BACKGROUND AND PURPOSE: Patients treated with interferon-beta (IFN-β) can develop neutralizing antibodies (NAbs) against IFN-β that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-β in Korean patients with multiple sclerosis (MS). METHODS: This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-β for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. RESULTS: NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who were treated with subcutaneous IFN-β-1b, 9 of the 60 (15%) who were treated with subcutaneous IFN-β-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-β-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80%) vs. 4/55 (7%), respectively; p < 0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80%) vs. 2/10 (20%), p=0.004]. CONCLUSIONS: These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-β.
Antibodies, Neutralizing* ; Follow-Up Studies ; Genes, Reporter ; Humans ; Interferon-beta* ; Luciferases ; Magnetic Resonance Imaging ; Multiple Sclerosis* ; Prevalence

PURPOSE: The purpose of this study was to analyze clinical outcomes from cervical cancer and stratify patients into risk groups for prognostic factors for early-stage disease. MATERIALS AND METHODS: We retrospectively reviewed patients with stage IB or IIA cervical cancer treated with adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) following primary surgery at Samsung Medical Center from 2001 to 2011. Adjuvant RT was added for patients with intermediate-risk factors, and adjuvant CCRT was performed on high-risk patients after surgery. RESULTS: We reviewed 247 patients—149 in the high-risk group and 98 in intermediate-risk group. The median follow-up was 62 months. Loco-regional failure (LRF) alone occurred in 7 patients (2.8%), distant metastasis alone in 37 patients (15.0%) and LRF with DM in 4 patients (1.6%). The 5-year disease-free survival (DFS) and overall survival (OS) rates for both groups were 79.7% and 87.6%, respectively. In the high-risk group, the 5-year DFS and OS probabilities were 72.5% and 81.9%, respectively. Histologic type, pathologic tumor size, and the number of pelvic lymph node (PLN) metastasis were significant prognostic factors for DFS and OS. We suggest a scoring system (0–3) using these prognostic factors to predict poor prognosis in high-risk patients. Using this system, patients with higher scores have higher recurrence and lower survival rates. CONCLUSION: In the high-risk cervical-cancer group who received primary surgery and adjuvant CCRT, non-squamous type, large tumor size and the number of PLN metastasis were significant prognostic factors, and the number of these factors was associated with survival rates.
Chemoradiotherapy ; Chemoradiotherapy, Adjuvant ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Hysterectomy ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Radiotherapy* ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms*

Drug-induced immune hemolytic anemia (DIIHA) is a rare side effect of drugs. DIIHA may cause a systemic inflammatory response that results in acute multi-organ failure and death. Ceftizoxime belongs to the class of third generation cephalosporins, which are the most common drugs associated with DIIHA. Herein, we present a case of a 66-year-old man who developed fatal DIIHA after receiving a second dose of ceftizoxime. He was admitted to receive photodynamic therapy. He had a history of a single parenteral dose of ceftizoxime 3 months prior to admission. On the day of the procedure — shortly after the infusion of ceftizoxime — the patient's mental status was altered. The blood test results revealed hemolysis. Oliguric acute kidney injury developed, and continuous renal replacement therapy had to be applied. On the suspicion of DIIHA, the patient underwent plasmapheresis. Diagnosis was confirmed by a detection of drug-dependent antibody with immune complex formation. Although his hemolysis improved, his liver failure did not improve. He was eventually discharged to palliative care, and subsequently died.
Acute Kidney Injury ; Aged ; Anemia, Hemolytic* ; Antigen-Antibody Complex ; Ceftizoxime ; Cephalosporins ; Diagnosis ; Hematologic Tests ; Hemolysis ; Humans ; Liver Failure ; Palliative Care ; Photochemotherapy ; Plasmapheresis ; Renal Replacement Therapy

Drug-induced immune hemolytic anemia (DIIHA) is a rare side effect of drugs. DIIHA may cause a systemic inflammatory response that results in acute multi-organ failure and death. Ceftizoxime belongs to the class of third generation cephalosporins, which are the most common drugs associated with DIIHA. Herein, we present a case of a 66-year-old man who developed fatal DIIHA after receiving a second dose of ceftizoxime. He was admitted to receive photodynamic therapy. He had a history of a single parenteral dose of ceftizoxime 3 months prior to admission. On the day of the procedure — shortly after the infusion of ceftizoxime — the patient's mental status was altered. The blood test results revealed hemolysis. Oliguric acute kidney injury developed, and continuous renal replacement therapy had to be applied. On the suspicion of DIIHA, the patient underwent plasmapheresis. Diagnosis was confirmed by a detection of drug-dependent antibody with immune complex formation. Although his hemolysis improved, his liver failure did not improve. He was eventually discharged to palliative care, and subsequently died.
Acute Kidney Injury ; Aged ; Anemia, Hemolytic ; Antigen-Antibody Complex ; Ceftizoxime ; Cephalosporins ; Diagnosis ; Hematologic Tests ; Hemolysis ; Humans ; Liver Failure ; Palliative Care ; Photochemotherapy ; Plasmapheresis ; Renal Replacement Therapy

To know the infection status of zoonotic trematode metacercariae in brackish water fish, we surveyed mullets collected from 18 coastal areas in the Republic of Korea. The metacercariae of Pygidiopsis summa were detected in 236 (68.2%) out of 346 mullets examined. They were found in mullets from 15 areas except for those from Boseong-gun (Jeollanam-do), Pohang-si, and Uljin-gun (Gyeongsangbuk-do). Especially in mullets from Taean-gun (Chungcheongnam-do) and Geoje-si (Gyeongsangnam-do), their prevalences were 100% and 95.5%, and the average metacercarial density was more than 1,000 per fish. They were also detected in mullets from 3 coastal lakes, Gyeongpoho, Songjiho, and Hwajinpoho, in Gangwon-do, and their average densities were 419, 147, and 672 per infected fish, respectively. The metacercariae of 5 other heterophyid species, including Heterophyes nocens, Heterophyopsis continua, Metagonimus sp., Stictodora fuscata, and Stictodora lari, were found in the mullets examined. The metacercariae of H. nocens were detected in 66.7, 100, 28.6, 81.6, 3.9, 61.5, and 27.3% of mullets from Muan-gun, Shinan-gun, Haenam-gun, Gangjin-gun, and Boseong-gun (Jeollanam-do), Hadong-gun, and Geoje-si (Gyeongsangnam-do), and their metacercarial intensities were 64, 84, 119, 99, 1, 24, and 24 per fish infected, respectively. From the above results, it has been confirmed that P. summa metacercariae are heavily infected in mullets from coastal areas of Korea. It is suggested that residents who frequently consume raw mullet dish can be easily infected with heterophyid flukes.
Gangwon-do ; Heterophyidae ; Korea ; Lakes ; Metacercariae ; Prevalence ; Republic of Korea* ; Saline Waters ; Smegmamorpha* ; Trematoda

PURPOSE: In some unusual cases, in patients with cervical cancer, an elevation of squamous cell carcinoma antigen (SCC-Ag) was not observed at diagnosis but was observed on recurrence, or vice versa. The objective of this study was to identify patient-, disease-, and treatment-related factors associated with this unusual level of SCC-Ag, and to determine whether SCC-Ag is a useful tumor marker in such patients. MATERIALS AND METHODS: Among 129 patients with recurrence, 14 who showed a normal SCC-Ag level at diagnosis but an elevated level at recurrence were classified as group I; 22 patients with an elevated SCC-Ag level at diagnosis but not at recurrence were classified as group II; and 76 patients with an elevated SCC-Ag level at both diagnosis and recurrence were classified as group III. RESULTS: In univariate analysis, unusual SCC-Ag showed statistically significant relationships with pathology and biochemical response to treatment. However, in the multivariate analysis, none of the clinicopathologic factors showed a statistical relationship with unusual levels of SCC-Ag. The 5-year disease-free survival rates for groups I, II, and III were 7.1%, 9.1%, and 0% (p=0.418), and the 5-year overall survival rates were 34.3%, 58.4%, and 33.3% (p=0.142), respectively. CONCLUSION: The value of SCC-Ag has been confirmed in all patients; thus, check of SCC-Ag level at follow-up should be considered. Although no statistically significant differences were observed among the groups, we conclude that patients with a high initial SCC-Ag and elevated SCC-Ag at relapse have poor prognosis due to high SCC-Ag level.
Antigens, Neoplasm ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Prognosis ; Recurrence ; Serpins ; Survival Rate ; Biomarkers, Tumor ; Uterine Cervical Neoplasms

PURPOSE: The relationship between treatment outcomes, alteration of the expression of biological markers, and tumor volume response during radiotherapy (RT) in patients with uterine cervical cancer was analyzed. MATERIALS AND METHODS: Twenty patients with cervical squamous cell carcinoma received definitive RT with (n = 17) or without (n = 3) concurrent chemotherapy. Tumor volumes were measured by three serial magnetic resonance imaging scans at pre-, mid-, and post-RT. Two serial punch biopsies were performed at pre- and mid-RT, and immunohistochemical staining for cyclooxygenase (COX)-2 and epidermal growth factor receptor was performed. The median follow-up duration was 60 months. RESULTS: The median tumor volume response at mid-RT (V2R) was 0.396 (range, 0.136 to 0.983). At mid-RT, an interval increase in the distribution of immunoreactivity for COX-2 was observed in 8 patients, and 6 of them showed poor mid-RT tumor volume response (V2R > or = 0.4). Four (20%) patients experienced disease progression after 10 to 12 months (median, 11 months). All 4 patients had poor mid-RT tumor volume response (p = 0.0867) and 3 of them had an interval increase in COX-2 expression. Overall survival (OS) and progression-free survival (PFS) decreased in patients with V2R > or = 0.4 (p = 0.0291 for both). An interval increase in COX-2 expression at mid-RT was also associated with a decreased survival (p = 0.1878 and 0.1845 for OS and PFS, respectively). CONCLUSION: Poor tumor volume response and an interval increase in COX-2 expression at mid-RT decreased survival outcomes in patients with uterine cervical cancer.
Biomarkers ; Biopsy ; Carcinoma, Squamous Cell ; Cyclooxygenase 2 ; Disease Progression ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Prostaglandin-Endoperoxide Synthases ; Receptor, Epidermal Growth Factor ; Tumor Burden ; Uterine Cervical Neoplasms

OBJECTIVE: To compare survival outcomes and treatment-related morbidities between radical hysterectomy (RH) and primary chemoradiation therapy (CRT) in patients with bulky early-stage cervical cancer. METHODS: We selected 215 patients with stage IB2 and IIA2 cervical cancer (tumor diameter > 4 cm on magnetic resonance imaging) who underwent RH followed by tailored adjuvant therapy (n=147) or primary CRT (n=68) at two tertiary referral centers between 2001 and 2010. RESULTS: About twenty nine percent of patients were cured by RH alone and these patients experienced the best survival outcomes with the lowest morbidity rates. After the median follow-up times of 40 months, 27 RH (18.4%) and 20 CRT (29.4%) patients had recurrence (p=0.068) and 23 (15.6%) and 17 (25%) patients died of disease (p=0.101). The 5-year progression-free survival were 77% and 66% (p=0.047), and the 5-year overall survival were 78% and 67% (p=0.048) after RH and primary CRT, respectively. In multivariate analysis, patients who received primary CRT was at higher risk for tumor recurrence (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.24 to 4.14; p=0.008) and death (OR, 3.02; 95% CI, 1.53 to 5.98; p=0.001) than those who received RH. Grade 3-4, early (17% vs. 30.9%, p=0.021) and late (1.4% vs. 8.8%, p=0.007) complications were significantly less frequent after RH than primary CRT. CONCLUSION: Thirty percent of patients were cured by RH alone. A treatment outcome was better in this retrospective study in terms of morbidity and survival. Randomized trials are needed to confirm this result.
Disease-Free Survival ; Follow-Up Studies ; Humans ; Hysterectomy ; Magnetic Resonance Spectroscopy ; Multivariate Analysis ; Recurrence ; Retrospective Studies ; Tertiary Care Centers ; Treatment Outcome ; Uterine Cervical Neoplasms

OBJECTIVE: To compare survival outcomes and treatment-related morbidities between radical hysterectomy (RH) and primary chemoradiation therapy (CRT) in patients with bulky early-stage cervical cancer. METHODS: We selected 215 patients with stage IB2 and IIA2 cervical cancer (tumor diameter > 4 cm on magnetic resonance imaging) who underwent RH followed by tailored adjuvant therapy (n=147) or primary CRT (n=68) at two tertiary referral centers between 2001 and 2010. RESULTS: About twenty nine percent of patients were cured by RH alone and these patients experienced the best survival outcomes with the lowest morbidity rates. After the median follow-up times of 40 months, 27 RH (18.4%) and 20 CRT (29.4%) patients had recurrence (p=0.068) and 23 (15.6%) and 17 (25%) patients died of disease (p=0.101). The 5-year progression-free survival were 77% and 66% (p=0.047), and the 5-year overall survival were 78% and 67% (p=0.048) after RH and primary CRT, respectively. In multivariate analysis, patients who received primary CRT was at higher risk for tumor recurrence (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.24 to 4.14; p=0.008) and death (OR, 3.02; 95% CI, 1.53 to 5.98; p=0.001) than those who received RH. Grade 3-4, early (17% vs. 30.9%, p=0.021) and late (1.4% vs. 8.8%, p=0.007) complications were significantly less frequent after RH than primary CRT. CONCLUSION: Thirty percent of patients were cured by RH alone. A treatment outcome was better in this retrospective study in terms of morbidity and survival. Randomized trials are needed to confirm this result.
Disease-Free Survival ; Follow-Up Studies ; Humans ; Hysterectomy ; Magnetic Resonance Spectroscopy ; Multivariate Analysis ; Recurrence ; Retrospective Studies ; Tertiary Care Centers ; Treatment Outcome ; Uterine Cervical Neoplasms

PURPOSE: Although the role of squamous cell carcinoma antigen (SCC-Ag) as a predictive and prognostic factor for uterine cervical cancer has been identified in previous studies, 1) the effective patient group of screening for recurrence with SCC-Ag, 2) the relationship between SCC-Ag and recurrence site, and 3) the relationship between the change of SCC-Ag and treatment outcome or recurrence have not been described. MATERIALS AND METHODS: The study included 506 patients with histologically proven uterine cervical cancer between January 1994 and December 2010. We determining the serum SCC-Ag level before treatment and after treatment, and conducted a retrospective review of the patients' records. We evaluated the sensitivity and specificity of SCC-Ag for the detection of tumor recurrence by comparing biochemical recurrence with clinical recurrence. RESULTS: The pretreatment SCC-Ag level and the proportion of patients over 1.5 ng/mL were higher in poor prognostic patient group. In the univariate and multivariate analysis, pretreatment SCC-Ag showed a statistically significant correlation with tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology. In patients with biochemical recurrence vs. those without, 5-year DFS and OS were 27.6 vs. 92.7% (p < or = 0.001) and 53.7 vs. 92.5% (p < or = 0.001), respectively. CONCLUSION: Our study reconfirmed the known function of pretreatment SCC-Ag, but could not confirm the function of biochemical response as a predictive factor for treatment and as a prognostic factor. There was no statistically significant relationship between SCC-Ag level and recurrence site. We confirmed the role of SCC-Ag as a follow-up tool for recurrence of disease and which patient groups SCC-Ag was more useful for.
Antigens, Neoplasm ; Carcinoma, Squamous Cell ; Cervix Uteri ; Female ; Follow-Up Studies ; Gynecology ; Humans ; Mass Screening ; Multivariate Analysis ; Obstetrics ; Recurrence ; Retrospective Studies ; Sensitivity and Specificity ; Serpins ; Treatment Outcome ; Uterine Cervical Neoplasms