Indeterminate pulmonary nodules are not associated with worse overall survival in Ewing Sarcoma

AimLung metastases are a negative prognostic factor in Ewing sarcoma, however, the incidence and significance of sub-centimetre pulmonary nodules at diagnosis is unclear. The aims of this study were to (1): determine the incidence of indeterminate pulmonary nodules (IPNs) in patients diagnosed with Ewing sarcoma (2); establish the impact of IPNs on overall and metastasis-free survival and (3) identify patient, oncological and radiological factors that correlate with poorer prognosis in patients that present with IPNs on their staging chest CT.Materials & methodsBetween 2008 and 2016, 173 patients with a first presentation of Ewing sarcoma of bone were retrospectively identified from an institutional database. Staging and follow-up chest CTs for all patients with IPN were reviewed by a senior radiologist. Clinical and radiologic course were examined to determine overall- and metastasis-free survival for IPN patients and to identify demographic, oncological or nodule-specific features that predict which IPN represent true lung metastases.ResultsFollowing radiologic re-review, IPN were found in 8.7% of patients. Overall survival for IPN patients was comparable to those with a normal staging chest CT (2-year overall survival of 73.3% [95% CI 43.6–89] and 89.4% [95% CI 81.6–94], respectively; p = 0.34) and was significantly better than for patients with clear metastases (46.0% [95% CI 31.9–59]; p < 0.0001). Similarly, there was no difference in metastasis-free survival between ‘No Metastases’ and ‘IPN’ patients (p = 0.16). Lung metastases developed in 40% of IPN patients at a median 9.6 months. Reduction of nodule size on neoadjuvant chemotherapy was associated with worse overall survival in IPN patients (p = 0.0084).ConclusionIPN are not uncommon in patients diagnosed with Ewing sarcoma. In this study, we were unable to detect a difference in overall- or metastasis-free survival between patients with IPN at diagnosis and patients with normal staging chest CTs.     

Pharmacokinetic study of the oral fluorouracil antitumor agent S‐1 in patients with impaired renal function

Although dose reduction of S‐1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5‐fluorouracil, 5‐chloro‐2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S‐1 in patients with renal impairment. We classified patients receiving S‐1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S‐1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m²), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m²), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m²), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m²). Those in cohorts 3 and 4 treated with an adjusted dose of S‐1 showed a similar area under the curve for 5‐fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S‐1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S‐1 in patients with impaired renal function using eGFR is appropriate and safe.     

D6S1043、D12S391基因座与主动攻击行为的关联研究

目的:探讨D6S1043、D12S391基因座的基因多态性对主动攻击行为的影响。方法:应用聚合酶链反应技术结合毛细管电泳法对114例男性主动攻击行为者(研究组)及120名健康男性(对照组)进行D6S1043、D12S391基因座的基因型及等位基因检测,分析D6S1043、D12S391基因座多态性与主动攻击行为的相关性。结果:研究组D6S1043基因座中12~19基因型频率(13.16%)明显高于对照组(1.67%)(P0.05);两组等位基因频率差异无统计学意义;两组D12S391基因座的基因型及等位基因频率差异无统计学意义。结论:D6S1043基因座中12~19基因型可能主动攻击行为有关。     

First Japanese autopsy case showing LRRK2 mutation G2019S and TDP-43 proteinopathy

This is the first Japanese autopsy case of Leucine-rich repeat kinase 2 (LRRK2) G2019S mutation with atypical TDP43 proteinopathy. Our case is important that presented clinically dysphagia and pathologically TDP-43 proteinopathy. TDP43 may play an important role of clinical presentation with LRRK2 G2019S mutation carriers.     

Secretion,blood levels and cutaneous expression of TL1A in psoriasis patients

TL1A is a TNF‐like cytokine which has been shown to co‐stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF‐α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti‐TNF‐α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large‐scale studies are warranted to investigate TL1A as a biomarker.