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To determine whether the tumor cell contamination of peripheral blood stem cells influences clinical impacts on high-dose chemotherapy in patients with metastatic breast cancer, we analyzed carcinoembryonic antigen (CEA) mRNA in the apheresis products by nested RT-PCR (reverse transcriptase-polymerase chain reaction). A total of 38 metastatic breast cancer patients and ten normal healthy subjects as a negative control were included. Twenty out of 38 (51.3%) apheresis products from patients with metastatic breast cancer were positive for CEA mRNA. CEA mRNA was noted in 54.8% (17/31) of patients mobilized with chemotherapy plus G-CSF and 42.8% (3/7) of patients with G-CSF alone. There was no significant difference in age, estrogen receptor, menopausal status, mobilization method, disease free interval, or number of metastasis sites (1 vs > or = 2) between positive and negative groups. The presence of CEA mRNA in apheresis products did not influence the time to progression and overall survival in both groups. However, both the univariate and the multivariate analysis disclosed that the number of metastasis was associated with survival significantly. We suggest that the tumor cell contamination does not predict poor treatment outcome in patients with metastatic breast cancer.

To investigate the role of angiogenesis in multiple myeloma (MM), bone marrow biopsy from 75 adults with newly diagnosed, untreated MM were evaluated. Microvessels were scored in at least 3 areas ( x 200 fields) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for CD34. Prognostic variables were also evaluated for the overall survival. Microvessel counts were significantly higher in patients with MM (n=69.42+/-9.67), compared with control (n=26.81+/-2.85). Microvessel density had a weak correlation with percentage of bone marrow plasma cells. By univariate analysis, age, beta2-microglobulin, serum albumin, serum creatinine, serum calcium, hemoglobin, platelet count, and bone marrow plasma cell percentage were correlated with survival. By multivariate analysis, age, serum albumin, serum creatinine, hemoglobin, platelet count and bone marrow plasma cell percentage were correlated with overall survival, whereas microvessel density was not. In summary, microvessel density in bone marrow of MM is significantly increased compared to control, but was not correlated with overall survival. Further studies regarding angiogeneic molecules are needed to determine the functional role of angiogenesis in MM.

Although eosinophilic fasciitis (EF) may precede hematologic malignancy or Hodgkin's disease, association with peripheral T-cell lymphoma (PTCL) is extremely rare. Only four cases of EF preceding or concomitant PTCL have been reported in the world literature. We experienced the first Korean case of EF complicated by the later relapse of peripheral T-cell lymphoma. A 63-year-old Korean male has been followed at our outpatient clinic periodically after treatment for stage IV PTCL. He had been in complete remission for seven and a half years when he developed edema of both lower extremities followed by sclerodermatous skin change in both hands with peripheral eosinophilia. Biopsy from the left hand showed fibrous thickening of the fascia with lymphoplasmacytic and eosinophilic infiltrate, consistent with EF. Twenty-five months later, a newly developed lymph node from the left neck showed recurrence of PTCL. EF may occur as a paraneoplastic syndrome associated with the relapse of PTCL. Therefore, in a patient with EF, the possibility of coexisting and/or future occurrence of hematologic neoplasm should be considered.

To determine whether the p53 expression might be a predictor for treatment response and overall survival in nodal non-Hodgkin's lymphoma (NHL), we analyzed the expression of p53 in 69 NHL patients. p53 protein expression was analyzed by immunohistochemistry with long-term follow up (1-148 months: median 12.2). p53 expression was noted in 23/69 (33.3%) patients. Complete response (CR) rate to systemic chemotherapy was correlated with stage (I/II) (p=0.038), but not with p53 expression (p=0.2856). Poor overall survival was associated with stage (p=0.0010) or IPI score (p=0.0076), but not with p53 expression (p=0.8601). From stratification analysis by stage, in stage III/IV patients, the p53 positive group had a trend to be associated with poor overall survival than the p53 negative group. Multivariate analysis revealed that p53 positive group was associated with less CR rate compared to the p53 negative group (p=0.046), whereas overall survival was correlated with stage (p=0.0320), not with p53 status. p53 expression was associated with less CR rate in patients with DLBL. Further studies with large numbers of samples and homogenous group of NHL are needed to determine the prognostic value of cell cycle regulator, p53 in NHL.

We analyzed the peripheral blood of patients with gastrointestinal tract cancer at different stages to assess the presence of carcinoembryonic antigen (CEA) mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR), which we used as an indicator for micrometastatic malignant cells. A total of 35 gastric, 24 colorectal, 4 esophageal and 4 biliary tract cancer patients and nine normal healthy subjects were studied. No CEA mRNA was detected in the nine normal healthy volunteers. CEA mRNA was detected in 100% (10/10) of metastatic, 33.3% (3/9) of early gastric cancer (EGC), and 18.8% (3/16) resectable gastric cancer patients, respectively. In colorectal cancer, 55.6% (5/9) of metastatic cancers were positive for CEA mRNA, and 26.7% (4/15) Duke stage B/C showed positive. One patient with stage III gastric cancer who was negative CEA mRNA initially and turned positive during follow-up, developed multiple bone metastasis one month later. Another stage III patient, who was positive for CEA mRNA, preoperatively revealed early relapse in two months. These results suggest that the identification of circulating tumor cells using RT-PCR for the detection of CEA mRNA is feasible and this analysis may be a promising tool for early detection of micrometastatic circulating malignant cells in patients with gastrointestinal tract cancer.

This study was designed to test the activity and feasibility of 5'-deoxy-5-fluorouridine (5'-DFUR) and cisplatin combination therapy in the treatment of advanced gastric cancer. Nineteen patients with inoperable and/or metastatic gastric cancer, which was histologically proven, were orally administered 5'-DFUR 1,200 mg/m2 on days 1 to 4 and days 15-18 combined with 70 mg/m2 of cisplatin being repeated every 4 weeks. Five partial responses (PRs) were achieved. Seven patients had stable disease and 6 progressed on therapy. The overall response rate was 27.7% (95% confidence interval: 9.69% to 53.5%). The median survival duration of all 18 patients was 25 weeks (9-64). The majority of patients had WHO grade I/II toxicity, but there was no treatment-related death. These data support that the combinations of oral 5'-DFUR and cisplatin are well tolerable and have a moderate activity with low toxicity in the treatment of advanced gastric cancer.

We report a case of leukemia cutis with atypical skin manifestations, presented with generalized various sized dark brownish to erythematous patches with plaques on the whole body of a 42-year-old man. Skin lesions developed 6 months ago and had no signs of itching or tenderness. He complained of sustaining fevers with abdominal discomfort. Laboratory findings showed elevation of leukocyte count and peripheral blood smear revealed 86% of lymphocyte. Histologic examination showed diffuse infiltration of abnormal cells that appeared to be leukemic in nature.

Cyclin D1 and cyclin E are the mammalian G1 cydins that are both required and rate limiting for entry into S phase. Alterations in cell cycle regulators and subsequent deregulation of the cell cycle are frequently involved in tumorigenesis and/or tumor progression. We investigated the expression of cyclin D1 and cyclin E protein in 84 gastric carcinoma by immunohistochemical staining and also the relevance of each cyclin expression to the clinical outcomes. Overexpression of cyclin D1 and cyclin E was noted in 21 of 84 (25.0%) and 34 of 84 (40.5%) gastric cancer tissues, respectively. There was a significant correlation between overexpression of cyclin E and lymph node metastasis (p=0.003), recurrence (p=0.043), disease free survival (p=0.0378) and overall survival (p=0.0319), but no correlation was noted between overexpression of cyclin D1 and other clinicopathologic variables. These findings suggest that overexpression of cyclin E and cyclin D1 is a frequent finding in gastric cancer and immunohistochemical analysis for cell cycle regulators, especially cyclin E might be a useful prognostic indicator in gastric cancer.

Evidence suggests that multiple molecular events, including alteration of cell cycle regulators are involved in the development and progression of gastric carcinoma. Recently, it has been reported that the expression of p21 and p27, integrating the effects of one or more cell cycle regulators, consequently, acting as a single indicator of several possible cell cycle gene alterations is associated with tumor suppression. In the present study, we studied the immunohistochemical expression of p21 and p27 in gastrectomy specimens from 84 patients with gastric adenocarcinoma, and analysed its correlation to clinicopathologic data, including patients survival. Loss of p21 and p27 expression was noted in 45 (53.6%) and 44 (52.4%) of the 84 gastric carcinoma tissues, respectively. The expression of p21 was significantly correlated with histological type (p= 0.005), recurrence (p=0.002) and death (p=0.002) after surgery, and p27 expression (p=0.001). Kaplan-Meier survival plots showed p21 negative group (p= 0.0014) or both p21 and p27 negative group (p=0.0048) was significantly poorer in overall survival than both p21 and p27 positive or one of both positive group. Our results suggest that the status of p21 and p27 expression in immunohistochemical stain may be a useful prognostic marker of gastric carcinoma.

Pernicious anemia is an autoimmune disease characterized by a gastric mucosal defect which results in an insufficiency of intrinsic factor to facilitate the absorption of the physiologic amount of cobalamin. Increased risk of cancers of the stomach has been reported for patients with pernicious anemia. We report here a case of a 65 year old woman who had been diagnosed as having pernicious anemia 16 months previously, was receiving monthly vitamin B12 injections, and developed early gastric cancer type IIa by routine follow-up gastroscopic examination. This patient underwent endoscopic mucosal resection for an early gastric cancer lesion with a free resection margin.

Virus associated hemophagocytic syndrome (VAHS) are a heterogeneous group of disorders in which viral infection is associated with a proliferation of hemophagocytic histiocytes through the reticuloendothelial system. We report the case of a 21-year-old Korean man who presented to us with high fever, marked hepatosplenomegaly, severe hepatic dysfunction, coagulopathy, pancytopenia and marked panhypogammaglobulinemia. Bone marrow aspiration and biopsy showed histiocytes proliferation with active phagocytosis of red cells and neutrophils. Primary Epstein-Barr (EB) viral infection at presentation was confirmed by the presence of IgM antibody to viral capsid antigen (VCA) with absence of antibody to EB viral nuclear antigen (EBNA). A liver biopsy performed one month after the presentation showed erythrophagocytic histiocytes within the sinusoids. EB virus was demonstrated in the liver biopsy tissue by DNA PCR method, and EBER mRNA in situ hybridization.

We report a case of prostate cancer in 34 year old man presenting with generalized lymphadenopathy mimicking malignant lymphoma without any urinary symptoms. Lymph node biopsy revealed metastatic adenocarcinoma and immunohistochemical stain was strongly positive to prostate antigen (PSA). Serum PSA level was also markedly elevated. Transrectal ultrasonogram showed mild enlargement in right lobe of prostate. Needle biopsy finding of prostate also was consistent with adenocarcinoma. Bone scan revealed multiple metastatic lesions including vertebrae, ribs, pelvis, and both femurs. Generalized lymphadenopathy and elevated PSA level was decreased after bilateral orchiectomy.

Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia (AML) and is distinguished from other subsets of AML by its distinctive morphology, specific chromosomal abnormality, associated consumptive coagulopathy, and response to treatment. Interestingly, patients with APL frequently enter complete remission without undergoing a characteristic period of bone marrow hypoplasia. In two cases in this report, complete remission was achieved without bone marrow hypoplasia without further additional course of chemotherapy despite the appearance of persistent malignant cells in the bone marrow after first induction chemotherapy. During the period of treatment, severe coagulopathy occurred in both cases but resolved as the patients entered into remission. Remission in patients with APL may occur even when induction therapy fails to cause marrow hypoplasia or to eradicate replicative cells. To avoid unnecessary exposure to toxic therapy, caution should be exercised in assessing the adequacy of remission induction treatment.