Treatment pattern of chronic lymphocytic leukemia/small lymphocytic lymphoma in Korea: a multicenter retrospective study (KCSG LY20-06)

Background/Aims@#Little attention is paid to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Korea due to the rarity of the disease. With its rising incidence, we aimed to evaluate recent changes in treatment patterns and survival outcomes of patients with CLL/SLL. @*Methods@#A total of 141 patients diagnosed with CLL/SLL between January 2010 and March 2020 who received systemic therapy were analyzed in this multicenter retrospective study. @*Results@#The median patient age was 66 years at diagnosis, and 68.1% were male. The median interval from diagnosis to initial treatment was 0.9 months (range: 0–77.6 months), and the most common treatment indication was progressive marrow failure (50.4%). Regarding first-line therapy, 46.8% received fludarabine, cyclophosphamide, plus rituximab (FCR), followed by chlorambucil (19.9%), and obinutuzumab plus chlorambucil (GC) (12.1%). The median progression-free survival (PFS) was 49.3 months (95% confidence interval [CI], 32.7–61.4), and median overall survival was not reached (95% CI, 98.4 mo– not reached). Multivariable analysis revealed younger age (≤ 65 yr) (hazard ratio [HR], 0.46; p < 0.001) and first-line therapy with FCR (HR, 0.64; p = 0.019) were independently associated with improved PFS. TP53 aberrations were observed in 7.0% (4/57) of evaluable patients. Following reimbursement, GC became the most common therapy among patients over 65 years and second in the overall population after 2017. @*Conclusions@#Age and reimbursement mainly influenced treatment strategies. Greater effort to apply risk stratifications into practice and clinical trials for novel agents could help improve treatment outcomes in Korean patients.

Comprehensive Analysis of Iron Deficiency Anemia and Its Related Disorders in Premenopausal Women Based on a Propensity Score Matching Case Control Study Using National Health Insurance Service Database in Korea

Background@#Menorrhagia is a common cause of iron deficiency anemia (IDA) in premenopausal women. However, the effects of menorrhagia on IDA in premenopausal women have been underestimated compared to those on other IDA-related disorders (IRDs) such as gastrointestinal malignancies (GIMs). To better understand the relationship between menorrhagia and IDA in premenopausal women, we analyzed the National Health Insurance Service-National Health Information Database (NHIS-NHID). @*Methods@#From 2005 to 2008, data about women between the age of 20 and 59 years were extracted from the NHIS-NHID to create a propensity score-matched case (IDA) and control group. The annual incidence of IDA was calculated per age group. A 10-year follow up of the study population was determined to detect IRDs in case and control groups. We compared the risk of detection (ROD) of IRDs, including GIM and gynecological disorders associated with menorrhagia - leiomyoma of uterus (LM) and adenomyosis (AM), in the case and the control group. @*Results@#From 2005 to 2008, women diagnosed with IDA (n = 535,249) and healthy women as a control group (n = 1,070,498) were identified from the NHIS-NHID. The annual incidence of IDA was 767.4 (2005), 948.7 (2006), 981.6 (2007), and 897.7 (2008) per 100,000 women.The age distribution of IDA was similar each year; IDA was common in women aged 30–39 years (36–37%) and 40–49 years (30–32%), and its incidence was significantly decreased in women aged 50–59 years (< 10%). The ROD of IRDs were significantly higher in the IDA group than in the control group (LM: 20.8% vs. 6.9%, AM: 5.6% vs. 1.6%, and GIM: 2.6% vs.0.7%). The corresponding hazard ratios were 3.89 (95% confidence interval [CI], 3.85–3.93) for LM, 4.99 (95% CI, 4.90–5.09) for AM, and 3.43 (95% CI, 3.32–3.55) for GIM. The ROD of the IRDs varied; the ROD of LM in the IDA group increased with age and decreased in the age group 50–59 years. AM was more frequently detected in women with IDA aged 30–39 years and less in women older than 40 years. The frequency of GIM increased with age. @*Conclusion@#In this study, we found that the gynecologic disease is the main cause of IDA in premenopausal women. Gynecological evaluations should be performed more actively in the clinic to prevent and control IDA and IRDs.

Treatment-free remission after discontinuation of imatinib, dasatinib, and nilotinib in patients with chronic myeloid leukemia

Patients with chronic myeloid leukemia (CML) in the chronic phase receiving tyrosine kinase inhibitor (TKI) therapy are expected to have long-term survival outcomes comparable to those of the general population. Many clinical trials have confirmed that some patients sustain molecular responses without continuing TKI therapy. Treatment-free remission (TFR) is a new goal in treating chronic CML. The safety and outcome of TFR were studied in clinical trials after discontinuing imatinib or the second-generation TKIs dasatinib or nilotinib. TFR was safe in approximately 50% of patients who achieved a deep molecular response to TKI therapy. Patients who relapsed after discontinuing TKI responded immediately to the reintroduction of TKI. The mechanism by which TFR increases the success rate still needs to be understood. The hypothesis that the modulation of immune function and targeting of leukemic stem cells could improve the TFR is under investigation.Despite the remaining questions, the TFR has become a routine consideration for clinicians in the practice of molecular remission in patients with CML.

Noise and Room Acoustic Conditions in a Tertiary Referral Hospital, Seoul National University Hospital

BACKGROUND AND OBJECTIVES: Noise levels and room acoustic parameters at a tertiary referral hospital, Seoul National University Hospital (SNUH) in Korea, are investigated. MATERIALS AND METHODS: Through a questionnaire, acoustically problematic rooms are identified. Noise levels in emergency rooms (ERs) and intensive care units (ICUs) are measured over about three days. Acoustically critical and problematic rooms in the otolaryngology department are measured including examination rooms, operating rooms, nurse stations, receptions, and patient rooms. RESULTS: The A-weighted equivalent noise level, L(Aeq), ranges from 54 to 56 dBA, which is at least 10 dB lower than the noise levels of 65 to 73 dBA measured in American ERs. In an ICU, the noise level for the first night was 66 dBA, which came down to 56 dBA for the next day. The noise levels during three different ear surgeries vary from 57 to 62 dBA, depending on the use of surgical drills and suctions. The noise levels in a patient room is found to be 47 dBA, while the nurse stations and the receptions have high noise levels up to 64 dBA. The reverberation times in an operation room, examination room, and single patient room are found to be below 0.6 s. CONCLUSIONS: At SNUH, the nurse stations and receptions were found to be quite noisy. The ERs were quieter than in the previous studies. The measured reverberation times seemed low enough but some other nurse stations and examination rooms were not satisfactory according to the questionnaire.

Effect of Ginkgo Biloba Extract on N-Methyl-D-Aspartic Acid Receptor Subunit 2B Expression in a Salicylate-Induced Ototoxicity Model

OBJECTIVES.: Sodium salicylate (SS) is well known for its ototoxic properties that induce functional and morphological changes in the cochlea and brain. Ginkgo biloba extract (GBE) has been widely used for treatment of various neurodegenerative diseases; however, its effects on salicylate-induced ototoxicity remain unclear. Herein, we examined the effects of EGb 761 (EGb), a standard form of GBE, on the plasticity of the N-methyl-D-aspartate receptor subunit 2B (GluN2B) in the inferior colliculus (IC) following SS administration. METHODS.: Seven-week-old Sprague Dawley rats (n=24) were randomly allocated to control, SS, EGb, and EGb+SS groups. The SS group received a single intraperitoneal SS injection (350 mg/kg), the EGb group received EGb orally for 5 consecutive days (40 mg/kg), and the EGb+SS group received EGb for 5 consecutive days, followed by an SS injection. The auditory brainstem responses (ABRs) were assessed at baseline and 2 hours after SS administration. GluN2B expression was examined by Western blot and immunohistochemistry. RESULTS.: There were no significant differences in ABR threshold shifts among the groups. The expression of the GluN2B protein normalized by which of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was significantly lower in the EGb+SS group, as compared to the SS group (P=0.012). Weak and diffused GluN2B immunoreactivity was detected in the IC neural cells of the EGb+SS group, while those of the SS group exhibited strong and diffused GluN2B positivity. CONCLUSION.: EGb may play a role in regulating the GluN2B expression in the IC of salicylate-induced ototoxicity model.

Multicenter Retrospective Analysis of Clinical Characteristics, Treatment Patterns, and Outcomes in Very Elderly Patients with Diffuse Large B-Cell Lymphoma: The Korean Cancer Study Group LY16-01 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The treatment strategy for elderly patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) has not been established because of poor treatment tolerability and lack of data. MATERIALS AND METHODS: This multicenter retrospective study was conducted to investigate clinical characteristics, treatment patterns and outcomes of patients older than 80 years who were diagnosed with DLBCL at 19 institutions in Korea between 2005 and 2016. RESULTS: A total of 194 patients were identified (median age, 83.3 years). Of these, 114 patients had an age-adjusted International Prognostic Index (aaIPI) score of 2-3 and 48 had a Charlson index score of 4 or more. R-CHOP was given in 124 cases, R-CVP in 13 cases, other chemotherapy in 17 cases, radiation alone in nine cases, and surgery alone in two cases. Twenty-nine patients did not undergo any treatment. The median number of chemotherapy cycles was three. Only 37 patients completed the planned treatment cycles. The overall response rate from 105 evaluable patients was 90.5% (complete response, 41.9%). Twentynine patients died due to treatment-related toxicities (TRT). Thirteen patients died due to TRT after the first cycle. Median overall survival was 14.0 months. The main causes of death were disease progression (30.8%) and TRT (27.1%). In multivariate analysis, overall survival was affected by aaIPI, hypoalbuminemia, elevated creatinine, and treatment. CONCLUSION: Age itself should not be a contraindication to treatment. However, since elderly patients show higher rates of TRT due to infection, careful monitoring and dose modification of chemotherapeutic agents is needed.

Crohn's disease and smoldering multiple myeloma: a case report and literature review

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that presents with abdominal pain, weight loss, and diarrhea. Although the etiology has not been fully elucidated, both environmental and genetic causes are known to be involved. In chronic inflammatory conditions such as IBD, B lymphocytes are chronically stimulated, and they induce monoclonal expansion of plasma cells, sometimes resulting in monoclonal gammopathy of undetermined significance. Immunomodulators that are commonly used to control inflammation, such as tumor necrosis factor-α (TNF-α) blockers could increase the possibility of hematologic malignancy. The pathogenesis of multiple myeloma in association with TNF-α inhibitor therapy is attributed to decreased apoptosis of plasma cell populations. Here, we describe a case of a 36-year-old male patient who was diagnosed with immunoglobulin A subtype smoldering multiple myeloma during the treatment for CD with infliximab and adalimumab. We report this case along with a review of the literature on cases of multiple myeloma that occurred in conjunction with CD.

The correlation between bone mineral density/trabecular bone score and body mass index, height, and weight

OBJECTIVES: This study investigated the correlation between bone mineral density (BMD)/trabecular bone score (TBS) and body mass index (BMI), height and weight in Korean adults. METHODS: We enrolled 2555 female participants in their 20s–80s and 1631 male participants in their 20s–70s. Participants with history of previous vertebral surgeries or current vertebral diseases were excluded. Female and male participants were divided into osteoporosis group (n = 136 and n = 31, respectively), osteopenia group (n = 822 and n = 460, respectively), and normal group (n = 1596 and n = 1140, respectively) based on their BMD T-score. Dual-energy X-ray absorptiometry image analysis and linear regression analysis were conducted on each participant in each group to determine the P-value and the correlation between BMD T-score/TBS T-score and BMI, weight, and height. RESULTS: We found a significant correlation between BMI and TBS in both male and female participants. In the male participants, the correlation coefficient increased progressively from the normal group to the osteoporosis group. In the female group, we observed a significant positive correlation between height and TBS, and in the male group a significant negative correlation between weight and TBS was observed. CONCLUSIONS: BMI and weight are closely correlated to body fat content. BMD was positively correlated to BMI and weight, while TBS was negatively correlated to BMI and weight. Therefore, although BMI causes an increase in BMD, it appears to be negatively affecting bone quality.

The Association between End-of-Life Care and the Time Interval between Provision of a Do-Not-Resuscitate Consent and Death in Cancer Patients in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We explored the relationship between the use of each medical intervention and the length of time between do-not-resuscitate (DNR) consent and death in Korea. MATERIALS AND METHODS: A total of 295 terminal cancer patients participated in this retrospective study. Invasive interventions (e.g., cardiopulmonary resuscitation, intubation, and hemodialysis), less invasive interventions (e.g., transfusion, antibiotic use, inotropic use, and laboratory tests), and the time interval between the DNR order and death were evaluated. The subjects were divided into three groups based on the amount of time between DNR consent and death (G1, time interval ≤ 1 day; G2, time interval > 1 day to ≤ 3 days; and G3, time interval > 3 days). RESULTS: In general, there were fewer transfusions and laboratory tests near death. Invasive interventions tended to be implemented only in the G1 group. There was also less inotrope use and fewer laboratory tests in the G3 group than G1 and G2. Moreover, the G3 group received fewer less invasive interventions than those in G1 (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.03 to 0.84; 3 days before death, and OR, 0.16; 95% CI, 0.04 to 0.59; the day before death). The frequency of less invasive interventions both 1 and 3 days before death was significantly lower for the G3 group than the G1 (p ≤ 0.001) and G2 group compared to G1 (p=0.001). CONCLUSION: Earlier attainment of DNR permission was associated with reduced use of medical intervention. Thus, physicians should discuss death with terminal cancer patients at the earliest practical time to prevent unnecessary and uncomfortable procedures and reduce health care costs.

In Reply: Dominance of Ossicular Route in Sound Transmission

No abstract available.

Erratum: Determinants of Conductive Hearing Loss in Tympanic Membrane Perforation: Correction of the Sixth Author Name

The sixth author's name should have been given as Myung-Whan Suh.

Comparison of End-of-Life Care Intensity between Cancer and Non-cancer Patients: a Single Center Experience / 한국호스피스완화의료학회지

PURPOSE: The aging of society has rapidly progressed, especially in Korea. Therefore, the necessity of research on end-of-life (EOL) care in elderly patients has increased. However, there are few studies on EOL care intensity for non-cancer patients. This study was designed to compare the EOL care intensity between cancer and non-cancer patients. METHODS: We retrospectively analyzed the EOL care intensity based on medical records of decedents of Kyung Hee University Medical Center, a tertiary referral hospital from December 2014 through March 2015. And we compared EOL care intensity between cancer patients and non-cancer patients using statistical analysis of the frequency of invasive procedures and logistic regression analysis for factors that affect the EOL care intensity. RESULTS: Statistical analysis showed invasive procedures, such as intensive care unit admission, endotracheal intubation followed by mechanical ventilation and emergency dialysis, were performed more frequently in non-cancer patients than cancer patients (29.3% vs. 72.4%, P<0.001). And age (P=0.038) and morbidity of cancer (P<0.001) influenced the invasive procedural decision when analyzed by logistic regression analysis. CONCLUSION: The EOL care was more intensive in non-cancer patients, and age and morbidity of cancer were major factors for the treatment intensity.

Determinants of Conductive Hearing Loss in Tympanic Membrane Perforation

OBJECTIVES: Tympanic membrane perforations are common, but there have been few studies of the factors determining the extent of the resulting conductive hearing loss. The aims of this study were to determine whether the size of tympanic membrane perforation, pneumatization of middle ear & mastoid cavity, and location of perforation were correlated with air-bone gap (ABG) of patients. METHODS: Forty-two patients who underwent tympanoplasty type I or myringoplasty were included and preoperative audiometry were analyzed. Digital image processing was applied in computed tomography for the estimation of middle ear & mastoid pneumatization volume and tympanic membrane photograph for the evaluation of perforation size and location. RESULTS: Preoperative mean ABG increased with perforation size (P=0.018), and correlated inversely with the middle ear & mastoid volume (P=0.005). However, perforations in anterior versus posterior locations showed no significant differences in mean ABG (P=0.924). CONCLUSION: The degree of conductive hearing loss resulting from a tympanic membrane perforation would be expected with the size of perforation and pneumatization of middle ear and mastoid.

Preoperative Vestibular Function in Adults with Cochlear Implantation: Comparison between Prelingual and Poslingual Deafness / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Cochlear system and vestibular system have close relationship anatomically and developmentally. According to previous literatures, there are high incidences of vestibular dysfunction in subjects with severe hearing loss. The aim of this study is to validate the status of vestibular function in adults with profound hearing loss, and to compare the status of vestibular function between pre-lingual and post-lingual deaf. SUBJECTS AND METHOD: Vestibular function of 59 patients who had profound hearing loss was reviewed retrospectively. Patient's information and audiometry, Korean version Central Institute for the Deaf (KCID) scores, caloric test, rotation chair test and vestibular evoked myogenic potential (VEMP) were analyzed. The subjects were divided into two groups, prelingual deaf (pre-LD, n=12) and postlingual deaf (post-LD, n=47). We analyzed the difference between two groups. RESULTS: Fifty nine point six percent of patients showed hypo-function in caloric test. In the rotational chair test, abnormality of step velocity gain (43.1%), time constant (51.8%), sinusoidal harmonic acceleration (SHA)-gain (53.4%), SHA-phase lead (29.1%) and SHA-asymmetry (23.6%) were found. There was unilateral (20.0%) and bilateral (37.5%) hypo-function when VEMP was tested. Between pre-LD and post-LD groups, VEMP test revealed statistically significant difference between two groups (p=0.020). Post-LD groups had more patients of unilateral or bilateral hypofunction in VEMP test. The KCID score showed no significant correlation with vestibular functions. CONCLUSION: The patients of bilateral profound hearing loss showed unilateral or bilateral vestibular functional abnormality despite of no dizziness. Prevalence of lateral canal dysfunction does not seem to be different between pre-LD group and post-LD group. And post-LD groups have higher probability of saccular dysfunction than pre-LD.

Combination of TRAP1 and ERCC1 Expression Predicts Clinical Outcomes in Metastatic Colorectal Cancer Treated with Oxaliplatin/5-Fluorouracil / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The novel heat shock protein tumor necrosis factor receptor-associated protein 1 (TRAP1) is associated with multidrug resistance in colorectal cancer (CRC) cells in vitro. Excision repair cross-complementation group 1 (ERCC1) expression levels in tumor tissues also predict clinical outcomes in metastatic CRC patients receiving combination oxaliplatin and 5-fluorouracil treatment. We investigated whether TRAP1 and ERCC1 protein expression by immunohistochemistry predict clinical outcomes in CRC patients. MATERIALS AND METHODS: The study population consisted of 56 patients with metastatic CRC who received first-line oxaliplatin/5-fluorouracil therapy. Clinical response and overall survival (OS) by levels of the markers TRAP1 and ERCC1 were evaluated. RESULTS: The rates of TRAP1 and ERCC1 expression were 21% and 52%, respectively. Patients negative for ERCC1 expression showed a tendency to respond to chemotherapy (p=0.066). Median OS was significantly longer in patients negative for TRAP1 than those positive for TRAP1 (p=0.023). Patients negative for ERCC1 expression also had a better OS than those positive for ERCC1 (p=0.021). The median OS was 30.9 months for patients negative for TRAP1 and ERCC1 compared to 13.2 months for those positive for TRAP1 and/or positive for ERCC1 expression (p=0.006). The combination of TRAP1 and ERCC1 expression was significantly associated with the response to chemotherapy (p=0.046) and independently predicted median OS in multivariate analysis (hazard ratio, 2.98; 95% confidence interval, 1.18 to 7.49). CONCLUSION: The present study demonstrates that the combination of TRAP1 and ERCC1 expression predicts the survival of metastatic CRC patients who were treated with oxaliplatin/5-fluorouracil.

Review of Molecular Markers for Thyroid Cancer / 이화의대지

The incidence of thyroid cancer has been rapidly increased in Korea. Although fine needle aspiration cytology is recommended for diagnosis of cancer, there are some limitations. Patients with indeterminate or suspicious cytology category in which malignancy cannot be ruled out usually undergone a thyroidectomy, however, only 10~25% of them finally diagnosed as cancer. According to the progress in understanding molecular mechanism, some mutations or other molecular alterations have been studied for the diagnostic and prognostic markers for thyroid cancer. The majority of papillary thyroid cancers have BRAF and RAS mutations or RET/PTC rearrangement, and approximately 80% of follicular thyroid cancers harbor a RAS mutation or PAX8/PPARgamma rearrangement. These genetic alterations are mostly studied and current clinical guidelines suggested that these molecular markers may help management for patients with indeterminate cytology. In addition, recent studies demonstrated the high sensitivity and specificity of thyroid-stimulating hormone receptor mRNA in diagnosing cancer in patients with indeterminate cytology. For the detection of recurrent or residual thyroid cancer, serum thyroglobulin is the only circulating marker in clinical practice. However, it lacks sensitivity and is unreliable specifically in the presence of antibodies to thyroglobulin. Recent studies demonstrated a significant role of measuring the mRNA of thyroglobulin, thyroid peroxidase, thyroid-stimulating hormone receptor, and sodium/iodine symporter in peripheral blood for monitoring of the recurrence of thyroid cancer.

Long-term outcomes of a 5-year follow up of patients with immune thrombocytopenic purpura after splenectomy / 대한혈액학회지

BACKGROUND: The long-term outcomes of adult patients with immune thrombocytopenic purpura (ITP) after splenectomy are not clear. METHODS: We retrospectively analyzed 31 patients who underwent splenectomy after diagnosis of ITP at our institution between 1990 and 2009. Long-term follow-up was defined as a follow-up that lasted 1 year or more from splenectomy to the last follow-up. RESULTS: The overall response rate to splenectomy was 84%. However, the response rate at 6 and 12 months decreased to 77% and 68%, respectively. During the 6 years of median follow-up after splenectomy, 11 patients (35%) relapsed. The long-term response rate was 55%. The long-term follow-up of 26 patients after responding to splenectomy showed that the median time from splenectomy to relapse was 19 months in the partial response (PR) group; however, there was no relapse after 9 months in the complete response (CR) group. Variables, including age, were not predictive of the long-term response after splenectomy. Additional treatment in patients who did not respond or relapsed after splenectomy was mostly effective. After a median follow-up of 7 years (range: 1-25 years) from the diagnosis, there were 2 deaths, including one due to spontaneous bleeding after repair of duodenal ulcer perforation. CONCLUSION: Although splenectomy is safe and effective, the response rate after splenectomy continuously decreases over time. The duration of response is different between the patients that achieved CR and those that achieved PR. Factors, including age, were not predictors of a response to splenectomy.

A case of ventriculitis caused by Vancomycin-Resistant Enterococcus durans / 대한내과학회지

Infections associated with Enterococcus durans have been rare in humans until now. E. durans is a frequent component of the intestinal flora of several domestic animal species and may cause septicemia and encephalomalacia in chicks. We report a case of ventriculoperitoneal shunt infection caused by vancomycin-resistant E. durans in a 17-year-old woman with Dandy-walker syndrome. To the best of our knowledge, this is the first human case of ventriculitis caused by vancomycin-resistant E. durans.

A case of ventriculitis caused by Vancomycin-Resistant Enterococcus durans / 대한내과학회지

Infections associated with Enterococcus durans have been rare in humans until now. E. durans is a frequent component of the intestinal flora of several domestic animal species and may cause septicemia and encephalomalacia in chicks. We report a case of ventriculoperitoneal shunt infection caused by vancomycin-resistant E. durans in a 17-year-old woman with Dandy-walker syndrome. To the best of our knowledge, this is the first human case of ventriculitis caused by vancomycin-resistant E. durans.

Parenteral Nutrition / 대한소아소화기영양학회지

Parenteral nutrition (PN) is effective and relatively safe method providing nutrients to patients with a nonfunctioning or insufficiently functioning gastrointestinal tract via peripheral or central vein. In last several decades, useful steps have been taken in the understanding of nutritional needs, physiological changes and complications of intravenously fed patients. PN includes amino acids, glucose, lipids, electrolytes, vitamins, iron, minerals and trace elements, and must be based on individual circumstances such as patient's age, health status and disease. The purpose of this review is to introduce overall components and recent updates of parenteral nutrition.