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Castleman’s disease is a rare non-neoplastic lymphoproliferative disorder of unknown origin. It is classified into unicentric or multicentric based on its anatomical distribution. Multicentric Castleman’s disease can be subdivided according to the presence of human herpesvirus-8 (HHV-8) infection. Castleman’s disease has a rare incidence, and HHV-8-positive multicentric Castleman’s disease is even rarer. There are several types of natural course for this disease, and the rapidly progressing type can lead to death within a few weeks, emphasizing the need for prompt diagnosis and treatment. We report a recent case from Korea, presenting with multiple lymphadenopathies, confirmed as HHV-8-positive multicentric Castleman’s disease through biopsy, and achieving complete response with rituximab monotherapy.
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Objective@#Bone marrow (BM) examinations are performed to evaluate hematological abnormalities. Focusing on patients with cytopenia, we aimed to determine the circumstances under which a BM examination can assist in the diagnosis of hematologic diseases. @*Methods@#The medical records of 738 patients who underwent BM examination from March 2011 to March 2019 at Soonchunhyang University Seoul Hospital were reviewed. In total, 234 patients underwent a BM examination to identify the cause of cytopenia. Excluded from the analysis were BM examinations performed to diagnose specific diseases and evaluate disease status. @*Results@#Results suggesting suboptimal outcome (n=6) or BM invasion of solid tumors (n=13) were excluded. Immune thrombocytopenic purpura patients (n=52) with normal BM examination results were also excluded. One hundred sixty-three patients who underwent BM examination to determine the cause of cytopenia were included in the analysis. A comparison of non-specific results (n=56) to those pointing to an underlying hematologic disease (n=107) showed that patients with severe neutropenia or severe thrombocytopenia were more likely to be diagnosed with a hematologic disease. Specifically, as the number of severe cytopenias increased, the likelihood of a hematologic disease diagnosis was significantly augmented. Patients with end-stage renal disease, autoimmune disease, or liver cirrhosis were more likely to receive non-specific results. @*Conclusion@#In conclusion, seeking the underlying disease or drug should be a primary target for patients with cytopenia. In cases of severe cytopenia in more than one lineage, BM examination should be strongly considered to diagnose an underlying hematologic disease.
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Purpose@#Erlotinib has been the only targeted agent to show significantly improved outcomes in pancreatic adenocarcinoma when combined with gemcitabine. We aimed to evaluate whether the addition of oxaliplatin to a combination gemcitabine/erlotinib treatment conferred a clinical benefit in patients with locally advanced unresectable or metastatic pancreatic cancer. @*Materials and Methods@#Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T [gemcitabine 1000 mg/m2 and oxaliplatin 50 mg/m2 on day 1 (D1) and D8 plus erlotinib 100 mg daily for 3 weeks] or GT (gemcitabine 1000 mg/m2 on D1 and D8 plus erlotinib 100 mg daily for 3 weeks). The primary endpoint was the overall response rate (ORR). @*Results@#Between 2013 and 2016, 65 patients were assigned to a treatment group (33 in the GEMOX-T arm, 32 in the GT arm). The ORR was 18.2% [95% confidence interval (CI), 8.82–27.58] in the GEMOX-T arm and 6.2% (95% CI, 0.34–12.06) in the GT arm (p=0.051). The disease control rate was significantly superior in the GEMOX-T arm compared to the GT arm (72.7% vs. 43.8%, p=0.019). After a median follow-up of 19.7 months, the median progression-free survival (PFS) was 3.9 months for the GEMOX-T arm and 1.4 months for the GT arm (p=0.033). However, this did not translate to an improvement in overall survival. The most common grade 3 or higher hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). @*Conclusion@#The addition of oxaliplatin to a first-line gemcitabine/erlotinib regimen demonstrated higher response rates and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.
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Background/Aims@#A better understanding of cancer cell biology has led to the discovery and development of several new targeted agents for cancer. These drugs are widely used in cancer treatment and have good toxicity profiles. However, some patients are extremely sensitive to these drugs and can develop severe toxicities. Among the toxicities, pulmonary complications are infrequent with most targeted therapies. This study aimed to identify the radiologic pulmonary complications in various targeted therapies and to analyze the characteristics of patients with pulmonary toxicity. @*Methods@#We retrospectively reviewed the medical records and chest image findings of 644 patients who were treated with targeted antineoplastic agents at Soonchunhyang University Hospital between May 2005 and September 2014. @*Results@#Of these 644 patients, 90 (14.0%) developed pulmonary complications as noted on chest computed tomography. Among these patients, 15 (2.3%) developed drug-related pulmonary toxicities. Treatment with targeted agents was discontinued in all patients, while 11 patients were simultaneously treated with glucocorticoids. Three patients died of drug-related pulmonary toxicity. @*Conclusions@#During targeted therapy, clinicians should assess for pulmonary toxicities and symptoms that occur with dyspnea. If drug-induced pulmonary toxicities are suspected, imaging studies should be performed immediately, and the possibility of variable radiological patterns should be considered. Discontinuing the use of implicated causative agents and treatment with glucocorticoids resulted in an improvement in both symptoms and imaging findings, but some patients still experienced fatal pulmonary toxicities.
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Purpose@#Erlotinib has been the only targeted agent to show significantly improved outcomes in pancreatic adenocarcinoma when combined with gemcitabine. We aimed to evaluate whether the addition of oxaliplatin to a combination gemcitabine/erlotinib treatment conferred a clinical benefit in patients with locally advanced unresectable or metastatic pancreatic cancer. @*Materials and Methods@#Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T [gemcitabine 1000 mg/m2 and oxaliplatin 50 mg/m2 on day 1 (D1) and D8 plus erlotinib 100 mg daily for 3 weeks] or GT (gemcitabine 1000 mg/m2 on D1 and D8 plus erlotinib 100 mg daily for 3 weeks). The primary endpoint was the overall response rate (ORR). @*Results@#Between 2013 and 2016, 65 patients were assigned to a treatment group (33 in the GEMOX-T arm, 32 in the GT arm). The ORR was 18.2% [95% confidence interval (CI), 8.82–27.58] in the GEMOX-T arm and 6.2% (95% CI, 0.34–12.06) in the GT arm (p=0.051). The disease control rate was significantly superior in the GEMOX-T arm compared to the GT arm (72.7% vs. 43.8%, p=0.019). After a median follow-up of 19.7 months, the median progression-free survival (PFS) was 3.9 months for the GEMOX-T arm and 1.4 months for the GT arm (p=0.033). However, this did not translate to an improvement in overall survival. The most common grade 3 or higher hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). @*Conclusion@#The addition of oxaliplatin to a first-line gemcitabine/erlotinib regimen demonstrated higher response rates and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.
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Background/Aims@#A better understanding of cancer cell biology has led to the discovery and development of several new targeted agents for cancer. These drugs are widely used in cancer treatment and have good toxicity profiles. However, some patients are extremely sensitive to these drugs and can develop severe toxicities. Among the toxicities, pulmonary complications are infrequent with most targeted therapies. This study aimed to identify the radiologic pulmonary complications in various targeted therapies and to analyze the characteristics of patients with pulmonary toxicity. @*Methods@#We retrospectively reviewed the medical records and chest image findings of 644 patients who were treated with targeted antineoplastic agents at Soonchunhyang University Hospital between May 2005 and September 2014. @*Results@#Of these 644 patients, 90 (14.0%) developed pulmonary complications as noted on chest computed tomography. Among these patients, 15 (2.3%) developed drug-related pulmonary toxicities. Treatment with targeted agents was discontinued in all patients, while 11 patients were simultaneously treated with glucocorticoids. Three patients died of drug-related pulmonary toxicity. @*Conclusions@#During targeted therapy, clinicians should assess for pulmonary toxicities and symptoms that occur with dyspnea. If drug-induced pulmonary toxicities are suspected, imaging studies should be performed immediately, and the possibility of variable radiological patterns should be considered. Discontinuing the use of implicated causative agents and treatment with glucocorticoids resulted in an improvement in both symptoms and imaging findings, but some patients still experienced fatal pulmonary toxicities.
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Objective@#Eosinophilia in patients on hemodialysis has already been reported. It has been associated with allergy to dialyzers and exaggerated activation of complement during hemodialysis. Its etiology, however, remains unknown. In addition, there are not enough studies on eosinophilia in patients on hemodialysis in Korea. Therefore, we performed this retrospective study to find out the prevalence and possible etiologic factors of blood eosinophilia in patients undergoing hemodialysis. @*Methods@#Between January 2013 to December 2015, the patients hospitalized for hemodialysis at Soonchunhyang University Hospital and National Health Insurance Service Medical Center (Ilsan Hospital) were included in this study. Eosinophilia was defined when absolute eosinophil count was greater than 500/μL, respectively. We retrospectively reviewed the medical records of patients about parasite infection, other malignancies, and history of kidney transplantation. @*Results@#Of the 2,155 patients hospitalized for hemodialysis at two centers, 1,057 patients (49%) were found to have eosinophilia. We investigated 1,199 patients’ information (Soonchunhyang University Hospital) by the medical records. Two hundred two patients (16.8%) had no identifiable and/or possible causes. Only two patients complained of symptoms such as itching. Steroids were administered to control symptoms, and both patients had normal eosinophil levels, and steroids were discontinued. Other patients did not complain of specific symptoms associated with eosinophilia and did not take medication such as steroids. Eosinophilia was improved in 49% of patients without special treatments. @*Conclusion@#We found that the eosinophil counts in patients with end stage renal disease on hemodialysis were frequently elevated. However, in most cases, eosinophilia was not clinically relevant.
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Myeloproliferative neoplasms (MPNs) are classified as chronic myeloid leukemia (CML) and Philadelphia chromosome-negative MPN. In MPN cases, the presence of a BCR-ABL1 translocation with a coexisting mutation is exceptionally rare. Herein, we report the first documented patient with CML harboring CALR mutation in Korea. A 33-year-old woman was referred to our hospital in February 2015 with splenomegaly, leukocytosis, and thrombocytosis. She was diagnosed with CML and started receiving nilotinib. In October 2015, a major molecular response was observed, but thrombocytosis persisted. A repeat bone marrow (BM) examination revealed no specific findings. However, as thrombocytosis worsened, we changed nilotinib to dasatinib. In May 2019, owing to persistent thrombocytosis, we repeated the BM examination and found CALR mutation (15.97%) on the MPN–next generation sequencing (NGS) test. We then retrospectively performed repeat MPN-NGS testing using the BM aspirate sample obtained in 2015 and found CALR mutation (10.64%).
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OBJECTIVE@#To prevent invasive fungal disease (IFD) in acute myeloid leukemia (AML) patients, the use of posaconazole as a prophylactic antifungal agent has become standard in patients undergoing induction chemotherapy. However, there are few data comparing itraconazole and posaconazole as prophylactic antifungal agents in the real world.@*METHODS@#Patients at the Soonchunhyang University Seoul Hospital, who were treated with itraconazole or posaconazole for preventing IFD during induction chemotherapy for AML from January 2009 to April 2018, were included in the study. The collected clinical data were reviewed, and IFD was diagnosed using the revised definition of IFD from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group.@*RESULTS@#A total of 53 patients were recruited to receive either posaconazole (n=29) or itraconazole (n=24). IFD occurred in seven patients (29.1%) who used posaconazole and in six patients (20.6%) who used itraconazole for antifungal prophylaxis (P=0.475). The 100-day mortality rate was 4 (13.8%) in the posaconazole group and 2 (8.3%) in the itraconazole group (P=0.535).@*CONCLUSION@#There was no significant difference in the incidence of IFD and 100-day mortality between the patients with induction chemotherapy for newly diagnosed AML who received posaconazole and itraconazole as prophylactic antifungal agents. These results suggest that it would be worthwhile to ascertain whether posaconazole is widely known as a better approach than itraconazole as prophylactic antifungal agents in the real-world.
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PURPOSE: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. METHODS: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed. RESULTS: Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found. CONCLUSION: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.
Subject(s)
Humans , Colorectal Neoplasms , Immunohistochemistry , Lymph Nodes , Lymphangiogenesis , Models, Animal , Neoplasm Metastasis , Receptors, Vascular Endothelial Growth Factor , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor C , Vascular Endothelial Growth Factor D , Vascular Endothelial Growth Factor Receptor-3ABSTRACT
Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.
Subject(s)
Humans , Breast Neoplasms , Breast , Consensus , Drug Therapy , Injections, Spinal , Meningeal Carcinomatosis , Methotrexate , ErbB ReceptorsABSTRACT
Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.
Subject(s)
Humans , Breast Neoplasms , Breast , Consensus , Drug Therapy , Injections, Spinal , Meningeal Carcinomatosis , Methotrexate , ErbB ReceptorsABSTRACT
PURPOSE: Leukemic promyelocytes have the unique ability to undergo differentiation after exposure to retinoic acid and both differentiation and apoptosis after exposure to arsenic trioxide (ATO). Recent studies have shown that inhibition of Src family kinases (SFKs) resulted in enhancement of retinoic acid-induced myeloid differentiation. MATERIALS AND METHODS: In this study, we investigated the question of whether the SFK inhibitor PP2 enhanced the differentiation of NB4 cells when combined with ATO as well as when combined with all-trans-retinoic acid (ATRA). In addition, we attempted to determine the difference in retinoic acid-induced gene expression between cells treated with PP2 in combination with ATRA and in combination with ATO. RESULTS: SFK inhibitor PP2 induced significant enhancement of ATRA- or ATO-induced differentiation of NB4 cells. A significantly stronger synergistic effect was observed when PP2 was combined with ATRA than when combined with ATO. Flow cytometric analysis demonstrated a significant increase in CD11b-positive granulocytes up to 60.73% and 31.58%, respectively. These results were confirmed by nitroblue tetrazolium staining. These effects were not related to apoptosis. Results of Annexin-V-fluorescein staining revealed that PP2 combined with ATRA or PP2 combined with ATO did not induce apoptosis in NB4 cells. Retinoic acid-induced gene expression was different in both groups. Intercellular adhesion molecule-1 expression showed a significant increase in cells treated with PP2 in combination with ATRA, whereas cathepsin D expression showed a significant increase in cells treated with PP2 in combination with ATO. CONCLUSION: Our data showed that SFK inhibitor PP2 enhanced acute promyelocytic leukemia cell differentiation when combined with either ATRA or ATO with difference in activation of retinoic acid-induced genes.
Subject(s)
Humans , Apoptosis , Arsenic , Arsenicals , Cathepsin D , Cell Differentiation , Cell Line , Gene Expression , Granulocyte Precursor Cells , Granulocytes , Intercellular Adhesion Molecule-1 , Leukemia, Promyelocytic, Acute , Nitroblue Tetrazolium , Oxides , Phosphotransferases , Pyrimidines , src-Family Kinases , TretinoinABSTRACT
Currently, 10% of cancer chemotherapy is provided to patients by oral formulation; however, by 2013 this percentage is predicted to increase to 25%. Chemotherapy is traditionally given by injection. Oral chemotherapy has been developed as a more convenient method for treating patients. Oral chemotherapy offers many advantages including the elimination of pain often caused by injections, the lack of fees for administering intravenous drugs, more time at home for patients, and a patient's increased sense of autonomy. The role of oral chemotherapy has been expanding because of the potential advantages in convenience and better quality of life for patients, and in the cost-effectiveness of treatment as compared to intravenous chemotherapy. A number of novel oral targeted and cytotoxic chemotherapeutic agents are entering the market or are in development. Many of the agents display significant clinical activity against various cancers. The growing availability of effective oral chemotherapy treatments, especially the new class of 'targeted biologic therapies', is one of the wonderful recent advances in cancer care. This manuscript describes the progress of clinical development and efficacy of these newly developed chemotherapeutic agents.