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Biomedical subjects

F Silvestri

Publications and source records attributed to F Silvestri.

At least 91 records · Page 5Linked to original sources

Interferon therapy in HCV-positive mixed cryoglobulinaemia: viral and host factors contributing to efficacy of the therapy.

BACKGROUND: In a previous paper, we reported on the short-term efficacy of alpha-interferon in the treatment of hepatitis C virus positive mixed cryoglobulinaemia. AIMS: We investigated the long-term effects of therapy in a larger group of patients, and the viral and host factors able to influence the response to treatment. METHODS: In 27 females and 15 males (mean age 54.8 +/- 9.1 years) affected by mixed cryoglobulinaemia, bone marrow biopsy and phenotyping of marrow cells were performed before treatment and at the end of follow-up. A liver biopsy was obtained from patients showing biochemical signs of chronic liver disease. The presence of hepatitis C virus was assessed by detection of serum anti-hepatitis C virus antibodies, and hepatitis C virus-RNA. The treatment schedule was 3 million units of recombinant interferon alpha-2b three times a week for one year. Follow-up lasted for 1 year after the end of treatment. The response was classified as follows: 1) Complete response: Disappearance of the cryocrit (or reduction of more than 50%) and of all clinical manifestations of the disease. 2) Partial response: Disappearance of all clinical signs of the disease, but reduction of cryocrit of less than 50%. 3) Minor response: Reduction of cryocrit of less than 20% associated with the disappearance of one or more (but not all) signs of vasculitis. RESULTS: Anti-hepatitis C virus antibodies were present in 41 (95%) patients, and hepatitis C virus-RNA was detectable in all cases. Before therapy, marrow histology showed a massive monomorphous infiltration by plasmacytoid lymphocytes indicating the presence of low-grade non-Hodgkin lymphoma in 7 cases (16.6%). After therapy, 13 (31%) patients achieved a complete response, 23 patients (55%) a partial response, and 6 patients (14%) a minor response. Seven of the responders and all patients showing partial or minor responses relapsed a few months after withdrawal of therapy. At the end of the follow-up, only 6 patients had obtained complete remission. Bone marrow examination showed that B-lymphocytic monoclonal infiltrate had disappeared in 3 long-term responders. No difference was found between responders and non-responders/relapsers in terms of age, sex, duration of the disease, severity of symptoms, liver function tests, rheumatoid factor or complement levels, while the lack of response was associated with the presence of genotype 1b, liver cirrhosis, and high cryoglobulin level. CONCLUSIONS: Mixed cryoglobulinaemia is associated with a high prevalence of B-cell lymphomas. Alpha-Interferon is an effective agent for the treatment of this disease and seems able to determine regression of the lymphoproliferative disorder. The hepatitis C virus genotype and cryoglobulin level are the most important predictive factors of response to therapy.

Antiviral Agents↗

Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders.

It has been recently hypothesized that the hepatitis C virus (HCV) might be involved in the pathogenesis of malignant B-cell non-Hodgkin's lymphomas (NHL). On the basis of this observation we sought to determine the prevalence of HCV infection in the patients affected by B-cell NHL and extended our analysis to all the patients affected by lymphoproliferation disorders seen at our institution in the last 30 months. Five hundred and thirty-seven unselected, consecutive patients were studied. HCV infection was investigated through detection of anti-HCV antibodies and HCV-RNA. HCV genotyping was performed on HCV-RNA positive specimens. The risk of being infected by HCV was compared with that of the general population of our area. Among all lymphoproliferative disorders, the prevalence and the relative risk (RR) of being infected by HCV were increased only among B-cell NHL (9%; RR 3.24; p < .0001). Among these, a strong prevalence of HCV was found only in the subgroup of immunocytomas (30%; RR 10.27; P < .0001), while other histotypes were associated with it only occasionally. Because HCV-positive lymphomas clinically behave as essential mixed cryoglobulinemia (EMC), the close association between HCV infection and EMC is confirmed, and evidence is provided that the pathological substrate of EMC corresponds to the immunocytoma. HCV genomic sequences were found in 84% of patients analyzed. Viral genotypes were those more frequent in our area.

Adult↗

Primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma of the adult: sequential intensive treatment with the F-MACHOP regimen (+/- radiotherapy) and autologous bone marrow transplantation.

Few series of adult patients with primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma (ALCL) are reported in the literature; most of them have been treated with combination chemotherapy (CHT), with only an occasional patient being autotransplanted, mainly after relapsing. The remission rate ranges from 60% to 90%, but relapses are frequent (up to 60%) and precocious (mainly in the first 24 months). The aim of our study was to analyze the outcome of a series of adult patients affected by primary systemic ALCL that were treated at our institution with a sequential intensive therapeutic program including CHT, radiotherapy (RT), and autologous bone marrow transplantation (ABMT). Sixteen consecutive, unselected patients with ALCL were identified. All of them were treated with the 5-fluorouracil, methotrexate, cytosine arabinoside, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP) regimen; 9 of 16 (56.2%) reached a complete remission (CR). In six cases with residual mediastinal disease, involved-field RT was performed, allowing three additional patients to become free of disease. All 16 were then autotransplanted with bone marrow stem cells after conditioning with the cytosine arabinoside, etoposide, cyclophasphamide, and carmustine (BAVC) regimen. A present, 16 of 16 patients are alive and in CR. The actuarial overall survival is 100% at a median of 45.5 months, and the actuarial disease-free survival is 100% at a median of 33.5 months. These data suggest that ALCL can be successfully managed with a sequential intensive treatment (CHT +/- RT + ABMT) that prevents early relapses and projects these patients as long-term survivors.

Adolescent↗

Laparoscopic splenectomy in the management of hematological diseases. Surgical technique and outcome of 17 patients.

After being successfully applied to other intraabdominal organs, the laparoscopic approach has been applied to the spleen since 1991. The experience with 17 cases of laparoscopic splenectomy performed due to immune thrombocytopenia purpura (10 instances), hereditary spherocytosis (2 cases), and Hodgkin's disease where the staging was done according to Standford (5 cases), have been reported. With the patient in anti-Trendelenburg position, and the surgeon between the patient's legs, four or five trocars are introduced into the upper abdominal quadrants and the spleen hilum is isolated. Hilar vessels are dissected and ligated with a surgical stapler. A plastic bag is introduced into the abdomen cavity and the spleen is slipped inside; it is then extracted through an umbilical incision after morcellation. Advantages of the open operation include a decrease in postoperative pain, a decrease in pulmonary sequelae, a reduced incidence of subphnic abscesses, and cosmetic advantages. The decrease of postoperative sequelae reduces hospitalization and costs, which are higher for the operation itself (materials and staff's training).

Adult↗

Laparoscopic management of acute small-bowel obstruction.

BACKGROUND: A retrospective review is given of the authors' experience with a consecutive series of acute small-bowel obstruction unresponsive to medical management. METHODS: There were 33 exploratory laparoscopies. The etiology was accurately diagnosed in 100% of the cases. Twenty-five (76%) were secondary to postoperative adhesions, of which 18 (72%) were successfully treated by laparoscopic lysis of adhesions. Minilaparotomy was needed to treat iatrogenic perforation (two), gangrenous bowel (one), and Meckel's diverticulectomy (one). Formal laparotomy was utilized for small-bowel resection (two), malignant adhesions (two), and intolerance of pneumoperitoneum (one). Four cases of incarcerated hernias were treated by conventional herniorrhaphy. RESULTS: Overall, 67% of our cases were spared formal laparotomy. CONCLUSION: We conclude that laparoscopy is an excellent diagnostic modality in acute small-bowel obstruction, the majority of which can be simultaneously managed laparoscopically. Laparotomy should be reserved for malignant adhesions, surgical misadventure, or when the pathology dictates.

Acute Disease↗

Improved method to create the common ostium variant of the distal arteriovenous fistula for enhancing crural prosthetic graft patency.

PURPOSE: Successful use of the distal adjunctive arteriovenous fistula (dAVF) for the enhancement of prosthetic graft patency rates in the crural position is critically dependent on the qualitative and quantitative aspects of the arterial and venous runoff. Precise technical performance of the fistula is equally vital to secure optimal results. The purpose of this study was to determine current prosthetic graft patency and limb salvage rates using a modified version of the common ostium dAVF. METHODS: The standard method to create the common ostium variant of dAVF has been modified to improve apposition of the "otomy" sites of the artery and vein, avoid twisting and stenosis by terminating the fistula suture line at the artery-vein junctures, reshaping the ovoid ostium to a rectangular shape, and finally, use of multiple interrupted heel-toe sutures. RESULTS: Since 1979 we have created 290 fistulas in 281 patients who required leg revascularization procedures. In different time periods we have documented improving graft patency and limb salvage rates. Fistula patency, reflected by annual attrition rates of 13% to 26% per year, continues as a challenge for long-term results. Current 3-year secondary cumulative graft patency and limb salvage rates by life table analysis are 61% and 74%, respectively. The conduit material may play a role with regard to steal phenomena and the need for banding techniques. CONCLUSION: Configuration of the adjunctive dAVF may impact on prosthetic graft patency in the crural position. In addition, the type of graft material used for bypass may be instrumental in preventing or precipitating the steal phenomenon. These issues require further study to better understand flow dynamics, patterns of intimal hyperplasia, and blood distribution as a function of conduit material and impedance of the arterial and venous runoff.

Adult↗

Pelvic radiation therapy as a risk factor for ischemic colitis complicating abdominal aortic reconstruction.

Ischemic colitis is an infrequent but potentially devastating complication of abdominal aortic reconstruction. Identification of patients with predisposing risk factors for the development of ischemic colitis can guide intraoperative measures to preserve or restore colonic blood flow during aortic surgery. Previous radiation therapy for pelvic malignancy may be one such predisposing risk factor. Two cases are presented in which ischemic colitis complicated abdominal aortic reconstruction in the setting of previous pelvic irradiation. In the months after radiation therapy for prostate cancer, one patient underwent infrarenal abdominal aortic aneurysm repair. Ischemic infarction of the sigmoid colon developed acutely after surgery and required emergent sigmoid colectomy. The second patient underwent reconstruction of an infrarenal abdominal aortic aneurysm after having had radiation therapy for a bladder tumor. Despite an initial satisfactory result, the patient's abdominal pain and diarrhea progressively worsened and he eventually required sigmoid colectomy for severe ischemic colitis. In both of these patients, the inferior mesenteric arteries were patent and had not been reimplanted. The association of pelvic radiation therapy with ischemic colitis after aortic reconstruction should focus attention to the operative details for maintaining the colonic circulation in these patients. Reimplantation of the inferior mesenteric artery in particular may prevent both the acute and the insidious variants of this complication in patients who undergo aortic surgery and decrease the incidence of this complication in patients with a history of radiation therapy to the pelvis.

Aged↗

Neutralizing anti-interferon-alpha antibodies and response to treatment in patients with Ph+ chronic myeloid leukaemia sequentially treated with recombinant (alpha 2a) and lymphoblastoid interferon-alpha.

Neutralizing anti-IFN alpha antibodies (nIFN alpha Abs) occur in a significant proportion of patients with hairy cell leukaemia, hepatitis or solid tumours treated with recombinant IFN alpha (IFN alpha 2a or IFN alpha 2b), but information on their incidence in chronic myeloid leukaemia (CML) is scanty and their clinical relevance is not yet completely defined. By using an IFN alpha antiviral neutralization bioassay, the frequency of nIFN alpha 2a Abs was evaluated in 67Ph+ CML patients during IFN alpha 2a therapy at doses ranging from 6 to 9 MU/d. 15 patients (22%) developed nIFN alpha 2a Abs (titre ranging from 1:40 to 1:20480) and 11/15 (73%) were haematologically and/or karyotypically unresponsive to treatment. 52 patients did not develop antibodies and 11 of them (21%) were unresponsive. The negative relationship between the positivity for nIFN alpha 2a Abs and the response to treatment was highly significant (P = 0.0001). In nine nIFN alpha 2a Abs positive patients, treatment was changed from recombinant IFN alpha 2a to lymphoblastoid IFN alpha (IFN alpha-ly), at the same dose and schedule. After 9 months of IFN alpha-ly treatment a haematological response was achieved in 4/7 cases who were non-responsive to prior IFN alpha 2a therapy and was maintained in the other two patients previously responsive to IFN alpha 2a. However, no karyotypic response was observed. This data shows that a significant proportion of Ph+ CML patients receiving treatment with IFN alpha 2a can develop neutralizing antibodies and that these antibodies are associated with a loss of IFN alpha 2a efficacy. Changing the patients to treatment with lymphoblastoid IFN alpha may restore haematological response but it is not likely to induce a karyotypic response.

Adult↗

More on false thrombocytopenias: EDTA-dependent pseudothrombocytopenia associated with a congenital platelet release defect.

We report herein the case of a 54-year-old woman with a moderate bleeding tendency, diagnosed as an EDTA-dependent pseudothrombocytopenia associated with a congenital platelet release defect. The patient, at the age of 12, had a misleading diagnosis of idiopathic thrombocytopenic purpura and all the recurrent bleeding problems she had during her life were referred to that disease. The recent correct diagnosis of a false thrombocytopenia stimulated further laboratory investigation on the cause of the patient's bleeding tendency with the consequent identification of a congenital platelet deficiency of the arachidonic acid pathway. This finding is of relevant importance for the management of the patient in case of elective surgery or hemorrhagic emergency.

Arachidonic Acid↗

Familial right ventricular dysplasia with biventricular involvement and inflammatory infiltration. Heart Muscle Disease Study Group.

The aetiology of right ventricular dysplasia/cardiomyopathy is presently unknown. A genetic background has been suggested, but myocarditis may play a part in its pathogenesis. Two familial cases of right ventricular dysplasia, one of whom had also a diagnosis of myocarditis, are reported. Both patients presented with ventricular arrhythmias. The father subsequently had a "flu-like" syndrome, heart failure, and biventricular dysfunction; "active" myocarditis was found at endomyocardial biopsy. Then the patient died suddenly. The daughter developed progressive biventricular dysfunction; then she was resuscitated from a cardiac arrest, and subsequently died suddenly. In both patients necropsy showed severe right ventricular atrophy and fibro-adipose substitution, associated with biventricular fibrosis. Inflammatory infiltration was also present in the first patient. This study shows the association of right ventricular dysplasia and myocarditis in the same family. These cases may represent a link between inherited and acquired ("inflammatory") forms of the disease.

Adult↗

Experience with a new valvulotome for lower-extremity revascularization procedures by the in situ method.

Between November 1990 and November 1992, 50 consecutive cases requiring lower-extremity revascularization by the in situ method were compared with regard to use of two different valve cutters, the Hall valvulotome and the Insitucat. There were no amputations in patients with patent grafts, nor were any infections or false aneurysms noted during the course of this study. In the Insitucat group (n = 25), primary patency was achieved in 19 cases. Five of the six graft failures underwent additional procedures of which three remained patent, adding to the secondary patency rate (22 of 25). The greatest problem with regard to maintaining primary graft patency was that of missed or retained valves, but the incidence of this problem decreased during the course of this study as experience was gained with the catheter in conjunction with angioscopy. Experience with the Insitucat valvulotome has demonstrated its efficacy, though enhanced by monitoring the results with angioscopy. The development and discovery of focal stenotic areas and retained valves by surveillance sonography have resulted in enhanced (assisted) primary graft patency rates. The incidence of these problems appears to be comparable with that occurring with other means of producing valvular incompetence for an in situ reconstruction where valvulotomes of similar design are employed. This was confirmed by comparative analysis with another group of 25 in situ vein bypasses performed during the same time period but during the Hall valvulotome.

Aged↗

Neoplastic and borderline lesions of the prostate: autopsy study and epidemiological data.

Early detection and management of prostatic cancer (PC) is an important public health problem in all industrialized countries, where the relative rate of the elderly population is rapidly increasing. We examined the epidemiology of PC in the province of Trieste, Italy and studied the relationship between prostatic intraepithelial neoplasia (PIN) and PC. The average annual incidence of PC was 99.3 per 100,000 (1,739 new prostatic cancer cases were histologically diagnosed at autopsy or in surgical specimens between 1980 and 1993). In patients over 85 years of age, the incidence rate was 1,209 per 100,000 compared with 64 per 100,000 in the 55-64 age group. Trends in PC incidence rates showed a significant increase among men under 64 years of age and those between 65-74 years. Survival analysis showed that 94% of the patients with well differentiated PC were alive at 5 years, compared with 80% and 40% of those with moderately differentiated and poorly differentiated cancer, respectively. We studied 130 whole autopsy prostates, 70 radical prostatectomies with carcinoma, 63 transurethral resections or adenomectomies without cancer from patients who later developed PC and 94 transurethral resections or adenomectomies from patients who did not develop PC. The 102 prostatic cases with cancer had a high rate of PIN, and the relative frequency of PIN 3 was high (almost 70%, versus almost 0% in benign prostates). In addition, the frequency of PIN was higher in benign prostates of patients who later developed PC (almost 50% of the cases) than in benign autopsy and surgical prostates. PIN was spatially associated with cancer in 75% of the cases. This study confirms the strong relationship between PIN and PC.

Adult↗

Mesoportal bypass: a unique operation for mesenteric hypertension.

A 47-year-old man was referred for evaluation and treatment of gastrointestinal variceal bleeding and possible transjugular intrahepatic portal-systemic shunting. Intrahepatic manometry disclosed a normal portal pressure, but selective mesenteric arteriography revealed occlusion of the superior mesenteric, splenic, and inferior mesenteric veins. Duodenal and gastric varices were noted, but no esophageal varices were seen. The portal vein was clearly patent. At surgery, a 2 cm mass was found at the superior mesenteric vein-splenic vein juncture, and subsequent pathologic examination confirmed the presence of suture material within dense fibrous tissue as the probable cause for this rare condition. The surgical procedure performed was a superior mesenteric vein-to-portal vein bypass, employing ringed expanded polytetrafluoroethylene. Graft patency and function have been confirmed postoperatively by means of both venous-phase mesenteric arteriography and duplex imaging. The surgical procedure was novel, in that it was possible to decompress the hypertensive mesenteric circulation from the distal superior mesenteric vein directly into the portal vein with a prosthetic bypass. The physiologic benefit of this operation is clear: the avoidance of the encephalopathic syndrome and the facilitation of hepatopetal blood flow.

Blood Pressure↗