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Chronic lymphocytic leukemia (CLL) clones are characterized by loss of a critical region in 13q14.3, (del(13)(q14)) involving the microRNA (miRNA) cluster miR-15a and miR-16-1. We have investigated the effects of replacement of miR-15a and miR-16-1. CLL cells transfected with these miRNA mimics exhibited a decrease in cell viability in vitroand impaired capacity for engraftment and growth in NOD/Shi-scid,γcnull (NSG) mice. No synergistic effects were observed when the two miRNA mimics were combined. The phenomena were not restricted to CLL with the del(13)(q14) lesion. Similar effects induced by miRNA mimics were seen in cells with additional chromosomal abnormalities with the exception of certain CLL clones harboring TP53alterations. Administration of miRNA mimics to NSG mice previously engrafted with CLL clones resulted in substantial tumor regression. CLL cell transfection with miR-15a and miR-16-1-specific inhibitors resulted in increased cell viability in vitroand in an enhanced capacity of the engrafted cells to grow in NSG mice generating larger splenic nodules. These data demonstrate that the strong control by miR-15a and miR-16-1 on CLL clonal expansion is exerted also at the level of full-blown leukemia and provide indications for a miRNA-based therapeutic strategy.

Background: We reviewed retrospectively the records of all patients who underwent laparoscopic splenectomy (LS) at our institution for a wide range of hematological disorders. We compared our experience to those reported in the literature and analyzed various aspects of the treatment that are still under discussion and in need of confirmation, such as the treatment of malignant blood diseases, the indication in case of splenomegaly, and the adequacy of the detection of accessory spleens. Methods: Between June 1997 and June 2001, we performed 43 LS. The patients were classified into three groups according to clinical diagnosis: idiopathic thrombocytopenic purpura (ITP) (n=23), hemolytic anemia (HA) (n=5) and hematological malignancy (HM) (n=15). Statistical analyses were done to compare the three groups. Results: LS was completed in 41 patients, with a conversion rate of 5%. Splenomegaly was present in 37% of all patients (73% of HM). Mean operative time was 128 min. The incidence of accessory spleens was 20%. A concomitant laparoscopic procedure was done in three cases (cholecystectomy). Postoperative complications occurred in eight patients (18%). Duration of surgery, length of hospital stay, transfusions rate, and some demographics features, such as age and spleen weight and length, were significantly different in each group. No deaths were attributed to the procedure. Conclusions: The statistical analysis of our series shows that, the laparoscopic approach reliable even in the management of malignant and nonmalignant blood diseases.

Abstract:  Castleman's disease (CD) is a rare disorder of the lymphoid tissue in which the clinical manifestations often mimic a malignant lymphoma. Despite the absence of monoclonality of the lymphoid proliferation, the multicentric variant of the disease (MCD) is characterized by severe symptoms and poor prognosis. Etiologic, pathogenetic, and therapeutic aspects of MCD are still uncertain. We report the case of a 57-year-old patient affected by MCD complicated by severe immunohemolytic anemia. Whereas the clinical and laboratory response to steroids and chemotherapeutic agents was only partial, splenectomy induced a complete remission of hemolysis and disappearance of the constitutional symptoms and of all generalized lymphadenopathies.

Dilatation and perforation of the prosthetic wall represent major problems limiting long-term function of biologic arterial substitutes. One case of multiple aneurysm formation and one of graft wall perforation, occurring nine and three years, respectively, after human umbilical vein (HUV) femoropopliteal recon structions, are reported. Both grafts were well functioning. At microscopic ex amination, the aneurysmal HUV wall showed no degenerative changes, while appearing thinner with respect to the undilated zones (about one third). The HUV flow surface remained thromboresistant, except for the dilated areas. Par tial endothelialization of the inner graft surface was documented. In conclusion, the risk of HUV graft dilatation and perforation increases when function is maintained for periods longer than three years from implantation. However, the umbilical vein retains over time its thromboresistant properties.

Thirty-five aggressive non-Hodgkin's lymphomas (NHL) with marrow involvement received high-dose cyclophosphamide (7 g/m2) and G-CSF in order to collect peripheral blood progenitor cells (PBPC). Fourteen patients were in partial remission, 16 patients were in relapse ("sensitive", 12; "resistant", 4) and 5 patients were in refractory to conventional treatment. A good yield of PBPC was obtained in 30 patients, while a low number of CD34+ cells and of CFU-GM was seen in two cases. Two patients entered progression and one patient died. Thirty patients underwent PBPC autografting. Twenty-nine out of 35 (83%) patients entered complete remission (CR). Two patients died in CR of infection following marrow aplasia 3 and 6 months after autografting. At 3 years the probability of survival and disease-free survival (DFS) are of 62% and 51% respectively.

The present study was performed to evaluate the potential of glutaraldehydetanned mandril-grown grafts as caval substitutes. Short-term experiments consisted of 30 tubular grafts (35 × 8 mm), either of tanned collagen or polytetrafluoroethylene, that were sutured in the infrarenal inferior vena cava of pigs and removed 1 hour after implantation. There was no significant difference between the extent of the thrombus-lined graft surface in the biologic group and that in the polytetrafluoroethylene group. The amount of inner thrombus on tanned collagen grafts was significantly correlated to platelet activity. Long-term experiments involved 30 similar segments of both materials, which were sutured in the inferior vena cava and harvested 7, 14, 28, 56, and 112 days after operation. The 112-day patency rate of collagen grafts was 67%. The 56-day patency rate of polytetrafluoroethylene grafts was 16%. The difference was statistically significant (p < 0.01). Collagen grafts were lined by a thin neointima (200 μm) in all but two cases. The neointima was completely endothelialized within 4 weeks from implantation. In conclusion, tanned collagen grafts may represent a suitable material for venous replacement

Summary In the attempt to induce graft-vs-host disease (GVHD) in patients undergoing autologous bone marrow transplantation (ABMT) or blood stem cell transplantation (BSCT), 12 consecutive patients received cyclosporin A (CyA) post transplant. CyA was given at a dose of 1.5 mg/kg/day intravenously for 28 days, starting on the day of transplant. Histologically proven acute GVHD of the skin occurred in seven patients 9–14 days after ABMT and lasted 7–11 days. CyA-induced GVHD after ABMT resembles mild GVHD after allogeneic bone marrow transplantation (BMT). Although the preliminary data reported here show that it is possible to induce GVHD in patients undergoing ABMT, it is not yet known whether GVHD after ABMT will have an antitumor activity.

Carbon has been used to improve the thromboresistance of synthetic vascular prostheses, and for this pur pose, dacron grafts have been coated with carbon. Owing to the contradic tory results reported in the literature, a new kind of vascular conduit, ex clusively textured from carbon fi bers, has been developed. The pres ent research study was undertaken to compare carbon and expanded poly tetrafluoroethylene (e-PTFE) grafts when used as vascular substitutes. Fifty-six experimental animals were divided into four equal groups and underwent substitution of segments of infrarenal aorta or inferior vena cava (IVC), through use of either carbon or e-PTFE grafts. Prosthetic segments were removed fifteen sec onds, or sixty minutes, or seven, fif teen, thirty, sixty, or one hundred twenty days after implantation. Spec imens were examined by light and scanning electron microscopy. Cumu lative patency rates, calculated by the life-table method at 120 days after surgery, were 72% for aortic carbon grafts, 41 % for aortic e-PTFE grafts, and 0% for both carbon and e-PTFE grafts implanted on the IVC. Carbon conduits performed significantly bet ter than e-PTFE conduits when used as small-caliber arterial substitutes (p < 0.05). Fifteen seconds after blood contact, the inner surface of carbon prostheses, regardless of the implantation site, was covered with a thin proteinaceous layer, whereas e- PTFE grafts appeared almost com pletely free from hematic deposits.One hour after implantation, a red thrombus was found to overlay the luminal surface of both carbon and e- PTFE prostheses. This layer ap peared to be thicker on the e-PTFE grafts than on the carbon grafts and thicker on the venous grafts than on the arterial. The endothelialization process of the blood-prosthesis inter face seemed to be slightly more rapid on the carbon than on the e-PTFE aortic grafts. In conclusion, this new carbon graft would appear to possess promising specifications, making it suitable for small-caliber arterial (but not venous) replacement.