Clinical outcomes of patients treated for cervical pregnancy with or without methotrexate

The objective of this study is to describe the clinical outcomes of patients treated for cervical pregnancy with or without methotrexate (MTX) and to evaluate the effects of MTX in the treatment of cervical pregnancy. Between January 1993 and February 2000, 31 patients were diagnosed with cervical pregnancy. Twenty-two patients were treated with MTX chemotherapy and nine patients were treated with surgical procedures without MTX treatment. In the non-MTX treatment group, three patients underwent total abdominal hysterectomy, five required adjuvant procedures to control the bleeding during dilatation and curettage (D&C) and only one patient was treated with a simple D&C. In the MTX treatment group, fourteen (63.6%) patients were treated with only MTX and eight (36.4%) cases underwent concomitant procedures (simple curettage, curettage and Foley catheter tamponade, cervical cerclage, ligation of the descending branches of uterine arteries, or ligation of hypogastric arteries). The uterus was preserved in all cases and three women delivered healthy babies in their subsequent pregnancy. In conclusion, early diagnosis, appropriate MTX regimen in combination of necessary adjuvant conservative procedures could contribute to successful treatment with preservation of the uterus and future reproductive ability.     

The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules

Low-dose methotrexate (MTX) is an established and highly effective treatment for severe psoriasis and rheumatoid arthritis; however, its mechanism of action remains unclear. We investigated the effects of low-dose MTX on antigen-stimulated peripheral blood mononuclear cells and explored through which cellular pathways these effects are mediated. We show that MTX caused a dose-dependent suppression of T cell activation and adhesion molecule expression, and this was not due to lymphocyte apoptosis. The suppression of intercellular adhesion molecule (ICAM)-1 was adenosine and folate-dependent, while MTX suppression of the skin-homing cutaneous lymphocyte-associated antigen (CLA) was adenosine-independent. The effect of MTX on CLA, but not ICAM-1, required the constant presence of MTX in cultures. Thus, the suppression of T cell activation and T cell adhesion molecule expression, rather than apoptosis, mediated in part by adenosine or polyglutamated MTX or both, are important mechanisms in the anti-inflammatory action of MTX.     

Development of patient derived organoids for cancer drug screening applications

Cancer is a disease characterised by abnormal cell growth that can invade or spread to other regions of the body. Organoids are three-dimensional ex vivo tissue cultures made from embryonic stem cells, induced pluripotent stem cells, progenitor cells or tissue that serve as a physiological model for cancer research. These are designed to recapitulate the in vivo properties of tumours. Importantly, effective recapitulation of the structure of tissues and function is believed to predict patient response, allowing for the creation of personalised therapy in a timely manner that may be used in the clinic. This Review discusses the pre-clinical model and different types of human organoids as models for the development of high throughput drug screening and also aims to highlight how organoids are shaping the future of cancer research.     

Utilization of fluorescence in situ hybridization with cytokeratin discriminators in TOP2A assessment of chemotherapy-treated patients with breast cancer

Tumor biomarkers increasingly provide information for predicting outcomes with chemotherapeutic regimens (personalized medicine). Topo2A is a DNA helicase targeted by anthracyclines, cytotoxic therapeutics used in both adjuvant and palliative treatments of breast cancer. TOP2A gene amplification/deletion is implicated in response to anthracycline-based chemotherapy. We describe an approach for analyzing formalin-fixed, paraffin-embedded breast tumors on tissue microarrays with TOP2A fluorescence in situ hybridization coupled with cytokeratin immunofluorescence to target tumor cells. Stained tissue from patient specimens was imaged and analyzed using Metafer/Metacyte (Metasystems, Waltham, MA, USA), including customized image classifiers. TOP2A/CEN17 ratios of 2.0 or greater (amplified) and 0.8 or less (deleted) were observed for 10.0% and 6.1% of the patients, respectively. Patient outcomes for adjuvant chemotherapy (cyclophosphamide-epirubicin-fluorouracil, cyclophosphamide-methotrexate-fluorouracil, no chemotherapy) were evaluated. No statistical significance was achieved for clinical end points regarding TOP2A status in anthracycline-treated patients. However, patients with TOP2A aberrations receiving methotrexate-based therapy exhibited a significant decrease in 5-year distant disease-free survival and breast cancer-specific overall survival, especially for patients with TOP2A deletions (disease-free survival: hazard ratio, 5.31 [P = .001], and breast cancer-specific overall survival: hazard ratio, 6.45 [P ≤ .001]). No significant differences were seen in patients included in the no-chemotherapy group. Topo2A protein levels were assessed by immunohistochemistry with no correlative statistical relevance to immunofluorescence/fluorescence in situ hybridization-based prognosis for cyclophosphamide-epirubicin-fluorouracil or cyclophosphamide-methotrexate-fluorouracil groups. Interestingly, aberrant (under)expressing patients in the no-chemotherapy group exhibited better 5-year distant disease-free survival (hazard ratio, 0.39; P = .004), trending toward more favorable breast cancer-specific overall survival (hazard ratio, 0.61; P = .11). Our results indicate a strategy by which fluorescence in situ hybridization scoring targeted to cytokeratin-positive tumor cells may provide a tool for added precision and efficiency in TOP2A evaluation from tumor tissue.     

Treatment with methotrexate of a cornual pregnancy following endometrial resection

ABSTRACT

Objectives Endometrial resection is a procedure often performed for treatment of menorrhagia. Despite the fact that amenorrhoea frequently ensues, some normal endometrium can remain present and become the implantation site of a pregnancy. Such an event is uncommon (0.7%); however, the likelihood of an ectopic pregnancy is increased. This case report calls the reader's attention to the risk of intra- and extrauterine pregnancies and the necessity for contraception after endometrial resection, even in cases where amenorrhoea supervenes.

Case A 46-year-old woman with prior endometrial resection and subsequent amenorrhoea, was diagnosed with a cornual pregnancy. She was successfully treated with systemic methotrexate, which was given in an outpatient clinic.

Conclusion Clinicians should be aware of the increased likelihood of an ectopic pregnancy after endometrial resection. All women submitting to this procedure should be counselled about the need for contraception, even in cases where amenorrhoea develops.     

腹腔镜保守手术联合药物防治输卵管妊娠后持续性异位妊娠的临床研究

目的:探讨米非司酮联合甲氨蝶呤用于防治输卵管妊娠腹腔镜保守手术后持续性异位妊娠(persistent ectopic pregnancy,PEP)的疗效。方法:为87例输卵管妊娠患者行腹腔镜保守手术,术前应用米非司酮50mg,2次/d,取出妊娠物后继续口服米非司酮50mg,2次/d,肌注甲氨蝶呤20mg,1次/d。结果:87例手术均获成功,术后无一例发生PEP。结论:术前用米非司酮,术后米非司酮联合甲氨蝶呤能预防输卵管妊娠腹腔镜保守手术后PEP的发生,患者痛苦少,无明显不良反应,具有临床应用价值。     

影响子宫动脉栓塞术在剖宫产疤痕妊娠中应用的因素分析

目的：探讨子宫动脉栓塞术（UAE）在剖宫产疤痕妊娠（CSP）治疗中的应用效果及其影响因素分析。 方法：选取2012年12月至2017年6月在我院拟采用药物保守治疗的CSP患者76例。其中26例采用肌内注射甲氨蝶呤+清宫术治疗（A组）,50例采用甲氨蝶呤+UAE+清宫术治疗（B组）。比较两组的一般资料及治疗结果,采用多因素Logistic回归模型分析影响采用UAE介入治疗的因素,并进一步应用ROC曲线得出最佳临界值。 结果：单因素分析显示：两组的年龄、孕次、产次、剖宫产史时间、血清β-HCG值比较差异无统计学意义。B组的停经时间较A组长[（53.6±20.2）d vs.（48.7±17.2）d],孕囊比A组大[（3.87 ±1.58）mm vs.（3.19±2.06）mm],疤痕肌层厚度比A组薄[（1.65±1.12）mm vs.（2.97±1.24）mm]、疤痕妊娠分型中Ⅱ型比例较高（66% vs. 35%）,与A组差异均有统计学意义（P<0.05）;Logistic回归分析显示：停经时间长、疤痕肌层厚度薄是影响采用UAE治疗CSP的独立危险因素。ROC曲线分析显示,妊娠时间≥51 d,疤痕肌层厚度≤2.7 mm为选择UAE的最佳临界值（ROC曲线下面积分别为0.813和0.808）。 结论：UAE可有效防治剖宫产疤痕妊娠保守治疗中的大出血;尤其对停经时间≥51 d,疤痕厚度≤2.7 mm的患者更具有重要的临床价值。     

剖宫产术后子宫瘢痕部妊娠19例临床分析

目的探讨剖宫产术后子宫瘢痕妊娠（CSP）的临床表现、诊断、治疗及预后。方法回顾性分析2003年1月～2009年11月我科收治的19例CSP患者的临床资料。结果 19例CSP患者中,12例（63.2%）患者有阴道少量不规则流血,3例（15.8%）伴有下腹隐痛;8例（42.1%）有一次剖宫产史,11例（57.9%）有两次剖宫产史;从前次剖宫产到此次瘢痕部位妊娠时间间隔为2～10年,平均（4.38±3.57）年。治疗方法：5例接受子宫动脉栓塞术＋MTX局部治疗后行清宫术,9例接受甲氨蝶呤治疗后行清宫术,1例接受甲氨蝶呤治疗后未清宫,4例误诊病例行清宫术发生大出血。其中前两者在术后血人绒毛膜促性腺激素水平下降百分比及清宫手术出血量方面进行比较,差异均无统计学意义（P〉0.05）,而平均出血量与病灶直径呈正相关（r=0.32,P〈0.05）,与治疗前血β-HCG水平也呈正相关（r=0.33,P〈0.05）。结论阴道彩超在早期诊断CSP方面起重要作用,子宫动脉栓塞术及甲氨蝶呤辅助治疗后行清宫术用于治疗CSP,如应用恰当都能取得良好效果。     

子宫动脉化疗栓塞术和子宫动脉栓塞术治疗子宫瘢痕妊娠的临床效果比较

目的：比较子宫动脉化疗栓塞术和子宫动脉栓塞术治疗剖宫产术后子宫瘢痕妊娠（cesarean scar pregnancy,CSP）的疗效。 方法：回顾分析山西医科大学第一医院2007年1月—2016年5月收治的诊断明确的CSP患者71例,分为A组33例和B组38例,A组行子宫动脉化疗栓塞术后行清宫术,B组行子宫动脉栓塞术后行清宫术。比较2组患者清宫过程的出血量、β-人绒毛膜促性腺激素（HCG）值下降至正常的时间及住院时间。 结果：2组患者的治疗成功率为100%,清宫过程中的出血量：A组为（40±30）ml,B组为（50±20）ml,差别无统计学意义。β-HCG值下降至正常的时间：A组为（16±3）d,低于B组的（21±5）d,差别有统计学意义。住院时间：A组为（11±3）d,低于B组的（13.5±4.5）d,差别有统计学意义。 结论：子宫动脉化疗栓塞术和子宫动脉栓塞术治疗CSP的成功率、清宫过程的出血量无明显差别,但子宫动脉化疗栓塞术能缩短患者的β-HCG值下降至正常的时间和住院时间。     

Effects of Long-Term Administration of Methotrexate on Bone Mineral Density in Rheumatoid Arthritis

Because previous studies of high-dose methotrexate usage have demonstrated an effect on bone formation and resorption, this study was done to determine whether long-term, low-dose use of methotrexate for the treatment of rheumatoid arthritis causes bone loss. Bone mineral density (BMD) of the lumbar spine and hip was measured in 10 Caucasian postmenopausal women who had never received methotrexate and 10 Caucasian postmenopausal women who had received the drug for 3 or more years. There were no significant differences in BMD at the lumbar spine (L2–L4) between patients who had used long-term methotrexate compared with patients never treated with methotrexate (1.08 ± 0.08 g/cm² versus 0.98 ± 0.14 g/cm², respectively; P= 0.08). Similarly, there were no significant differences in BMD at the femoral neck between methotrexate users and nonusers (0.81 ± 0.08 g/cm² versus 0.76 ± 0.15 g/cm², respectively; P= 0.42). These results suggest that long-term low-dose methotrexate treatment for rheumatoid arthritis is not associated with accelerated bone loss. Received: 16 October 1997 / Accepted: 9 July 1998