Impact of Day +11 Methotrexate on the Incidence of Graft-versus-host Disease after HLA-identical Allogeneic Peripheral Blood Stem Cell Transplantation / 대한혈액학회지

BACKGROUND: Cyclosporine (CSA) plus 4 doses of methotrexate (MTX) is the commonly used regimen for GVHD prophylaxis. It has been previously found that the omission of the day +11 dose of MTX was associated with an increased risk of acute GVHD in the allogeneic BMT setting. However, little is known about its impact in the PBSCT setting. METHODS: Of the 68 patients, 30 patients (44%) received 4 doses of MTX (the MTX4 group), while 38 patients (56%) received less than 4 doses (the MTX3 group) because of their severe mucositis, hepatic dysfunction or renal failure. RESULTS: The cumulative incidence of acute GVHD was 60% in the MTX4 and 86% in the MTX3 group (P=0.038), while that of grade III and IV acute GVHD was 7% in the MTX4 group and 39% in the MTX3 group (P=0.017). Of the 61 patients evaluated for chronic GVHD, the cumulative incidence of chronic GVHD was 54% in the MTX4 group and 97% in the MTX3 group (P=0.001), while that of extensive chronic GVHD was 26% in the MTX4 group and 63% in the MTX3 group (P=0.004). There were no differences in the overall survival and the incidence of relapse between the two groups. On multivariate analyses, MTX3 was a poor prognostic factor in terms of acute GVHD and extensive chronic GVHD. CONCLUSION: This study suggested that omitting day +11 MTX and the clinical situation of the MTX3 group seemed to be associated with an increased incidence of acute and chronic GVHD. Accordingly, administration of day +11 MTX accompanied by active treatment of mucositis may prevent GVHD in the allogeneic PBSCT setting, but we need to conduct a large scale prospective study.

Unpredicted Severe Toxicity after 5-Fluorouracil Treatment due to Dihydropyrimidine Dehydrogenase Deficiency

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). Thus, patients with a DPD deficiency are at risk of developing severe 5-FU-associated toxicity. A 37-year-old female with gastric cancer underwent a curative operation, followed by adjuvant chemotherapy consisting of 5-FU and epirubicin. After the first cycle of chemotherapy, the patient manifested grade 2 mucositis and febrile neutropenia, and when her treatment was subsequently continued with doxifluridine she developed severe mucositis and febrile neutropenia. A PCR study revealed that her DPD mRNA level was lower than that in a control group. Thus, when considering the routine use of 5-FU for the treatment of cancer patients, an analysis of DPD activity or screening for DPD mutations is warranted in confined patients who experience unpredicted severe toxicity after initial 5-FU administration, even though DPD deficiency is a rare metabolic defect.

Clinical Significance of Platelet Count at day +60 After Allogeneic Peripheral Blood Stem Cell Transplantation

Thrombocytopenia (TP) is a frequent complication after allogeneic stem cell transplantation (SCT) and regarded as a poor prognostic factor, especially in patients with chronic graft-versus-host disease (GVHD), although various factors were related to the development of TP after allogeneic SCT. Sixty-three patients receiving allogeneic peripheral blood stem cell transplantation (PBSCT) were stratified according to platelet count (PC) at day +60 and analyzed in terms of overall survival (OS) and the incidence of non-relapse mortality (NRM). Ten patients (15.9%) were stratified in group 1 (PC or =80 x 10(9)/L). Group 3 was associated with lower incidence of extensive chronic GVHD (p=0.013), better 3-yr OS (p=0.0030), and lower NRM rate (p<0.0001). In multivariate analyses, the PC at day +60 was identified as an independent prognostic factor (p=0.003) together with CD34+ cell dose (p<0.001), disease risk (p=0.004), and acute GVHD (p=0.033) in terms of NRM, and the PC (p=0.047) and CD34+ cell dose (p=0.026) in terms of incidence of infectious events. Measuring the platelet count at day +60 is a simple method for predicting the risk of chronic GVHD development and prognosis after allogeneic PBSCT.

Treatment outcomes of primary central nervous system lymphoma: Multi-center retrospective study / 대한내과학회지

BACKGROUND: A primary central nervous system lymphoma (PCNSL) is a rare neoplasm with a poor prognosis. The treatment of PCNSL involves a combination of chemotherapy, intrathecal chemotherapy and radiotherapy. This study retrospectively evaluated the treatment outcomes and prognostic factors of Korean patients with PCNSL. METHODS: Between 1995 and 2003, 58 patients diagnosed with PCNSL from the multi-center hospitals were enrolled in this study. Among 56 patients who had received treatment, 16 patients were treated with radiotherapy alone, while 40 patients were treated with combined chemotherapy (CHOP; 9 cases, high-dose methotrexate; 31 cases) and radiotherapy. RESULTS: The median age of the patients was 58 years (range, 19-76). A diffuse large B-cell lymphoma was diagnosed in 56 cases (96.6%), while a peripheral T-cell lymphoma was diagnosed in 2 cases. Of the 47 patients who could be assessed for their response after treatment, a CR and PR was observed in 32 (68%) and 11 patients (23%), respectively, giving an overall response rate of 91% (95% CI, 82~100%). The estimated 3-year overall survival rate for all the patients was 67+/-7.9% and the 3-year disease free survival rate was 53+/-8.3%. The overall survival of the high-dose methotrexate group was superior to that of the CHOP group (77+/-10% versus 47+/-19%, p=0.05). Leukoencephalopathy was observed as a late complication in 9 patients (21%). No significant prognostic factors affecting survival were found by univariate analysis. CONCLUSIONS: Approximately half of the patients could have long-term survival after treatment in this study. High-dose methotrexate containing chemotherapy followed by radiotherapy was found to be an effective treatment.

Variable Number of Tandem Repeats (VNTR) Disparity between Donor and Recipient has a Potential to Predict the Outcomes of HLA-identical Allogeneic Stem Cell Transplantation / 대한혈액학회지

BACKGROUND: Detection of variable number of tandem repeats (VNTR) between recipient and donor has been adopted to monitor the degree of chimerism after allogeneic stem cell transplantation (SCT). In allogeneic SCT, besides MHC-disparity, the disparity of various polymorphous proteins encoded by several genes may play a critical role in the pathogenesis of graft-versus-host disease (GVHD). However, the biologic effect of VNTR disparity has been scarcely studied. METHODS: We analyzed 84 patients receiving SCT from HLA-identical sibling (n=68) or unrelated donors (n=16). Enrolled diseases included AML 48, ALL 8, CML 15, NHL 10, and high-risk MDS 3. The PCR was performed to amplify 3 VNTR regions (D1S80, D1S111, and D17S5). RESULTS: We observed strong correlation between the D1S80 disparity and transplant outcomes in terms of OS (P=0.0179) or non-relapse mortality (NRM) (P=0.0305), but not for D1S111 or D17S5 disparity. The D1S80-fully matched pair showed a better OS (72% vs 38%) and lower NRM (17% vs 50%) compared to partially matched or mismatched pairs. In multivariate analyses, D1S80-fully matched pair was found to be independent favorable prognostic factor for OS (P=0.03) or NRM (P=0.05). In addition, the D1S80 disparity was significantly associated with the myeloid engraftment speed (P=0.01) or the occurrence of gut chronic GVHD (P=0.05). CONCLUSION: Our data suggest that disparities in D1S80-located on chromosome1-seemed to be associated with increased incidence of gut chronic GVHD and NRMs, thus suggesting the existence of unknown genes of minor histocompatibility antigens targeting gut or cytokine/cytokine receptor on chromosome 1.

Biweekly Irinotecan and Cisplatin as Second-line Chemotherapy in Pretreated Patients with Advanced Gastric Cancer: A Multicenter Phase II Study

The current phase II study was conducted to evaluate the response rate and safety of a combination regimen of biweekly irinotecan plus cisplatin in pretreated patients with advanced gastric cancer. Patients with previously treated metastatic or recurrent gastric cancer received intravenous irinotecan 70 mg/m2 and cisplatin 30 mg/m2 on day 1 and 15 every 4-week cycle. Thirty-two patients were enrolled in the current study. Of these, 31 patients were assessable for efficacy and all for toxicity. No complete response and 5 partial responses were confirmed, giving an overall response rate of 15.6% (95% CI; 2.3-28.9%). The median time to progression and median overall survival for all patients was 113 days and 184 days, respectively. Grade 3/4 neutropenia occurred in 6 patients (18.8%), yet no febrile neutropenia was observed. In addition, grade 3 anorexia was observed in 4 patients (12.5%) and grade 3 diarrhea occurred in 2 patients (6.2%). The combination chemotherapy of biweekly irinotecan and cisplatin was found to be moderately effective and well tolerated in pretreated patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important second-line treatment option for advanced gastric cancer.

Biodistribution of (99m) Tc-Lactosylated Serum Albumin in Mice with Diethylnitrosamine or Thiacetamide Induced Liver Injury / 대한핵의학회잡지

PURPOSE: Tc-99m labeled diethylenetriaminepentaacetic acid (DTPA) -coupled galactosylated human serum albumin (GSA) is a currently used imaging agent for asialoglycoprotein receptor (ASGPR) of the liver, but, it has several shortcomings. Recently a new ASGPR imaging agent, (99m) Tc-lactosylated human serum albumin (LSA), with simple labeling procedure, high labeling efficiency, high stability was developed. In order to assess the feasibility of the (99m) Tc-LSA as a ASGPR imaging radiopharmaceuticals, we performed biodistribution study of the tracer in liver injured mice model and the results were compared with histolgic data. MATERIALS AND METHODS: To induce hepatic damage in ICR mice, diethylnitrosamine (DEN) (60 mg/kg/week X 5 time, low dose or 180 mg/kg/week X 2 times, high dose) and thioacetamide (TAA) (50 mg/kg X 1 time) were administrated intraperitoneally. Degree of liver damage was evaluated by tissue hematoxilin-eosin stain, and expression of asialoglycoprotein receptor (ASGPR) was assessed by immunohistochemistry using ASGPR antibody. (99m) Tc-LSA was intravenously administrated via tail vein in DEN or TAA treated mice, and biodistribution study of the tracer was also performed. RESULTS: DEN treated mice showed ballooning of hepatocyte and inflammatory cell infiltration in low dose group and severe hapatocyte necrosis in high dose group, and low dose group showed higher ASGPR staining than control mice in immunohistochemical staining. TAA treated mice showed severe hepatic necrosis. (99m) Tc-LSA Biodistribution study showed that mice with hepatic necrosis induced by high dose DEN or TAA revealed higher blood activity and lower liver activity than control mice, due to slow clearance of the tracer by the liver. The degree of liver uptake was inversely correlated with the degree of histologic liver damage. But low dose DEN treated mice with mild hepatic injury showed normal blood clearance and hepatic activity, partly due to overexpression of ASGPR in mice with mild degree hepatic injury. CONCLUSION: Liver uptake of (99m) Tc-LSA was inversely correlated with degree of histologic hepatic injury in DEN and TAA treated mice. These results support that (99m) Tc-LSA can be used to evaluate the liver status in liver disease patients.

Effects of Anti-thyroglobulin Antibody on the Measurement of Thyroglobulin: Differences Between Immunoradiometric Assay Kits Available / 대한핵의학회잡지

PURPOSE: Thyroglobulin (Tg) is a valuable and sensitive tool as a marker for diagnosis and follow-up for several thyroid disorders, especially, in the follow-up of patients with differentiated thyroid cancer (DTC). Often, clinical decisions rely entirely on the serum Tg concentration. But the Tg assay is one of the most challenging laboratory measurements to perform accurately owing to antithyroglobulin antibody (Anti-Tg). In this study, we have compared the degree of Anti-Tg effects on the measurement of Tg between availale Tg measuring kits. MATERIALS AND METHODS: Measurement of Tg levels for standard Tg solution was performed with two different kits commercially available (A/B kits) using immunoradiometric assay technique either with absence or presence of three different concentrations of Anti-Tg. Measurement of Tg for patient's serum was also performed with the same kits. Patient's serum samples were prepared with mixtures of a serum containing high Tg levels and a serum containg high Anti-Tg concentrations. RESULTS: In the measurements of standard Tg solution, presence of Anti-Tg resulted in falsely lower Tg level by both A and B kits. Degree of Tg underestimation by A kit was more prominent than B kit. The degree of underestimation by B kit was trivial therefore clinically insignificant, but statistically significant. Addition of Anti-Tg to patient serum resulted in falsely lower Tg levels with only A kit. CONCLUSION: Tg level could be underestimated in the presence of anti-Tg. Anti-Tg effect on Tg measurement was variable according to assay kit used. Therefore, accuracy test must be performed for individual Tg-assay kit.

Docetaxel plus cisplatin combination chemotherapy in patients with advanced gastric cancer / 대한내과학회지

BACKGROUND: We evaluated the efficacy and toxicity of docetaxel plus cisplatin combination as first-line chemotherapy for advanced gastric cancer. METHODS: Patients with metastatic or recurrent gastric adenocarcinoma, performance score

Reproducibility of Adenosine Tc-99m sestaMIBI SPECT for the Diagnosis of Coronary Artery Disease / 대한핵의학회잡지

PURPOSE: Adenosine myocardial perfusion SPECT has proven to be useful in the detection of coronary artery disease, in the follow up the success of various therapeutic regimens and in assessing the prognosis of coronary artery disease. The purpose of this study is to define the reproducibility of myocardial perfusion SPECT using adenosine stress testing between two consecutive Tc-99m sestaMIBI (MIBI) SPECT studies in the same subjects. METHODS: Thirty patients suspected of coronary artery disease in stable condition underwent sequential Tc-99m MIBI SPECT studies using intravenous adenosine. Gamma camera, acquisition and processing protocols used for the two tests were identical and no invasive procedures were performed between two tests. Mean interval between two tests were 4.1 days (range: 2-11 days). The left ventricular wall was divided into 18 segments and the degree of myocardial tracer uptake was graded with four-point scoring system by visual analysis. Images were interpretated by two independent nuclear medicine physicians and consensus was taken for final decision, if segmental score was not agreeable. RESULTS: Hemodynamic responses to adenosine were not different between two consecutive studies. There were no serious side effects to stop infusion of adenosine and side effects profile was not different. When myocardial uptake was divided into normal and abnormal uptake, 481 of 540 segments were concordant (agreement rate 89%, Kappa index 0.74). With four-grade scoring system, exact agreement was 81.3% (439 of 540 segments, tau b=0.73). One and two-grade differences were observed in 97 segments (18%) and 4 segments (0.7%) respectively, but three-grade difference was not observed in any segment. Extent and severity scores were not different between two studies. The extent and severity scores of the perfusion defect revealed excellent positive correlation between two test (r value for percentage extent and severity score is 0.982 and 0.965, p< 0.001) CONCLUSION: Hemodynamic responses and side effects profile were not different between two consecutive adenosine stress tests in the same subjects. Adenosine Tc-99m sestaMIBI SPECT is highly reproducible, and could be used to assess temporal changes in myocardial perfusion in individual patients.

Dopamine Transporter Density of the Basal Ganglia Assessed with I-123 IPT SPECT in Methamphetamine Abusers / 대한핵의학회잡지

PURPOSE: Functional imaging of dopamine transporter (DAT) defines integrity of the dopaminergic system, and DAT is the target site of drugs of abuse such as cocaine and methamphetamine. Functional imaging the DAT may be a sensitive and selective indicator of neurotoxic change by the drug. The aim of the present study is to evaluate the clinical implications of qualitative/quantitative analyses of dopamine transporter imaging in methamphetamine abusers. MATERIALS AND METHODS: Six detoxified methamphetamine abusers (abuser group) and 4 volunteers (control group) were enrolled in this study. Brain MRI was performed in all of abuser group. Abuser group underwent psychiatric and depression assessment using brief psychiatric rating scale (BPRS) and Hamilton depression rating scale (HAMD), respectively. All of the subjects underwent I-123 IPT SPECT (IPT SPECT). IPT SPECT image was analysed with visual qualitative method and quantitative method using basal ganglia dopamine transporter (DAT) specific/non-specific binding ratio (SBR). Comparison of DAT SBR between abuser and control groups was performed. We also performed correlation tests between psychiatric and depression assessment results and DAT SBR in abuser group. RESULTS: All of abuser group showed normal MRI finding, but had residual psychiatric and depressive symptoms, and psychiatric and depressive symptom scores were exactly correlated (r=1.0, p=0.005) each other. Five of them showed abnormal finding on qualitative visual I-123 IPT SPECT. Abuser group had lower basal ganglia DAT SBR than that of control (2.38+/-0.20 vs 3.04+/-0.27, p=0.000). Psychiatric and depressive symptoms were negatively well correlated with basal ganglia DAT SBR (r=-0.908, p=0.012, r=-0.924, p=0.009). CONCLUSION: These results suggest that dopamine transporter imaging using I-123 IPT SPECT may be used to evaluate dopaminergic system of the basal ganglia and the clinical status in methamphetamine abusers.

Simultaneous Visualization of the Sublingual Thyroid and Lactating Breasts with Tc-99m Pertechnetate Scintigraphy / 대한핵의학회잡지

PURPOSE: The thyroglossal duct runs from the base of the tongue to the thyroid. Rarely the thyroid completely fails to migrate and results in ectopic thyroid tissue, which can be demonstrated scintigraphically. A 31-year old female patient was referred for thyroid scintigraphy due to protruding mass at the base of the tongue. She was mildly hypothyroid. Tc-99m pertechnetate thyroid scan was performed to rule out ectopic thyroid gland. There showed a focal area of intense tracer uptake in sublingual area, suggesting the sublingual thyroid. In addition there noted diffusely increased tracer uptake in both breasts. The patient delivered a baby 6 months prior to the scan and was on breast-feeding. Free Tc-99m pertechnetate physiologically secrets into the salivary glands, the stomach, the gastrointestinal tract, the genitourinary tract and the mammary glands and sodium-iodide symporter plays a role in the accumulation of free Tc-99m pertechnetate. We report simultaneous visualization of lactating breasts and ectopic thyroid gland in the base of the tongue.

Malignant Peripheral Nerve Sheath Tumor in Neurofibromatosis Type I: Unusual Presentation of Intraabdominal or Intrathoracic Mass

A malignant peripheral nerve sheath tumor (MPNST) is an extremely rare soft tissue tumor in the general population. On the other hand, there is a higher incidence of MPNST in patients with neurofibromatosis type I (von Recklinghausen's disease). The common sites are the extremities, trunk, head and neck. However, an intraabdominal or intrathoracic manifestation is uncommon. This paper reports two patients, a 31 year-old woman with multiple neurofibromatosis presenting as an intraabdominal malignant peripheral nerve sheath tumor, and a 33 year-old woman with an intrathoracic malignant peripheral nerve sheath tumor. The patients were treated with chemotherapy followed by radiotherapy. However, one patient died as a result of disease progression 21 months after the diagnosis and the other patient is currently being treated with radiotherapy.

Single Center Experience of Allogeneic Peripheral Blood Stem Cell Transplantation for Acute Myeloid Leukemia / 대한혈액학회지

BACKGROUND: Recently, peripheral blood (PB) stem cells have been used widely for allogeneic stem cell transplantation (SCT), instead of bone marrow (BM). The current study analyzed the outcome of allogeneic PBSCT for the patients with acute myeloid leukemia (AML). METHODS: Twenty-nine patients with AML excluding AML M3 were included for the analysis. PB stem cells were collected from HLA-matched sibling donors mobilized with G-CSF with or without GM-CSF. RESULTS: Engraftment for neutrophil and platelet were achieved in a median 15.0 days and 14.0 days, respectively. The incidence of grade II~III acute graft versus host disease (GVHD) was 82.8% (24/29 patients), while of chronic GVHD 78.6% (22/28 patients, limited 11, extensive 11). During the median follow-up of 340 days (range, 86~1,603 days), 3 years overall survival and disease free survival was 51.4% and 40.0%, respectively. CONCLUSION: PB may be considered as a feasible source of allogeneic SCT for patients with AML.

Serial Changes of Serum Thyroid-Stimulating Hormone after Total Thyroidectomy or Withdrawal of Suppressive Thyroxine Therapy in Patients with Differentiated Thyroid Cancer / 대한핵의학회잡지

BACKGROUND: Radioactive iodine (RAI) therapy and whole-body scanning are the fundamentals of treatment and follow-up of patients with differentiated thyroid cancer. It is generally accepted that a Thyroid-Stimulating Hormone (TSH) level of at least 30 micro U/ml is a prerequisite for the effective use of RAI, and that it requires 4-6 weeks of off-thyroxine to attain these levels. Because thyroxine withdrawal and the consequent hypothyroidism are often poorly tolerated, and occasionally might be hazardous, it is important to be certain that these assumptions are correct. We have measured serial changes in serum TSH after total thyroidectomy or withdrawl of thyroxine in patients with thyroid cancer. SUBJECTS AND METHODS: Serum TSH levels were measured weekly after thyroidectomy in 10 patients (group A) and after the discontinuation of thyroxine in 12 patients (group B). Symptoms and signs of hypothyroidism were also evaluated weekly by modified Billewicz diagnostic index. RESULTS: By the second week, 78% of group A patients and 17% of group B patients had serum TSH levels > or= 30 micro U/ml. By the third week, 89% of group A patients and 90% of group B patients had serum TSH levels > or= 30 micro U/ml. By the fourth week, all patients in two groups achieved target TSH levels and there were no overt hypothyroidism. CONCLUSION: In all patients, serum TSH elevated to the target concentration (> or=30 micro U/ml) within 4 weeks without significant manifestation of hypothyroidism. The schedule of RAI administration could be adjusted to fit the needs and circumstances of individual patients with a shorter preparation period than the conventional.

Two Cases of Visualization of Bowel Activity on Whole Body Bone Scan: Swallowed Urine and Intestinal Activity Due to Previous Myocardial Perfusion Scan / 대한핵의학회잡지

No abstract available.

Characteristic Findings of Exercise ECG Test, Perfusion SPECT and Coronary Angiography in Patients with Exercise Induced Myocardial Stunning / 대한핵의학회잡지

PURPOSE: Transient wall motion abnormality and contractile dysfunction of the left ventricle (LV) can be observed in patients with coronary artery disease due to post-stress myocardial stunning. To understand clinical characteristics of stress induced LV dysfunction, we have compared the findings of exercise stress test, myocardial perfusion SPECT and coronary angiography between subjects with and without post-stress LV dysfunction. MATERIALS AND METHODS: Among subjects who underwent exercise stress test, myocardial perfusion SPECT and coronary angiography within a month of interval, we enrolled 36 patients with post-stress LV ejection fraction (LVEF) was > or=5% lower than rest (stunning group) and 16 patients with difference of post-stress and rest LVEF was lesser than 1% (non-stunning group) for this study. Treadmill exercise stress gated myocardial perfusion SPECT was performed with dual head SPECT camera using 740 MBq Tc-99m MIBI and coronary angiography was also performed by conventional Judkins method. RESULTS: Stunning group had a significantly higher incidence of hypercholesterolemia than non-stunning group (45.5 vs. 7.1%, p=0.01). Stunning group also had higher incidence of diabetes mellitus and lower incidence of hypertension, but these were not statistically significant. Stunning group had larger and more severe perfusion defect in stress perfusion myocardial SPECT than non-stunning group (extent 18.2 vs. 9.2%, p=0.029; severity 13.5 vs. 6.9, p=0.040). Stunning group also had higher degree of reversibility of perfusion defect, higher incidence of positive exercise stress test and higher incidence of having severe stenosis (80~99%) in coronary angiography than non-stunning group, but these were not statistically significant. In stunning group, all of 4 patients without perfusion defect had significant coronary artery stenosis and had received revascularization treatment. CONCLUSION: Patients with post-stress LV dysfunction had larger and more severe perfusion defect and severe coronary artery stenosis than patients without post-stress LV dysfunction. All of the patients without perfusion defect in stunning group had significant coronary artery stenosis and needed revascularization. Therefore, we suggest that invasive diagnostic procedures and therapeutic interventions might be needed in patients with post-stress LV dysfunction.

Phase II Study of Cyclophosphamide, Epirubicin, Vincristine, Prednisone, and Etoposide (CEOP-E) for Aggressive Non-Hodgkin 's Lymphoma

The main objectives of the current study were to evaluate the efficacy and safety of a CEOP-E regimen for patients with aggressive non-Hodgkin's lymphoma (NHL). Fifty-one consecutive patients with newly diagnosed aggressive NHL were enrolled in the study. Median age of patients was 57 (range, 18-75) yr old, and male to female ratio was 1.32:1. Diffuse large B cell lymphoma (68.8%) was the most common histological subtype. Thirty patients (58.8%) had Ann Arbor stage III or IV diseases at diagnosis. One course of chemotherapy consisted of an intravenous combination of cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, vincristine 2 mg, etoposide 80 mg/m 2 on day 1 and oral administration of 100 mg prednisone on days 1 to 5 (CEOP-E). A complete response or unconfirmed complete response was achieved in 31 (63.3%) out of 49 evaluated patients. With a median follow-up of 16.3 months, 26 events including relapse and death were observed. The estimated 2-yr survival rate for all patients and disease free survival rate for patients achieving complete re-sponse was 58.9% and 57.1%, respectively. Episodes of febrile neutropenia occurred in 5 (10.2%) patients. Transient episodes of ECG abnormality (1st degree AV block) were observed in 2 patients. Accordingly, the CEOP-E regimen produced comparable results to those of other regimens, including CHOP, in terms of the response rate and overall survival. The current regimen seemed to minimize the cardiac toxicity due to an accumulated dose of anthracycline in the treatment of aggressive NHL.

Influence of Anti-thyroglobulin Antibody on the Measurement of Thyroglobulin using the Immunoradiometric Assay / 대한내분비학회지

BACKGROUND: Serum thyroglobulin(Tg) is a valuable and sensitive tool needed in the follow-up of patients with differentiated thyroid cancer(DTC), but antithyroglobulin antibody(Anti-Tg), common in patients with DTC, can interfere with the assay for Tg. In this study, we evaluated the influence of Anti-Tg on the measurement of Tg using the immunoradiometric assay(IRMA). METHODS: In using ELSA-hTg in vivo test(CIS international, Schering, France), a solid phase two-site IRMA was used to measure Tg(23.5ng/mL, 62.5ng/mL) under the absence or presence of three concentrations of Anti-Tg(25U/mL, 50U/mL, 100U/mL). We also performed Tg measurement using patients serum that was mixed with patients serum containing high Anti-Tg. ANOVA and Scheffe tests were performed to evaluate the effect of Anti-Tg on Tg IRMA, and an inverse regression was made to calculate the level of Tg from measured Tg and used Anti-Tg levels and also to assess the degree of effect of anti-Tg on Tg IRMA. RESULTS: In measuring Tg using the standard solution, the presence of Anti-Tg resulted in a falsely suppressed Tg value. The IRMAs for 23.5ng/mL of the standard Tg solution resulted in 24.5+/-.1 ng/mL under no Anti-Tg, 11.8+/-.4ng/mL under 25U/mL of Anti-Tg, 7.7+/-.1ng/mL under 50U/mL of Anti-Tg, and 4.5+/-.4ng/mL under 100U/mL of Anti-Tg. IRMAs 62.5ng/mL of the standard Tg solution resulted in 65.9+/-.7ng/mL under no Anti-Tg, 36.3+/-.2ng/mL under 25U/mL of Anti-Tg, 23.7+/-.7ng/mL under 50U/mL of Anti-Tg, and 14.0+/-.0ng/mL under 100U/mL of Anti-Tg. (ANOVA test, p=0.000). The degree of suppression of the measured Tg value was positively correlated with the Anti-Tg level (Quadratic model regression, Sig T=0.000). The presence of Anti-Tg also resulted in a falsely suppressed Tg value for the Tg measurement using patient's serum. CONCLUSION: The presence of Anti-Tg could consist of the use of Tg as a tumor, therefore Anti-Tg should be measured in all patients diagnosed with DTC. The interpretation of the Tg level must be performed with extreme caution in patients with Anti-Tg.

Effect of Verapamil on Cellular Uptake of Tc-99m MIBI and Tetrofosmin on Several Cancer Cells / 대한핵의학회잡지

PURPOSE: Cellular uptake of 99mTc-sestamibi (MIBI) and 99mTc-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance (MDR) by p-glycoprotein (Pgp) or multidrug related protein (MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. MATERIALS AND METHODS: Cellular uptakes of Tc-99m MIBI and TF were measured in erythroleukemia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562 (Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto 200 micro M at 1x10 (6) cells/ml at 37degrees C. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. RESULTS: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562 (Adr) cell at a concentration of 100 micro M and the maximal increase at 50 micro M was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over 1 micro M. With a concentration of 200 micro M verapamil, MIBI and TF uptakes in K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with 10 micro M, but were also decreased with verapamil higher than 10 micro M, resulting 40% and 5% of baseline at 50 micro M. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at 200 micro M. CONCLUSION: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.