Estriol add-back therapy in the long-acting gonadotropin-releasing hormone agonist treatment of uterine leiomyomata

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa.

Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg sc every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group.

In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.     

超声刀在甲状腺肿瘤手术中的应用效果及安全性评价

目的探讨超声刀在甲状腺肿瘤手术中的应用效果及安全性评价。 方法选择2015年6月至2018年6月手术治疗的甲状腺瘤手术患者100例为研究对象,按随机数字表法分为超声刀组和电刀组,每组患者各50例。电刀组给予常规的高频电刀切除,超声刀组患者给予超声刀手术切除。以SPSS 22.0进行数据处理与分析,组间术中术后各项指标、TSH、PTH、PCT水平等计量资料以( ±s)表示,独立t检验;并发症发生率采用χ²检验,当P<0.05时差异有统计学意义。 结果①超声刀组患者的手术时间、术中失血量、术后引流量、术后住院时间均低于电刀组(P<0.05)。②术前两组患者的血清促甲状腺激素(TSH)、血清甲状旁腺激素(PTH)、血清降钙素原(PCT)水平比较差异无统计学意义(P>0.05),治疗后超声刀组患者的TSH、PTH水平均高于电刀组,而PCT水平则低于电刀组(P<0.05)。③超声刀组患者术后并发症发生率为6.0%(3/50),低于电刀组患者22.0%(11/50),差异有统计学意义(P<0.05)。 结论与常规电切术相比,超声刀手术切除甲状腺肿瘤的效果更为显著,能够降低患者术中出血量、缩短手术时间,术后恢复快,且手术并发症少,安全性高,可在临床上进一步推广应用。     

甲状旁腺切除术用于难治性肾性继发性甲状旁腺功能亢进的安全性及近远疗效

背景与目的:甲状旁腺切除术(PTX)是治疗药物不能控制的难治性肾性继发性甲状旁腺功能亢进症(SHPT)的重要手段,但PTX术后仍有可能发生永久性甲状旁腺功能减退,无动力性骨病或难治性骨软化症,且国内尚缺乏对PTX术后远期的疗效观察的研究。本研究进一步评价PTX治疗难治性肾性SHPT的安全性与近远期疗效。方法:纳入2011年1月—2014年12月在安徽医科大学第二附属医院行PTX治疗的139例伴有难治性肾性SHPT的维持性透析患者。收集患者术前及术后3 d、6个月及1、2、3年的临床资料、血全段甲状旁腺激素(iPTH)、血钙、血磷、血红蛋白(Hb)及红细胞压积(Hct)等,观察并记录术后症状缓解情况、术后并发症和随访情况。结果:139例患者的PTX手术成功率为95.7%(133/139),术中共计切除甲状旁腺腺体537枚,平均切除3.86枚/例。12例(8.6%)术后发生一过性喉返神经损伤,其中声音嘶哑9例(6.5%),饮水呛咳3例(2.2%),未予处理术后3个月内均自行好转。术后低钙血症或缺乏维生素D者120例(86.3%),给予西那卡塞、补钙及补充活性维生素D治疗后得到有效控制。全组未发生切口感染、出血、窒息及甲状腺功能减退等外科并发症。患者的贫血状况均有不同程度地改善,Hb和Hct术后6个月明显升高并在随访期间保持稳定;术后iPTH明显降低,术后3 d的血钙、磷、钙磷乘积水平最低,随访3年仍低于手术前,所有变化与术前均有统计学差异(均P0.05)。随访期间无死亡病例。患者术前的骨痛、顽固性皮肤瘙痒、失眠、异位钙化、肌无力伴萎缩症状在术后1 d即明显缓解;身高缩短、骨骼畸形患者随访期间无进行性加重;纳差、全身营养状况及自理能力术后3个月内不同程度地改善。11例(7.9%)持续性SHPT,包括4例(2.9%)术中未完全切除甲状旁腺腺体,1例(0.7%)术中1枚腺体较小而未切除完全,6例(4.3%)术后检查存在纵隔异位甲状旁腺。随访期间,5例(3.5%)腺体未切除完全者的iPTH均800 pg/mL,肌无力及顽固性皮肤瘙痒临床症状明显,再次行PTX;6例(4.3%)存在异位甲状旁腺腺体者,因手术风险较大患者拒绝再次手术,予以药物治疗;8例(5.8%)术后复发,其中6例(4.3%)系前臂移植物复发所致,均在局麻下行前臂皮下移植物切除;2例(1.4%)系颈部原位残留腺体过度增生,予以二次手术,术后症状缓解。所有进行二次手术的患者在随访结束时无明显的临床症状,均未复发。结论:PTX可改善难治性肾性SHPT患者临床症状、贫血及钙磷代谢,且近远期疗效均较好,是治疗难治性SHPT的安全有效方法。     

Prolonged clinical benefit from the maintenance hormone therapy in patients with metastatic breast cancer

ObjectiveWe investigated the efficacy of maintenance hormone therapy (MHT), which was given to hormone positive metastatic breast cancer (MBC) patients in non-progression status to the previous chemotherapy.MethodsThis study retrospectively analyzed 76 MBC patients who had been treated with MHT from 2006 to 2010 at a single institute.ResultsFor the 76 patients reviewed, the median progression free survival (PFS) to MHT was 14.4 months (95% CI, 11.6–17.3). Prolonged PFS was associated with less previous palliative chemotherapy, fewer metastatic sites, and the absence of visceral metastasis in univariate analysis. Multivariate analysis showed that only the number of previous palliative chemotherapy (HR 1.73, 95% CI, 1.00–2.98; P = 0.04) remained as a significant variable. MHT was generally well tolerated.ConclusionsMHT showed considerable efficacy and tolerability in this study. Further randomized prospective study is warranted.     

Real world initial palliative treatment patterns and clinical outcomes in premenopausal patients with hormone receptor-positive,HER2-negative metastatic breast cancer: A study of the National Cancer Center,China

BackgroundTo observe whether guideline non-adherence in initial palliative treatment choices for premenopausal hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) patients result in worse clinical outcomes in the Chinese population.MethodsThe China National Cancer Center database was used to identify 2194 patients diagnosed between 2004 and 2015. A total of 451 premenopausal patients with HR + HER2- MBC were included. Clinicopathological features and survival information were extracted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using log-rank test.ResultsThe number of patients receiving initial chemotherapy, endocrine therapy and chemo-endocrine therapy were 222 (49.2%), 80 (17.7%), and 149 (33.0%), respectively. Patients receiving initial chemotherapy were more likely to be luminal B subtype, had more de novo stage IV disease and more liver metastasis, compared with patients receiving initial endocrine therapy. Both PFS and OS were significantly longer for chemo-endocrine therapy group (median PFS 18.9 months and OS 75.0 months), than for endocrine therapy group (median PFS 11.7 months and OS 53.5 months), and chemotherapy group (median PFS 7.1 months and OS 43.9 months). In multivariate analysis, none of the three treatment strategies were independently associated with PFS or OS.ConclusionIn real world, a high percentage of premenopausal patients with HR + HER2- disease received chemotherapy as initial palliative treatment in China, which was not associated with worsened survival. Further studies with larger sample size across China are needed to explore the relationship between this guideline non-adherence and clinical outcomes.     

The continuing conundrum in oligometastatic breast carcinoma: A real-world data

The optimal management in Oligometastatic (OM) breast carcinoma is not defined.ObjectivesTo identify the prognostic factors influencing OM and the effect of Locoregional treatment (LRT) on survival in OM.MethodologyPatients with ≤5 metastases and each with ≤ 5 cm size were defined as OM. Data of OM were extracted from the Institute Registry between 2012 and 2018. The impact of prognostic factors on survival was analysed by univariate and multivariate Cox regression. The Kaplan Meier survival curves were used to plot PFS and OS.ResultsThere were 170 patients with OM. The median follow-up was 61 months. Median OS was 43.3 months. The median OS was 74 months in OMD vs 22.7 months in Oligorecurrent disease (ORD) with 5year OS rate of 55.3% vs 16.5% respectively. In the multivariate analyses of OMD both Ki67 ≤ 50% and hormone therapy (HT) showed significant favourable survival outcome. While premenopausal status and HT showed significant survival benefits in ORD. The worse survival outcome in ORD could be because of their aggressive biology and deficit in LRT compared to literature review. The prognostic factors were swayed by the uneven distribution of HR status, grade and Ki67.ConclusionThe survival of OM was influenced by OMD, Ki67 ≤ 50%, premenopausal status and HT. The lesser survival rates of OM in the long term suggest the need for curative LRT to metastatic sites and primary tumor. The potential role of HT and targeted therapy with or without LRT need to be assessed in future randomised trials.     

Real-world data of HER2-low metastatic breast cancer: A population based cohort study

BackgroundWith the introduction of investigational human epidermal growth factor receptor 2 (HER2) targeting treatments, thorough understanding of breast cancer with different HER2 expression levels is critical. The aim of this study was to compare clinicopathologic characteristics and survival of patients with metastatic breast cancer according to the level of HER2 expression.MethodsWomen with distant metastatic breast cancer during 2008–2016 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO Database Network. Breast cancer samples were categorised as HER2 immunohistochemistry score 0 (IHC0), HER2-low or HER2+.ResultsAmong women with hormone receptor (HR) positive metastatic breast cancer (n = 989), 373 (38%) cancers were HER2 IHC0, 472 (48%) were HER2-low and 144 (15%) were HER2+. Among HR negative patients (n = 272), the proportion of HER2 IHC0, HER2-low and HER2+ was 110 (40%), 104 (38%) and 58 (21%) respectively.Within the HR + cohort, patients with HER2 IHC0 or HER2-low cancer were significantly older compared to HER2+ patients. This age difference was not seen in the HR-cohort. The localisation of distant metastases differed significantly between HER2 IHC0 or HER2-low versus HER2+ cases. Survival rates did not differ markedly by subtypes.ConclusionSubstantial proportion of patients had a HER2-low breast cancer. No clear differences in survival were found when comparing HER2 and HR status. Getting more granular insights in the level of HER2 expression and addressing HER2-low as a separate category could help to assess the impact of emerging treatment strategies. Therefore, more detailed information on HER2 expression should be routinely reported.     

甲状腺术后的甲状腺功能维护

甲状腺功能减退是甲状腺手术最常见的并发症.左甲状腺素钠（L-T4）是治疗甲状腺功能减退的首选药物,甲状腺功能维护可于术后早期进行,L-T4的需要量受多个因素及目标TSH的影响,实施过程中应考虑患者的特殊性（依从性差、妊娠、老年）,并定期（4～6周）复查甲状腺功能,根据目标TSH调整最佳用药剂量,避免治疗不足和治疗过度.T3分次给药或L-T4/T3联合治疗可作为L-T4治疗失败患者的选择.     

血清抗苗勒管激素和血清抑制素B水平对隐睾症患者睾丸功能评价的意义

目的探讨血清抗苗勒管激素(AMH)和血清抑制索B(INH-B)对隐睾症患者睾丸功能评价的意义。方法采用酶免疫吸附试验(ELISA)检测2018年11月至2019年7月本院收治的53例隐翠症患儿的INH-B及AMH水平(设为病例组),其中单侧隐翠患儿31例(右侧隐睾19例,左侧隐睾12例),双侧隐睾患儿22例。年龄(55.0±3.5)个月。另随机选取51例正常男性儿童作为对照组,年龄(54.6±2.7)个月。两组在术前及术后6个月时随访测定血清AMH和INH-B以及相关发育参数。分析比较各组之间和手术前后血清激素水平差异。结果两组除睾丸体积参数外的其余生殖器发育相关参数比较,差异均有统计学意义(P<0.05)。单侧隐睾与双侧隐翠患者的血清INH-B值[(71.36±6.80)pg/mLvs.(68.08±7.10)pg/mL]和AMH值[(115.44±8.90)ng/mL vs.(110.32±9.10)ng/mlL]比较,差异有统计学意义(P<0.05)。两组术前检测血清INH-B值,分别是(69.97±7.50)pg/mL和(75.15±6.30)pg/mL,差异有统计学意义(P<0.05)。两组术前检测血清AMH值,分别是(113.32±9.30)ng/ml,(127.80±8.7)ng/mL,差异均有统计学意义(P<0.05)。病例组术后6个月随访时检测血清INH-B值为(72.81±6.80)pg/mL,血清AMH值为(119.79 ± 7.3)ng/mL;与术前血清AMH.INH-B水平比较,差异均有统计学意义(P<0.05)。结论血清AMH和INH-B水平可作为评估隐睾症患者评估睾丸功能的可靠指标,并且能评价睾丸固定术后睾丸功能恢复情况。