases have shown low or undetectable antibody levels, a few years after full recovery from an acute attack of hepatitis B.