Background
Retroperitoneal soft tissue sarcomas comprise a heterogeneous group of rare tumors of mesenchymal origin that include several well-defined histologic subtypes. In 2015, the Transatlantic ...Australasian RPS Working Group (TARPSWG) published consensus recommendations for the best management of primary retroperitoneal sarcoma (RPS). Since then, through international collaboration, new evidence and knowledge have been generated, creating the need for an updated consensus document.
Methods
The primary aim of this study was to critically evaluate the current evidence and develop an up-to-date consensus document on the approach to these difficult tumors. The resulting document applies to primary RPS that is non-visceral in origin, with exclusion criteria as previously described. The relevant literature was evaluated and an international group of experts consulted to formulate consensus statements regarding the best management of primary RPS. A level of evidence and grade of recommendation were attributed to each new/updated recommendation.
Results
Management of primary RPS was considered from diagnosis to follow-up. This rare and complex malignancy is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, and an individualized management plan should be made based on the 29 consensus statements included in this article, which were agreed upon by all of the authors. Whenever possible, patients should be enrolled in prospective trials and studies.
Conclusions
Ongoing international collaboration is critical to expand upon current knowledge and further improve outcomes of patients with RPS. In addition, prospective data collection and participation in multi-institution trials are strongly encouraged.
Protocol biopsy is a reliable method for assessing allografts status after kidney transplantation (KT). However, due to the risk of complications, it is necessary to establish indications and ...selectively perform protocol biopsies by classifying the high-risk group for early subclinical rejection (SCR). Therefore, the purpose of this study is to analyze the incidence and risk factors of early SCR (within 2 weeks) and develop a prediction model using machine learning. Patients who underwent KT at Samsung Medical Center from January 2005 to December 2020 were investigated. The incidence of SCR was investigated and risk factors were analyzed. For the development of prediction model, machine learning methods (random forest, elastic net, extreme gradient boosting XGB) and logistic regression were used and the performance between the models was evaluated. The cohorts of 987 patients were reviewed and analyzed. The incidence of SCR was 14.6%. Borderline cellular rejection (BCR) was the most common type of rejection, accounting for 61.8% of cases. In the analysis of risk factors, recipient age (OR 0.98, p = 0.03), donor BMI (OR 1.07, p = 0.02), ABO incompatibility (OR 0.15, p < 0.001), HLA II mismatch (two OR 6.44, p < 0.001), and ATG induction (OR 0.41, p < 0.001) were associated with SCR in the multivariate analysis. The logistic regression prediction model (average AUC = 0.717) and the elastic net model (average AUC = 0.712) demonstrated good performance. HLA II mismatch and induction type were consistently identified as important variables in all models. The odds ratio analysis of the logistic prediction model revealed that HLA II mismatch (OR 6.77) was a risk factor for SCR, while ATG induction (OR 0.37) was a favorable factor. Early SCR was associated with HLA II mismatches and induction agent and prediction model using machine learning demonstrates the potential to predict SCR.
The use of kidneys from donation after brain death (DBD) donors with acute kidney injury (AKI) is a strategy to expand the donor pool. The aim of this study was to evaluate how kidney transplantation ...(KT) from a donor with AKI affects long-term graft survival in various situations. All patients who underwent KT from DBD donors between June 2003 and April 2016 were retrospectively reviewed. The KDIGO (Kidney Disease: Improving Global Outcomes) criteria were used to classify donor AKI. The cohort included 376 donors (no AKI group, n = 117 31.1%; AKI group n = 259 68.9%). Death-censored graft survival was similar according to the presence of AKI, AKI severity, and the AKI trend (p = 0.929, p = 0.077, and p = 0.658, respectively). Patients whose donors had AKI who received using low dose (1.5 mg/kg for three days) rabbit anti-thymocyte globulin (r-ATG) as the induction agent had significantly superior death-censored graft survival compared with patients in that group who received basiliximab (p = 0.039). AKI in DBD donors did not affect long-term death-censored graft survival. Low-dose r-ATG may be considered as an induction immunosuppression in recipients receiving kidneys with AKI because it showed better graft survival than basiliximab.
Abstract BK virus-associated nephropathy (BKVAN) exerts a substantial impact on allograft survival, however, the absence of robust clinical evidence regarding treatment protocols adds to the ...complexity of managing this condition. This study aimed to compare the two treatment approaches. The study population consisted of patients who underwent kidney transplantation between January 2016 and June 2020 at two tertiary hospitals in Korea. Patients diagnosed with BK viremia were evaluated based on their initial viral load and the treatment methods. The ‘Reduction group’ involved dose reduction of tacrolimus while the ‘Conversion group’ included tacrolimus discontinuation and conversion to sirolimus. A total of 175 patients with an initial viral load (iVL) ≥ 3 on the log10 scale were evaluated within two iVL intervals (3–4 and 4–5). In the iVL 4–5 interval, the Reduction group showed potential effectiveness in terms of viral clearance without statistically significant differences. However, within the iVL 3–4 interval, the Reduction group demonstrated superior viral clearance and a lower incidence of biopsy-proven acute rejection (BPAR) than the Conversion group. The renal function over 12 months after BKV diagnosis showed no statistically significant difference. Reducing tacrolimus compared to converting to mTORi would be a more appropriate treatment approach for BK viral clearance in kidney transplantation. Further research is warranted in a large cohort of patients.
Recently, waist to hip ratio (WHR) has been reported to be a better indicator of predicting cardiovascular outcomes than body mass index (BMI). We evaluated the effects of pre or post-transplant ...changes of WHR or BMI on the new onset cardiovascular diseases (CVD) in recipients of kidney transplantation (KT). A total of 572 patients were enrolled from a multicenter observational cohort (KNOW-KT). Measurement of WHR and BMI was done at pre-KT, first and last visit year after KT, and the changes of these parameters and their effect on the incident CVD were analyzed. During the median follow up period of 32.73 ± 15.26 months, the new onset CVD developed in 31 out of 572 patients. The older age, diabetes mellitus and increase of WHR from pre KT or previous follow up year were found to be independent factors predicting the new onset CVD in these patients. However, baseline BMI, WHR prior to KT did not predict the incident CVD. The new metabolic burden, presented as increase of WHR in KT patients has a critical impact on the development of new onset CVD. Strategies to prevent the metabolic burden after KT might improve cardiovascular outcomes and patient's survival.
We investigated the clinical relevance of urinary cytokines/chemokines reflecting intrarenal immunologic micromilieu as prognostic markers and the optimal measurement timing after living donor kidney ...transplantation (LDKT). This prospective cohort study included 77 LDKT patients who were followed for ≥ 5 years. Patients were divided into control (n = 42) or acute rejection (AR, n = 35) group. Early AR was defined as AR occurring within 3 months. Serum and urine cytokines/chemokines were measured serially as follows: intraoperative, 8/24/72 h, 1 week, 3 months, and 1 year after LDKT. Intrarenal total leukocytes, T cells, and B cells were analyzed with immunohistochemistry followed by tissueFAXS. Urinary MCP-1 and fractalkine were also analyzed in a validation cohort. Urinary MCP-1 after one week was higher in the AR group. Urinary MCP-1, fractalkine, TNF-α, RANTES, and IL-6 after one week were significantly higher in the early AR group. Intrarenal total leukocytes and T cells were elevated in the AR group compared with the control group. Urinary fractalkine, MCP-1, and IL-10 showed positive correlation with intrarenal leukocyte infiltration. Post-KT 1 week urinary MCP-1 showed predictive value in the validation cohort. One-week post-KT urinary MCP-1 may be used as a noninvasive diagnostic marker for predicting AR after LDKT.
Acute rejection is hazardous to graft survival in kidney transplant recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of acute T cell-mediated rejection (TCMR) in urinary ...exosomes of KTRs.
Among 458 graft biopsies enrolled in a cross-sectional multicenter study, 22 patients with stable graft function (STA) who had not shown pathologic abnormality and 25 patients who diagnosed biopsy-proven TCMR were analyzed. We performed proteomic analysis using nano-ultra performance liquid chromatography-tandem mass spectrometry (nano-UPLC-MS/MS) to identify candidate biomarkers for early TCMR diagnosis on urinary exosomes. We confirmed the protein levels of each candidate biomarker by western blot analysis.
A total of 169 urinary exosome proteins were identified by nano-UPLC-MS/MS. Forty-six proteins showed increased expression in STA patients, while 17 proteins were increased in TCMR patients. Among them, we selected five proteins as candidate biomarkers for early diagnosis of TCMR according to significance, degree of quantity variance, and information from the ExoCarta database. We confirmed the proteomic expression levels of five candidate biomarkers by western blot analysis in each patient. Of all candidate biomarkers, tetraspanin-1 and hemopexin were significantly higher in TCMR patients (STA:TCMR ratio = 1:1.8, P = 0.009, and 1:3.5, P = 0.046, respectively).
Tetraspanin-1 and hemopexin were detected in KTR urine and could act as potential diagnostic proteins for TCMR.
Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal ...glycemia without exogenous insulin after transplantation in primate models or on the relationship between rejection and islet amyloid polypeptide (IAPP) expression. We evaluated the dose (10,000, 20,000, and > 25,000 islet equivalents (IEQ)/kg) needed to achieve normal glycemia without exogenous insulin after transplantation using eleven cynomolgus monkeys, and we analyzed the characteristics exhibited in the islets after transplantation. 10,000 IEQ/kg (N = 2) failed to control blood glucose level, despite injection with the highest dose of exogenous insulin, and 20,000 IEQ/kg group (N = 5) achieved unstable control, with a high insulin requirement. However, 25,000 IEQ/kg (N = 4) achieved normal glycemia without exogenous insulin and maintained it for more than 60 days. Immunohistochemistry results from staining islets found in liver biopsies indicated that as the number of transplanted islets decreased, the amount of IAPP accumulation within the islets increased, which accelerated CD3
T cell infiltration. In conclusion, the optimal transplantation dose for achieving a normal glycemia without exogenous insulin in our cynomolgus monkey model was > 25,000 IEQ/kg, and the accumulation of IAPP early after transplantation, which depends on the transplanted islet dose, can be considered one factor in rejection.
QuantiFERON-TB Gold Plus (QFT-Plus) is a new-generation QuantiFERON-TB Gold In-Tube (QFT-GIT) assay which has two antigen-coated tubes called TB1, which contains long peptides derived from ESAT-6 and ...CFP-10, and TB2, which contains the same components as TB1 and additional short peptides which potentially stimulate CD8
T cells through the presentation of major histocompatibility complex class I. This is the first study to compare QFT-Plus and QFT-GIT for use in the diagnosis of latent tuberculosis infection (LTBI) among immunocompromised patients in the Republic of Korea. Among 317 consecutive patients who underwent screening for LTBI before solid organ or hematopoietic stem cell transplantation and tumor necrosis factor alpha inhibitor treatment, LTBI was identified in 92 (29.0%) and 88 (27.8%) patients by QFT-GIT and QFT-Plus, respectively. The rate of concordance between QFT-GIT and QFT-Plus was 93.7% (κ value, 0.860), and the indeterminate rate (3.2%) was similar between QFT-GIT and QFT-Plus. Of 20 (6.3%) samples with discordant results, 11 (55.0%) and 7 (35.0%) were positive by QFT-GIT alone and QFT-Plus alone, respectively, and 2 (15.0%) were indeterminate by each assay. The interferon gamma level in samples with discordant results ranged from 0.39 to 1.10 IU/ml, except for one sample, in which the gamma interferon level was 2.97 IU/ml only in TB2. Conclusively, there was a high degree of agreement between the results of QFT-GIT and QFT-Plus for the screening of immunocompromised patients for LTBI. The reactivity in TB2 contributed substantially to the difference between QFT-GIT and QFT-Plus, particularly in solid organ transplant candidates. The significance of the discrete responses in TB1 and TB2 of QFT-Plus needs to be explored further by means of an immunological and clinical approach in different patient groups and clinical settings.
Abstract
While
18
F-fluorodeoxyglucose positron emission tomography/computed tomography (
18
F-FDG PET/CT) has been investigated in extremity sarcomas, there is no evidence on its usefulness in ...retroperitoneal sarcoma. This study was designed to evaluate the usefulness of
18
F-FDG PET/CT in predicting aggressiveness of retroperitoneal liposarcoma. Patients experienced surgery for retroperitoneal liposarcoma from November 2007 to February 2018 and underwent preoperative
18
F-FDG PET/CT were included. Preoperative maximum standardized uptake value (SUV
max
) was calculated. To evaluate the predictability of SUV
max
for Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade 3, receiver operating characteristics (ROC) curve analysis was performed. To analyze whether SUV
max
can be a risk factor for prognosis, multivariable Cox regression was performed including potential risk factors regarding operation and histopathology. A total of 133 patients were included. ROC curve showed area under the curve of 0.877 (P < 0.001), with a cut-off point of 4.5 SUV
max
showing 85.7% sensitivity and 78.3% specificity. Cox analyses showed that SUV
max
> 4.5 was a significant factor for recurrence-free survival (HR = 2.148, CI 1.301–3.546, P = 0.003) and overall survival (HR = 5.052, CI 1.854–13.766, P = 0.002). SUV
max
is highly predictive of FNCLCC grade 3 and SUV
max
> 4.5 can be used as a prognostic factor before obtaining the histopathology.
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