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1.
Article in English | WPRIM | ID: wpr-913828

ABSTRACT

Purpose@#Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs. @*Materials and Methods@#We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening. @*Results@#In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs. @*Conclusion@#Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

2.
Cancer Research and Treatment ; : 1195-1203, 2021.
Article in English | WPRIM | ID: wpr-913804

ABSTRACT

Purpose@#Angiosarcoma is a highly aggressive mesenchymal tumor. Although systemic chemotherapy is often considered for the inoperable or metastatic angiosarcoma, the outcome of such treatment is unsatisfactory and poorly delineated. @*Materials and Methods@#We reviewed electronic medical records of 75 patients with angiosarcoma who were treated with systemic chemotherapy for inoperable or metastatic disease. Patients were classified as having liver involvement if they had either primary or metastatic hepatic lesions. @*Results@#Among the patients evaluated, 51 patients were male (68%) and 24 patients (32%) had primary cutaneous angiosarcoma. Liver involvement was present in 28 patients (37.3%). A total of 59 patients received first-line weekly paclitaxel (wPac) and showed an objective response rate (ORR) of 23.7% (n=14), a median progression free survival (mPFS) of 4.0 months (95% confidence interval [CI] 3.0–6.1), and a median overall survival (mOS) of 10.2 months (95% CI 7.0–14.6). Among patients without liver involvement, patients receiving wPac (n=35) had significantly prolonged mPFS (5.8 vs. 3.2 months, respectively, p=0.014) with a tendency for prolonged mOS (13.8 vs. 11.6 months, respectively, p=0.13) than those receiving other regimens (n=12). A total of 24 patients received second- or later-line pazopanib monotherapy and showed an ORR of 16.7% (n=4), a mPFS of 2.4 months (95% CI 1.8–4.3) and a mOS of 5.4 months (95% CI 3.5–NA). @*Conclusion@#Treatment with first-line wPac and later-line pazopanib seems to provide survival benefit, especially for patients with advanced angiosarcoma without liver involvement.

3.
Article in English | WPRIM | ID: wpr-895970

ABSTRACT

Background/Aims@#Programmed death-ligand 1 (PD-L1) expression, a validated predictive biomarker for anti-PD-1/PD-L1 inhibitors, is reported to change over time. This poses challenges during clinical application in non-small cell lung cancer. @*Methods@#This study included patients with non-small cell lung cancer who underwent surgery or biopsy and evaluation of PD-L1 expression in tumor cells via immunohistochemistry more than twice. We set the threshold of PD-L1 positivity to 10% and categorized patients into four groups according to changes in PD-L1 expression. Clinicopathologic information was collected from medical records. Statistical analyses, including Fisher’s exact test and log-rank test, were performed. @*Results@#Of 109 patients, 38 (34.9%) and 45 (41.3%) had PD-L1 positivity in archival and recent samples, respectively. PD-L1 status was maintained in 78 (71.6%) patients, but changed in 31 (28.4%), with 19 (17.4%) from negative to positive. There were no significant differences in characteristics between patients who maintained PD-L1 negativity and whose PD-L1 status changed from negative to positive. Patients harboring PD-L1 positivity in either archival or recent samples achieved better responses (p = 0.129) and showed longer overall survival than those who maintained PD-L1 negativity when they received immune checkpoint inhibitors after platinum failure (median overall survival 14.4 months vs. 4.93 months; hazard ratio, 0.43; 95% confidence interval, 0.20 to 0.93). @*Conclusions@#PD-L1 status changed in about one-fourth of patients. PD-L1 positivity in either archival or recent samples was predictive of better responses to immune checkpoint inhibitors. Therefore, archival samples could be used for assessment of PD-L1 status. The need for new biopsies should be decided individually.

4.
Article in English | WPRIM | ID: wpr-903674

ABSTRACT

Background/Aims@#Programmed death-ligand 1 (PD-L1) expression, a validated predictive biomarker for anti-PD-1/PD-L1 inhibitors, is reported to change over time. This poses challenges during clinical application in non-small cell lung cancer. @*Methods@#This study included patients with non-small cell lung cancer who underwent surgery or biopsy and evaluation of PD-L1 expression in tumor cells via immunohistochemistry more than twice. We set the threshold of PD-L1 positivity to 10% and categorized patients into four groups according to changes in PD-L1 expression. Clinicopathologic information was collected from medical records. Statistical analyses, including Fisher’s exact test and log-rank test, were performed. @*Results@#Of 109 patients, 38 (34.9%) and 45 (41.3%) had PD-L1 positivity in archival and recent samples, respectively. PD-L1 status was maintained in 78 (71.6%) patients, but changed in 31 (28.4%), with 19 (17.4%) from negative to positive. There were no significant differences in characteristics between patients who maintained PD-L1 negativity and whose PD-L1 status changed from negative to positive. Patients harboring PD-L1 positivity in either archival or recent samples achieved better responses (p = 0.129) and showed longer overall survival than those who maintained PD-L1 negativity when they received immune checkpoint inhibitors after platinum failure (median overall survival 14.4 months vs. 4.93 months; hazard ratio, 0.43; 95% confidence interval, 0.20 to 0.93). @*Conclusions@#PD-L1 status changed in about one-fourth of patients. PD-L1 positivity in either archival or recent samples was predictive of better responses to immune checkpoint inhibitors. Therefore, archival samples could be used for assessment of PD-L1 status. The need for new biopsies should be decided individually.

5.
Article in English | WPRIM | ID: wpr-875253

ABSTRACT

Percutaneous transthoracic needle biopsy (PTNB) is one of the essential diagnostic procedures for pulmonary lesions. Its role is increasing in the era of CT screening for lung cancer and precision medicine. The Korean Society of Thoracic Radiology developed the first evidence-based clinical guideline for PTNB in Korea by adapting pre-existing guidelines. The guideline provides 39 recommendations for the following four main domains of 12 key questions: the indications for PTNB, pre-procedural evaluation, procedural technique of PTNB and its accuracy, and management of post-biopsy complications. We hope that these recommendations can improve the diagnostic accuracy and safety of PTNB in clinical practice and promote standardization of the procedure nationwide.

6.
Article | WPRIM | ID: wpr-831998

ABSTRACT

Distal clavicle fractures are less common than mid-shaft fractures in adults and there is no consensus on the best classification system or the ideal treatment approach considering that high nonunion rates have been reported. Although there are numerous treatment options for distal clavicle fractures, a gold standard treatment has not yet been established. Each surgical technique has its pros and cons. In this review article, we provide an overview of classification systems and treatment methods for distal clavicle fractures.

7.
Article | WPRIM | ID: wpr-834985

ABSTRACT

Background@#Periprosthetic infection after total knee arthroplasty is a challenging problem, and physicians should identify risk factors to decrease recurrence. However, risk factors for reinfection with two-stage reimplantation have not yet been well established. The purpose of this study was to assess treatment outcomes of subsequent twostage knee reimplantation and identify risk factors for uncontrolled periprosthetic knee joint infections. @*Methods@#We retrospectively reviewed 70 knees diagnosed with a periprosthetic knee joint infection treated with two-stage reimplantation between September 2011 and October 2016 at our institution. Patients in the controlled infection group (group C) required no further medication or surgical treatment within 2 years after reimplantation.Patients in the uncontrolled infection group (group U) displayed symptoms of active infection after resection arthroplasty or were reinfected after two-stage reimplantation. We compared group C and group U, and analyzed potential risk factors for uncontrolled prosthetic joint infection (PJI). @*Results@#Of 70 knees included in this analysis, 53 (75.7%) were clinically deemed free from infection at the latest follow-up. The remaining 17 knees (24.3%) required additional surgical procedures after two-stage reimplantation.Demographics were not statistically significantly different between the two groups. Wound complications were statistically more frequent in group U (p = 0.030). Pre-reimplantation C-reactive protein (CRP) was statistically different between groups C and U (0.44 and 1.70, respectively, (p = 0.025). Among the cultured microorganisms, fungus species were statistically more frequently detected in group U compared with group C ((p = 0.031). @*Conclusions@#The reinfection rate of our two-stage reimplantation protocol was 24.3% in the included cases.Wound complications, higher pre-reimplantation CRP levels, and fungus species were statistically more common in group U compared with group C. Our findings will help in counseling patients and physicians to understand that additional caution may be required when treating PJI if the aforementioned risk factors are present.Level of evidence: IV, case series.

8.
Cancer Research and Treatment ; : 1112-1119, 2020.
Article | WPRIM | ID: wpr-831143

ABSTRACT

Purpose@#The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. @*Materials and Methods@#Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. @*Results@#Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. @*Conclusion@#This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

9.
Article | WPRIM | ID: wpr-831069

ABSTRACT

Purpose@#Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR sensitizing mutation and EGFR T790M and has demonstrated efficacy in non-small cell lung cancer (NSCLC) central nervous system (CNS) metastases. We present results of a subgroup analysis of Korean patients from the pooled data of two global phase II trials: AURA extension (NCT01802632) and AURA2 (NCT02094261). @*Materials and Methods@#Enrolled patients had EGFR T790M-positive NSCLC and disease progression during or after EGFR-TKI therapy. Patients received osimertinib 80 mg orally once daily until disease progression. The primary endpoint was objective response rate (ORR). @*Results@#In total, 66 Korean patients received osimertinib treatment with a median treatment duration of 19 months. In the evaluable-for-response population (n=62), ORR was 74% (95% confidence interval [CI], 61.5 to 84.5) and median duration of response was 9.8 months (95% CI, 7.1 to 16.8). In the full analysis set (n=66), median progression-free survival was 10.9 months (95% CI, 8.3 to 15.0; data cutoff November 1, 2016), and median overall survival was 29.2 months (95% CI, 24.8 to 35.7; data cutoff May 1, 2018). Eight patients with CNS metastases were evaluable for response, none of whom showed CNS progression. The most common adverse events were rash (53%), cough (33%), paronychia, diarrhea, and decreased appetite (each 32%). @*Conclusion@#Efficacy and safety profiles of osimertinib in this subgroup are consistent with the global phase II pooled population, which supports osimertinib as a recommended treatment for Korean patients with T790M positive NSCLC.

10.
Article in English | WPRIM | ID: wpr-919139

ABSTRACT

BACKGROUND/AIMS@#Although crizotinib is standard chemotherapy for advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), clinical factors affecting progression-free survival (PFS) have not been reported. The purpose of this study was to identify clinical factors affecting PFS of crizotinib and develop a prognostic model for advanced ALK-positive NSCLC.@*METHODS@#Clinicopathologic features of patients enrolled in PROFILE 1001, 1005, 1007, and 1014 (training cohort) were reviewed. We conducted multivariate Cox analysis for PFS and overall survival (OS) in the training cohort (n = 159) and generated a proportional hazards model based on significant clinicopathologic factors, and then validated the model in an independent validation cohort (n = 40).@*RESULTS@#In the training cohort, the objective response rate was 81.5%. Median PFS and OS from the start of crizotinib were 12.4 and 31.3 months, respectively. Multivariate Cox analysis showed poor performance status, number of metastatic organs (≥ 3), and no response to crizotinib independently associated shorter PFS. Based on a score derived from these three factors, median PFS and OS of patients with one or two factors were significantly shorter compared to those without these factors (median PFS, 22.4 months vs. 10.5 months vs. 6.5 months; median OS, not reached vs. 29.1 months vs. 11.8 months, respectively; p < 0.001 for each group). This model also had validated in an independent validation cohort.@*CONCLUSIONS@#Performance status, number of metastatic organs, and response to crizotinib affected PFS of crizotinib in ALK-positive NSCLC. Based on these factors, we developed a simple and useful prediction model for PFS.

11.
Article in English | WPRIM | ID: wpr-919113

ABSTRACT

BACKGROUND/AIMS@#Since patients with human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) have favorable outcomes after treatment, treatment de-escalation for these patients is being actively investigated. However, not all HPV-positive HNSCCs are curable, and some patients have a poor prognosis. The purpose of this study was to identify poor prognostic factors in patients with HPV-positive HNSCC.@*METHODS@#Patients who received a diagnosis of HNSCC and tested positive for HPV from 2000 to 2015 at a single hospital site (n = 152) were included in this retrospective analysis. HPV typing was conducted using the HPV DNA chip assay or liquid bead microarray system. Expression of p16 in the tumors was assessed by immunohistochemistry. To determine candidate factors associated with overall survival (OS), univariate and multivariable Cox regression analyses were performed.@*RESULTS@#A total of 152 patients with HPV-positive HNSCC were included in this study; 82.2% were male, 43.4% were current or former smokers, and 84.2% had oropharyngeal cancer. By univariate analysis, old age, performance status ≥ 1, non-oropharyngeal location, advanced T classification (T3–4), and HPV genotype 18 were significantly associated with poor OS. By multivariable analysis, performance status ≥ 1 and non-oropharyngeal location were independently associated with shorter OS (hazard ratio [HR], 4.36, p = 0.015; HR, 11.83, p = 0.002, respectively). Furthermore, HPV genotype 18 positivity was also an independent poor prognostic factor of OS (HR, 10.87, p < 0.001).@*CONCLUSIONS@#Non-oropharyngeal cancer, poor performance status, and HPV genotype 18 were independent poor prognostic factors in patients with HPV-positive HNSCC. Patients with these risk factors might not be candidates for de-escalation treatment.

12.
Article in English | WPRIM | ID: wpr-919028

ABSTRACT

BACKGROUND/AIMS@#This study was to evaluate the clinical significance of infusion-related reaction (IRR) of rituximab in diffuse large B-cell lymphoma (DLBCL) patients who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) as a first-line chemotherapy.@*METHODS@#The medical records of 326 patients diagnosed with DLBCL were re trospectively analyzed. Both doctor's progress records and nursing records were reviewed. IRR was graded according to the National Cancer Institute Common Terminology Criteria.@*RESULTS@#IRR was not associated with overall survival (OS) or progression-free survival (PFS) of DLBCL patients as compared to those who did not have IRR (OS: median 78.0 months vs. 69.0 months, p = 0.700; PFS: median 65.4 months vs. 64.0 months, p = 0.901). IRR grade did not affect OS or PFS. B symptoms was independently associated with IRR (hazard ratio [HR], 1.850; 95% confidence interval [CI], 1.041 to 3.290; p = 0.036). Further, bone marrow involvement was independently associated with re-IRR (HR, 4.904; 95% CI, 0.767 to 3.118; p = 0.029).@*CONCLUSIONS@#Our study shows that IRR of rituximab is not associated with OS or PFS of DLBCL patients who received R-CHOP. Furthermore, our study suggests a need for more careful observation for IRR in patients with B symptoms or bone marrow involvement.

13.
Article in English | WPRIM | ID: wpr-763184

ABSTRACT

PURPOSE: Amplified mesenchymal-epithelial transition factor, MET, is a receptor tyrosine kinase (RTK) that has been considered a druggable target in non-small cell lung cancer (NSCLC). Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated. To understand the mechanisms of resistance and establish therapeutic strategies, we developed an in vitro model using the MET-amplified NSCLC cell line EBC-1. MATERIALS AND METHODS: We established capmatinib-resistant NSCLC cell lines and identified alternative signaling pathways using 3′ mRNA sequencing and human phospho-RTK arrays. Copy number alterations were evaluated by quantitative polymerase chain reaction and cell proliferation assay; activation of RTKs and downstream effectors were compared between the parental cell line EBC-1 and the resistant cell lines. RESULTS: We found that EBC-CR1 showed an epidermal growth factor receptor (EGFR)‒dependent growth and sensitivity to afatinib, an irreversible EGFR TKI. EBC-CR2 cells that had overexpression of EGFR-MET heterodimer dramatically responded to combined capmatinib with afatinib. In addition, EBC-CR3 cells derived from EBC-CR1 cells that activated EGFR with amplified phosphoinositide-3 kinase catalytic subunit α (PIK3CA) were sensitive to combined afatinib with BYL719, a phosphoinositide 3-kinase α (PI3Kα) inhibitor. CONCLUSION: Our in vitro studies suggested that activation of EGFR signaling and/or genetic alteration of downstream effectors like PIK3CA were alternative resistance mechanisms used by capmatinib-resistant NSCLC cell lines. In addition, combined treatments with MET, EGFR, and PI3Kα inhibitors may be effective therapeutic strategies in capmatinib-resistant NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Catalytic Domain , Cell Line , Cell Proliferation , Humans , In Vitro Techniques , Parents , Phosphotransferases , Polymerase Chain Reaction , Protein-Tyrosine Kinases , ErbB Receptors , RNA, Messenger
14.
Cancer Research and Treatment ; : 1231-1240, 2019.
Article in English | WPRIM | ID: wpr-763157

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the relationships between the resistance of anaplastic lymphoma kinase (ALK)‒positive non-small cell lung cancer (NSCLC) to ALK inhibitors and the programmed cell death-1/programmed cell death–ligand 1 (PD-L1) pathway, we evaluated alterations in PD-L1 following acquisition of resistance to ALK inhibitors in ALK-positive lung cancer. MATERIALS AND METHODS: We established ALK inhibitor-resistant cell lines (H3122CR1, LR1, and CH1) by exposing the parental H3122 ALK-translocated NSCLC cell line to ALK inhibitors. Then, the double-resistant cell lines H3122CR1LR1 and CR1CH1 were developed by exposing the H3122CR1 to other ALK inhibitors. We compared the alterations in PD-L1 expression levels using western blotting, flow cytometry, and quantitative polymerase chain reaction. We also investigated gene expression using RNA sequencing. The expression of PD-L1 in the tumors from 26 ALK-positive metastatic NSCLC patients (11 ALK inhibitor-naïve and 15 ALK inhibitor-resistant patients) was assessed by immunohistochemistry and analyzed. RESULTS: PD-L1 was expressed at higher levels in ALK inhibitor-resistant cell lines than in the ALK inhibitor-naïve parental cell line at the total protein, surface protein, and mRNA levels. Furthermore, PD-L1 expression in the double-resistant cell lines was much higher than that in the single resistant cell lines. RNA sequencing demonstrated that expression of immune-related genes were largely involved in ALK inhibitor resistance. The mean value of the PD-L1 H-score was 6.5 pre-treatment and 35.0 post-treatment, and the fold difference was 5.42 (p=0.163). CONCLUSION: PD-L1 expression increased following acquisition of ALK inhibitor resistance in ALK-positive NSCLC cell lines and tumors.


Subject(s)
B7-H1 Antigen , Blotting, Western , Carcinoma, Non-Small-Cell Lung , Cell Line , Drug Resistance , Flow Cytometry , Gene Expression , Humans , Immunohistochemistry , Lung Neoplasms , Lung , Lymphoma , Parents , Phosphotransferases , Polymerase Chain Reaction , RNA, Messenger , Sequence Analysis, RNA
15.
Article in English | WPRIM | ID: wpr-719712

ABSTRACT

PURPOSE: This randomized phase III study was designed to compare the efficacy and safety of irinotecan plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC). MATERIALS AND METHODS: Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival. RESULTS: A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP. CONCLUSION: The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.


Subject(s)
Anemia , Arm , Cisplatin , Diarrhea , Disease Progression , Disease-Free Survival , Drug Therapy , Etoposide , Humans , Lung Neoplasms , Male , Nausea , Small Cell Lung Carcinoma
16.
Article in English | WPRIM | ID: wpr-719707

ABSTRACT

PURPOSE: Despite the successful use of tyrosine kinase inhibitors (TKIs) in cancer patients, their effect on herpes zoster development has not been studied. The aim of this study was to evaluate and compare the effects of epidermal growth factor receptor (EGFR) TKI and cytotoxic chemotherapy on the risk of herpes zoster development in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: We conducted a medical review of all eligible NSCLC patients in Seoul National University hospital between 2002 and 2015. We classified patients based on whether they previously underwent EGFR TKI therapy into either the TKI group or the cytotoxic group. We compared the incidence rates of herpes zoster during TKI therapy and cytotoxic chemotherapy. Additionally, the longitudinal risk of herpes zoster from TKIs was analyzed using the incidence rate ratio (IRR) of the TKI group to the cytotoxic group and the log-rank test of the Kaplan-Meier method. RESULTS: Of the 2,981 NSCLC patients, 54 patients (1.54%) developed herpes zoster. In the TKI group (2,002 patients), the IRR of herpes zoster during TKI therapy compared to that during cytotoxic chemotherapy was 1.05 (95% confidence interval [CI], 0.53 to 2.09). The IRR of the TKI group compared to the cytotoxic group was 1.33 (95% CI, 0.64 to 2.76). The Kaplan-Meier cumulative risk of both groups was not significantly different. CONCLUSION: Our results show that the incidence rate of herpes zoster in the TKI group was not statistically different from the incidence in the cytotoxic group during and after chemotherapy in NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Drug Therapy , Erlotinib Hydrochloride , Herpes Zoster , Humans , Incidence , Methods , Protein-Tyrosine Kinases , ErbB Receptors , Seoul , Tyrosine
17.
Article in English | WPRIM | ID: wpr-917076

ABSTRACT

With the rising number of anterior cruciate ligament (ACL) reconstructions, revision ACL reconstructions are becoming increasingly common. A revision procedure may be performed to improved knee function, correct instability, and facilitate a return to normal activities. When performing a revision reconstruction, the surgeon decides between a single-stage or a two-stage revision. Two-stage revisions are rarely performed, but are particularly useful when addressing substantial tunnel-widening, active infection, and concomitant knee pathology (e.g., malalignment, other ligamentous injuries, meniscal or chondral lesions). Among these potential scenarios requiring a two-stage revision, tunnel-widening is the most common cause; the first stage involves graft removal, tunnel curettage, and bone grafting, followed by revision ACL reconstruction in the second stage. The purpose of this article is to review the preoperative planning, surgical considerations, rehabilitation, and outcomes of two-stage revision ACL reconstructions and summarize the recent literature outlining treatment results.

18.
Article in English | WPRIM | ID: wpr-764914

ABSTRACT

BACKGROUND: Digital replantation has become a well-established technique that has revolutionized hand surgery. One of the most important factors to a successful replantation is less than 12 hours of warm and 24 hours of cold ischemia time. The purpose of this article was to present a concept of door-to-surgery time and test the hypothesis that success in distal digital replantation is associated with this time. METHODS: Forty-five patients with 49 distal amputations were included in the study. Data regarding patient demographics, amputation characteristics, ischemia time, and surgical outcome were collected. Factors related to a successful replantation were analyzed. Fisher's exact test was used for statistical analysis. RESULTS: Type I, II, and III Yamano classification were noted in 11 (22.4%), 11 (22.4%), and 27 (55.1%) amputations. All the digits had arterial anastomoses while 19 (38.8%) digits were replanted without venous anastomosis. The mean door-to-surgery time was 229 minutes. The overall success rate was 77.6%. There were no differences in the survival rates between replantations with or without venous anastomosis. Patients with less than 180 minutes of door-to-surgery time had a significantly better survival rate compared to patients with greater time. CONCLUSION: The overall success rate was 77.6%. Patients with less than 180 minutes of door-to-surgery time had a significantly greater success rate (95.0%) compared to patients with longer door-to-surgery time (65.5%). Further effort must be made to achieve this goal in digital replantation.


Subject(s)
Amputation , Classification , Cold Ischemia , Demography , Hand , Humans , Ischemia , Replantation , Survival Rate
19.
Article in English | WPRIM | ID: wpr-739729

ABSTRACT

Hereditary multiple exostosis (HME) is an autosomal dominant disorder manifested by the presence of multiple osteochondromas. Although the lesions are benign in nature, exostoses are often associated with characteristic progressive skeletal deformity and displaying clinical symptoms such as mechanical irritation or impingement. We present the successful arthroscopic resection in a 24-year-old HME male with impingement syndrome and long head tendon tear of the biceps caused by osteochondroma arising from the distal clavicle.


Subject(s)
Clavicle , Congenital Abnormalities , Exostoses , Exostoses, Multiple Hereditary , Head , Humans , Male , Osteochondroma , Shoulder Impingement Syndrome , Shoulder , Tears , Tendons , Young Adult
20.
Article in English | WPRIM | ID: wpr-716737

ABSTRACT

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV core protein has been shown to modulate various cellular signaling pathways including the nuclear factor κB (NF-κB) pathway which is associated with inflammation, cell proliferation and apoptosis. However, there have been conflicting reports about the effect of HCV core protein on NF-κB pathway, and the mechanism by which the core protein affects NF-κB activity remains nuclear. In this study, the functional interaction of HCV core protein and IκB kinase γ (IKKγ) was investigated using the expression plasmids of core and the components of IKK complex. The data revealed that HCV core protein activates NF-κB. Also, HCV core protein up-regulated the phosphorylation and degradation of IκBα. The activating effect of HCV core protein on NF-κB was synergistically elevated by IKKγ. It was noticed that the N-terminal IKKβ binding site, C-terminal leucine zipper, and zinc finger domains of IKKγ are not necessary for its synergistic effect. HCV core protein and IKKγ appeared to activate NF-κB by up-regulating the IKKβ activity resulting in the degradation of IκBα. As expected, HCV core protein induced the expression of NF-κB-targeted pro-inflammatory genes such as iNOS, IL-1β and IL-6 in the transcription level. These results suggest that HCV core protein induces NF-κB through the interaction with IKKγ and may play a critical role in the development of inflammation and related liver diseases.


Subject(s)
Apoptosis , Binding Sites , Carcinoma, Hepatocellular , Cell Proliferation , Hepacivirus , Hepatitis C , Hepatitis , Hepatitis, Chronic , Inflammation , Interleukin-6 , Leucine Zippers , Liver Cirrhosis , Liver Diseases , Phosphorylation , Phosphotransferases , Plasmids , Zinc Fingers
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