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Background/Aims@#Optimal risk stratification based on simplified geriatric assessment to predict treatment-related toxicity and survival needs to be clarified in older patients with diffuse large B-cell lymphoma (DLBCL). @*Methods@#This multicenter prospective cohort study enrolled newly diagnosed patients with DLBCL (≥ 65 yr) between September 2015 and April 2018. A simplified geriatric assessment was performed at baseline using Activities of Daily Living (ADL), Instrumental ADL (IADL), and Charlson’s Comorbidity Index (CCI). The primary endpoint was event-free survival (EFS). @*Results@#The study included 249 patients, the median age was 74 years (range, 65-88), and 125 (50.2%) were female. In multivariable Cox analysis, ADL, IADL, CCI, and age were independent factors for EFS; an integrated geriatric score was derived and the patients stratified into three geriatric categories: fit (n = 162, 65.1%), intermediate-fit (n = 25, 10.0%), and frail (n = 62, 24.9%). The established geriatric model was significantly associated with EFS (fit vs. intermediate-fit, HR 2.61, p < 0.001; fit vs. frail, HR 4.61, p < 0.001) and outperformed each covariate alone or in combination. In 87 intermediate-fit or frail patients, the relative doxorubicin dose intensity (RDDI) ≥ 62.4% was significantly associated with worse EFS (HR, 2.15, 95% CI 1.30–3.53, p = 0.002). It was related with a higher incidence of grade ≥ 3 symptomatic non-hematologic toxicities (63.2% vs. 27.8%, p < 0.001) and earlier treatment discontinuation (34.5% vs. 8.0%, p < 0.001) in patients with RDDI ≥ 62.4% than in those with RDDI < 62.4%. @*Conclusions@#This model integrating simplified geriatric assessment can risk-stratify older patients with DLBCL and identify those who are highly vulnerable to standard dose-intensity chemoimmunotherapy.
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Background/Aims@#Although rituximab, an antiCD20 monoclonal antibody, has dramatically improved the clinical outcomes of diffuse large B-cell lymphoma, rituximab resistance remains a challenge. @*Methods@#We developed a rituximab-resistant cell line (RRCL) by sequential exposure to gradually increasing concentrations of rituximab in a rituximab-sensitive cell line (RSCL). When the same dose of rituximab was administered, RRCL showed a smaller decrease in cell viability and apoptosis than RSCL. To determine the differences in gene expression between RSCL and RRCL, we performed next-generation sequencing. @*Results@#In total, 1,879 differentially expressed genes were identified, and in the over-representation analysis of Consensus-PathDB, mitogen-activated protein kinase (MAPK) signaling pathway showed statistical significance. MAPK13, which encodes the p38δ protein, was expressed more than four-fold in RRCL. Western blot analysis revealed that phosphop38 expression mainwas increased in RRCL, and when p38 inhibitor was administered, phosphop38 expression was significantly decreased. Therefore, we hypothesized that p38 MAPK activation was associated with rituximab resistance. Previous studies have suggested that p38 is associated with NF-κB activation. Deferasirox has been reported to inhibit NF-κB activity and suppress phosphorylation of the MAPK pathway. Furthermore, it also has cytotoxic effects on various cancers and synergistic effects in overcoming drug resistance. In this study, we confirmed that deferasirox induced dose-dependent cytotoxicity in both RSCL and RRCL, and the combination of deferasirox and rituximab showed a synergistic effect in RRCL at all combination concentrations. @*Conclusions@#We suggest that p38 MAPK, especially p38δ, activation is associated with rituximab resistance, and deferasirox may be a candidate to overcome rituximab resistance.
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The fifth edition of the WHO classification (2022 WHO) and the International Consensus Classification (2022 ICC) of myeloid neoplasms have been recently published. We reviewed the changes in the diagnosis distribution in patients with MDS with excess blasts (MDS-EB) or AML using both classifications. Forty-seven patients previously diagnosed as having AML or MDS-EB with available mutation analysis data, including targeted next-generation and RNA-sequencing data, were included. We reclassified 15 (31.9%) and 27 (57.4%) patients based on the 2022 WHO and 2022 ICC, respectively. One patient was reclassified as having a translocation categorized as a rare recurring translocation in both classifications. Reclassification was mostly due to the addition of mutation-based diagnostic criteria (i.e., AML, myelodysplasia-related) or a new entity associated with TP53 mutation. In both classifications, MDS diagnosis required the confirmation of multi-hit TP53 alterations. Among 14 patients with TP53 mutations, 11 harbored multi-hit TP53 alterations, including four with TP53 mutations and loss of heterozygosity. Adverse prognosis was associated with multi-hit TP53 alterations (P=0.009) in patients with MDS-EB, emphasizing the importance of detecting the mutations at diagnosis. The implementation of these classifications may lead to the identification of different subtypes from previously heterogeneous diagnostic categories based on genetic characteristics.
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Attrition is the loss of tooth hard tissue due to contact between teeth, and in severe cases, dentin is exposed, accompanied by selective corrosion and excessive wear of teeth, which is called cupping. If these lesions are left untreated, the size of the lesion gradually increases, breaking the unsupported enamel, resulting in a decrease in aesthetics and chewing function. In this case report, patients with cupping and enamel fracture due to severe attrition were directly restored using a resin with soft properties containing organic fillers. In the follow-up observation six years later, most of the filling of the occlusal surface was eliminated, but the filling on the buccal surfaces remained relatively intact, and it was confirmed that this type of resin was suitable for the area where the occlusal force was relatively weak rather than the area where the occlusal force was greatly applied.
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Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.
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Immune thrombocytopenia (ITP) is isolated thrombocytopenia characterized by autoimmune-mediated disruption of platelet without other etiologies. Treatments for chronic ITP consist of corticosteroids, intravenous immunoglobulins, anti-D immunoglobulin, rituximab, thrombopoietin receptor agonists, immunosuppressants and splenectomy. Although current therapies are effective in over two-thirds of patients, some patients are refractory to therapies or fail to achieve long-term responses. Recently, great advance has been made in identifying various mechanisms involved in ITP pathogenesis, and new treatments targeting these pathways are being developed. Novel agents such as splenic tyrosine kinase inhibitor, Bruton kinase inhibitor, plasma cell targeting therapies, neonatal Fc receptor inhibitor, platelet desialylation inhibitor, and inhibition of the classical complement pathway are expected to be effective for ITP treatment. This review summarizes current strategies and emerging therapies of ITP.
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Background@#Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea. @*Methods@#The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%). @*Results@#The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P ＜0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively. @*Conclusion@#This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.
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Background/Aims@#Relatively little data are available on how the response to the coronavirus disease 2019 (COVID-19) pandemic has affected treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. We aimed to determine the effect of COVID-19 countermeasures on treatment outcomes in this patient population. @*Methods@#We retrospectively analyzed data on patients treated for lymphoma or multiple myeloma in two tertiary hospitals in Seoul. Patients were divided into two groups: group 1 included patients who received chemotherapy between September and December 2019 (the control period), and group 2 included patients who received chemotherapy between September and December 2020 (the study period). Countermeasures to COVID-19 were applied to the patients in group 2. The countermeasures implemented included mask wearing and regular handwashing at home and in hospital; COVID-19 risk assessments on all hospital visitors; and pre-emptive COVID-19 screening for all newly hospitalized patients and their resident guardians. @*Results@#No differences in treatment outcomes, including treatment response, incidence and duration of neutropenia or neutropenic fever, delays in chemotherapy, or number of deaths during chemotherapy, were observed between the g roups. None of the patients in group 2 tested positive for COVID-19, and there were no COVID-19-related deaths during the study period. @*Conclusions@#Countermeasures to COVID-19 did not affect treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. Data on the effect of countermeasures to COVID-19 on treatment outcomes should continue to be analyzed to ensure that treatment outcomes are not adversely affected.
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Nilotinib is used for treating patients with imatinib-sensitive or -resistant chronic myeloid leukemia (CML); however, nilotinib-resistant cases have been observed in recent years. In addition, a considerable number of patients receiving nilotinib developed diabetes. Metformin is a front-line drug for the treatment of type 2 diabetes, and several studies have shown that diabetes patients treated with metformin have reduced incidence of cancer. This study aimed to define the effect of metformin on CML cells to determine whether metformin overcomes nilotinib resistance, and to identify novel targets for the treatment of nilotinib resistance. Methods: We observed the effects of metformin and nilotinib on K562 and KU812 human CML cell lines. Nilotinib-resistant CML cell lines were generated by exposing cells to gradually increasing doses of nilotinib. Then, we investigated the driving force that makes resistance to nilotinib and the effect of metformin on the driving force. Results: Sub-toxic doses of metformin enhanced nilotinib efficacy by reducing Bcl-xL expression, which induces apoptosis in CML cells. Next, we generated nilotinib-resistant K562 and KU812 cell lines that overexpressed the c-Jun N-terminal kinase (JNK) gene. JNK silencing by a JNK inhibitor restored sensitivity to nilotinib. Furthermore, metformin was effective in decreasing phosphorylated JNK levels, restoring nilotinib sensitivity. Combined treatment with nilotinib and metformin was more effective than combined treatment with nilotinib and a JNK inhibitor in terms of cell proliferation inhibition. Conclusions: This study suggested that combination therapy with metformin and nilotinib may have clinical benefits of enhancing antileukemia efficacy and overcoming resistance to nilotinib.
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Background@#To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. @*Methods@#Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. @*Results@#A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). @*Conclusion@#Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.
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Background@#To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. @*Methods@#Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. @*Results@#A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). @*Conclusion@#Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.
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Background/Aims@#Patients with pancreatic cancer (PC) generally have poor clinical outcomes. Early determination of their prognosis is crucial for developing a therapeutic strategy. Recently, various inflammatory markers have been validated as prognostic indicators for many cancers, including PC. However, few studies have evaluated these markers together. Thus, the purpose of this study was to comprehensively evaluate the value of inflammatory markers as prognostic indicators in patients with advanced PC treated with gemcitabine-based chemotherapy as the first line regimen. @*Methods@#This was a single-center retrospective study evaluating 302 patients with advanced PC who began first line treatment between November 2004 and August 2016. These patients were monitored until June 2017. Survival rates were assessed with univariate and multivariate analyses. Continuous variables were separated using the normal range or ideal cut-off levels determined by receiver operating curve analyses. @*Results@#Among inflammatory markers evaluated, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) to albumin ratio (CRP-albumin ratio) were independent predictors of overall survival (hazard ratio, 1.712, 1.345, and 1.454, respectively). Difference in survival rates was significant (p < 0.001) among three groups divided by the number of marker-related risks. @*Conclusions@#Baseline inflammatory markers including NLR, PLR, and CRP-albumin ratio are useful in predicting survival rates in patients with PC. Combining these three markers is proven to be valuable.
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Background/Aims@#The diagnosis of immune thrombocytopenia (ITP) is based on clinical manifestations and there is no gold standard. Thus, even hematologic malignancy is sometimes misdiagnosed as ITP and adequate treatment is delayed. Therefore, novel diagnostic parameters are needed to distinguish ITP from other causes of thrombocytopenia. Immature platelet fraction (IPF) has been proposed as one of new parameters. In this study, we assessed the usefulness of IPF and developed a diagnostic predictive scoring model for ITP. @*Methods@#We retrospectively studied 568 patients with thrombocytopenia. Blood samples were collected and IPF quantified using a fully-automated hematology analyzer. We also estimated other variables that could affect thrombocytopenia by logistic regression analysis. @*Results@#The median IPF was significantly higher in the ITP group than in the non-ITP group (8.7% vs. 5.1%). The optimal cut-off value of IPF for differentiating ITP was 7.0%. We evaluated other laboratory variables via logistic regression analysis. IPF, hemoglobin, lactate dehydrogenase (LDH), and ferritin were statistically significant and comprised a diagnostic predictive scoring model. Our model gave points to each of variables: 1 to high hemoglobin (> 12 g/dL), low ferritin (≤ 177 ng/ mL), normal LDH (≤ upper limit of normal) and IPF ≥ 7 and < 10, 2 to IPF ≥ 10. The final score was obtained by summing the points. We defined that ITP could be predicted in patients with more than 3 points. @*Conclusions@#IPF could be a useful parameter to distinguish ITP from other causes of thrombocytopenia. We developed the predictive scoring model. This model could predict ITP with high probability.
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Background/Aims@#Various preoperative screening tests, such as platelet count, prothrombin time, activated partial thromboplastin time, and bleeding time, have been widely used to evaluate the risk of bleeding during surgery. Use of platelet function analyzer (PFA)-100/200 for assessing platelet function instead of bleeding time is increasing. However, its role in predicting the perioperative risk of bleeding remains controversial. @*Methods@#Data of 703 patients who underwent surgery under general anesthesia were retrospectively analyzed. Preoperative platelet function was measured using PFA-200 system and the association with intraoperative bleeding was assessed. Additionally, other variables that could affect PFA-200 results were assessed by logistic regression analysis. @*Results@#Collagen/epinephrine (COL/EPI) test was prolonged in 199/703 (28.3%) patients (EPI group), while 99/212 (46.7%) patients showed COL/adenosine diphosphate test abnormalities. Bleeding over 300 mL during surgery occurred in 14.3% and 20.1% of patients in the normal and EPI groups, respectively (p = 0.058). In addition, red blood cell transfusion within 72 hours after surgery rate was significantly higher in the EPI group than in the normal group (31.7% vs. 23.4%,p= 0.024). In multivariate logistic analysis, prolongation closure time with COL/EPI (p = 0.068) was marginally associated with risk of bleeding during surgery. Furthermore, PFA-200 results were influenced by various factors, such as nonsteroidalanti-inflammatory drug use, blood group, hematocrit, and time of blood collection. @*Conclusions@#Preoperative PFA-200 test may be helpful in predicting the risk of perioperative bleeding. However, its results should be carefully interpreted becausethey are affected by several factors.
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Purpose@#Allogeneic hematopoietic stem cell transplantation (HSCT) with optimal conditioning has helped better long-term survival in acute lymphoblastic leukemia (ALL). This study investigated the efficacy and safety of reduced-intensity conditioning (RIC) with busulfan and fludarabine in adult ALL patients unfit for myeloablation. @*Materials and Methods@#Records of 78 patients who underwent HSCT with RIC consisting of 3.2 mg/kg/day of busulfan for 2 or 3 days and 30 mg/m2/day of fludarabine for 5 or 6 days were analyzed. @*Results@#The median age at diagnosis was 49 years. Over a median follow-up of 22 months, 2-year estimates of relapse-free survival (RFS) and overall survival were 57.4% and 68.7%, respectively. Multivariate analysis showed a trend of improved RFS in patients with chronic graft-versus-host disease (GVHD) (hazard ratio, 0.53; 95% confidence interval, 0.26–1.08; p=0.080). The cumulative incidences of relapse and non-relapse mortality were 42.9% and 19.6%, respectively and one case of central nervous system relapse was noted. No hepatic veno-occlusive disease was reported. Grade II–IV acute GVHD and any grade chronic GVHD occurred in 21.1% and 41.7%, respectively. @*Conclusion@#RIC with busulfan and fludarabine is an effective and safe conditioning regimen for adult ALL patients unfit for myeloablation.
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BACKGROUND/AIMS@#Bortezomib plus melphalan-prednisone (VMP) is a standard treatment for multiple myeloma, particularly for patients who are ineligible for high-dose therapy. However, early discontinuation or treatment modification is often needed owing to adverse events. The aim of this study was to investigate the clinical outcomes of modifying the dose of melphalan-prednisone (MP) in patients receiving VMP.@*METHODS@#We examined 67 patients who received a modified dose of MP, and 38 patients who received the regularly planned dose of MP. We then analyzed clinical differences between the groups.@*RESULTS@#Although there was no difference in the proportion of discontinuation due to adverse events between dose groups, more patients in the planned-dose group experienced earlier discontinuation in general. The overall response rate (ORR) was 81.0% and complete response (CR) rate was 30.5%. After a median 15.7 months of follow-up, the median progression-free survival (PFS) and overall survival (OS) were 25.0 and 47.8 months, respectively. There was no significant difference in the ORR, CR, PFS, and OS of the two dose groups. A median of four cycles were delivered, and the median cumulative bortezomib dose was 41.6 mg/m². The median PFS in patients with doses ≥ 41.6 mg/m² was longer than that in patients with doses < 41.6 mg/m² (35.1 months vs. 9.6 months). However, when MP was < 50% of the planned dose, PFS and OS were poor.@*CONCLUSIONS@#Modifying the dose of MP might be a feasible and effective therapeutic approach for multiple myeloma patients receiving VMP treatment.
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BACKGROUND/AIMS: The staging work-up for patients with non-Hodgkin's lymphoma includes bone marrow aspiration and biopsy. Consistent results of both procedures can clarify the diagnosis. However, no clear guidelines have been established regarding positive results for bone marrow aspiration alone. The aim of this study was, therefore, to analyze the overall survival (OS) for the clinical diagnoses of these patients using morphological methods. METHODS: We performed a retrospective analysis of patients who were consecutively enrolled in the Korea University Lymphoma Registry from 1991 to 2016. OS was compared according to the bone marrow group: without bone marrow involvement (BMA−/BMBx−), with positive results for aspiration and negative results for biopsy (BMA+/BMBx−), and with bone marrow involvement in biopsy (BMBx+). OS was assessed using the Kaplan-Meier method and multivariate analysis. RESULTS: Of 1,735 patients, 1,326 were analyzed and 409 were excluded. In the Kaplan-Meier survival analysis, OS was significantly worse for patients in the BMBx+ group compared with those in the BMA−/BMBx− group (p < 0.001). However, there was no significant difference in OS between patients in the BMA+/BMBx− group and those in other groups (vs. BMA−/BMBx−, p = 0.163; BMBx+, p = 0.292). In multivariate analysis, by adjusting survival-related variables, the BMA+/BMBx− group showed marginal significance compared to the BMA−/BMBx− group (p = 0.081), and showed significance in the subgroup of indolent non-Hodgkin's lymphoma patients (p = 0.003). CONCLUSIONS: This study suggested that even if there are positive results in bone marrow aspiration alone in patients with non-Hodgkin lymphoma, attention to patient characteristics, involving significance as a poor prognosis for OS, is required.
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Humanos , Biópsia , Medula Óssea , Diagnóstico , Coreia (Geográfico) , Linfoma , Linfoma não Hodgkin , Métodos , Análise Multivariada , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND/AIMS@#The staging work-up for patients with non-Hodgkin's lymphoma includes bone marrow aspiration and biopsy. Consistent results of both procedures can clarify the diagnosis. However, no clear guidelines have been established regarding positive results for bone marrow aspiration alone. The aim of this study was, therefore, to analyze the overall survival (OS) for the clinical diagnoses of these patients using morphological methods.@*METHODS@#We performed a retrospective analysis of patients who were consecutively enrolled in the Korea University Lymphoma Registry from 1991 to 2016. OS was compared according to the bone marrow group: without bone marrow involvement (BMA−/BMBx−), with positive results for aspiration and negative results for biopsy (BMA+/BMBx−), and with bone marrow involvement in biopsy (BMBx+). OS was assessed using the Kaplan-Meier method and multivariate analysis.@*RESULTS@#Of 1,735 patients, 1,326 were analyzed and 409 were excluded. In the Kaplan-Meier survival analysis, OS was significantly worse for patients in the BMBx+ group compared with those in the BMA−/BMBx− group (p < 0.001). However, there was no significant difference in OS between patients in the BMA+/BMBx− group and those in other groups (vs. BMA−/BMBx−, p = 0.163; BMBx+, p = 0.292). In multivariate analysis, by adjusting survival-related variables, the BMA+/BMBx− group showed marginal significance compared to the BMA−/BMBx− group (p = 0.081), and showed significance in the subgroup of indolent non-Hodgkin's lymphoma patients (p = 0.003).@*CONCLUSIONS@#This study suggested that even if there are positive results in bone marrow aspiration alone in patients with non-Hodgkin lymphoma, attention to patient characteristics, involving significance as a poor prognosis for OS, is required.
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Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society of Thyroid Radiology (KSThR) developed recommendations for the optimal use of radiofrequency ablation for thyroid tumors in 2012. As new meaningful evidences have accumulated, KSThR decided to revise the guidelines. The revised guideline is based on a comprehensive analysis of the current literature and expert consensus.
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Humanos , Comitês Consultivos , Ablação por Cateter , Consenso , Glândula Tireoide , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , UltrassonografiaRESUMO
No abstract available.