Chemonucleolysis is a significant innovation in the treatment of herniated lumbar disc disease. The prodedure is relatively safe and the results are highly acceptable, but in most studies, the failure rate is 20-25%. Computed tomography was performed from January, 1986 to June, 1987 at the Department of Orthopedic Surgery, Yonsei University on six patients with herniated lumbar discs who did not improve with chemonucleolysis. The results of this study are as follows : 1. The herniated lumbar disc remained unchanged in 4 cases and was reduced in 2 cases. 2. In 2 cases of hernia reduced, the development of a diffuse annular bulging was noted and compression of the dural sac unchanged. 3. Chemonucleolysis was carried out at two levels in 2 cases and the herniated lumbar disc was not changed in these cases. 4. Thickening of the ligament flavum was noted in 1 cases. 5. Computed tomography findings after chemonucleolysis were good correlation with the clinical results in failed cases. In the cases not relieved the symptoms over 3–6 months after chemonucleolysis, it is necessary follow up computed tomography to decide the further treatment.
Follow-Up Studies ; Hernia ; Humans ; Intervertebral Disc Chemolysis ; Ligaments ; Orthopedics

No abstract available.
Shoulder Fractures*

The authors observed thirty two cases of nephrotic syndrome admitted at Pediatric Department of St. Benedict Hospital, Busan, Korea. No specific cause for nephrotic syndrome was found in all patients. Respnse to the initial continuous steroid therapy, relapsing patterns and onset of diuresis between steroid only and steroid combined with furosemide especially in severely illed patients were evaluated in this study. The mean period of observation was 3.2 years. 1) The mean age of onset was 7.1 years. Most of them(97%) showed under the 10 years of age at onset. The ratio of male and female was 4.3 to 1. The seasonal incidence showed prevalence from September to October (31%). 2) Upper respiratory infection (21.9%) was the most common associated infection at onset. 3) Complete remission was showed in 23 children (71.8%) after initial continuous steroid therapy. Partial remission in which mild biochemical abnormalities and residual proteinuria wer still present after initial continuous steroid therapy was showed in 6 patients (18.8%), but biochemical abnormalities and residual proteinuria returned to normal within subsequent several months. Three patients (9.4%) were restant to initial steroid therapy. 4) Proteinuria abolished in most of them (87.4%) after 3 weeks of prednisolone therapy in complete remitted patient group, and also abolished after not more than 6 months treatment and their subsequent course in partial remitted patient group. 5) 10 patients (45.4%) had an episode of relapses more than one time, though most of them once or twice, 7 patients (31.8%) relapsed at first year and 2 patients (9%) at second year of follow up period. 6) Steriod responsiveness in relapsing cases was the same as first attack except one. 7) Hematuria, hypertension and transient azotemia were observed in 18.7%, 18.7% and 21.8% of he 32 patiets respectively. These findings at onset of illness were present more frequently in patients with poor steroid response and partial remitted patients than with complete remitted patients, and these episodes were also obtained to correlation with a less favorable initial steroid response and outcome. 8) Duration of illness before institution of steroid therapy had no influences on the steroid response. 9) Diruesis was achieved by 5.2 days in group steroid only and by 4.8 days in group of steroid combined with furosemide, 1~2mg/kg/day, p.o. 10) Two cases were remitted after combined therapy with cyclophosphamide (2mg/kg/day for 4~8 weeks) and prednisolone (60mg/m(2)/day as a single dose on alternate days). One of them was early steroid resistant patient and the other frequent relapsing patient. 11) In one patient, chronic renal insufficiency developed progressively during the follow up period. The other one, whohad no responsiveness to initial steroid therapy and youngest at onset, expired with itercurrent infection.
Age of Onset ; Azotemia ; Busan ; Child* ; Cyclophosphamide ; Diuresis ; Female ; Follow-Up Studies ; Furosemide ; Hematuria ; Humans ; Hypertension ; Incidence ; Korea ; Male ; Nephrotic Syndrome* ; Prednisolone ; Prevalence ; Proteinuria ; Recurrence ; Renal Insufficiency, Chronic ; Seasons

Purpose: Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors. Materials and Methods: We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1–mouse model for in vivo experiments to confirm our findings. Results: In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3β serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion. Conclusion Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken toget

This study was conducted to investigate the association of the occurrence of pediatric disease with environmental, seasonal and atmospheric factors. The data were collected at 5 pediatric clinics in Seoul and the Department of Pediatrics of Yongin Severance Hospital from May 1986 to April 1987. The results were as follows: 1. Vacation periods had a great influence upon the occurrence of pediatric diseases. 2. The majority of pediatric diseases occurred mainly in spring and autumn, not in summer and winter. 3. The higher the average relative humidity was, the less diseases occurred; and the higher the maximum change of daily temperature, the more diseases occurred. 4. In summer, the pattern of diseases varied along with the environmental factors(eg., toilet).
Gyeonggi-do ; Humidity ; Pediatrics ; Seasons* ; Seoul

PURPOSE: The soluble programmed death-ligand 1 (sPDL1) has immunosuppressive activity and is a candidate biomarker for immuno-oncology drug development. In this study, we measured sPDL1 at pre- and post-chemotherapy and at disease progression to uncover the dynamics of sPDL1 during treatment in biliary tract cancer (BTC) patients. MATERIALS AND METHODS: From 90 BTC patients (training cohort, 53; validation cohort, 37) who were candidates for palliative first-line chemotherapy, blood was collected at pre- and post-chemotherapy (at the time of best response) and at disease progression. The sPDL1 levels were measured using an enzyme-linked immunosorbent assay. Responses to chemotherapy, overall survival (OS), and other prognostic factors including the neutrophil-lymphocyte ratio (NLR) were analyzed. RESULTS: The OS of all patients was 11.5 months (confidence interval [CI], 9.7 to 16.2). The best response was complete response in seven (7.8%), partial response in 20 (22.2%), stable disease in 52 (57.8%), and disease progression (PD) in 11 patients (12.2%). Patients with high pre-chemotherapy sPDL1 (≥ 1.30 ng/mL) showed worse OS than patients with low prechemotherapy sPDL1 (9.1 months vs. 12.5 months, p=0.003). In multivariate analyses, high pre-chemotherapy sPDL1 (hazard ratio [HR], 1.96; 95% CI, 1.2 to 3.9; p=0.011) and high pre-chemotherapy NLR (HR, 1.82; 95% CI, 1.1 to 3.0; p=0.020) were independent poor prognostic factors for OS. At the time of PD, sPDL1 was increased significantly compared with pre-chemotherapy sPDL1 (1.59 ng/mL vs. 0.72 ng/mL, p=0.003). CONCLUSION: The sPDL1 at pre-chemotherapy confers the prognostic value for OS in BTC patients under palliative chemotherapy. The dynamics of sPDL1 during chemotherapy correlate with disease burden and have prognostic value.
Biliary Tract Neoplasms ; Biomarkers ; Cohort Studies ; Disease Progression ; Drug Therapy ; Enzyme-Linked Immunosorbent Assay ; Humans ; Multivariate Analysis ; Prognosis

PURPOSE: The DNA damage response (DDR) is a multi-complex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints, and apoptosis. In the case of biliary tract cancer (BTC), the strategy of DDR targeting has not been evaluated, even though many patients have DNA repair pathway alterations. The purpose of this study was to test the DDR-targeting strategy in BTC using an ataxia-telangiectasia and Rad3-related (ATR) inhibitor. MATERIALS AND METHODS: A total of nine human BTC cell lines were used for evaluating anti-tumor effect of AZD6738 (ATR inhibitor) alone or combination with cytotoxic chemotherapeutic agents through MTT assay, colony-forming assays, cell cycle analyses, and comet assays. We established SNU478-mouse model for in vivo experiments to confirm our findings. RESULTS: Among nine human BTC cell lines, SNU478 and SNU869 were the most sensitive to AZD6738, and showed low expression of both ataxia-telangiectasia mutated (ATM) and p53. AZD6738 blocked p-Chk1 and p-glycoprotein and increased γH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis, G2/M arrest and p21, and decreased CDC2. Combinations of AZD6738 and cytotoxic chemotherapeutic agents exerted synergistic effects in colony-forming assays, cell cycle analyses, and comet assays. In our mouse models, AZD6738 monotherapy decreased tumor growth and the combination with cisplatin showed more potent effects on growth inhibition, decreased Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling than monotherapy with each drug. CONCLUSION: In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC.
Animals ; Apoptosis ; Ataxia Telangiectasia ; Biliary Tract Neoplasms ; Biliary Tract ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; Cisplatin ; Comet Assay ; DNA Damage ; DNA Repair ; DNA ; Humans ; Mice ; P-Glycoprotein

PURPOSE: Jab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied. MATERIALS AND METHODS: We performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC. RESULTS: Among 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and p27 expression. CONCLUSION: Jab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.
Animals ; Biliary Tract Neoplasms ; Biliary Tract ; Cell Line ; Cisplatin ; DNA Damage ; G1 Phase Cell Cycle Checkpoints ; Half-Life ; Heterografts ; Humans ; In Vitro Techniques ; Mice ; Phosphorylation ; Prognosis ; PTEN Phosphohydrolase ; RNA, Small Interfering ; Transfection

Purpose: Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC. Materials and Methods: In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models. Results: AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy. Conclusion Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

PURPOSE: To report the early results of preopeartive concurrent radio-chemotherapy (CRCT) for treating rectal cancer. MATERIALS AND METHODS: From June 1999 to April 2002, 40 rectal cancer patients who either had lesions with a questionable resectability or were candidates for sphincter-sacrificing surgery received preoperative CRCT. Thirty-seven patients completed the planned CRCT course. 45 Gy by 1.8 Gy daily fraction over 5 weeks was delivered to the whole pelvis in the prone position. The chemotherapy regimens were oral UFT plus oral leucovorin (LV) in 12 patients, intravenous bolus 5-FU plus LV in 10 patients, and intravenous 5-FU alone in 15 patients (bolus infusion in 10, continuous infusion in 5). Surgery was planned in 4~6 weeks of the completion of the preoperative CRCT course, and surgery was attempted in 35 patients. RESULTS: The compliance to the current preoperative CRCT protocol was excellent, where 92.5% (37/40) completed the planned treatment. Among 35 patients, in whom surgery was attempted after excluding two patients with new metastatic lesions in the liver and the lung, sphincter-preservation was achieved in 22 patients (62.9%), while resection was abandoned during laparotomy in two patients (5.7%). Gross complete resection was performed in 30 patients, gross incomplete resection was performed in one patient, and no detailed information on the extent of surgery was available in two patients. Based on the surgical and pathological findings, the down-staging rate was 45.5% (15/33), and the complete resection rate with the negative resection margin 78.8% (26/33). During the CRCT course, grade 3~4 neutropenia developed in four patients (10.8%). Local recurrence after surgical resection developed in 12.1% (4/33), and distant metastases after the preoperative CRCT start developed in 21.6% (8/37). The overall 3-years survival rate was 87%. CONCLUSION: Preoperative CRCT in locally advanced rectal cancer is well tolerated and can lead to high resection rate, down-staging rate, sphincter preservation rate, however, longer term follow-up will be necessary to confirm these results.
Compliance ; Drug Therapy ; Fluorouracil ; Follow-Up Studies ; Humans ; Laparotomy ; Leucovorin ; Liver ; Lung ; Neoplasm Metastasis ; Neutropenia ; Pelvis ; Prone Position ; Rectal Neoplasms* ; Recurrence ; Survival Rate