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Biomedical subjects

Sung-Won Kim

Publications and source records attributed to Sung-Won Kim.

At least 19 recordsLinked to original sources

The clinical use of staging bone scan in patients with breast carcinoma: reevaluation by the 2003 American Joint Committee on Cancer staging system.

BACKGROUND: Using the new 2003 American Joint Committee on Cancer (AJCC) staging system, the authors evaluated the usefulness of the staging bone scan in patients with primary breast carcinoma. METHODS: The authors examined 1939 patients with primary breast carcinoma for staging bone scan who were treated at a single institution. Pathologic stage was assigned retrospectively according to the 1988 and the 2003 AJCC staging systems. RESULTS: Bone metastasis rates were 0.7% (4 of 586) for patients with Stage I disease, 0.7% (5 of 699) for patients with Stage IIA disease, 2.1% (10 of 479) for patients with Stage IIB disease, 4.5% (7 of 154) for patients with Stage IIIA disease, and 10.5% (2 of 19) for patients with Stage IIIB disease according to the 1988 AJCC staging system. The authors found a significant difference in the bone metastasis rate between patients with Stages IIA and IIB disease in the 1988 staging system (P = 0.039). Reevaluating the patients by the 2003 system resulted in significant upstaging, especially for patients with Stage II/III disease. According to the 2003 staging system, bone metastasis rates were 0.7% (4 of 586) for patients with Stage I disease, 0.6% (4 of 648) for patients with Stage IIA disease, 0.6% (2 of 310) for patients with Stage IIB disease, 4.0% (9 of 225) for patients with Stage IIIA disease, 16.7% (2 of 12) for patients with Stage IIIB disease, and 4.4% (7 of 158) for patients with Stage IIIC disease. It was noteworthy that there was a significant difference between Stages IIB and IIIA in the 2003 staging system (P = 0.010). CONCLUSIONS: Stage reclassification using the new AJCC staging system resulted in upstaging of high-risk patients, as well as a significant decrease in the bone metastasis rate in patients with Stage IIB breast carcinoma. Considering the cost-effectiveness of staging bone scan, the data suggested that it was of little value for patients with Stage I and II breast carcinoma, but was highly recommended for patients with worse than Stage III disease by the new 2003 staging system.

Adult↗

A haplotype analysis of HER-2 gene polymorphisms: association with breast cancer risk, HER-2 protein expression in the tumor, and disease recurrence in Korea.

PURPOSE: A single-nucleotide polymorphism (SNP) in codon 655 of HER-2 has been extensively studied with inconclusive results. The purpose of this study was to investigate the association between common variants of HER-2 and breast cancer risk, HER-2 expression, and survival using a haplotype-based stepwise approach. EXPERIMENTAL DESIGN: Twenty-nine SNPs listed in the National Center for Biotechnology Information database were screened to identify novel polymorphisms of HER-2 gene in 90 healthy Korean women. Six of 29 SNPs were polymorphic and had greater than 10% of minor allele frequencies. Using these six SNPs, linkage disequilibrium and haplotype patterns were characterized. We tested association between the haplotypes and breast cancer in a large case-control study (n=1,039 cases and 995 controls). Six-hundred two breast cancer patients with follow-up at least 24 months were analyzed for outcome in relation to haplotype. Expression of HER-2 protein was determined by immunohistochemistry in 1,094 cases of invasive breast cancer. RESULTS: All six SNPs showed a strong linkage disequilibrium pattern and were considered to belong to one haplotype block. Two haplotype-tagging SNPs (I655V and P1170A) for three common haplotypes (>5%) were genotyped in cases and controls. The haplotypes and individual SNPs were not associated with breast cancer risk. In patients with at least one copy of haplotype I (the most common haplotype), HER-2 expression was 1.5 times higher (P = 0.009) and the prognosis was worse (P = 0.032) compared with patients without having that haplotype. CONCLUSIONS: Our results suggest that the currently identified genetic polymorphisms of HER-2 are not associated with an increased risk of breast cancer in Korean women, whereas one haplotype does affect protein expression of the tumor and disease outcome.

Adult↗

Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with positron emission tomography.

Racemic and enantiomerically pure ((S,S) and (R,R)) 2-[alpha-(2-(2-[(18)F]fluoroethoxy)phenoxy)benzyl]morpholine ([(18)F]FRB) and its tetradeuterated form [(18)F]FRB-D(4), analogs of the highly selective norepinephrine reuptake inhibitor reboxetine (2-[alpha-(2-ethoxyphenoxy)benzyl]morpholine, RB), have been synthesized for studies of norepinephrine transporter (NET) system with positron emission tomography (PET). The [(18)F]fluorinated precursor, (S,S)/(R,R)-N-tert-butyloxycarbonyl-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-N-Boc-desethylRB), was prepared by the N-protection of (S,S)/(R,R)-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-desethylRB) with a tert-butyloxycarbonyl (Boc) group followed by enantiomeric resolution with chiral HPLC to provide both (S,S) and (R,R) enantiomers with >99% enantiomeric purity. These compounds were then used for radiosynthesis to prepare enantiomerically pure [(18)F]FRB and [(18)F]FRB-D(4) via the following three-step procedure: (1) formation of 1-bromo-2-[(18)F]fluoroethane ([(18)F]BFE or [(18)F]BFE-D(4)) by nucleophilic displacement of 2-bromoethyl triflate (or D(4) analog) with no-carrier added [(18)F]F(-) in THF; (2) reaction of [(18)F]BFE (or [(18)F]BFE-D(4)) with N-Boc-desethylRB in DMF in the presence of excess base; and (3) deprotection with trifluoroacetic acid. The racemates, (S,S) and (R,R) enantiomers of [(18)F]FRB and [(18)F]FRB-D(4) were obtained in 11-27% (decay corrected to the end of bombardment, EOB) in 120-min synthesis time with a radiochemical purity of >98% and specific activities of 21-48 GBq/micromol (EOB). The results of the whole-body biodistribution studies with (S,S)-[(18)F]FRB-D(4) were similar to those with (S,S)-[(18)F]FRB but showed relatively faster blood clearance and no significant in vivo defluorination. Positron emission tomography studies in baboon brain also showed that (S,S)-[(18)F]FRB-D(4) may be a potentially useful ligand for imaging NET with PET.

Animals↗

Visualization of jejunal bleeding by capsule endoscopy in a case of eosinophilic enteritis.

Eosinophilic enteritis is a rare disease characterized by tissue eosinophilia, which can affect different layers of bowel wall. Normally, the disease presents as colicky abdominal pain, and rarely as an acute intestinal obstruction or perforation. In this paper, we report a case of eosinophilic enteritis, hitherto unreported, presenting as an ileal obstruction, and followed by jejunal bleeding, which was visualized by capsule endoscopy. A 62-year-old man received a 15 cm single segmental ileal resection at a point 50 cm from the IC valve due to symptoms of obstruction, which were diagnosed as eosinophilic enteritis. Seventeen days after operation, intermittent abdominal pain occurred again, and subsided upon 30 mg per day treatment with prednisolone. Fourteen days after this pain attack, the patient exhibited hematochezia, in spite of continuous prednisolone treatment. Capsule endoscopy showed fresh blood spurting from the mid-to-distal jejunum, in the absence of any mass or ulcer. This hematochezia rapidly disappeared following a high-dose steroid injection, suggesting it was a manifestation of jejunal eosinophilic enteritis.

Endoscopy, Gastrointestinal↗

Reduced-intensity allogeneic hematopoietic stem-cell transplantation as an immunotherapy for metastatic colorectal cancer.

BACKGROUND: Allogeneic stem-cell transplantation (allo-SCT) can induce curative graft-versus-leukemia reactions for hematologic malignancies through allogeneic immunity. Because the gastrointestinal tract is a target of graft-versus-host disease (GvHD), colorectal cancer might be a candidate for allo-SCT. METHODS: Four patients with metastatic colorectal cancer underwent reduced-intensity stem-cell transplantation (RIST) in the National Cancer Center Hospital between July 2002 and February 2003. Three patients received transplants from an human leukocyte antigen (HLA)-identical related donor, and the remaining patient received selected CD34-positive cells from a two-loci HLA-mismatched donor. The basis of preparative regimen was busulfan 4 mg/kg for 2 days and fludarabine 25 mg/kg for 6 days. RESULTS: All the patients tolerated the preparative regimen and achieved engraftment without significant toxicities. All developed acute or chronic GvHD. Although serum levels of CA19-9 and carcinoembryonic antigen were transiently elevated after RIST in all the patients, the levels subsequently decreased below the levels from before RIST in all but one patient. Three had measurable lesions before RIST, one achieved partial response, and the others stable disease, which was durable for 120 and 60 days. Three patients died; the causes of death were progressive disease, GvHD, and accident. Postmortem examination was obtained for two patients; in one patient, the peritoneal metastatic lesions macroscopically disappeared, and in the other patient, the supraclavicular lymph node disappeared while the other measurable lesions remained stable. CONCLUSIONS: All the patients showed some evidence suggesting the presence of a graft-versus-tumor effect for colorectal cancer, which should be confirmed in a future prospective trial.

Adult↗

Young age: an independent risk factor for disease-free survival in women with operable breast cancer.

BACKGROUND: The incidence of breast cancer in young women (age < 35) is low. The biology of the disease in this age group is poorly understood, and there are conflicting data regarding the prognosis for these women compared to older patients. METHODS: We retrospectively analyzed 2040 consecutive primary invasive breast cancer patients who underwent surgical procedures at our institution between 1990 and 1999. The younger age group was defined as patients aged <35 years at the time of diagnosis. The clinicopathological characteristics and treatment outcomes were compared between younger and older age groups. RESULTS: A total of 256 (12.5%) patients were aged <35. There was a significantly higher incidence of nuclear grade 3 and medullary histological-type tumors in younger patients compared to older patients. Axillary lymph node status, T stage, histological grade, c-erbB2 expression and estrogen receptor status did not differ significantly between the two age groups. Younger patients had a greater probability of recurrence and death at all time periods. Although there was no significant difference in disease-free survival between the two age groups in lymph node-negative patients, the younger group showed worse prognosis among lymph node-positive patients (p < 0.001). In multivariate analysis, young age remained a significant predictor of recurrence (p = 0.010). CONCLUSION: Young age (<35) is an independent risk factor for relapse in operable breast cancer patients.

Adult↗

Successful engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with advanced hematological diseases.

PURPOSE: The purpose of this research was to evaluate the feasibility of reduced-intensity unrelated cord-blood transplantation (RI-UCBT) in adult patients with advanced hematological diseases. EXPERIMENTAL DESIGN: Thirty patients (median age, 58.5 years; range, 20-70 years) with advanced hematological diseases underwent RI-UCBT at Toranomon Hospital between September 2002 and August 2003. Preparative regimen composed of fludarabine 25 mg/m(2) on days -7 to -3, melphalan 80 mg/m(2) on day -2, and 4 Gy total body irradiation on day -1. Graft-versus-host disease prophylaxis was composed of cyclosporin alone. RESULTS: Twenty-six patients achieved primary neutrophil engraftment after a median of 17.5 days. Median infused total cell dose was 3.1 x 10(7)/kg (range, 2.0-4.3 x 10(7)/kg). Two transplant-related mortalities occurred within 28 days of transplant, and another 2 patients displayed primary graft failure. Cumulative incidence of complete donor chimerism at day 60 was 93%. Grade II-IV acute graft-versus-host disease occurred in 27% of patients, with median onset 36 days. Primary disease recurred in 3 patients, and transplant-related mortality within 100 days was 27%. Estimated 1-year overall survival was 32.7%. Excluding 7 patients with documented infection, 19 patients displayed noninfectious fever before engraftment (median onset, day 9). Manifestations included high-grade fever, eruption, and diarrhea. The symptoms responded well to corticosteroid treatments in 7 of 13 treated patients. CONCLUSION: This study demonstrated the feasibility of RI-UCBT in adults.

Adult↗

Development of early neutropenic fever, with or without bacterial infection, is still a significant complication after reduced-intensity stem cell transplantation.

Little information is available on the clinical characteristics of infectious complications that occur in the early period after reduced-intensity stem cell transplantation (RIST). We retrospectively investigated the clinical features of neutropenic fever and infectious episodes within 30 days after RIST in 76 patients who had received fluoroquinolones as part of their antibacterial prophylaxis. Preparative regimens included cladribine 0.66 mg/kg or fludarabine 180 mg/m2 plus busulfan 8 mg/kg. All but 1 patient survived 30 days after transplantation, and 75 patients (99%) became neutropenic within a median duration of 9 days. Neutropenic fever was observed in 29 patients (38%), and bacterial infection was confirmed in 15 (20%) of these, including bacteremia (n = 13), bacteremia plus pneumonia (n = 1), and urinary tract infection (n = 1). The causative organisms were gram-positive (n = 9) and gram-negative organisms (n = 7), with a mortality rate of 6%. Neither viral nor fungal infection was documented. Multivariate analysis showed that the presence of neutropenia at the initiation of preparative regimens was an independent risk factor for subsequent documented bacterial infections (P =.026; 95% confidence interval, 1.25-35.1). We conclude that neutropenic fever and bacteremia remain common complications in RIST.

Adolescent↗

Early central nervous system complications after reduced-intensity stem cell transplantation.

To investigate clinical characteristics of early central nervous system (CNS) complications after reduced-intensity stem cell transplantation (RIST), we reviewed the medical records of 232 patients who had undergone RIST for hematologic diseases at our institutions between September 1999 and June 2003. All patients had received purine analog-based preparative regimens. Stem cell sources comprised granulocyte colony-stimulating factor-mobilized blood from HLA-identical or 1 locus-mismatched related donors (n = 151), unrelated bone marrow (n = 44), or unrelated cord blood (n = 37). Graft-versus-host disease prophylaxis incorporated cyclosporine with or without methotrexate. Diagnosis of CNS complications was based on clinical, radiologic, and microbiological findings. CNS complications occurred in 18 patients (7.8%), with a median onset of 22 days, and were infectious (n = 1), metabolic (n = 15), or cerebrovascular (n = 2). Symptoms included seizures (n = 7), visual disturbance (n = 2), headache (n = 8), nausea (n = 8), vomiting (n = 6), impaired consciousness (n = 16), and hemiparesis (n = 3). Complications improved promptly in 10 patients, and 8 patients died without improvement within 30 days. Multivariate analysis with logistic regression identified umbilical cord blood transplantation as a significant risk factor for early CNS complications (odds ratio, 14.5; 95% confidence interval, 3.7-56.9; P <.0001). CNS complications are a significant problem after RIST, particularly with umbilical cord blood. Limbic encephalopathy is an unrecognized subtype of neurotoxicity after umbilical cord blood transplantation.

Adult↗

Allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen for treatment of metastatic renal cell carcinoma: single institution experience with a minimum 1-year follow-up.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen (RIST) for interferon-alpha-refractory metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Of 26 patients referred to the National Cancer Center Hospital for possible RIST between June 2000 and April 2002, an HLA-identical relative was identified for 12 patients. Nine patients underwent RIST. The conditioning regimen consisted of fludarabine 180 mg/m2 or cladribine 0.66 mg/kg, plus busulfan 8 mg/kg and rabbit antithymocyte globulin 5 mg/kg. Graft-vs-host disease (GVHD) prophylaxis was cyclosporine alone. RESULTS: All patients achieved engraftment without grade III to IV nonhematologic regimen-related toxicity. All patients achieved complete donor-type chimerism without donor lymphocyte infusion by day 60. Four patients developed acute GVHD, and four developed chronic GVHD. One patient (11%) achieved partial response. As of July 2003, six patients were alive at median follow-up of 681 days. The actuarial overall survival rate was 89% at 1 year and 74% at 2 years. The overall survival rate tended to be higher in the 12 patients with a matched donor than in the other 14 patients without a matched donor (p = 0.088). CONCLUSION: Our RIST procedure is feasible without severe toxicity. The efficacy of RIST for RCC should be confirmed in phase II/III clinical trials.

Acute Disease↗

Balance between acute graft-versus-host disease and graft-versus-tumor effect after reduced-intensity transplantation for metastatic renal cell carcinoma.

We describe a patient who had received reduced-intensity stem cell transplantation (RIST) for metastatic renal cell carcinoma (RCC). A 37-year-old man developed rapid progression of RCC during steroid therapy for immune-mediated thrombocytopenia and graft-versus-host disease (GVHD). After discontinuation of corticosteroid, RCC achieved long stable disease with the presence of chronic GVHD, despite low dose of prednisolone. This case suggests the impact of immunosuppression on progression of metastatic RCC after RIST.

Acute Disease↗

Fatal hepatic failure associated with graft rejection following reduced-intensity stem-cell transplantation for chronic idiopathic myelofibrosis (CIMF).

A 54-year-old man with chronic idiopathic myelofibrosis (CIMF) underwent RIST. His clinical course had been uneventful until day 60, when splenomegaly reappeared. Hepatic dysfunction developed on day 75. Recipient-type hematopoiesis increased to 51% on day 90. After rapid tapering of cyclosporin, serum levels of AST and ALP normalized in parallel with recovery of complete chimerism on day 134. Yet, jaundice progressed. He died of liver failure on day 176. Postmortem examination revealed neither GVHD nor VOD. Graft rejection following RIST for CIMF may lead to fatal hepatic damage through extramedullary hematopoiesis in the liver or cytokine-mediated immune dysregulations.

Chronic Disease↗

Comparative analysis of clinical outcomes after allogeneic bone marrow transplantation versus peripheral blood stem cell transplantation from a related donor in Japanese patients.

A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen-identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 37.4% for PBSCT and 32.0% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P < 0.01). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations.

Acute Disease↗

Fatal deep vein thrombosis after allogeneic reduced intensity hematopoietic stem cell transplantation for the treatment of metastatic gastric cancer.

A 61-year-old man received reduced intensity stem cell transplantation (RIST) for the treatment of metastatic gastric cancer. The cytoreductive course of RIST was uneventful until day 0, when fever suddenly developed and his performance status deteriorated. Edema developed in the bilateral lower extremities by day 7, which was diagnosed by Doppler ultrasonography as deep vein thrombosis (DVT) involving the femoral veins to the inferior vena cava. While the edema improved with anticoagulation treatment, gastrointestinal graft-versus-host disease (GVHD) followed on day 13. Diarrhea subsided spontaneously, but hypoalbuminemia persisted, with the subsequent development of oliguria and jaundice on day 18. He died of sepsis on day 30, without any evidence of cancer progression. This case demonstrates that DVT is a potentially significant problem following RIST for solid tumors.

Anticoagulants↗

Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution.

BACKGROUND: There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). METHODS: To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. RESULTS: The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. CONCLUSIONS: We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.

Acute Disease↗

Feasibility of acute physiology and chronic health evaluation (APACHE) II and III score-based screening in patients receiving allogeneic hematopoietic stem-cell transplantation.

Patients who require management in the intensive care unit (ICU) for complications after allogeneic hematopoietic stem-cell transplantation (HSCT) generally have a poor outcome. We retrospectively studied whether the risk-prediction stratification systems commonly used for patients admitted to the ICU, that is, the Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III systems, could be useful for identifying patients who should receive intensive care earlier. We reviewed the medical records of 210 patients who underwent allogeneic HSCT and found that 18 (8.6%) had been admitted to the ICU for acute respiratory failure (n=9), acute renal failure (n=7), and septic shock (n=2). The median APACHE II and III scores were, respectively, 16 (10-27) and 55 (22-87) at the onset of complications and 26 (15-43) and 101 (65-157) upon admission to the ICU. Thus, both the APACHE II and APACHE III scores at ICU admission were higher than those at the onset of complications (P <0.0001). Seventeen patients (94%) subsequently died, with a median ICU stay of 7.5 days (1-51 days), as a result of multiorgan failure (n=14), respiratory failure (n=2), and septic shock (n=1). The APACHE II and III scores of the sole surviving patient were, respectively, 21 and 71 at the onset and 24 and 86 upon transfer to the ICU. Thus, the APACHE scores in this study were lower than those reported for other surgical or medical patients treated in the ICU, despite their uniform poor prognosis. Although nine patients had developed grade III to IV acute graft-versus-host disease, which is the most common cause of morbidity and mortality after allogeneic HSCT, this was not fully evaluated in the current scoring systems. Application of these systems to HSCT will require adequate modification, with particular attention to organ dysfunction secondary to graft-versus-host disease.

APACHE↗