Impact of Everolimus Initiation and Corticosteroid Weaning During Acute Phase After Heart Transplantation on Clinical Outcome: Data from the Korean Organ Transplant Registry (KOTRY).

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9 years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

Oral anticoagulants and concurrent rifampin administration in tuberculosis patients with non-valvular atrial fibrillation.

BACKGROUND: Evidence and guidelines for Non-vitamin K antagonist oral anticoagulants (NOACs) use when prescribing concurrent rifampin for tuberculosis treatment in patients with non-valvular atrial fibrillation (NVAF) are limited. METHODS: Using the Korean National Health Insurance Service database from January 2009 to December 2018, we performed a population-based retrospective cohort study to assess the net adverse clinical events (NACE), a composite of ischemic stroke or systemic embolism and major bleeding, of NOACs compared with warfarin among NVAF patients taking concurrent rifampin administration for tuberculosis treatment. After a propensity matching score (PSM) analysis, Cox proportional hazards regression was performed in matched cohorts to investigate the clinical outcomes. RESULTS: Of the 735 consecutive patients selected, 465 (63.3%) received warfarin and 270 (36.7%) received NOACs. Among 254 pairs of patients after PSM, the crude incidence rate of NACE was 25.6 in NOAC group and 32.8 per 100 person-years in warfarin group. There was no significant difference between NOAC and warfarin use in NACE (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.48-1.14; P = 0.172). Major bleeding was the main driver of NACE, and NOAC use was associated with a statistically significantly lower risk of major bleeding than that with warfarin use (HR, 0.63; 95% CI, 0.40-1.00; P = 0.0499). CONCLUSIONS: In our population-based study, there was no statically significant difference in the occurrence of NACE between NOAC and warfarin use. NOAC use may be associated with a lower risk of major bleeding than that with warfarin use.

Safety and efficacy of immediate heparin reversal with protamine after complex percutaneous coronary intervention.

BACKGROUND: Compared to simple percutaneous coronary intervention (PCI), complex PCI is associated with higher bleeding and thrombotic risk. No previous study has evaluated the use of protamine after PCI with contemporary technologies. This study aimed to evaluate the safety and efficacy of manual compression with and without protamine after transfemoral complex PCI. METHODS: We retrospectively analyzed 160 patients (protamine group, n = 92; non-protamine group, n = 68) who underwent complex PCI via the femoral artery. The primary outcome was a composite of in-hospital death, myocardial infarction, stent thrombosis, stroke/systemic embolism, bleeding requiring blood transfusion, and vascular access complications. RESULTS: The primary outcome was significantly lower in the protamine group than in the non-protamine group (4.3% vs. 17.6%; p = 0.006). This was driven mainly by the lower incidences of hematoma in the protamine group (3.3% vs. 13.2%, p = 0.020). Furthermore, the protamine group had a significantly shorter hospital stay than the non-protamine group (4.8 ± 3.7 days vs. 8.4 ± 8.3 days, p = 0.001). While > 90% of the patients had acute coronary syndrome, there were no incidences of myocardial infarction or stent thrombosis in either group. CONCLUSIONS: Among patients who underwent complex PCI via transfemoral access, immediate protamine administration was associated with a significantly lower rate of vascular access complications, especially hematoma, and shorter hospital stay than no protamine administration.

A Case of Heart Transplantation for Fulminant Myocarditis After ChAdOx1 nCoV-19 Vaccination.

Vaccines have become the mainstay of management against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019; COVID-19) in the absence of effective antiviral therapy. Various adverse effects of COVID-19 vaccination have been reported, including cardiovascular complications such as myocarditis or pericarditis. Herein, we describe clinical records of a 63-year woman with fulminant myocarditis following ChAdOx1 nCoV-19 vaccination that was salvaged by heart transplantation. She complained chest pain, nausea, vomiting, and fever after the second vaccination. After the heart transplantation, the patient died due to necrotizing pneumonia on the 54th day of onset. Fulminant myocarditis is very rare after ChAdOx1 nCoV-19 vaccination but can be fatal.

Quantitative analysis and contamination profiles of PCBs, OCPs, and PAHs in black-tailed gull eggs in the Republic of Korea.

The simultaneous determination of 8 polychlorinated biphenyls (PCBs), 23 organic chlorine pesticides (OCPs), and 35 polycyclic aromatic hydrocarbons (PAHs) in black-tailed gull eggs was described using ultrasound-assisted extraction and gas chromatography-tandem mass spectrometry (GC-MS/MS). The ranges of the lower limits of detection for PCBs, OCPs, and PAHs were 0.006-0.029, 0.01-0.10, and 0.01-0.20 µg kg-1, respectively. The intraday precision was in the range of 0.650-12.9% and the intraday accuracy was in the range of 86.6-113%. When the proposed method was used to analyze the target compounds in gull eggs collected from six sites in the Republic of Korea, the analytical results demonstrated concentration ranges of 113.32-394.07 µg kg-1 for total PCBs, 422.92-1082.09 µg kg-1 for total OCPs, and 134.50-231.27 µg kg-1 for total PAHs in the samples. The PCA results for PAHs and OCPs were well differentiated by sampling site, whereas those for PCBs differed little by sampling site. There were more pyrogenic PAHs in the West Sea and the South Sea with many industrial areas than in the East Sea with few industrial areas. Differences in the OCP patterns of samples from the West Sea close to China were considered to be related to the use of DDT in China until recently. PCBs were accumulated in the samples regardless of region, so there was no significant difference in the PCB patterns between the samples obtained from the three Seas.

Early experience of pump-controlled retrograde trial off for weaning from veno-arterial extracorporeal membrane oxygenation in adult patients with cardiogenic shock.

INTRODUCTION: Pump-controlled retrograde trial off has recently been introduced as an effective method for weaning from veno-arterial extracorporeal membrane oxygenation in pediatric patients. However, studies on pump-controlled retrograde trial off in adults are still lacking. Thus, this study aimed to examine the outcomes of pump-controlled retrograde trial off for weaning from veno-arterial extracorporeal membrane oxygenation in adult patients. METHODS: Between January 2018 and July 2019, 87 consecutive adult patients underwent veno-arterial extracorporeal membrane oxygenation support, of whom 47 (54.0%) underwent pump-controlled retrograde trial off for weaning from extracorporeal membrane oxygenation and were enrolled in this study. The pump-controlled retrograde trial off results, extracorporeal membrane oxygenation reapplication rate, and clinical outcomes were analyzed. RESULTS: Of the 47 patients, 38 (80.9%) were weaned from veno-arterial extracorporeal membrane oxygenation on the first attempt of pump-controlled retrograde trial off, 5 (10.6%) on the second attempt, and 4 (8.5%) on the third attempt. Three patients were converted to venovenous extracorporeal membrane oxygenation by desaturation but had stable blood pressure during pump-controlled retrograde trial off. No extracorporeal membrane oxygenation reapplication was performed within 3 days after removal, and two patients underwent veno-arterial extracorporeal membrane oxygenation during follow-up. No complications associated with pump-controlled retrograde trial off occurred during the weaning process, including thromboembolic events. Five in-hospital deaths (10.6%) occurred after weaning from extracorporeal membrane oxygenation. CONCLUSION: Pump-controlled retrograde trial off is an effective method to safely wean from veno-arterial extracorporeal membrane oxygenation in adult patients. It is simple and can be easily implemented without additional invasive procedures and may help prevent deterioration of the cardiovascular system after weaning from veno-arterial extracorporeal membrane oxygenation.

Early extubation after left ventricular assist device implantation in a patient with Duchenne muscular dystrophy: a case report.

Management of Duchenne muscular dystrophy (DMD) cardiomyopathy is increasingly important for the survival of these patients. Left ventricular assist device (LVAD) is an alternative treatment for refractory heart failure in DMD. A 20-year-old man with DMD and dilated cardiomyopathy underwent surgery for LVAD implantation. Respiratory failure may occur due to muscle weakness after surgery under general anesthesia in patients with DMD, and weaning from mechanical ventilation may be delayed or difficult. Considering the application of fast-track anesthesia (FTA), preoperative pulmonary rehabilitation which includes thoracic expansion exercise, air stacking exercise with manual resuscitation bag and manually assisted cough technique, hight-frequency chest wall oscillation, and mechanical insufflation-exsufflation was performed. We report on a patient with DMD in whom FTA and early extubation within 6 h after LVAD implantation was successfully performed without complications.

Incidence and clinical impact of early recurrence of atrial tachyarrhythmia after surgical ablation for atrial fibrillation.

BACKGROUND: Atrial tachyarrhythmias (ATAs) are common within the 3-month blanking period after catheter ablation of atrial fibrillation (AF). However, little evidence is available regarding the current guidelines on the blanking period after surgical AF ablation. We investigate the incidence and significance of early recurrence of atrial tachyarrhythmia (ERAT) and evaluate the optimal blanking period after surgical AF ablation. METHODS: Data from 259 patients who underwent surgical AF ablation from 2009 to 2016 were collected. ERAT was defined as documented ATA episodes lasting for 30 s. A multivariate Cox proportional hazard model was constructed to evaluate the role of ERAT as a predictor of late recurrences (LR) for AF. RESULTS: In total, 127 patients (49.0%) experienced their last episodes of ERAT during the first (n = 65), second (n = 14), or third (n = 48) month of the 3-month blanking period (p < .001). One year freedom from ATAs was 97.8% in patients without ERAT compared with 95.4%, 64.3%, and 8.3% in patients with ERAT in the first, second, and third months after the index procedure, respectively (p < .001). Hazard ratios of LR according to the timing of the last episode of ERAT first, second, and third months after the procedure were 2.84, 16.70, and 119.75, respectively. CONCLUSIONS: The ERAT occurred in 49.0% of patients within the first 3 months after surgical ablation. The occurrence of ERAT within 3 months after surgical AF ablation was a significant independent predictor of LR. Hence, the currently accepted 3-month blanking period may be considered for redefining in patients with AF surgical ablation.

Incidence of Cardiovascular Events and Safety Profile of Prasugrel in Korean Patients With Acute Coronary Syndrome.

BACKGROUND: Dual antiplatelet therapy is commonly used for patients with acute coronary syndrome (ACS). This study aimed to evaluate the safety and efficacy of aspirin and prasugrel at standard dosages in Korean patients using clinical outcome data.Methods and Results:For this prospective multicenter phase IV post-marketing surveillance (PMS) study, ACS patients from 29 July 2012 to 28 July 2016 were recruited. Patients received aspirin at a dose of 75-150 mg daily and a standard dose of prasugrel. Bleeding events were recorded and summarized to evaluate safety. Data on adverse events (AEs) and composite events such as cardiovascular (CV) death, myocardial infarction (MI), and stroke were recorded and summarized to assess efficacy. Of the 3,283 patients recruited, data from 3,110 and 3,044 patients were included in the safety and efficacy analyses, respectively (median treatment duration, 172 days). The most frequently reported AE was ecchymosis (2.8%). The number of patients with major bleeding was 29/3,110 (0.93%). The discontinuation rate for any reason was 12.6%. The number of cases that ended in CV death, MI, stroke, stent thrombosis, or unplanned coronary revascularization was 26/3,044 (0.85%). CONCLUSIONS: The present results are similar to those observed in clinical trials where administration of low-dose aspirin plus prasugrel was associated with a low rate of major bleeding and CV events.

Heart-lung transplantation for refractory diffuse alveolar hemorrhage supported by prolonged extracorporeal membrane oxygenation after cardiogenic shock from ST segment elevation myocardial infarction: a case report.

Diffuse alveolar hemorrhage after percutaneous coronary intervention is a rare but fatal complication. Although timely application of extracorporeal membrane oxygenator and discontinuation of antiplatelet/anticoagulation is the treatment of choice, bleeding is often irreversible. Herein, we introduce a patient with refractory diffuse alveolar hemorrhage after prolonged extracorporeal membrane oxygenator and percutaneous coronary intervention, who was eventually rescued with heart-lung transplantation.

Value of Coronary Angiography in the Cardiac Myxoma.

Preoperative coronary angiography for cardiac myxoma not only excludes coronary artery disease but also detects the artery feeding the cardiac myxoma, which has several clinical implications. In this study, we examined cardiac myxoma cases in two tertiary hospitals using coronary angiography to identify the artery feeding the myxoma. We retrospectively reviewed 42 patients with cardiac myxoma who had undergone surgical removal between July 2008 and December 2015 in two tertiary hospitals, and recorded their baseline characteristics, echocardiographic findings, and coronary angiography. Among those 42 patients, 23 (55%) had coronary angiography before surgery and in no case was significant luminal narrowing observed. In 21 of the coronary angiograms, the artery feeding the cardiac myxoma had a vascular branch (100%), clusters of tortuous vessels with contrast medium pooling (67%), an arteriocavity fistula (33%), and a mobile feeding artery (67%). No significant relationship was found between coronary artery dominance type and the origin of the artery feeding the cardiac myxoma (P = 0.362). Identification of the artery feeding the cardiac myxoma, with a distinctive vascular appearance in coronary angiography, is important for several clinical applications such as helping to diagnose cardiac myxoma and to plan the surgical approach. Clin. Anat. 33:833-838, 2020. © 2019 Wiley Periodicals, Inc.

Agreement between self and psychiatrist reporting of suicidal ideation at a Veterans Administration psychiatric emergency clinic.

BACKGROUND: With suicide rising in the United States, identifying and preventing suicides is increasingly important. To provide a valuable step toward achieving effective suicide risk assessment, this study examines the agreement between self-report measures and psychiatrist documentation of suicidal ideation and behaviors (SI) at a Veterans Administration (VA) psychiatric emergency clinic. METHODS: A total of 377 veterans presenting at a VA psychiatric emergency clinic completed a self-report survey on SI and other acute risk factors for suicidal behavior. We examined agreement between veterans' self-reported SI and psychiatrists' clinical notes regarding SI. RESULTS: A total of 199 veterans (53%) self-reported SI; 80 psychiatrist notes (21%) indicated SI. Psychiatrists and veterans differed in 44% (164/377) of cases. Among the discordant cases, the veterans' self-report was more severe than the psychiatrists' in 97% of cases. Of the 120 veterans with SI and documented as having no SI by psychiatrists, 31 (26%) reported having a suicide plan and 18 (15%) plan preparations. Findings were similar when controlling for presenting problem, current depression, presence of a standardized suicide risk assessment, psychiatrist training level, past suicide attempt, homelessness, diagnosis of personality, or substance use disorder. CONCLUSIONS: Agreement between veterans' self-reports and psychiatrists' documentation of SI was generally low, with veterans self-reporting SI significantly more often than psychiatrists documented SI in their clinical notes. This suggests that inclusion of a self-report questionnaire provides an additional source of data to complement information gleaned from the clinical interview for a more comprehensive risk assessment, but only if actually examined by the clinician.

Complications of Cardiac Perforation and Lead Dislodgement with an MRI-Conditional Pacing Lead: a Korean Multi-Center Experience.

Medtronic CapSureFix MRI 5086 pacing lead (5086; Medtronic, Inc., Minneapolis, MN, USA) has been reported to be associated with increased cardiac perforation and lead dislodgement. This study aimed to compare the incidence of cardiac perforation and lead dislodgement within 30 days after pacemaker implantation between 5086 MRI lead and previous Medtronic CapSureFix Novus 5076 non-MRI pacing lead. This was a nationwide, multicenter retrospective study in which we compared the incidence of adverse events between 277 patients implanted with 5086 lead and 205 patients implanted with 5076 lead between March 2009 and September 2014. Cardiac perforation within 30 days of pacemaker implantation occurred in 4 patients (1.4%) with the 5086 lead and in no patient with the 5076 lead (P = 0.084). Lead dislodgement occurred in 8 patients (2.9%) with the 5086 lead and in 5 patients (2.4%) with the 5076 lead (P = 0.764). On multivariate logistic regression analysis, age was significantly associated with cardiac perforation. Congestive heart failure and implantation of right atrial (RA) lead at RA free wall or septum were significant factors for the incidence of lead dislodgement and lead revision. The incidence of cardiac perforation and lead dislodgement were not statistically different between the patients with 5086 lead and the patients with 5076 lead. However, careful attention for cardiac perforation may be needed when using the 5086 MRI lead, especially in elderly patients.

Prediction of response to neoadjuvant chemotherapy in osteosarcoma using dual-phase (18)F-FDG PET/CT.

OBJECTIVES: We evaluated the ability of dual-phase (18)F-FDG PET/CT to predict the histological response after neoadjuvant chemotherapy (NAC) in osteosarcoma. METHODS: Thirty-one patients with osteosarcoma treated with NAC and surgery were prospectively enrolled. After injection of (18)F-FDG, both early (~60 min) and delayed (~150 min) PET were acquired before and after the completion of NAC. SUVmax, early/delayed SUVmax change (RImax), and early/delayed SUVmean change (RImean) of tumour were measured before (SUV1, RImax1, and RImean1) and after NAC (SUV2, RImax2, and RImean2). Then, we calculated the percentage changes between SUV1 and SUV2 (%SUV). RESULTS: Twelve patients (39%) exhibited good histological response after NAC. SUVmax, RImax, and RImean significantly decreased after NAC. Before NAC, only RImean1 predicted good histological response with the optimal criterion of < 10%, sensitivity of 92%, specificity of 57%, and accuracy of 71%. After NAC, %SUV, SUV2, and RImax2 predicted histological response. By using combined criterion of %SUV and RImax2 or SUV2 and RImean1 or SUV2 and RImax2, accuracies were 81%, 77%, and 77%, respectively. CONCLUSIONS: The histological response after NAC could be predicted by using RImean1 before the initiation of NAC in osteosarcoma. The combined use of SUV and RI values may provide a better prediction. KEY POINTS: • Pretreatment dual-phase FDG-PET was useful to predict histological response in osteosarcoma. • A combination of early and delayed PET may increase the predictive value. • Early/delayed SUV change of tumours significantly decreased after neoadjuvant chemotherapy.

Temporary hemiarthroplasty with a synthetic device in children with osteosarcoma around the knee as a bridging procedure until skeletal maturity.

BACKGROUND: We hypothesized that hemiarthroplasty with a synthetic device in skeletally immature patients with osteosarcoma around the knee would be functional due to high adaptability in the pediatric age group, and may decrease the number of surgeries until limb equalization by preserving the nearby physis. METHODS: We analyzed the outcomes of 25 hemiarthroplasties (12 distal femur, 13 proximal tibia). Average patient age was 11.8 years. We assessed (1) whether hemiarthroplasty could be considered as a viable option and could preserve growth of the nearby physis, and (2) whether these patients could reach the final goal of adult-type tumor prosthesis implantation within a preplanned number of surgeries. RESULTS: Three (12%) of 25 hemiarthroplasties showed failure. Average Musculoskeletal Tumor Society functional score of 23 patients was 25.1. Average tibial and femoral shortening for the corresponding reconstruction was 0.3 cm and 0.5 cm, respectively. In terms of number of surgeries for limb equalization, 19 patients (76%) had less, four (16%) had equal, and two (8%) had more surgeries than planned. CONCLUSIONS: Hemiarthroplasty is a sound option until skeletal maturity, allowing surgeons to choose the appropriate procedure based on the patient's growth status, and may reduce the amount of shortening by preserving nearby physis.

Usefulness of increased 18F-FDG uptake for detecting local recurrence in patients with extremity osteosarcoma treated with surgical resection and endoprosthetic replacement.

OBJECTIVE: To investigate the changes of increased F-18 fluorodeoxyglucose ((18)F-FDG) uptake around the prosthesis and its ability to differentiate local recurrence from postsurgical change after endoprosthetic replacement in extremity osteosarcoma. MATERIALS AND METHODS: A total of 355 positron emission tomography (PET)/computed tomography (CT) scans in 109 extremity osteosarcoma patients were retrospectively analyzed. All patients were followed up with (18)F-FDG PET/CT for more than 3 years after tumor resection. For semiquantitative assessment, we drew a volume of interest around the entire prosthesis of the extremity and measured the maximum standardized uptake value (SUV max). Independent samples t test was used to compare SUV max at each follow-up time. SUV max at 3 months (SUV1) and SUV max at the time of local recurrence in patients with recurrence or at the last follow-up in others (SUV2) were compared using the Mann-Whitney test. Diagnostic performances of PET parameters were assessed using ROC curve analyses. RESULTS: Nine patients (8 %) showed a local recurrence. Mean SUV max at 3, 12, 24, and 36 months was 3.1 ± 1.5, 3.8 ± 1.9, 3.6 ± 1.9, and 3.7 ± 1.5 respectively. In ROC curve analysis, the combination of SUV2 >4.6 and ΔSUV >75.0 was a more useful parameter for predicting local recurrence than SUV2 or ΔSUV alone. The sensitivity, specificity, and accuracy for identifying local recurrence were 89, 76, 77 % for SUV2; 78, 81, 81 % for ΔSUV; and 78, 94, 93 % for the combined criterion respectively. CONCLUSION: The combination of SUV2 and ΔSUV was more useful than the SUV2 or ΔSUV used alone for the prediction of local recurrence.

Clinical outcome of low-grade central osteosarcoma and role of CDK4 and MDM2 immunohistochemistry as a diagnostic adjunct.

INTRODUCTION: Low-grade osteosarcoma encompasses parosteal osteosarcoma (POS) and low-grade central osteosarcoma (LCOS), with LCOS more rare than POS. LCOS is also more likely to be misdiagnosed and inappropriately treated with an intralesional procedure, due to its misleading radiological features and the overlap of its pathological characteristics with those of benign bone tumors. Therefore, as a diagnostic adjunct for LCOS, immunohistochemical assay with murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) have been tried with controversial results. We investigated (1) the clinical course and surgical outcome of LCOS, and (2) the diagnostic role of immune-histochemical markers (CDK4, MDM2) and their correlation with clinico-radiologic findings. MATERIALS AND METHODS: We retrospectively reviewed 16 LCOS patients with regard to age, gender, tumor location, plain radiographic pattern, tumor volume, extraosseous extension, initial diagnosis, initial treatment, definitive diagnosis, definitive treatment, surgical margins, histochemical markers, and oncological outcome. RESULTS: Final survival status was continuous disease-free in 14, alive with disease in 1, and remaining 1 patient died of other cancer. Except for 1 patient who had not undergone excision of their primary lesion, no patients developed a local recurrence. Eight tumors (50%) showed diffuse immunostaining for CDK4. Three of 8 tumors labeled for CDK4 were also positive for MDM2. Six (75%) of 8 CDK4-positive tumors displayed lytic lesions on a plain radiograph; in contrast, 2 (33%) of 6 tumors showing a sclerotic pattern on a plain radiograph were positive for CDK4. CONCLUSIONS: The diagnosis of LCOS is challenging; however, if it is properly diagnosed, there is a high chance of a cure with wide excision alone. Positive immunostaining for CDK4 or MDM2 may be used as a diagnostic adjunct, although negative immunostaining cannot rule out this tumor. The clinical, radiological, and typical pathological findings are vital in raising the suspicion of this rare tumor.

Spontaneous necrosis and additional tumor necrosis induced by preoperative chemotherapy for osteosarcoma: a case-control study.

BACKGROUND: Extent of spontaneous necrosis in untreated osteosarcoma may imply tumor aggressiveness. Reports regarding this issue are scarce and there are several points to be clarified; (1) the correlation between tumor size and extent of spontaneous necrosis displayed was conflicting, (2) whether there is difference in necrosis rate between intra- and extra-medullary portion of tumor is not described, if it does, its relation with other clinico-pathologic variables, (3) in patients with surgical treatment only, >20 % spontaneous necrosis was a poor prognostic factor, however, whether that cutoff is still valid in chemotherapy cohort remains to be determined, (4) expected additional tumor necrosis by chemotherapy was made by simply comparing the necrosis rates of untreated and treated osteosarcoma cohort. METHODS: We evaluated spontaneous necrosis in 43 osteosarcoma patients (39 Stage IIB, 4 Stage III). We evaluated overall necrosis rate and separately evaluated the necrosis rate of intra- and extra-medullary portion of tumor. These results were compared with other clinico-pathologic variables. To evaluate additional tumor necrosis induced by neoadjuvant chemotherapy, case (38 without preoperative chemotherapy)-control (76 with preoperative chemotherapy) study was performed. RESULTS: The mean spontaneous necrosis rate was 23 %. Overall spontaneous necrosis was not associated with tumor volume. Necrosis rate of extramedullary tumors was higher in cases of large tumors (p = 0.02). In patients with upfront surgery followed by chemotherapy, 5-year event-free survival rate of patients with >20 and <20 % spontaneous necrosis were 82 ± 17 and 79 ± 18.5 %, respectively (p = 0.75). After chemotherapy, regardless of tumor volume and location, control group tumors showed an increase in the tumor necrosis of approximately 50 %. CONCLUSION: In chemotherapy era, the extent of spontaneous necrosis has no relation with survival. The expected additional tumor-killing effect of preoperative chemotherapy is around 50 % of initial tumor volume.

Correlation between fluid-fluid levels on initial MRI and the response to chemotherapy in stage IIb osteosarcoma.

BACKGROUND: The presence of fluid-fluid levels (FFLs) on osteosarcoma magnetic resonance imaging (MRI) is underestimated as a nonspecific finding; however, we hypothesized that FFL in conventional osteosarcoma may be indicative of chemoresistance. METHODS: In 567 stage IIB osteosarcoma patients, we evaluated the following: the incidence of FFL and their correlation with other clinicopathological variables; tumor volume change after chemotherapy and survival according to the presence of FFL; and the relationship between survival and the extent of FFL. RESULTS: One hundred eight (19 %) tumors showed FFL on initial MRI. FFL were correlated with proximal humeral location (P = 0.017), osteolytic on plain radiographs (P < 0.001), tumor enlargement after chemotherapy (P < 0.001), and poor histological response (P = 0.005). Large tumor (P < 0.01), proximal tumor location (P = 0.01), and presence of FFL (P < 0.01) were independent predictors of poor survival. Compared to the extensive FFL (more than one third of the tumor), small foci of FFL (less than one third of the tumor) showed a high tendency for tumor enlargement after chemotherapy (P < 0.001), poor histologic response (P = 0.001), and worse survival (P < 0.001). CONCLUSIONS: FFL on initial MRI could predict tumor progression after chemotherapy. Notably, tumors with small foci of FFL (less than one third of the tumor) have a high propensity for poor outcome. Patients with this finding should be considered for risk-adapted therapy.