Radiologic Subtypes and Treatment Outcome of Unclassifiable Type Mycobacterium avium Complex Pulmonary Disease

Methods@#Ninety-six patients with unclassifiable type MAC-PD who initiated a macrolidecontaining regimen from 2001 to 2020 were identified at a tertiary referral center in South Korea. Among these 96 patients, 1-year culture conversion rate was analyzed for 48 patients who received standard treatment (three-drug oral-antibiotic combination with or without an injectable agent) for ≥ 1 year. @*Results@#The mean age of the 96 patients was 65.4 ± 10.8 years, and 72.9% of them were male. These patients were classified into four major radiologic subtypes; the most common subtype was the focal cavity subtype (n = 31, 32.3%), followed by the focal mass or nodule (n = 23, 24.0%), consolidation upon emphysema (n = 21, 21.9%), and bronchiolitis (n = 21, 21.9%) subtypes. For the 48 patients who received standard treatment for ≥ 1 year, the overall rate of culture conversion at 1-year was 93.8%. All patients in the focal cavity subtype and focal mass or nodule subtype categories achieved 1-year culture conversion. Additionally, 1-year culture conversion rate was 92.9% in consolidation upon emphysema subtype and 75.0% in bronchiolitis subtype. @*Conclusion@#Unclassifiable type MAC-PD can be radiologically further categorized into four major radiologic subtypes. The treatment outcome of all of these subtypes seems to be favorable.

Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. @*Materials and Methods@#Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. @*Results@#A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. @*Conclusion@#Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Comparison of rivaroxaban and dalteparin for the long-term treatment of venous thromboembolism in patients with gynecologic cancers / 부인종양

Comparison of rivaroxaban and dalteparin for the long-term treatment of venous thromboembolism in patients with gynecologic cancers / 부인종양

Objectives@#Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous thromboembolism (VTE) have previously been performed. However, gynecologic cancers accounted for approximately 10% of the study populations. We compared the outcomes of patients with primary gynecological cancers who were treated for cancer-associated VTE with either rivaroxaban or dalteparin. @*Methods@#The 162 eligible patients with gynecologic cancers who were treated with either dalteparin (n=60) or rivaroxaban (n=102) were reviewed. The primary outcome was a composite event, which included recurrence or clinically relevant bleeding events during the therapeutic period. Secondary outcomes were recurrence, clinically relevant bleeding events, and mortality. @*Results@#During the therapeutic period, there were no significant differences between the groups in the proportion of composite events, recurrence, or clinically relevant bleeding. Multivariate analysis using the Cox proportional hazards model also showed no significant difference in the number of composite events and clinically relevant bleeding between the groups. In the rivaroxaban group, 44.0% of patients experienced gastrointestinal bleeding and 24.0% experienced urinary tract bleeding. In the dalteparin group, bleeding was most common in the urinary tract (44.4%) and at the injection site (22.2%). @*Conclusion@#In this study, although there were no significant differences in effectiveness or safety between the rivaroxaban and dalteparin groups, rivaroxaban use was associated with a higher rate of clinically relevant bleeding than dalteparin. Therefore, caution should be taken when prescribing rivaroxaban for gynecologic cancer-associated VTE and bleeding events should be carefully monitored.

Changes in chest X-ray findings in 1- and 2-month group after treatment initiation forsuspected pulmonary tuberculosis

Background/Aims@#Although re-evaluation of radiographic follow-up after 2 to 3 months of therapy is recommended for patients administered anti-tuberculosis medication owing to suspected pulmonary tuberculosis, reported findings are limited. Therefore, this study aimed to investigate changes in 1- and 2-month chest X-ray (CXR) findings after the treatment initiation and compared them according to the final diagnosis of tuberculosis or non-tuberculosis. @*Methods@#Patients who started anti-tuberculosis medication for suspected pulmonary tuberculosis were selected at a tertiary referral hospital in South Korea between January 2012 and December 2015. Changes in the 1- and 2-month CXR findings were classified as improved, unchanged, and aggravated. @*Results@#Among the 120 patients enrolled in the 1-month CXR group, 76 (63.3%) had the final diagnosis of tuberculosis. Comparison between the 1-month CXR changes and diagnosis showed that the final diagnosis was tuberculosis in 81.8% (45/55), 50.0% (26/52), and 38.5% (5/13) of patients whose 1-month CXR was improved, unchanged, and aggravated, respectively. In the 2-month CXR group, 167 patients were enrolled, and 139 (83.2%) of them were diagnosed with tuberculosis. Tuberculosis was the final diagnosis in 92.6% (100/108), 70.0% (35/50), and 44.4% (4/9) patients with improved, unchanged, and aggravated 2-month CXR findings, respectively. In patients with the final diagnosis of non-tuberculosis, nontuberculousmycobacteria and malignancy were the most common causes of improved and aggravated 1- and 2-month CXR findings, respectively. @*Conclusions@#Two-month CXR findings were of limited value for deciding on whether to continue anti-tuberculosis treatment. One-month CXR findings could help determine the need for further work-up.

Association between urinary sodium levels and iodine status in Korea

Background/Aims@#To evaluate the association between the urinary sodium concentration and iodine status in different age groups in Korea. @*Methods@#This nationwide, population-based, cross-sectional study used data from the Korean National Health and Nutrition Examination Survey (VI 2-3, 2014 to 2015). We included 3,645 subjects aged 10 to 75 years with normal kidney function and without a history of thyroid disease. Adequate iodine intake was defined as a urinary iodine/creatinine (I/Cr) ratio of 85 to 220 µg/g. The urinary sodium/ creatinine (Na/Cr) ratios were classified as low ( 114 mmol/g). @*Results@#The median urinary iodine concentration (UIC) was 292 µg/L (interquartile range [IQR], 157 to 672), and the median urinary I/Cr ratio was 195 µg/g (IQR, 104 to 478). Iodine deficiency ( 300 µg/L) were observed in 11.3% and 49.0% of subjects, respectively. The UIC was significantly associated with the urinary sodium concentration, and the urinary I/Cr ratio was significantly correlated with the urinary Na/Cr ratio (both p < 0.001). The distributions of UIC, urinary I/Cr ratio, and Na/Cr ratio varied among age groups. Low urinary I/Cr and Na/Cr ratios were most common in young adults (age, 19 to 29 years), while high urinary I/Cr and Na/Cr ratios were most common in elderly people (age, 60 to 75 years). @*Conclusions@#Iodine intake was significantly associated with sodium intake in the Korean population. Our study suggested that an adequately low salt intake might be helpful for preventing iodine excess in Korea.

Colonic Intramucosal Cancer in the Interposed Colon Treated with Endoscopic Mucosal Resection: A Case Report and Review of Literature

Colon interposition is a surgical procedure used for maintenance of luminal conduit after esophagectomy. Although epithelial neoplasia, such as adenoma and adenocarcinoma, may develop in the interposed colon, there are only few case reports on the condition. Due to the rarity of this condition, there is no definite consensus on recommending screening endoscopy for the early detection of neoplasia in the interposed colons. Here, we report a case of intramucosal adenocarcinoma in an interposed colon. Initial endoscopic resection for this tumor failed to accomplish complete resection. A subsequent endoscopic resection was performed 1 month later and complete resection was achieved. Based on our experience and recommendation on screening endoscopy for gastric cancer in Korea, we suggest that regular screening esophagogastroduodenoscopies should be performed following esophagectomy to detect early neoplasia in the stomach and interposed colon and avoid adverse results induced by delayed detection.

Primary Lymphoma of Pancreatic Mucosa-Associated Lymphoid Tissue (MALT) / 대한내과학회지

Primary lymphoma of pancreatic mucosa-associated lymphoid tissue (MALT) is extremely rare. Initial suspicion of primary pancreatic lymphoma is hampered by its low incidence. However, it should always be included in a differential diagnosis of pancreatic mass with unusual features, because an accurate diagnosis can avoid unnecessary surgical intervention. A 70-year-old woman presented with melena associated with a mass on the pancreatic head. Endoscopic ultrasonography-guided core-needle biopsy of the pancreatic mass revealed MALT lymphoma. The patient is currently undergoing radiation therapy. We present a case of primary lymphoma of the pancreatic MALT with a review of the literature.

Immunoglobulin G4-Related Gastric Ulcer Mimicking Advanced Stomach Cancer in a Patient with Type I Autoimmune Pancreatitis / 대한내과학회지

Type I autoimmune pancreatitis (AIP), a form of chronic pancreatitis, is included within the spectrum of immunoglobulin G4-related diseases (IgG4-RD). IgG4-RD can involve the salivary glands, bile ducts, kidneys and retroperitoneum, and the pancreas, and responds well to corticosteroid treatment. However, gastric involvement in IgG4-RD has been rarely reported. Here we report the case of a 56-year-old man with type I autoimmune pancreatitis who presented with a giant gastric ulcer mimicking advanced gastric cancer, which was subsequently determined to be IgG4-RD. Both the patient' symptoms and his ulcerative lesions in the stomach responded to steroid treatment, which obviated the need for major surgery such as gastrectomy. Our case demonstrates the importance of recognizing potential gastric involvement in IgG4-RD, especially in a patient with concurrent AIP/IgG4-RD or a history of the disease, who is evaluated for an intractable and/or atypical gastric ulcer. A prompt diagnosis and proper management will avoid unnecessary surgery.

Pancreatic Neuroendocrine Tumor with Primary Hepatic B Cell Lymphoma / 대한내과학회지

Pancreatic neuroendocrine tumors (NETs) frequently accompany metastatic lesions, and hepatic metastases are the most common of all NETs. However, another disease may also be present, potentially leading to misdiagnosis and metastasis of a NET. Clinicians should consider an active diagnostic evaluation for metastatic lesions, including liver biopsy, particularly when the hepatic lesion has distinct characteristics from the primary tumor. In our case, the patient had both a pancreatic NET and a primary hepatic lymphoma. She underwent laparoscopic distal pancreatectomy with splenectomy, and progress of the primary hepatic lymphoma was observed in the outpatient clinic.

A Study on the Efficacy and Safety of Rivaroxaban in Urologic Cancer-Associated Venous Thromboembolism

PURPOSE@#Although direct oral anticoagulants (DOACs) are recommended as an alternative to low-molecular weighted heparin for cancer-associated venous thromboembolism (VTE), there is no firm evidence on the efficacy and safety of DOACs in patients with urologic cancer. Therefore, we compared the efficacy and safety of rivaroxaban and dalteparin for treating cancer-associated VTE in urologic cancer.@*MATERIALS AND METHODS@#We reviewed the medical records of 124 eligible VTE patients with urologic cancers who were treated with dalteparin or rivaroxaban. The primary outcome was the composite event of clinically relevant bleeding or VTE recurrence. The secondary outcomes were VTE recurrence, clinically relevant bleeding events, and all-cause mortality.@*RESULTS@#During anticoagulation period, there was no significant difference in primary and secondary outcomes between the groups. In Cox proportional hazards model for composite events, although there was no statistical significance, rivaroxaban presented lower hazard ratio (HR) than dalteparin (HR, 0.472; 95% confidence interval [CI], 0.210–1.060; p=0.069 in univariate analysis; HR, 0.505; 95% CI, 0.206–1.234; p=0.134 in multivariate analysis). In clinically relevant bleeding events, there was no significance difference between rivaroxaban and dalteparin (HR, 0.568; 95% CI, 0.238–1.358; p=0.203 in univariate analysis; HR, 0.617; 95% CI, 0.232–1.636; p=0.331 in multivariate analysis).@*CONCLUSIONS@#Rivaroxaban can be regarded as a valuable option for VTE in urologic cancer. Further prospective studies are warranted to prove the safety or efficacy of rivaroxaban for treating VTE in patients with urologic cancer.

Primary Lymphoma of Pancreatic Mucosa-Associated Lymphoid Tissue (MALT) / 대한내과학회지

Primary lymphoma of pancreatic mucosa-associated lymphoid tissue (MALT) is extremely rare. Initial suspicion of primary pancreatic lymphoma is hampered by its low incidence. However, it should always be included in a differential diagnosis of pancreatic mass with unusual features, because an accurate diagnosis can avoid unnecessary surgical intervention. A 70-year-old woman presented with melena associated with a mass on the pancreatic head. Endoscopic ultrasonography-guided core-needle biopsy of the pancreatic mass revealed MALT lymphoma. The patient is currently undergoing radiation therapy. We present a case of primary lymphoma of the pancreatic MALT with a review of the literature.

Immunoglobulin G4-Related Gastric Ulcer Mimicking Advanced Stomach Cancer in a Patient with Type I Autoimmune Pancreatitis / 대한내과학회지

Type I autoimmune pancreatitis (AIP), a form of chronic pancreatitis, is included within the spectrum of immunoglobulin G4-related diseases (IgG4-RD). IgG4-RD can involve the salivary glands, bile ducts, kidneys and retroperitoneum, and the pancreas, and responds well to corticosteroid treatment. However, gastric involvement in IgG4-RD has been rarely reported. Here we report the case of a 56-year-old man with type I autoimmune pancreatitis who presented with a giant gastric ulcer mimicking advanced gastric cancer, which was subsequently determined to be IgG4-RD. Both the patient' symptoms and his ulcerative lesions in the stomach responded to steroid treatment, which obviated the need for major surgery such as gastrectomy. Our case demonstrates the importance of recognizing potential gastric involvement in IgG4-RD, especially in a patient with concurrent AIP/IgG4-RD or a history of the disease, who is evaluated for an intractable and/or atypical gastric ulcer. A prompt diagnosis and proper management will avoid unnecessary surgery.

Pancreatic Neuroendocrine Tumor with Primary Hepatic B Cell Lymphoma / 대한내과학회지

Pancreatic neuroendocrine tumors (NETs) frequently accompany metastatic lesions, and hepatic metastases are the most common of all NETs. However, another disease may also be present, potentially leading to misdiagnosis and metastasis of a NET. Clinicians should consider an active diagnostic evaluation for metastatic lesions, including liver biopsy, particularly when the hepatic lesion has distinct characteristics from the primary tumor. In our case, the patient had both a pancreatic NET and a primary hepatic lymphoma. She underwent laparoscopic distal pancreatectomy with splenectomy, and progress of the primary hepatic lymphoma was observed in the outpatient clinic.

Rivaroxaban versus Low-Molecular-Weight Heparin for Venous Thromboembolism in Gastrointestinal and Pancreatobiliary Cancer

BACKGROUND: Low-molecular-weight heparin (LMWH) is the standard treatment for venous thromboembolism (VTE) in patients with active cancer. However, use of factor Xa inhibitors, such as rivaroxaban, is increasing on the basis of limited clinical evidence. The present single-center study compared the incidence of bleeding and other treatment outcomes in gastrointestinal and pancreatobiliary cancer (GI tract cancer) patients administered rivaroxaban or LMWH for the treatment of VTE. METHODS: Retrospective data from 281 GI tract cancer patients who were treated for VTE with rivaroxaban (n = 78) or LMWH (n = 203) between 1 January 2012 and 31 December 2016, were analyzed. Primary end-point was the incidence of major and clinically relevant bleeding. Secondary outcomes included the incidence of recurrent VTE and mortality. RESULTS: Clinically relevant bleeding occurred in 19 patients (24.4%) in the rivaroxaban group and 31 (15.3%) in the LMWH group (P = 0.074). No inter-group difference was observed for rate of VTE recurrence (3.8% with rivaroxaban vs. 3.9% with LMWH; P > 0.999) or incidence of major bleeding (5.1% with rivaroxaban vs. 8.9% with LMWH; P = 0.296). Multivariate Cox proportional hazards analysis for age, cancer type, metastasis, history of chemotherapy or recent surgery, and Eastern Cooperative Oncology Group performance status revealed a 1.904-fold higher risk of bleeding with rivaroxaban than LMWH (1.031–3.516; P = 0.040). No significant inter-group difference was found in terms of hazard ratio for all-cause mortality. CONCLUSION: Compared to LMWH, rivaroxaban was associated with a higher incidence of clinically relevant bleeding in GI tract cancer patients presenting with VTE.

Identification of Mucorales From Clinical Specimens: A 4-Year Experience in a Single Institution

Mucormycosis, a fatal opportunistic infection in immunocompromised hosts, is caused by fungi belonging to the order Mucorales. Early diagnosis based on exact identification and multidisciplinary treatments is critical. However, identification of Mucorales fungi is difficult and often delayed, resulting in poor prognosis. This study aimed to compare the results of phenotypic and molecular identification of 12 Mucorales isolates collected from 4-yr-accumulated data. All isolates were identified on the basis of phenotypic characteristics such as growth rate, colony morphology, and reproductive structures. PCR and direct sequencing were performed to target internal transcribed spacer (ITS) and/or D1/D2 regions. Target DNA sequencing identified five Lichtheimia isolates, two Rhizopus microsporus isolates, two Rhizomucor pusillus isolates, one Cunninghamella bertholletiae isolate, one Mucor fragilis isolate, and one Syncephalastrum racemosum isolate. Five of the 12 (41.7%) isolates were incorrectly identified on the basis of phenotypic identification. DNA sequencing showed that of these five isolates, two were Lichtheimia isolates, one was Mucor isolate, one was Rhizomucor isolate, and one was Rhizopus microspores. All the isolates were identified at the species level by ITS and/or D1/D2 analyses. Phenotypic differentiation and identification of Mucorales is difficult because different Mucorales share similar morphology. Our results indicate that the molecular methods employed in this study are valuable for identifying Mucorales.

A Case of Misidentification of Aspergillus versicolor Complex as Scopulariopsis Species Isolated from a Homograft / 대한임상미생물학회지

We report a case of the isolation of the Aspergillus versicolor complex, initially misidentified by morphological characteristics as the Scopulariopsis species, from a homograft with a bicuspidalized pulmonary valve. An eighteen-month-old female, who had critical pulmonary stenosis, underwent pulmonary valve replacement. On postoperative day 8, she developed a fever, which did not respond to empiric broad-spectrum antibiotics. While no definitive source was identified, a filamentous fungus was isolated from the thawed homograft tissue culture prior to implantation on the operation day. The colonies were powdery green with white edges on Sabouraud dextrose agar. Microscopic examination showed septate hyphae with branched conidiophores and chains of spiny conidia, which suggested Scopulariopsis species. After direct sequencing of the internal transcribed spacer (ITS) regions, the fungus was identified as the A. versicolor complex. To our knowledge, the isolation of the A. versicolor complex from a homograft valve has not been previously described. This case shows that laboratory staff should be aware that microscopic morphology of the A. versicolor complex can resemble that of a number of other genera, including Scopulariopsis species.

Isolation and Identification of Geosmithia argillacea from a Fungal Ball in the Lung of a Tuberculosis Patient

Geosmithia argillacea, an anamorph of Talaromyces eburneus, is a thermophilic filamentous fungus that has a phenotype similar to that of the Penicillium species, except for the creamy-white colonies and cylindrical conidia. Recently, a new genus called Rasamsonia has been proposed, which is to accommodate the Talaromyces and Geosmithia species. Here, we report the first Korean case of G. argillacea isolated from a patient with a fungal ball. The patient was a 44-yr-old Korean man with a history of pulmonary tuberculosis and aspergilloma. The newly developed fungal ball in his lung was removed and cultured to identify the fungus. The fungal colonies were white and slow-growing, and the filaments resembled those of Penicillium. Molecular identification was carried out by sequencing the internal transcribed spacer (ITS) region of the 28S rDNA and the beta-tubulin genes. A comparative sequence analysis using the GenBank (http://blast.ncbi.nlm.nih.gov/) database was performed with the basic local alignment search tool (BLAST) algorithm. The results revealed a 97-100% similarity with the G. argillacea ITS sequence. This case should increase awareness among physicians about the pathogenic potential of G. argillacea in humans and help them accurately identify this fungus, because it can be easily confused with Penicillium and Paecilomyces species owing to their similar phenotypic and microscopic characteristics. A molecular approach should be employed to enable accurate identification of G. argillacea.

Subcutaneous Phaeohyphomycosis Caused by Exophiala salmonis

We report a case of subcutaneous infection in a 55-yr-old Korean diabetic patient who presented with a cystic mass of the ankle. Black fungal colonies were observed after culturing on blood and Sabouraud dextrose agar. On microscopic observation, septated ellipsoidal or cylindrical conidia accumulating on an annellide were visualized after staining with lactophenol cotton blue. The organism was identified as Exophiala salmonis by sequencing of the ribosomal DNA internal transcribed spacer region. Phaeohyphomycosis is a heterogeneous group of mycotic infections caused by dematiaceous fungi and is commonly associated with immunocompromised patients. The most common clinical manifestations of subcutaneous lesions are abscesses or cystic masses. To the best of our knowledge, this is the first reported case in Korea of subcutaneous phaeohyphomycosis caused by E. salmonis that was confirmed by molecular analysis and identification of morphological characteristics. This case suggests that E. salmonis infections are no longer restricted to fish.

Identification of Clinical Mold Isolates by Sequence Analysis of the Internal Transcribed Spacer Region, Ribosomal Large-Subunit D1/D2, and beta-Tubulin

BACKGROUND: The identification of molds in clinical laboratories is largely on the basis of phenotypic criteria, the classification of which can be subjective. Recently, molecular methods have been introduced for identification of pathogenic molds in clinical settings. Here, we employed comparative sequence analysis to identify molds. METHODS: A total of 47 clinical mold isolates were used in this study, including Aspergillus and Trichophyton. All isolates were identified by phenotypic properties, such as growth rate, colony morphology, and reproductive structures. PCR and direct sequencing, targeting the internal transcribed spacer (ITS) region, the D1/D2 region of the 28S subunit, and the beta-tubulin gene, were performed using primers described previously. Comparative sequence analysis by using the GenBank database was performed with the basic local alignment search tool (BLAST) algorithm. RESULTS: For Aspergillus, 56% and 67% of the isolates were identified to the species level by using ITS and beta-tubulin analysis, respectively. Only D1/D2 analysis was useful for Trichophyton identification, with 100% of isolates being identified to the species level. Performances of ITS and D1/D2 analyses were comparable for species-level identification of molds other than Aspergillus and Trichophyton. In contrast, the efficacy of beta-tubulin analysis was limited to genus identification because of the paucity of database information for this gene. CONCLUSIONS: The molecular methods employed in this study were valuable for mold identification, although the different loci used had variable usefulness, according to mold genus. Thus, a tailored approach is recommended when selecting amplification targets for molecular identification of molds.