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.

Evaluation of the prevalence of musculoskeletal symptoms, presumptive diagnosis, medical care use, and sick leave among female school meal service workers

BACKGROUND: Most of the school meal service workers in Korea are middle-aged individuals. They have high workload, which increases their incidence of musculoskeletal disorders. This study aimed to evaluate the prevalence and risk factors of subjective musculoskeletal symptoms, presumptive diagnosis, medical care use, and sick leave among female school meal workers. METHODS: We analyzed the results of musculoskeletal disease screening of 1581 female school meal workers. The screening consisted of self-administered questionnaire, history taking by occupational physicians, and physical examination. The prevalence of subjective musculoskeletal symptoms, presumptive diagnosis after initial examination by occupational physicians, use of medical care for more than 7 days, and sick leave due to musculoskeletal diseases during the past year were evaluated in this study. The relative risk of four outcome indicators of musculoskeletal disorders was compared with respect to potential factors, such as age, subjective physical loading, present illness, injury experience, and type of school, using log-binomial regression. RESULTS: The prevalence of subjective musculoskeletal symptom was 79.6%; presumptive diagnosis, 47.6%; hospital visits over 7 days, 36.4%; and sick leave, 7.3%. The relative risk of musculoskeletal symptoms by age (≥50 years vs < 50 years) was 1.04 (95% confidence interval (CI): 1.00–1.09); presumptive diagnosis of musculoskeletal disease, 1.17 (95% CI: 1.06–1.30); hospital visits over 7 days, 1.26 (95% CI: 0.85–1.85); and sick leave, 1.17 (95% CI: 1.02–1.34). The relative risk of musculoskeletal symptoms due to subjective physical loading (very hard vs low) was 1.45 (95% CI: 1.33–1.58); presumptive diagnosis, 2.92 (95% CI: 2.25); hospital visits over 7 days, 1.91 (95% CI: 1.02–3.59); and sick leave, 2.11 (95% CI: 1.63–2.74). CONCLUSIONS: Subjective physical loading was a more important factor in musculoskeletal disorders than the age of female school meal workers.

Effects of work-related factors on self-reported smoking among female workers in call centers: a cross-sectional study

OBJECTIVES: This study conducted to investigate work-related factors in relation to smoking among women working in call centers in Gwangju, South Korea. METHODS: From 56 call centers (7320 employees), we selected 10 and conducted a survey using a structured questionnaire by randomly selecting 10% of workers from each center. A total of 387 subjects participated in this survey We analyzed for 375 respondents, after excluding men and those with missing responses. We analyzed the relationships of work-related factors such as emotional labor, workplace violence, employment type, annual salary, working hours, employment period with smoking, using multiple logistic regression analysis. Emotional labor and workplace violence were measured using the Korean Emotional Labor Scale (K-ELS) and Korean Workplace Violence Scale (K-WVS). RESULTS: The prevalence of current smoking among call center female workers was 13.6%. Univariate analysis showed that “Emotional disharmony and hurt”, “Experience of psychological and sexual violence from supervisors and co-workers” among items of K-ELS and K-WVS, working hours, annual salary correlated with smoking. After adjusting for emotional labor, workplace violence, employment type, annual salary, working hours, employment period, and age, only working hours show a significant association with smoking. Women who worked 40–49 h had 3.50 times (95% CI = 1.04–11.80) and worked more than 50 h had 8.68 times (95% CI = 1.89–39.78) greater odds of smoking as compared with women who worked less than 40 h. CONCLUSIONS: Smoking was associated with working hours among female workers in call center. However, emotional labor and workplace violence did not show significant relationships with smoking.

Clinical Implications of Elevated Antiphospholipid Antibodies in Adult Patients with Primary Immune Thrombocytopenia

BACKGROUND/AIMS: Antiphospholipid antibodies (aPL) have been detected in various proportions of patients with primary immune thrombocytopenia (ITP), but the clinical significance of this is debatable. The present study aimed to determine the frequency and clinical implications of elevated aPL in adult patients with ITP. METHODS: We prospectively studied newly diagnosed adult patients with ITP who were enrolled between January 2003 and December 2008 at Chungnam National University Hospital. They were evaluated for the presence of lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) at diagnosis and were followed for the development of thrombosis. RESULTS: Seventy consecutive patients with ITP (median age, 48 years; range, 18 to 79) were enrolled. Twenty patients (28.5%) were positive for aPL at the time of diagnosis: aCL alone in 15 (75%), aCL and LA in two (10%), and LA alone in three (15%). Patients who had platelet counts < 50,000/microL were administered oral prednisolone with or without intravenous immune globulin. No difference was found between the aPL-positive and -negative groups regarding gender, initial platelet count, and response to the therapy. After a median follow-up of 20 months (range, 2 to 68), two of 20 patients who were aPL-positive (10%) developed thrombosis, whereas no thrombotic event was found among those who were aPL-negative. CONCLUSIONS: Our data suggest that aPL levels should be determined at the initial presentation of ITP and that patients found to be aPL-positive should receive closer follow-up for thrombotic events.

A Case of Central Nervous System Myelomatosis Developing after Allogeneic Hematopoietic Stem Cell Transplantation / 대한혈액학회지

Central nervous system (CNS) myelomatosis, which is the presence of monoclonal plasma cells in the cerebrospinal fluid (CSF), is extremely rare. We report a case of CNS myelomatosis developed in a 45-year-old woman with multiple myeloma in complete response, which was achieved by allogeneic peripheral blood stem cell transplantation using a reduced-intensity conditioning regimen consisting of melphalan, fludarabine, and antithymocyte globulin. Two months after the transplant, she developed a moderate motor and sensory weakness in both lower extremities. Atypical plasma cells were found in the CSF, and immunofixation revealed monoclonal light chain in the CSF. She was given three courses of weekly intra-thecal chemotherapy consisting of methotrexate, cytarabine, and dexamethasone, which cleared the CSF. This case indicates that the allogeneic transplantation could not control CNS myelomatosis, despite successfully treating the bone marrow myeloma.

Role of Pertussis Toxin-sensitive G Protein-coupled Receptor Signaling in the Proliferation of Bone Marrow Mesenchymal Stem Cells / 대한혈액학회지

BACKGROUND: Bone marrow (BM) mesenchymal stem cells (MSCs) can be expanded over 20~30 cell doublings in vitro even in the absence of any growth factors. However, the mechanisms that govern MSC proliferation are not well understood. METHODS: We investigated the role of signaling of the pertussis toxin (PTX)-sensitive G protein-coupled receptor in the proliferation of BM MSCs. RESULTS: PTX inhibited the proliferation of human BM MSCs and murine BM stromal MS-5 cells in a dose-dependent manner. Among the chemokines produced by the BM stromal cells, stromal cell-derived factor-1 (SDF-1) enhanced the proliferation of BM MSCs, while MIP-1alpha, MCP-3 or RANTES did not. PTX also inhibited the proliferation of some fibroblasts, such as MRC-5 and NIH-3T3, but did not affect the proliferation of HeLa and HSF cells. HSF cells did not express CXCR4 mRNA, but did produce SDF-1. In contrast, HeLa cells expressed CXCR4 strongly on the cell surface, but did not produce SDF-1. BM MSCs, MS-5, MRC-5, and NIH-3T3 cells all expressed CXCR4 minimally on the cell surface. These cells, however, had abundant CXCR4 protein in their cytoplasm, which was demonstrated by flow cytometric analysis performed after permeabilization of the cells. In addition, an ELISA performed on the culture supernatants of the cells revealed that these cells constitutively produce and secrete SDF-1. CONCLUSION: These results indicate that the signaling through the PTX-sensitive G protein-coupled receptor, which is induced by autocrine factors, plays an important role in the proliferation of BM MSCs and in some fibroblasts, and that SDF-1 is the most probable candidate for the autocrine growth factor.

Prevalence of Meniscus Tear in Tibial Plateau Fractures

PURPOSE: To evaluate the pattern of meniscal tear according to the type of the tibial plateau fracture of Schatzker. MATERIALS AND METHODS: Sixty two cases of tibial condyle fracture treated between the period of 1994 and 2003 were evaluated. The fracture type was classified according to Schatzker. The pattern and extent of the meniscus tear were compared with the fracture classification. Statistical analysis was made with the Fisher's exact test. RESULTS: Meniscus tear was noted in 29 cases out of 62 fractures (46.8%). The twenty cases of minimally displaced fractures treated conservatively showed no meniscal tear. Of 18 cases of the most common type I fracture 2 (11.2%) had a meniscus tear. Of 16 type II fractures 12 (75%) had a meniscus tear. The type III fracture showed the highest prevalence of meniscus tear (76.9%, 10/13). There was statistically significant relationtionship between the type of fractures and the rate of meniscus tear (p<0.0001). CONCLUSION: The meniscus tear frequently occurred in tibial plateau fractures in Schatzker type II and III. Associated meniscus tears should be born in mind when those types of fracture are encountered.

A Case of Recurrent Solid Pseudopapillary Tumor of the Pancreas with Involvement of the Spleen and Kidney / Journal of the Korean Cancer Association, 대한암학회지

Solid pseudopapillary tumor of the pancreas (SPTP) is a rare primary pancreatic tumor of an unknown etiology that is usually diagnosed in adolescent girls and young women. Most SPTPs are considered to be benign and only rarely metastasize. We report here on a 27-year old woman with recurrent SPTP with involvement of both the spleen and left kidney at the time of the initial diagnosis, and with aggressive behavior. In July 1995, she was admitted with abdominal discomfort and mass. She underwent exploratory laparotomy with distal pancrea tectomy, left nephrectomy and splenectomy, and was diagnosed with SPTP with invasion to both the spleen and left kidney. In June 2001, she again presented with abdominal pain and was diagnosed as having recurrence of the tumor. She underwent mass excision and omentectomy. Then she was lost to follow-up. In November 2005, she presented once again with an abdominal mass and was diagnosed with recurred SPTP, which formed a huge intraperitoneal mass with peritoneal seeding and the tumor showed multiple metastases in the liver. She is currently being treated conservatively.

Pernicious Anemia: A Retrospective Analysis of 22 Cases / 대한혈액학회지

BACKGROUND: Pernicious anemia is the most common cause of vitamin B12 deficiency in western populations, but to date, only case reports or small series dealing with this malady have been reported in Korea. This study describes the clinical characteristics of pernicious anemia in Koreans. METHODS: We retrospectively analyzed the clinical data for twenty-two Korean patients with pernicious anemia who were diagnosed during the period from 1995 to 2004 at Chungnam National University Hospital. RESULTS: Only two patients were diagnosed before 2000. The median age of the patients was 66 years and the male/female ratio was 1.8. Anemia-associated discomfort was the most common symptom (95.5%); this was followed by gastrointestinal and neurological symptoms (77.2% and 50.0%, respectively). Autoimmune disorders were found in five patients (22.7%). The median hemoglobin level was 7.0g/dL (range: 3.1~11.8g/dL) and pancytopenia was found in 12 patients (54.5%). The median serum vitamin B12 Level was 26pg/mL (range: 12~189pg/mL). Fifteen (78.9%) and eight (42.1%) of the 19 patients who underwent tests for antibodies were positive for anti-intrinsic factor and anti-parietal cell antibody, respectively. Nineteen of 21 patients who were treated with intramuscular cobalamin recovered from their cytopenia within 3 months. The gastrointestinal symptoms resolved completely for all the patients, while neurological symptoms remained for some of the patients. CONCLUSION: This study shows that the clinical features of pernicious anemia in Koreans are not different from those of the western cases. In addition, pernicious anemia is not a rare finding in Korea.

A Case of Soft Tissue Bleeding Due to a Possible Drug Interaction between Warfarin and TS-1 / 대한혈액학회지

Warfarin is one of the most commonly used oral anticoagulant. It is well established that a wide range of drugs, including the anticancer drug 5-fluorouracil, interact with warfarin; this results in altered coagulation parameters and bleeding sequelae. To date, any drug interaction between warfarin and TS-1 has not been reported on. A 58-yr old woman visited emergency department with gross hematuria and soft tissue swelling involving her left thigh and buttock. She had been diagnosed as having advanced colon cancer (Duke's classification D); she had undergone right hemicolectomy and partial hepatectomy, and she had received 5-FU/leucovorin chemotherapy two years prior to admission. Recurrent disease was revealed in the liver and lungs, and so 6 cycles of FOLFIRI (5-FU, leucovorin and irinotecan) chemotherapy were given. Follow-up abdominal CT scan showed progressive disease and then TS-1 oral chemotherapy was started. She took warfarin 2mg per day because of partial thrombosis in the lower inferior vena cava and left ovarian vein. The initial laboratory tests revealed a prothrombin time of 120 seconds and an international normalized ratio of 35. Fresh frozen plasma and a parenteral vitamin K injection were given. After resorption of the subcutaneous hematoma, warfarin was restarted at a dose of 1mg per day. This case shows the significant increased bleeding tendency following the combined administration of warfarin and TS-1. Because of the potential severity of this interaction, close monitoring of the coagulation parameters is recommended for patients receiving warfarin together with TS-1.