Atypical Dysphagia in an Anti-Hu Positive Non-Small-Cell Lung Cancer Patient / 대한연하장애학회지

Anti-Hu antibodies usually present in small cell lung cancer are associated with encephalomyelitis, encephalitis, cerebellitis, and neuropathies. However, to our knowledge, non-small-cell lung cancer (NSCLC) related anti-Hu syndrome presenting acute exacerbation of dysphagia has not been reported. Herein, we report a rare case of atypical dysphagia in an anti-Hu positive NSCLC patient resulting in a fatal outcome. A 73-year-old Korean male went through surgical interventions for recurrent tongue cancer and NSCLC. After the surgery, he resumed full oral feeding with a regular diet. However, four weeks later, he developed a sudden difficulty in swallowing. Neck computed tomography angiography, brain magnetic resonance imaging, brain positron emission tomography, computed tomography and electromyography all showed nonspecific findings. A paraneoplastic antibody test was positive for anti-Hu antibodies. His dysphagia worsened and eventually, he expired due to malignant pleural effusion. Our case shows that anti-Hu antibodies can be expressed in NSCLC and when associated with dysphagia, the outcome can be fatal.

Real-World Clinical Data of Palbociclib in Asian Metastatic Breast Cancer Patients: Experiences from Eight Institutions / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Use of cyclin-dependent kinase 4/6 inhibitors improved survival outcome of hormone receptor (HR) positive metastatic breast cancer (MBC) patients, including Asian population. However, Asian real-world data of palbociclib is limited. We analyzed the real-world clinical practice patterns and outcome in HR-positive, MBC Asian patients treated with palbociclib. @*Materials and Methods@#Between April 2017 to November 2019, 169 HR-positive, human epidermal growth factor-2–negative MBC patients treated with letrozole or fulvestrant plus palbocilib were enrolled from eight institutions. Survival outcome (progression-free survival [PFS]), treatment response and toxicity profiles were analyzed. @*Results@#Median age of letrozole plus palbociclib (145 patients, 85.8%) and fulvestrant plus palbociclib (24 patients, 14.2%) was 58 and 53.5 years, with median follow-up duration of 14.63 months (range 0.2 to 33.9 months). Median PFS (mPFS) of letrozole plus palbociclib and fulvestrant plus palbociclib was 25.6 (95% confidence interval [CI], 19.1 to not reached) and 6.37 months (95% CI, 5.33 to not reached), comparable to previous phase 3 trials. In letrozole plus palbociclib arm, luminal A (hazard ratio, 2.86; 95% CI, 1.20 to 6.80; p=0.017) and patients with good performance (Eastern Cooperative Oncology Group 0-1 [hazard ratio, 3.68; 95% CI, 1.70 to 7.96]) showed better mPFS. In fulvestrant plus palbociclib group, chemotherapy naïve patients showed better mPFS (hazard ratio, 12.51, 95% CI, 1.59 to 99.17; p=0.017). The most common grade 3 or 4 adverse event was neutropenia (letrozole 86.3%, fulvestrant 88.3%). @*Conclusion@#To our knowledge, this is the first real-world data of palbociclib reported in Asia. Palbociclib showed comparable benefit to previous phase 3 trials in Asian patients during daily clinical practice.

Real-World Clinical Data of Palbociclib in Asian Metastatic Breast Cancer Patients: Experiences from Eight Institutions / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Use of cyclin-dependent kinase 4/6 inhibitors improved survival outcome of hormone receptor (HR) positive metastatic breast cancer (MBC) patients, including Asian population. However, Asian real-world data of palbociclib is limited. We analyzed the real-world clinical practice patterns and outcome in HR-positive, MBC Asian patients treated with palbociclib. @*Materials and Methods@#Between April 2017 to November 2019, 169 HR-positive, human epidermal growth factor-2–negative MBC patients treated with letrozole or fulvestrant plus palbocilib were enrolled from eight institutions. Survival outcome (progression-free survival [PFS]), treatment response and toxicity profiles were analyzed. @*Results@#Median age of letrozole plus palbociclib (145 patients, 85.8%) and fulvestrant plus palbociclib (24 patients, 14.2%) was 58 and 53.5 years, with median follow-up duration of 14.63 months (range 0.2 to 33.9 months). Median PFS (mPFS) of letrozole plus palbociclib and fulvestrant plus palbociclib was 25.6 (95% confidence interval [CI], 19.1 to not reached) and 6.37 months (95% CI, 5.33 to not reached), comparable to previous phase 3 trials. In letrozole plus palbociclib arm, luminal A (hazard ratio, 2.86; 95% CI, 1.20 to 6.80; p=0.017) and patients with good performance (Eastern Cooperative Oncology Group 0-1 [hazard ratio, 3.68; 95% CI, 1.70 to 7.96]) showed better mPFS. In fulvestrant plus palbociclib group, chemotherapy naïve patients showed better mPFS (hazard ratio, 12.51, 95% CI, 1.59 to 99.17; p=0.017). The most common grade 3 or 4 adverse event was neutropenia (letrozole 86.3%, fulvestrant 88.3%). @*Conclusion@#To our knowledge, this is the first real-world data of palbociclib reported in Asia. Palbociclib showed comparable benefit to previous phase 3 trials in Asian patients during daily clinical practice.

Clinical Characteristics of Clear Cell Ovarian Cancer: A Retrospective Multicenter Experience of 308 Patients in South Korea / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in earlystage. @*Materials and Methods@#Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected. @*Results@#Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence. @*Conclusion@#Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.

Prognostic role of beclin-1 in locally advanced non-small cell lung cancer in patients receiving docetaxel-platinum induction chemotherapy

BACKGROUND/AIMS@#The outcome of local treatment for advanced non-small cell lung cancer (NSCLC) remains poor, with therapies such as induction chemotherapy (IC) yielding conflicting results. This study aimed to assess the clinicopathologic and prognostic significance of the excision repair cross-complementation group 1 (ERCC1), beclin-1, and glucose-regulated protein of molecular mass 78 (GRP78) in patients with locally advanced NSCLC receiving docetaxel-platinum IC, along with efficacy and safety.@*METHODS@#This is a retrospective observational cohort study. We reviewed medical records of 31 NSCLC patients receiving docetaxel-platinum IC, and conducted immunohistochemical staining of ERCC1, beclin-1, and GRP78.@*RESULTS@#Response rate was 67.8% with 10.7 months of median relapse-free survival (RFS) and 23.1 months of median overall survival (OS), and no treatment-related death was reported. High expression of ERCC1, beclin-1, and GRP78 was identified in 67.7%, 87.1%, and 67.7%, respectively. Expression of ERCC1 and GRP78 did not reveal statistical significance in survival, whereas high beclin-1 expression revealed longer OS (7.6 months vs. 23.2 months; log-rank p = 0.024). In multivariate analysis, histologic differentiation (hazard ratio [HR], 3.48; p < 0.001), stage (HR, 8.5; p = 0.024), and adjuvant treatment (HR, 16.1; p = 0.001) were related to RFS, and in OS, stage (HR, 5.4; p = 0.037), adjuvant treatment (HR, 8.6; p = 0.004), and beclin-1 expression (HR, 8.2; p = 0.011) were identified as significant prognostic factors.@*CONCLUSIONS@#Our findings suggest that high beclin-1 expression predicts longer survival in locally advanced NSCLC and docetaxel-platinum IC is a treatment option that deserves consideration.

Novel Therapeutics for Recurrent or Metastatic Gastric Cancer / 대한내과학회지

Despite advances in cancer therapy, gastric cancer has a poor prognosis and high cancer-related mortality. Based on the molecular characteristics of cancer, specific targeted therapies have shown clinical benefits for various tumors. In addition, immunotherapy using immune checkpoint inhibitors has led to a paradigm shift in cancer treatment and shown remarkable results in some solid tumors. Although immunotherapy has been actively applied to gastric cancer, the efficacy is unsatisfactory compared with other solid tumors, such as melanoma and lung cancers. This is because of the complex mechanism of gastric cancer, tumor heterogeneity, heterogeneity among patients, and the absence of appropriate biomarkers to predict response. An effective new cancer treatment strategy that combines targeted therapies and various immunotherapies based on biological markers such as tumor mutation burden and microsatellite instability is urgently needed. Furthermore, customized treatment is necessary to overcome tumor heterogeneity.

Novel Therapeutics for Recurrent or Metastatic Gastric Cancer / 대한내과학회지

Despite advances in cancer therapy, gastric cancer has a poor prognosis and high cancer-related mortality. Based on the molecular characteristics of cancer, specific targeted therapies have shown clinical benefits for various tumors. In addition, immunotherapy using immune checkpoint inhibitors has led to a paradigm shift in cancer treatment and shown remarkable results in some solid tumors. Although immunotherapy has been actively applied to gastric cancer, the efficacy is unsatisfactory compared with other solid tumors, such as melanoma and lung cancers. This is because of the complex mechanism of gastric cancer, tumor heterogeneity, heterogeneity among patients, and the absence of appropriate biomarkers to predict response. An effective new cancer treatment strategy that combines targeted therapies and various immunotherapies based on biological markers such as tumor mutation burden and microsatellite instability is urgently needed. Furthermore, customized treatment is necessary to overcome tumor heterogeneity.

GRP78 Protein Expression as Prognostic Values in Neoadjuvant Chemoradiotherapy and Laparoscopic Surgery for Locally Advanced Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We investigated the relationships between biomarkers related to endoplasmic reticulum stress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1 [teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis in locally advanced rectal cancer. MATERIALS AND METHODS: All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5-fluorouracil (400 mg/m2/day) and leucovorin (20 mg/m2/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GRP78 and Cripto-1 proteins was determined by immunohistochemistry and was assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). RESULTS: High expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and 49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with a significantly high rate of down staging (80.0% vs. 52.3%, respectively; p=0.046) and a significantly low rate of recurrence (0% vs. 33.7%, respectively; p=0.008) compared with high expression of GRP78 protein. Mean recurrence-free survival according to GRP78 expression could not be estimated because the low expression group did not develop recurrence events but showed a significant correlation with time to recurrence, based on the log rank method (p=0.007). GRP78 also showed correlation with overall survival, based on the log rank method (p=0.045). CONCLUSION: GRP78 expression is a predictive and prognostic factor for down staging, recurrence, and survival in rectal cancer patients treated with 5-fluorouracil and leucovorin neoadjuvant CRT.

A Randomized Double-Blind, Double-Dummy, Multicenter Trial of Azasetron versus Ondansetron to Evaluate Efficacy and Safety in the Prevention of Delayed Nausea and Vomiting Induced by Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to evaluate the efficacy and safety of azasetron compared to ondansetron in the prevention of delayed chemotherapy-induced nausea and vomiting. MATERIALS AND METHODS: This study was a multi-center, prospective, randomized, double-dummy, double-blind and parallel-group trial involving 12 institutions in Korea between May 2005 and December 2005. A total of 265 patients with moderately and highly emetogenic chemotherapy were included and randomly assigned to either the azasetron or ondansetron group. All patients received azasetron (10 mg intravenously) and dexamethasone (20 mg intravenously) on day 1 and dexamethasone (4 mg orally every 12 hours) on days 2-4. The azasetron group received azasetron (10 mg orally) with placebo of ondansetron (orally every 12 hours), and the ondansetron group received ondansetron (8 mg orally every 12 hours) with placebo of azasetron (orally) on days 2-6. RESULTS: Over days 2-6, the effective ratio of complete response in the azasetron and ondansetron groups was 45% and 54.5%, respectively (95% confidence interval, -21.4 to 2.5%). Thus, the non-inferiority of azasetron compared with ondansetron in delayed chemotherapy-induced nausea and vomiting was not proven in the present study. All treatments were well tolerated and no unexpected drug-related adverse events were reported. The most common adverse events related to the treatment were constipation and hiccups, and there were no differences in the overall incidence of adverse events. CONCLUSION: In the present study, azasetron showed inferiority in the control of delayed chemotherapy-induced nausea and vomiting compared with ondansetron whereas safety profiles were similar between the two groups.

Age Specificity in General and Rehabilitation Medical Services in Children With Cerebral Palsy

OBJECTIVE: To review the medical utilization in children with cerebral palsy according to age and discern particularities METHODS: From January 2007 to December 2007, 10,659 children and adolescents between 1 and 18 years of age who had filed national insurance claims for a diagnosis of cerebral palsy were selected. Age was chosen as an independent variable, and the population was categorized into specific age groups to verify any differences in medical service utilization. Admission duration to rehabilitation, number of visits to rehabilitation outpatient clinics, numbers of admission dates and outpatient clinic visits for general medical services, number of rehabilitation utilizations, and type of rehabilitations treatment were selected as dependent variables. One-way ANOVA was used for statistical evaluation, and analysis was done with SAS software. RESULTS: In general medical use, adolescences diagnosed with cerebral palsy had the highest mean admission duration (p<0.001). The mean visit day to outpatient clinics for general medical services was highest for infants (p<0.001). In rehabilitation treatment, infants diagnosed with cerebral palsy had the highest mean admission duration (p<0.001). The mean visit day to outpatient clinics for rehabilitation treatment was highest for infants (p<0.001). CONCLUSION: Significant differences in use of general and rehabilitation medical services among pediatric age groups with cerebral palsy were evident. This implies that particular attention is necessary when setting up a national medical care policy for patient with cerebral palsy.

Secondary Prophylaxis of Docetaxel Induced Diarrhea with Loperamide: Case Report

Diarrhea is a common adverse event of docetaxel with 20%-40% of incidence and severe diarrhea occurs in 5%-6%. Several treatment guidelines for chemotherapy induced diarrhea (CID) exist, however the prophylaxis for that is not well known. We describe a new prophylactic approach for the CID with loperamide. A 72-yr-old male patient with stage IV non-small-cell lung cancer developed diarrhea repeatedly after docetaxel-cisplatin chemotherapy. His diarrhea persisted despite treatment including loperamide and fasting. However, the diarrhea was successfully prevented when loperamide was given before and after the chemotherapy. To our knowledge, this is the first report of prophylactic approach for the CID with loperamide.

A Case of Bilateral Coronary to Pulmonary Artery Fistulas Associated With Severe Aortic Regurgitation

Coronary artery fistula (CAF) is a rare form of congenital anomalies of the coronary arteries, and this is usually discovered by chance during coronary angiography. However, this type of fistula can cause important coronary morbidity and mortality leading to angina, syncope, congestive heart failure, myocardial infarction and sudden death. Bilateral CAFs are even rarer, and especially when combined with valvular heart disease. The coincidence of CAF with aortic regurgitation is relatively rare and this might sometimes cause myocardial ischemia. We present here a case of bilateral coronary-pulmonary artery fistulas that arose from the first diagonal branch of the left anterior descending artery and the conal branch of the right coronary artery combined with severe aortic regurgitation, and this all caused myocardial ischemia.

Progressive Multifocal Leukoencephalopathy in a Patient with Systemic Lupus Erythematosus / 대한류마티스학회지

Progressive multifocal leukoencephalopathy (PML) is a rare, serious, and usually fatal demyelinating disease that occurs predominantly in severely immunosuppressed patients. The disease is caused by the infection of oligodendrocytes with JC virus that is widely distributed as a latent infection in the general populations. PML has been described mainly in patients infected with the human immunodeficiency virus. However, other immune-suppressed patients including malignancies and organ transplants can be affected with JC virus infection. Recently it is suggested that rheumatologic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis, dermatomyositis, polymyositis, wegener`s granulomatosis be known to be at risk of developing PML. We report a case of PML in a patient with SLE.

Spontaneous Subcapsular Hematoma of the Liver in a Patient on Maintenance Hemodialysis / 대한신장학회지

Spontaneous bleeding in various parts of the body has been reported in patients receiving maintenance hemodialysis, but reports on spontaneous subcapsular hematoma of the liver are scarce. We present a case of spontaneous subcapsular hematoma of the liver which developed in a 53-year-old man with maintenance hemodialysis. He was admitted to our hospital with epigastric pain and abnormal liver function test. On abdominal computed tomographic (CT) scan, a large, well-defined subcapsular mass of the liver with a density consistent with blood was observed. We performed embolization of the bleeding vessel and percutaneous drainage of the hematoma. Five months later, follow up abdominal CT scan revealed a moderate reduction of the subcapsular hematoma. In conclusion, the possibility of spontaneous hematoma of the liver should be considered in hemodialysis patients with epigastric pain, unexplained anemia and abnormal liver function.

Renal Biopsy Findings of Prospective Kidney Donors and Clinical Course of Renal Allografts / 대한이식학회지

PURPOSE: To evaluate the pathology of prospective kidney donors and assess the clinical outcomes of the renal allografts. METHODS: We reviewed the records of 12 prospective kidney donors who underwent kidney biopsy. The indications of kidney biopsy were asymptomatic microscopic hematuria (n=88, 66.7%), decreased glomerular filtration rate (GFR, n=22, 16.7%), mild proteinuria (n=11, 8.3%), history of gross hematuria (n=11, 8.3%). RESULTS: Kidney biopsy in 8 prospective donors with asymptomatic microscopic hematuria showed: 5 (62.5%) thin basement membrane disease (TBMD); 1 IgA nephropathy; 1 Alport's syndrome; 1 mild mesangial widening. Two prospective donors with decreased GFR showed IgA nephropathy and tubulointerstitial lesion. The one with mild proteinuria showed arterionephrosclerosis and the one with a history of gross hematuria showed tubulointerstitial lesion. 4 (33.3%) of the 12 who underwent kidney biopsy were accepted as kidney donors.; 3 donors with TBMD and the donor with mild mesangial widening, who all had microscopic hematuria. Among the 4 donations, there was 1 graft failure and 3 allografts (1 mild mesangial widening, 2 TBMD) have maintained graft function at latest follow up. CONCLUSION: The most common cause of asymptomatic microscopic hematuria in prospective kidney donors was TBMD. Long-term follow up is needed to assess the clinical outcomes of these allografts.

Lymphocele Presenting by Scrotal Swelling after Kidney Transplantation / 대한신장학회지

The lymphocele after renal transplantation is usually observed around the graft. We here report an unusual case of lymphocele mimicking hydrocele. The patient was admitted due to scrotal edema. We initially diagnosed this patient as a case of hydrocele, but biochemical data of aspirated fluid was consistent with lymphatic fluid, and abdominal CT revealed fistula between scrotum and graft. This finding suggests that the lymphatic fluid accumulated around the transplant kidney has migrated to the scrotum to form a lymphocele. In conclusion, lymphocele is a rare cause of scrotal swelling but should be considered as a possibility when a transplant patient develops scrotal swelling.

The Association Between Adiponectin and Diabetes in the Korean Population / 한국역학회지

BACKGROUND: As indicators of obesity, waist circumference (WC), body mass index (BMI), and adiponectin are well known risk factor for diabetes mellitus. The objectives of this study were to measure the independent association between these obesity indicators and diabetes and to examine the combined effect of these indicators on diabetes in a Korean population. METHODS: The WC, BMI, and serum adiponectin were measured in 6,505 healthy Koreans and were classified into tertile groups for men and women. The independent and combined associations of the obesity indicators with diabetes were measured using logistic regression analyses. Diabetes was defined as fasting serum glucose greater than 126 mg/dL or taking medication. RESULTS: Levels of adiponectin were inversely associated with BMI and WC and directly associated with age and high density lipoprotein cholesterol (HDL) cholesterol (P <0.001). After adjusting for age, WC, and other lifestyle factors, low levels of adiponectin were associated with an increased prevalence of diabetes. Further adjustment for HDL cholesterol and triglyceride attenuated this association in both men and women. The best cut-off value of adiponectin in terms of identifying the presence of diabetes was 5.5 /ml with a sensitivity and specificity of 46.7% and 63.9% for men and 9.5 /ml with a sensitivity and specificity of 68.2% and 55.2 for women. CONCLUSIONS: These results suggest that adiponectin was associated with diabetes. The association was independent of WC and was partly modified by HDL and triglyceride. There were no effect modifications of adiponectin with WC on diabetes.

Development of ELISA-kit of Quantitative Analysis for Adiponectin and Their Correlation with Cardiovascular Risk Factors / 한국역학회지

PURPOSES: To develop a rapid, sensitive, qualitative ELISA-kit for serum adiponectin and examine correlation with adiponectin and cardiovascular risk factors. METHODS: On the base of monoclonal antibodies against adiponectin, apply indirect ELISA to study the performance parameter of the kit. The correlation was examined between adiponectin and cardiovascular risk factors including waist circumference, body mass index, triglyceride, and HDL cholesterol. RESULTS: The limited concentration of detection of the ELISA-kit was 1ug/ml. Linearity with R&D system and AdipoGen with this ELISA-kit was acceptable: the linear equation with R&D system was y=1.0116x + 0.4629 (R2=0.97) and linear equation with AdipoGen was y=0.9562x + 1.1961 (R2=0.93), respectively. The average recovery rate of the ELISA-kit ranged 92 to 104%. The correlation coefficient of waist circumference with adiponectin was -0.2276 (p<0.0001) among men and -0.2328 (p<0.0001) among women. CONCLUSION: This ELISA-kit was quick, sensitive, and stable and can be used to determine adiponectin in serum.

Spontaneous Cauda Equina Syndrome in a Renal Transplant Patient with Long-term Azathioprine Treatment / 대한이식학회지

Azathioprine is a conventional immunosuppressant in renal transplantation but long-term administration may lead to hematologic complications. We here report a cauda equina syndrome caused by spontaneous epidural hematoma in a renal transplant recipient who had undergone long-term azathioprine treatment. A 34 year-old male was admitted to our hospital with complaints of numbness of the lower extremities and back pain. He had received renal transplantation 14 years ago and had been on sole therapy with azathioprine for 11 years. Three months before admission, the patient developed pancytopenia, and a subsequent bone marrow biopsy revealed hypocellularity. Azathioprine was replaced by tacrolimus and steroids thereafter. After a three months discontinuation of azathioprine, an epidural hematoma developed and resulted in cauda equina syndrome. Regular follow-up of complete blood count and change of immunosuppressants with less bone marrow toxicity should be considered in patients receiving azathioprine for long-term period.