A pilot study of thalidomide in recurrent GI bleeding due to angiodysplasias.

Angiodysplasias are a major cause of lower gastrointestinal bleeding in patients over the age of 60 years. Although multiple treatment modalities, both medical and surgical, are being used, there is no effective treatment option currently available. Our study defines the use of a novel drug that might be effective against bleeding from vascular malformations. Three patients with a diagnosis of angiodysplasia, who were transfusion dependent, were placed on the study drug. The need for blood transfusions was recorded over the study period and for 6 months after the end of the study. We saw a decreased need for transfusions within 12 weeks of starting the treatment in two patients, and they continued to remain free of transfusion requirement during the immediate follow-up period. The study drug was well tolerated. Thalidomide, with its antiangiogenic mechanism of action, seems to be a promising drug in bleeding angiodysplasias as a treatment option for patients unable to benefit from other available modalities of treatment.

PRDX4, a member of the peroxiredoxin family, is fused to AML1 (RUNX1) in an acute myeloid leukemia patient with a t(X;21)(p22;q22).

The AML1 gene (also known as RUNX1) at 21q22 codes for core binding factor (CBF) alpha, which forms a heterodimer with CBF beta that acts as a transcriptional activating factor. CBF is a critical regulator in the generation and differentiation of definitive hematopoietic stem cells and is frequently disrupted in leukemia through chromosome translocations. We cloned a novel AML1 partner gene, PRDX4, in an X;21 translocation in a 74-year-old male patient diagnosed with acute myeloid leukemia-M2. Chromosome analysis detected a t(X;21)(p22;q22) as the sole abnormality in bone marrow samples. The involvement of AML1 was confirmed by fluorescence in situ hybridization studies. Using 3' RACE-PCR, we cloned a fusion between exon 5 of AML1 and exon 2 of PRDX4. RT-PCR confirmed the fusion and detected another fusion between exon 6 of AML1 and exon 2 of PRDX4, indicating alternative splicing of exon 6 of AML1 in the fusion transcripts. PRDX4 is one of six peroxiredoxin-family genes that are highly conserved in eukaryotes and prokaryotes and are ubiquitously expressed. Peroxiredoxin genes exhibit thioredoxin-dependent peroxidase activity and have been implicated in a number of other cellular functions such as cell proliferation and differentiation. PRDX4 plays a regulatory role in the activation of the transcription factor NF-kappaB and is significantly down-regulated in acute promyelocytic leukemia. This is the first example of antioxidant enzyme involvement in a chromosome translocation in leukemia.

Chronic abdominal pain caused by heterotopic ossification with functioning bone marrow: a case report and review of the literature.

Heterotopic ossification is rarely seen after midline abdominal surgery. The etiology of heterotopic ossification is unknown. Although it is well recognized that heterotopic ossification may contain osteogenic cells and/or hematopoietic cells, to our knowledge, no case has ever been reported to have histologic evidence of hematopoiesis. We report the occurrence of heterotopic bone with bone marrow showing normal trilineage hematopoiesis in the incision scar of a woman who underwent gastric reduction surgery for the treatment of obesity. The literature regarding heterotopic ossification and extramedullary hematopoiesis is reviewed in this report, and discussion focuses on the mechanism of this pathophysiologic process.

Surgical indications in idiopathic splenomegaly.

HYPOTHESIS: The incidence of primary lymphoma of the spleen in patients with idiopathic splenomegaly is significant. DESIGN: Retrospective review of all patients referred to a general surgical service for splenectomy. SETTING: A large tertiary care hospital. PATIENTS: Between 1994 and 2001, 86 nontrauma patients were referred for splenectomy. Of these, 18 had idiopathic splenomegaly despite prior workup with computed tomography, peripheral smear, bone marrow biopsy, and laboratory testing. All patients were symptomatic and displayed varying degrees of cytopenia. INTERVENTION: All 18 patients underwent open splenectomy for diagnosis and treatment of their cytopenias. MAIN OUTCOME MEASURE: Incidence of lymphoma in the pathologic specimens. RESULTS: The mean size of the spleens was 21 cm (range, 14-34 cm) and mean weight was 996 g (range, 320-1840 g). In all 18 patients, the surgical specimen provided a diagnosis. Sarcoidosis was discovered in 4 patients, and 1 patient had Castleman disease. Six patients with the benign diagnosis of hypersplenism received no further interventions, and the cytopenias resolved in all 6 cases. The 7 remaining patients (39%) were diagnosed with lymphoma. Five had marginal zone lymphoma, and 2 had a more aggressive B-cell lymphoma. Three patients required chemotherapy, but 4 are still in remission since their splenectomies and show no evidence of active disease. The mean follow-up was 20 months. CONCLUSIONS: A high percentage of patients with splenomegaly of unknown etiology will have primary lymphoma of the spleen. Splenectomy is both diagnostic and therapeutic and should be considered for all patients with idiopathic splenomegaly.