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Background:Uveal melanoma is the most frequent primary tumour of the eye. It is molecularly clearly distinct from cutaneous melanoma and shows a different pattern of driver mutations. The influence of sunlight ultraviolet (UV) exposure on the aetiology of uveal melanoma is a matter of debate. The recent identification of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene with UV-induced cytidine-to-thymidine transitions in cutaneous melanoma prompted us to investigate whether these mutations also occur in uveal melanoma.Methods:We analysed 50 cases of uveal melanoma obtained from enucleation surgery for mutations in the genes GNAQ, GNA11, BAP1, SF3B1, EIFAX1 and TERT, measured gene expression using microarrays and analysed gene copy numbers by SNP arrays.Results:We detected a TERT mutation in only one case of a 57-year-old white male patient with clinical and histopathological features typical for uveal melanoma. The tumour showed mutations in GNA11 and EIF1AX that are typical for uveal melanoma and absent from cutaneous melanoma. No mutations were detected in GNAQ, BAP1 and SF3B1 that are frequently mutated in uveal melanoma. Both copies of chromosome 3 were retained. Several tumours among which the one carrying the TERT promoter mutation showed elevated TERT expression. Consistent with previous reports, GNAQ is inversely associated with chromosome 3 monosomy and metastasis. BAP1 mutations are significantly associated with chromosome 3 monosomy but not with relapse.Conclusion:These data indicate that TERT mutations are rare in uveal melanoma. No conclusion can be drawn on their potential influence on tumour progression. [ABSTRACT FROM AUTHOR]

Using proteomic analysis of the nuclear matrix (NM), we found that heterogeneous nuclear ribonucleoprotein K (hnRNP K), a member of the hnRNP family with pleiotropic functions, was differentially expressed in prostate cancer (PCa) tissues. This study aimed to characterise the expression of hnRNP K and its subcellular localisation in PCa, utilising immunohistochemical and quantitative western blot techniques. Furthermore, the hnRNP K expression was studied in human PCa cell lines in order to determine its modulation by bicalutamide, the anti-androgen widely used in PCa therapy. Immunohistochemical staining of paraffin-embedded tissues showed that hnRNP K was overexpressed in PCa, where it was localised both in the cytoplasm and in the nucleus. Staining of non-tumour tissues showed exclusively nuclear localisation and a less intense or absent signal. Immunoblot analysis demonstrated that the hnRNP K level within the NM was higher in PCa compared with non-tumour tissues and closely correlated with Gleason score (P=0.008). Higher expression within the NM was significantly (P=0.032) associated with poor prognosis. In two-dimensional western blot analysis hnRNP K presented several isoforms; the one with pI 5.1 was the most differently expressed between non-tumour and PCa tissues. Preliminary results indicate that hnRNP K can be modulated in vitro by a non-steroidal anti-androgen. Taken together, our findings suggest that hnRNP K has potential implications at the diagnostic, prognostic and therapeutic levels in PCa. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Background: Follicular center lymphoma displays widespread lymph node involvement at diagnosis. The chemoattractants that control the locomotion of follicular center lymphoma B cells have not been established. Stromal cell-derived factor-1 (SDF-1) is a CXC-class chemokine that enhances the migration of normal human B cells and is expressed in peripheral lymphoid tissues. Here we have investigated 1) whether SDF-1 stimulates the in vitro locomotion of follicular center lymphoma B cells and of their presumed normal counterparts (i. e., germinal center B cells) and 2) whether the same cells express SDF-1 transcripts.Methods: B cells were purified by immunomagnetic bead manipulation. Messenger RNA was detected by reverse transcription-polymerase chain reaction. Migration was assessed by the filter and collagen invasion assays. All P values were two sided.Results: Follicular center lymphoma B lymphocytes showed a statistically significant migratory response to 300 ng/mL SDF-1, both in the filter and in the collagen assays (P =.002 for each). Such response was mediated by the SDF-1 receptor, CXCR4. CD40 monoclonal antibody (MAb) and tonsillar germinal center B cells treated with CD40 MAb and recombinant interleukin 4, but not freshly isolated, migrated statistically significantly faster in the presence than in the absence of SDF-1 (P =.002 in both filter and collagen assays). Freshly isolated follicular center lymphoma and germinal center B cells expressed SDF-1 transcripts.Conclusions: This study shows that SDF-1 substantially enhances the migration of follicular center lymphoma B cells but not the migration of freshly purified germinal center B cells. This difference may be related to the extended survival of follicular center lymphoma versus germinal center B cells. SDF-1 produced in follicular center lymphoma lymph nodes may play a role in the local dissemination of tumor cells. [ABSTRACT FROM AUTHOR]

Although in recent years the use of purine analogues has increased the percentage of long‐term complete response the effect on overall survival of HCL patients is not yet clear. This study aimed to evaluate the long‐term outcome (mean follow up of 92 months) of sixty‐four patients receiving IFN as first‐line therapy. IFN was well tolerated and effective. The overall response rate was 91% (PR 65%, CR 13%, GPR 13%). Forty‐one patients (63%) received IFN 3 MU/wk as maintenance therapy. The 10‐yr projected survival rate of responding patients (CR and GPR 100%; PR 95%) and non responders (SD, PD 80%) clearly shows that type of response does not affect survival. Patients receiving IFN maintenance had a statistically higher PFS than those who did not (p<0.01). This study shows that IFN is still one of the standard therapies for this disease, that achieving CR has no primary relevance for the control of the disease, and that good utilization of therapeutic resources may assure HCL patients a survival rate comparable to that of a normal, healthy population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM PUBLISHER]

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 reconstructions, are reported. Both grafts were well functioning. At microscopic examination, 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. Partial endothelialization ofthe 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. [ABSTRACT FROM AUTHOR]

Carbon has been used to improve the thromboresistance of synthetic vascular prostheses, and for this purpose, dacron grafts have been coated with carbon. Owing to the contradictory results reported in the literature, a new kind of vascular conduit, exclusively textured from carbon fibers, has been developed. The present research study was undertaken to compare carbon and expanded polytetrafluoroethylene (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 seconds, or sixty minutes, or seven, fifteen, thirty, sixty, or one hundred twenty days after implantation. Specimens were examined by light and scanning electron microscopy. Cumulative 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 better 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 completely 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 appeared 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 interface 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 arteri... [ABSTRACT FROM AUTHOR]

HER2 expression or gene amplification is crucial for performing targeted therapy. We assessed p185HER2 (p185) expression, HER2 amplification and copy number of chromosome 17 centromere (CEP 17) in pancreatic adenocarcinoma (PAC). We analyzed 26 tumours at diagnosis, 21 metastatic lymph nodes (mLN) and 38 distant metastases (mTS) by immunohistochemistry and by FISH, p 185 overexpression was shown in 4% of primary PAC, 6% of mLN and 29% of mTS. Amplification was found restricted to 10% of the mTS and increased CEP 17 in 21% of mTS and 16% of mLN. Overexpression of pi 85 was present in all amplified cases but in only 36% of increased CEP 17. In conclusion HER2 amplification and increased CEP 17 were mainly related to mTS or mLN and increased CEP 17 was not always linked to overexpression of p 185. [ABSTRACT FROM AUTHOR]

The article discusses the cases of two patients who underwent endocytoscopic (ECS) follow-up of the resection of the colon for malignant adenomas. Topics discussed include the pre-operative marking of the colonic mucosa using India ink, the failure of the ECS to visualize submucosal black staining, and pathologic examination of the tattooed areas.

The article presents a case study of two patients with signet ring cell (SRC) cancer of the stomach, wherein the results of endocytoscopy (ECS) correlated with histologic examination.