PURPOSE: Sonic hedgehog (Shh) signaling pathway is known to play a crucial role in carcinogenesis in various malignancies, including lung cancer regarding tumorigenesis, angiogenesis, and cellular differentiation. The aim of this study was to investigate the value of components of Shh pathway as a prognostic marker in extensive stage small cell lung cancer (ES-SCLC) patients. MATERIALS AND METHODS: We retrospectively analyzed data of 36 patients who were diagnosed with ES-SCLC between 2008 and 2012 at a single center. We performed immuo-histochemistry for glioma-associated oncogene homolog zinc finger protein 1 (Gli1), patched, Shh, and Ptch-mediated repression of smoothened (Smo) proteins using formalin-fixed, paraffin-embedded tissue derived from primary tumors. We then conducted survival analysis to evaluate the prognostic impact of these markers. RESULTS: All 36 patients received platinum-based doublet chemotherapy. The median progression free survival and median overall survival were 6.9 months [95% confidence interval (CI), 6.5–7.3] and 11.7 months (95% CI, 9.1–14.3), respectively. The overall response rate was 84%. Of the 36 tissue specimens examined, over-expression of Gli1, Patched, Shh, and Smo was found in 12 (33.3%), five (13.9%), five (13.9%), and six (16.7%) cases, respectively. We found that high expression of Shh was associated with worse progression free survival (6.3 vs. 7.6 months, p=0.005) and overall survival (9.2 vs. 12.0 months, p=0.039) by both univariate and multivariate analyses, whereas other markers were not related to patient prognosis. CONCLUSION: A high proportion of small cell lung cancer tumors express proteins related to Shh pathway, and over-expression of Shh is correlated with poor prognosis.
Carcinogenesis ; Disease-Free Survival ; Drug Therapy ; Hedgehog Proteins ; Hedgehogs ; Humans ; Lung Neoplasms ; Multivariate Analysis ; Oncogenes ; Prognosis ; Repression, Psychology ; Retrospective Studies ; Small Cell Lung Carcinoma ; Zinc Fingers

Background/Aims: The multidisciplinary team (MDT) approach is a cornerstone of clinical oncology. This study investigated the current state of MDT care, including patient satisfaction, in Korea. Methods: We obtained the annual number of cancer patients who have received MDT care since 2014 from the registry of the Health Insurance Review and Assessment Service (HIRA). In addition, patients who received MDT care from August 2014 to May 2017 at four university hospitals were further characterized, and patient satisfaction was measured prospectively using a patient-reported questionnaire. Results: The total number of patients who received MDT care increased from 2014 to 2016 (2,113 to 9,998 patients, respectively) in the HIRA Cohort. The type of cancer that most often required MDT was breast cancer (23.8%), followed by colorectal cancer (19.1%). In the Representative Cohort (n = 1,032), MDT was requested by the surgeon more than half the time (55.7%). The main focus of MDT was decision making for further treatment planning (99.0%). The number of doctors participating in the MDT was usually five (70.0%). After initiating an MDT approach, the treatment plan changed for 17.4% of patients. Among these patients, 359 completed a prospective satisfaction survey regarding their MDT care. The overall satisfaction with the MDT approach was very high, with an average score of 9.6 out of 10 points. Conclusions The application of MDT care is a rapidly growing trend in clinical oncology, and shows high patient satisfaction. Further research is needed to determine which types of cancer patients could benefit most from MDT, and to enable MDT care to operate more efficiently so that it may expand successfully throughout Korea.

Wernicke's encephalopathy is an acute neurolopsychiatric syndrome caused by thiamine deficiency, and classically presents with the triad of opthalmopathy, ataxia and altered mentality. Both prolonged total parenteral nutrition and reduced oral intake can induce Wernicke's encephalopathy during hematopoietic stem cell transplantation (HSCT). Although early treatment is important for recovery from Wernicke's encephalopathy, the vague symptoms and characteristics hinder early diagnosis. Furthermore, Wernicke's encephalopathy is not infrequent and can develop at any age during HSCT. Herein, we present two young patients developing Wernicke's encephalopathy during HSCT.
Ataxia ; Early Diagnosis ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Parenteral Nutrition, Total ; Thiamine ; Thiamine Deficiency ; Wernicke Encephalopathy*

Humoral hypercalcemia of malignancy (HHM) is rarely associated with cholangiocarcinoma (CC), and represents dismal prognosis. A 63-year-old male was admitted for evaluation of an intrahepatic mass. He was diagnosed with HHM associated with locally advanced CC. As the tumor responded to the concurrent chemoradiotherapy with capecitabine and cisplatin, serum calcium level was normalized. However, according to the disease progression, he suffered recurrence of HHM and he expired approximately one year after initial diagnosis. A 68-year-old male who presented with abdominal pain was diagnosed with metastatic CC. After the eighth cycle of gemcitabine and cisplatin, progression of the disease was found with HHM. He was treated with the best supportive care, until his demise approximately one month after the diagnosis of HHM. We report on two cases of HHM associated with CC that demonstrate strong correlation between hypercalcemia and disease burden.
Abdominal Pain ; Calcium ; Chemoradiotherapy ; Cholangiocarcinoma ; Cisplatin ; Deoxycytidine ; Disease Progression ; Fluorouracil ; Humans ; Hypercalcemia ; Male ; Paraneoplastic Syndromes ; Parathyroid Hormone-Related Protein ; Prognosis ; Recurrence ; Capecitabine

PURPOSE: To examine the usefulness of various receptor tyrosine kinase expressions as prognostic markers and therapeutic targets in muscle invasive urothelial cancer (UC) patients. MATERIALS AND METHODS: We retrospectively analyzed the data of 98 patients with muscle invasive UC who underwent radical cystectomy between 2005 and 2010 in Yonsei Cancer Center. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemical staining was done for human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 3 (FGFR3). RESULTS: There were 41 (41.8%), 44 (44.9%), and 14 (14.2%) patients who have over-expressed HER2, FGFR1, and FGFR3, respectively. In univariate analysis, significantly shorter median time to recurrence (TTR) (12.9 months vs. 49.0 months; p=0.008) and overall survival (OS) (22.3 months vs. 52.7 months; p=0.006) was found in patients with FGFR1 overexpression. By contrast, there was no difference in TTR or OS according to the HER2 and FGFR3 expression status. FGFR1 remained as a significant prognostic factor for OS with hazard ratio of 2.23 (95% confidence interval: 1.27-3.90, p=0.006) in multivariate analysis. CONCLUSION: Our result showed that FGFR1 expression, but not FGFR3, is an adverse prognostic factor in muscle invasive UC patients after radical cystectomy. FGFR1 might be feasible for prognosis prediction and a potential therapeutic target after thorough validation in muscle invasive UC.
Adult ; Aged ; Aged, 80 and over ; Carcinoma/*metabolism/*mortality/surgery ; Cystectomy ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Muscles/pathology ; Neoplasm Invasiveness ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2/metabolism ; Receptor, Fibroblast Growth Factor, Type 1/*metabolism ; Receptor, Fibroblast Growth Factor, Type 3/metabolism ; Retrospective Studies ; Survival Rate ; Urinary Bladder Neoplasms/*metabolism/*mortality/surgery ; Urothelium/pathology

The prevalence of multi-drug resistant tuberculosis (MDR-TB), which is resistant to isoniazid and rifampin, has been increasing in Korea. And the side effects of 2nd line anti-tuberculosis medications, including drug-induced hepatitis, are well known. Although prothionamide (PTH) is one of the most useful anti-TB medications and although TB medication-induced acute hepatitis is a severe complication, there are only a few published case reports about prothionamide induced hepatitis. In this case report, a 22 year old male was diagnosed with pulmonary MDR-TB and was administered 2nd line anti-TB mediations, including PTH. Afterwards, he had a spiking fever and his liver enzymes were more than 5 times greater than the upper limit of the normal range. He was then diagnosed with drug-induced hepatitis by liver biopsy. His symptoms and liver enzyme elevation were improved after stopping PTH. Accordingly, we report this case of an association between PTH and acute hepatitis.
Biopsy ; Drug-Induced Liver Injury ; Fever ; Hepatitis ; Humans ; Isoniazid ; Korea ; Liver ; Male ; Prevalence ; Prothionamide ; Reference Values ; Rifampin ; Tuberculosis, Multidrug-Resistant ; Tuberculosis, Pulmonary

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammation of the intestines. IBD treatment may require anti-inflammatory agents such as sulfasalazine or 5-aminosalicylate (5-ASA) and immunomodulators to control the symptoms. However, these agents have a variety of common adverse effects such as nausea, vomiting, skin rash, leukopenia, thrombocytopenia, and infections. Moreover, rare side effects such as nephrotic syndrome, pneumonitis, and pericarditis can occur. A 21-year-old male was admitted to the hospital due to acute chest pain, fever, and sweating. The patient had a history of Crohn's disease and had been taking mesalazine for 3 weeks. Chest x-ray, echocardiography, and clinical manifestations revealed that the patient had acute pericarditis. However, we did not recognize the relationship between these findings and 5-ASA at that time. Two years later, the patient took 5-ASA again, and similar symptoms occurred, which led us to confirm that he suffered from pericarditis induced by this drug. We report a case of acute recurrent pericarditis that developed after taking 5-ASA for IBD treatment with a review of the literature.
Anti-Inflammatory Agents ; Chest Pain ; Colitis, Ulcerative ; Crohn Disease ; Echocardiography ; Exanthema ; Fever ; Humans ; Immunologic Factors ; Inflammation ; Inflammatory Bowel Diseases ; Intestines ; Leukopenia ; Male ; Mesalamine ; Nausea ; Nephrotic Syndrome ; Pericarditis ; Pneumonia ; Sulfasalazine ; Sweat ; Sweating ; Thorax ; Thrombocytopenia ; Vomiting ; Young Adult

BACKGROUND: The aim of this study was to investigate the effects of balsamic vinegar on beta-cell dysfunction. METHODS: In this study, 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed a normal chow diet or a high-fat diet (HFD) and were provided with tap water or dilute balsamic vinegar for 4 weeks. Oral glucose tolerance tests and histopathological analyses were performed thereafter. RESULTS: In rats fed both the both chow diet and the HFD, the rats given balsamic vinegar showed increased insulin staining in islets compared with tap water administered rats. Balsamic vinegar administration also increased beta-cell ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression in islets and decreased cholesterol levels. CONCLUSION: These findings provide the first evidence for an anti-diabetic effect of balsamic vinegar through improvement of beta-cell function via increasing beta-cell ABCA1 expression.
Acetic Acid ; Animals ; Cholesterol ; Diet ; Diet, High-Fat ; Glucose Tolerance Test ; Insulin ; Rats ; Water

Purpose: At the end of life, communication is a key factor for good care. However, in clinical practice, it is difficult to adequately discuss end-of-life care. In order to understand and analyze how decision-making related to life-sustaining treatment (LST) is performed, the shared decision-making (SDM) behaviors of physicians were investigated. Methods: A questionnaire was designed after reviewing the literature on attitudes toward SDM or decision-making related to LST. A final item was added after consulting experts. The survey was completed by internal medicine residents and hematologists/medical oncologists who treat terminal cancer patients. Results: In total, 202 respondents completed the questionnaire, and 88.6% said that the decision to continue or end LST is usually a result of SDM since they believed that sufficient explanation is provided to patients and caregivers, patients and caregivers make their own decisions according to their values, and there is sufficient time for patients and caregivers to make a decision. Expected satisfaction with the decisionmaking process was the highest for caregivers (57.4%), followed by physicians (49.5%) and patients (41.1%). In total, 38.1% of respondents said that SDM was adequately practiced when making decisions related to LST. The most common reason for inadequate SDM was time pressure (89.6%). Conclusion Although most physicians answered that they practiced SDM when making decisions regarding LST, satisfactory SDM is rarely practiced in the clinical field. A model for the proper implementation of SDM is needed, and additional studies must be conducted to develop an SDM model in collaboration with other academic organizations.

Purpose: We investigated the consistent efficacy and safety of eflapegrastim, a novel long-acting granulocyte-colony stimulating factor (G-CSF), in Koreans and Asians compared with the pooled population of two global phase 3 trials. Materials and Methods: Two phase 3 trials (ADVANCE and RECOVER) evaluated the efficacy and safety of fixed-dose eflapegrastim (13.2 mg/0.6 mL [3.6 mg G-CSF equivalent]) compared to pegfilgrastim (6 mg based on G-CSF) in breast cancer patients who received neoadjuvant or adjuvant docetaxel/cyclophosphamide. The primary objective was to demonstrate non-inferiority of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN) in cycle 1, in Korean and Asian subpopulations. Results: Among a total of 643 patients randomized to eflapegrastim (n=314) or pegfilgrastim (n=329), 54 Asians (29 to eflapegrastim and 25 to pegfilgrastim) including 28 Koreans (14 to both eflapegrastim and pegfilgrastim) were enrolled. The primary endpoint, DSN in cycle 1 in the eflapegrastim arm was non-inferior to the pegfilgrastim arm in Koreans and Asians. The DSN difference between the eflapegrastim and pegfilgrastim arms was consistent across populations: –0.120 days (95% confidence interval [CI], –0.227 to –0.016), –0.288 (95% CI, –0.714 to 0.143), and –0.267 (95% CI, –0.697 to 0.110) for pooled population, Koreans and Asians, respectively. There were few treatment-related adverse events that caused discontinuation of eflapegrastim (1.9%) or pegfilgrastim (1.5%) in total and no notable trends or differences across patient populations. Conclusion This study may suggest that eflapegrastim showed non-inferior efficacy and similar safety compared to pegfilgrastim in Koreans and Asians, consistently with those of pooled population.