Longitudinal associations of lifetime adiposity with leukocyte telomere length and mitochondrial DNA copy number

Adiposity may cause adverse health outcomes by increasing oxidative stress and systemic inflammation, which can be reflected by altered telomere length (TL) and mitochondrial DNA copy number (mtCN) in peripheral blood leukocytes. However, little is known about the influence of lifetime adiposity on TL and mtCN in later life. This study was performed to investigate the associations of lifetime adiposity with leukocyte TL and mtCN in 9613 participants from the Nurses’ Health Study. A group-based trajectory modelling approach was used to create trajectories of body shape from age 5 through 60 years, and a genetic risk score (GRS) was created based on 97 known adiposity susceptibility variants. Associations of body shape trajectories and GRS with dichotomized TL and mtCN were assessed by logistic regression models. After adjustment for lifestyle and dietary factors, compared with the lean-stable group, the lean-marked increase group had higher odds of having below-median TL (OR?=?1.18, 95% CI 1.04, 1.35; P?=?0.01), and the medium-marked increase group had higher odds of having below-median mtCN (OR?=?1.28, 95% CI 1.00, 1.64; P?=?0.047). There was a suggestive trend toward lower mtCN across the GRS quartiles (P for trend?=?0.07). In conclusion, telomere attrition may be accelerated by marked weight gain in middle life, whereas mtCN is likely to be reduced persistently by adiposity over the life course. The findings indicate the importance of lifetime weight management to preserve functional telomeres and mitochondria.     

Extraperitonealization of ileal conduit reduces parastomal hernia after cystectomy and ileal conduit diversion

ObjectiveParastomal hernia (PSH) is a common complication of ileal conduit diversion after radical cystectomy. Novel surgical techniques for preventing PSH formation are needed. We aimed to evaluate surgical technique of extraperitonealizing the ileal conduit (modified ileal conduit) for preventing PSH.MethodsA retrospective analysis of 375 consecutive patients who underwent ileal conduit after cystectomy at the Sun Yat-sen University Cancer Center between January 1, 2000 and June 31, 2019 was conducted. 214 patients had modified ileal conduit diversion and 161 patients conventional ileal conduit (Bricker) diversion. The demographic and clinicopathologic characteristics of patients in the 2 groups were compared using the t test and Chi square test. Univariable and multivariable Cox regression analyses were used to predict the risk of PSH formation.ResultsThe 2 groups were comparable in regard to all demographic and clinicopathologic variables. The incidence of PSH diagnosed by CT scan was 7.5% in the modified group and 21.1% in the conventional group (P < 0.001). High BMI and history of prior abdominal surgery was identified by univariable analysis as risk factors of PSH formation. Multivariable analyses revealed that technique of extraperitonealizing ileal conduit significantly reduced incidence of PSH in patients with or without risk factors of PSH formation (OR = 0.29, 95% CI 0.16–0.54, P < 0.001).ConclusionsTechnique of extraperitonealizing ileal conduit appeared to be effective in reducing PSH formation after ileal conduit diversion.     

Optimizing prediction of new-baseline glomerular filtration rate after radical nephrectomy: are algorithms really necessary?

International Urology and Nephrology - Radical nephrectomy (RN) is an important consideration for the management of localized renal-cell-carcinoma (RCC) whenever the tumor appears aggressive,...     

Optimal acquisition time to discriminate between breast cancer subtypes with contrast-enhanced cone-beam CT

PurposeTo identify the optimal acquisition time to best discriminate between benign and malignant breast lesions on contrast-enhanced cone beam CT (CE-CBCT) and evaluate the potential of CE-CBCT to differentiate between breast cancer subtypes.Material and methodA total of 98 women with a mean age of 49 ± 10 (SD) years (range: 29–77 years) with 100 BI-RADS 4 or 5 breast lesions were prospectively included. CE-CBCT images were obtained at 1- and 2-min after intravenous administration of iodinated contrast material. Contrast enhancement of breast lesions on CE-CBCT were evaluated and compared between different subtypes. Cut-off values for best discriminating between benign and malignant breast lesions with CE-CBCT were obtained from receiver operating characteristic curves.ResultsMalignant breast lesions showed greater enhancement than benign ones at 1-min (67.28 ± 39.79 [SD] HU vs. 42.27 ± 40.31 [SD] HU, respectively; P = 0.007) and 2-min (70.93 ± 38.05 [SD] HU vs. 48.94 ± 41.83 [SD] HU, respectively; P = 0.016) after intravenous administration of contrast material. At 1-min after intravenous administration of contrast material, an optimal cut-off value of 54.43 HU was found to best discriminate between malignant and benign breast lesions (AUC = 0.681; 95%CI: 0.558–0.805; P = 0.006) yielding 69.0% sensitivity (95%CI: 56.9–79.5%) and 69.2% specificity (95% CI: 48.2–85.7%). At 2-min, an optimal cut-off value of 72.65 HU was found to best discriminate between malignant and benign breast lesions (AUC = 0.654; 95%CI: 0.535–0.774; P = 0.020) yielding 50.7% sensitivity (95%CI: 38.6–62.8%) and 80.8% specificity (95%CI: 60.6–93.4%). CE-CBCT helped differentiate between immunohistochemical subtypes of breast lesions with lowest enhancement for triple negative lesions. No differences in enhancement were found among histopathological subtypes lesions at 1-min (P = 0.478) and 2-min (P = 0.625).ConclusionCE-CBCT helps discriminate between malignant and benign breast lesions, with best capabilities obtained at 1-min after intravenous administration of contrast material. For malignant lesions, quantitative analysis of enhancement on CE-CBCT helps differentiate between immunohistochemical subtypes.     

靶向治疗时代转移性肾癌多学科综合治疗的单中心经验总结

目的总结在靶向药物治疗基础上单中心转移性肾癌的多学科诊疗经验。方法回顾性分析2007年12月至2019年2月中山大学肿瘤防治中心经多学科诊疗团队(multi-disciplinary team,MDT)诊治的168例转移性肾癌(metastatic renal cell,mRCC)患者的临床数据。根据治疗方式将患者分为3组。单纯靶向药物治疗(A组)76例,男55例,女21例;年龄52(17~73)岁;透明细胞癌60例,非透明细胞癌16例;国际转移性肾细胞癌联合数据库(International Metastatic Renal Cell Carcinoma Database consortium,IMDC)预后评分低危11例,中危48例,高危17例;初诊时即有转移44例;行原发灶切除术63例。靶向药物治疗+局部治疗(B组)66例,男55例,女11例;年龄54(21~86)岁;透明细胞癌49例,非透明细胞癌17例;IMDC预后评分低危13例,中危39例,高危14例;初诊时即有转移32例;行原发灶切除术56例。靶向药物治疗+局部治疗+免疫治疗(C组)26例,男19例,女7例;年龄52(23~83)岁;透明细胞癌15例,非透明细胞癌11例;IMDC预后评分低危9例,中危13例,高危4例;初诊时即有转移9例;行原发灶切除术26例。3组患者一般资料比较差异均无统计学意义(P>0.05)。一线靶向治疗药物为舒尼替尼、索拉非尼、阿昔替尼。舒尼替尼50 mg,每日1次,用药4周停2周;索拉非尼400 mg,每日2次;阿昔替尼5 mg,每日2次。接受舒尼替尼、索拉非尼、阿昔替尼一线治疗者分别为103、18、39例。靶向药物治疗时间均>6个月。免疫治疗采用派姆单抗(Pembrolizumab)2 mg/kg静脉应用,每3周1次,或低剂量(20 mg)派姆单抗孵育经体外扩增后的自体外周血树突状细胞细胞因子诱导杀伤细胞(dendritic cells cytokine induced killer,DC.CIK),每周1次,4次后改为每2周1次。18例采用DC.CIK,8例采用派姆单抗。局部治疗方式包括立体定向放疗(stereotactic body radiation therapy,SBRT)和外科治疗(手术切除或能量消融治疗)。根据靶向药物治疗效果,转移灶部位、数量、与周围器官关系,以及患者的意愿,经MDT专家讨论后决定局部治疗方式。92例接受局部治疗,其中单纯外科治疗34例,单纯SBRT 37例,外科治疗+SBRT 21例。比较3组的疗效和不良反应情况,分析不同治疗方法与患者总生存时间(overall survival,OS)的关系。结果168例中位随访23个月(6~117个月)。中位无进展生存时间(progression free-survival,PFS)为18.3个月,中位OS为33.5个月;2年生存率为66%,5年生存率为35%。A、B、C组的中位OS分别为29.8个月、44.6个月和未达,2年生存率分别为58%、67%和89%,5年生存率分别为12%、46%和57%。在靶向药物治疗的基础上接受联合治疗者的预后均优于单纯靶向药物治疗者,5年总OS分别为51%和11%。C组的中高危mRCC患者预后明显优于A、B组。在接受免疫治疗的患者中,靶向药物治疗联合DC.CIK与联合派姆单抗的中位OS分别为49.1个月和53.1个月,差异无统计学意义(P=0.541)。单因素分析结果显示,OS与IMDC评分、原发灶切除、治疗模式相关(P<0.05)。多因素分析结果显示,OS与治疗模式、原发灶切除显著相关(P<0.05),靶向药物治疗+免疫治疗+局部治疗可使mRCC患者死亡风险下降约60%(HR=0.39,95%CI 0.17~0.89,P=0.026)。78例使用靶向药物治疗发生3~4级不良反应,12例因无法耐受一线靶向药物治疗不良反应而停药或换药。16例采用靶向药物联合免疫治疗发生3~4级药物不良反应,主要为疲乏8例次、白细胞降低4例次、血小板降低3例次、转氨酶和胆红素升高3例次。靶向药物治疗联合DC.CIK治疗的严重不良反应发生例数少于联合派姆单抗治疗(6例与12例),特别是显著降低了血液学毒性(2例与5例)和肝毒性(0例与3例),差异均有统计学意义(P<0.05)。外科治疗后出现ClavienⅢ~Ⅳ级并发症16例次,主要为感染和切口延期愈合6例次、不全肠梗阻4例次,围手术期输血15例次。SBRT治疗后6例出现美国放射肿瘤协作组评分(Radiotherapy Oncology Group,RTOG)3级不良反应,其中骨髓抑制4例,皮肤反应和放射性神经炎2例,未观察到≥4级不良反应。结论在靶向药物治疗基础上联合免疫治疗和局部治疗的mRCC患者预后明显优于采用单纯靶向药物治疗的患者。经MDT诊疗的综合治疗可使mRCC患者生存获益。     

Hypofractionated intensity modulated radiotherapy with temozolomide in newly diagnosed glioblastoma multiforme

We conducted a phase I study to determine (a) the maximum tolerated dose of peri-radiation therapy temozolomide (TMZ) and (b) the safety of a selected hypofractionated intensity modulated radiation therapy (HIMRT) regimen in glioblastoma multiforme (GBM) patients. Patients with histological diagnosis of GBM, Karnofsky performance status (KPS) ⩾ 60 and adequate bone marrow function were eligible for the study. All patients received peri-radiation TMZ; 1 week before the beginning of radiation therapy (RT), 1 week after RT and for 3 weeks during RT. Standard 75 mg/m²/day dose was administered to all patients 1 week post-RT. Dose escalation was commenced at level I: 50 mg/m²/day, level II: 65 mg/m²/day and level III: 75 mg/m²/day for 4 weeks. HIMRT was delivered at 52.5 Gy in 15 fractions to the contrast enhancing lesion (or surgical cavity) plus the surrounding edema plus a 2 cm margin. Six men and three women with a median age of 67 years (range, 44–81) and a median KPS of 80 (range, 80–90) were enrolled. Three patients were accrued at each TMZ dose level. Median follow-up was 10 months (range, 1–15). Median progression free survival was 3.9 months (95% confidence interval [CI]: 0.9–7.4; range, 0.9–9.9 months) and the overall survival 12.7 months (95% CI: 2.5–17.6; range, 2.5–20.7 months). Time spent in a KPS ⩾70 was 8.1 months (95% CI: 2.4–15.6; range, 2.4–16 months). No instance of irreversible grade 3 or higher acute toxicity was noted. HIMRT at 52.5 Gy in 15 fractions with peri-RT TMZ at a maximum tolerated dose of 75 mg/m²/day for 5 weeks is well tolerated and is able to abate treatment time for these patients.     

Treatment response,survival, and safety profile of camrelizumab plus apatinib regimen as third-line treatment in metastatic gastric cancer patients

BackgroundCamrelizumab, as a PD-1 inhibitor on the market recently, presents favorable therapeutic efficacy in several advanced cancers, while its application in metastatic gastric cancer (mGC) lacks data. This study aimed to assess treatment response, survival profile, and adverse events of camrelizumab plus apatinib regimen as third-line treatment in mGC patients.MethodsNineteen mGC patients who received camrelizumab plus apatinib as third-line treatment were analyzed in this observational study. Subsequently, treatment response and adverse events were documented, then progression-free survival (PFS) and overall survival (OS) were calculated.ResultsNo (0.0%) patient achieved complete response; 5 (26.3%) patients achieved partial response; 8 (42.1%) patients had stable disease; 6 (31.6%) patients had progressive disease, resulting in objective response rate and disease control rate of 26.3% and 68.4%, respectively. Meanwhile, the median PFS and OS were 7.0 (95%CI: 2.9–11.0) months and 10.0 (95%CI: 7.4–12.6) months, accordingly. Besides, multiple metastases linked with worse PFS (P = 0.029) and OS (P = 0.021); Eastern Cooperative Oncology Group performance status (ECOG PS) score 1 (vs. 0) related to shorter OS (P = 0.030). Worth noting, the common adverse events were fatigue (42.1%), anemia (42.1%), neutropenia (42.1%), leukopenia (36.8%), pruritus (31.6%), proteinuria (31.6%), nausea and vomiting (31.6%), reactive capillary hemangioma (31.6%) and thrombocytopenia (31.6%). Meanwhile, grade 3–4 adverse events only included: thrombocytopenia (5.3%), hypertension (5.3%), and proteinuria (5.3%).ConclusionCamrelizumab plus apatinib as third-line treatment achieves satisfactory therapeutic efficacy and survival profile with generally manageable adverse events in mGC patients.     

Modeling the risk of radiation pneumonitis in esophageal squamous cell carcinoma treated with definitive chemoradiotherapy

Esophagus - To develop and validate a nomogram for the prediction of symptomatic radiation pneumonitis (RP) in patients with esophageal squamous cell carcinoma (ESCC) who received definitive...     

Perspectives on Cancer Pain Assessment and Management in Children

ObjectiveTo report evidence regarding pain assessment and management for children and adolescents receiving treatment for cancer.Data SourcesPublished research and clinical guidelines.ConclusionChildren and adolescents experience multiple sources of pain across the cancer continuum. They require developmentally relevant approaches when assessing and managing pain. This review suggests that consideration of the developmental stage and age of the child are essential in both pain assessment and pain management.Implications for Nursing PracticePediatric oncology nurses play a key role in developmentally appropriate pain assessment, identification of potential strategies to manage pain, and delivery of pharmacologic and nonpharmacologic therapies.