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A clinicopathological and molecular analysis in uterine leiomyomas and concurrent/metachronous peritoneal nodules: New insights into disseminated peritoneal leiomyomatosis.

子宫肌瘤和并发/异时腹膜结节的临床病理和分子分析: 播散性腹膜平滑肌瘤病的新见解。

  • 影响因子:1.80
  • DOI:10.1016/j.prp.2020.152938
  • 作者列表:"Ma Y","Wang S","Liu Q","Lu B
  • 发表时间:2020-03-24
Abstract

:Disseminated peritoneal leiomyomatosis (DPL) is a rare, benign entity, but DPL following morcellation has become a major concern recently. This study aimed to investigate the molecular relationship between uterine leiomyoma and DPL. We analyzed the clinicopathological and molecular features of 8 DPL patients including 6 (#3-8) with and 2 (#1 and 2) without antecedent morcellation. Patients 1 and 2 were characterized by numerous, small peritoneal nodules whereas patients 4-8 harbored less but larger peritoneal nodules. Patient 3 had a peritoneal carcinomatosis-like dissemination, but she has been alive with disease for 68 months. Histological examination confirmed the diagnosis of leiomyomas in the uterus and extra-uterine sites. Immunohistochemistry demonstrated that both uterine and extra-uterine tumors were invariably positive for HMGA2 and MED12. MED12 mutation (c.130 G > A, p.G44S) was found in original uterine (n = 3) and peritoneal (n = 11) tumors from patients 3, 6, 7 and 8. Microsatellite instability at TPOX and D19S433 was observed in the uterine leiomyoma (patient 2) whereas LOH at CSF1PO was found in the peritoneal tumors (patient 1). D13S317 LOH was present in both uterine and peritoneal tumors detected (patient 8). However, D3S1358 LOH and D19S433 LOH was only found in the peritoneal tumors (patient 8) and recurrent tumors (patient 3), respectively. We suggested that DPLs following morcellation might be closely associated with original uterine leiomyomas. DPLs with and without prior morcellation may harbor different pathogenetic pathways. These findings are critical for the clinical intervention and prevention of DPL patients.

摘要

: 播散性腹膜平滑肌瘤病 (DPL) 是一种罕见的良性病变,但分生后 DPL 已成为近年来关注的主要问题。本研究旨在探讨子宫肌瘤与 DPL 的分子关系。我们分析了 8 例 DPL 患者的临床病理和分子特征,包括 6 例 (#3-8) 伴和 2 例 (#1 和 2) 未合并前间隔。患者 1 和 2 的特征是大量的小腹膜结节,而患者 4-8 的腹膜结节较少但较大。患者 3 患有腹膜癌样播散,但她已存活 68 个月。组织学检查证实诊断为子宫和子宫外部位的平滑肌瘤。免疫组化显示子宫和子宫外肿瘤 HMGA2 和 med12 均呈阳性。MED12 突变 (c.130 gg  > a a,p.G44S) 见于 3 、 6 、 7 和 8 例患者的原始子宫 (n = 3) 和腹膜 (n = 11) 肿瘤。在子宫肌瘤 (患者 2) 中观察到 TPOX 和 D19S433 处的微卫星不稳定性,而在腹膜肿瘤 (患者 1) 中发现 CSF1PO 处的 LOH。D13S317 LOH 存在于检测到的子宫和腹膜肿瘤中 (患者 8)。而 D3S1358 LOH 和 D19S433 LOH 分别仅见于腹膜肿瘤 (患者 8) 和复发肿瘤 (患者 3)。我们认为,分体形成后的 DPLs 可能与原始子宫肌瘤密切相关。DPLs 伴和不伴早期分裂可能有不同的发病途径。这些发现对于 DPL 患者的临床干预和预防至关重要。

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影响因子:1.69
发表时间:2020-01-01
DOI:10.1016/j.jmig.2019.03.015
作者列表:["Oxley SG","Mallick R","Odejinmi F"]

METHODS:STUDY OBJECTIVE:To evaluate the differences in perioperative outcomes and immediate complication rates between laparoscopic myomectomy for submucous myomas and laparoscopic myomectomy for myomas in other locations. DESIGN:Retrospective cohort study. SETTING:University-affiliated hospital in London. PATIENTS:A total of 350 patients with symptomatic uterine myomas underwent laparoscopic myomectomy. Thirty-three of these were performed for submucous myomas (group 1), and 317 were for myomas in other uterine locations (group 2). INTERVENTIONS:Analysis of prospectively collected data on patient demographics, myoma characteristics, perioperative outcomes, and immediate complications. MEASUREMENTS AND MAIN RESULTS:Patient demographics, including age, body mass index, and parity, were similar in the 2 groups. No significant differences in myoma characteristics were seen between groups 1 and 2, including the mean dimension of largest myoma (7.1 vs 7.8 cm, respectively; p = .35), mean number of myomas removed (3.8 vs 4.1; p = .665), and mean mass of myomas removed (142.0 g vs 227.3 g; p = .186). There were also no significant between-group differences in any perioperative outcomes, including mean blood loss (226.8 mL vs 266.4 mL; p = .373), duration of surgery (103 minutes vs 113 minutes; p = .264), and duration of hospital stay (1.4 days vs 1.7 days; p = .057). No complications arose from laparoscopic resection of submucous myomas. CONCLUSION:Laparoscopic myomectomy for submucous myomas has similar perioperative outcomes and immediate complications as laparoscopic myomectomy for other myomas and can be considered for large or type 2 submucous myomas.

翻译标题与摘要 下载文献
影响因子:2.21
发表时间:2020-01-01
DOI:10.1111/aogs.13713
作者列表:["de Milliano I","Huirne JAF","Thurkow AL","Radder C","Bongers MY","van Vliet H","van de Lande J","van de Ven PM","Hehenkamp WJK"]

METHODS:INTRODUCTION:Laparoscopic myomectomy can be difficult when fibroids are large and numerous. This may result in extensive intraoperative bleeding and the need for a conversion to a laparotomy. Medical pretreatment prior to surgery might reduce these risks by decreasing fibroid size and vascularization of the fibroid. We compared pretreatment with ulipristal acetate (UPA) vs gonadotropin-releasing hormone agonists (GnRHa) prior to laparoscopic myomectomy on several intra- and postoperative outcomes. MATERIAL AND METHODS:We performed a non-inferiority double-blind randomized controlled trial in nine hospitals in the Netherlands. Women were randomized between daily oral UPA for 12 weeks and single placebo injection or single intramuscular injection with leuprolide acetate and daily placebo tablets for 12 weeks. The primary outcome was intraoperative blood loss. Secondary outcomes were reduction of fibroid volume, suturing time, total surgery time and surgical ease. RESULTS:Thirty women received UPA and 25 women leuprolide acetate. Non-inferiority of UPA regarding intraoperative blood loss was not demonstrated. When pretreated with UPA, median intraoperative blood loss was statistically significantly higher (525 mL [348-1025] vs 280 mL[100-500]; P = 0.011) and suturing time of the first fibroid was statistically significantly longer (40 minutes [28-48] vs 22 minutes [14-33]; P = 0.003) compared with GnRHa. Pretreatment with UPA showed smaller reduction in fibroid volume preoperatively compared with GnRHa (-7.2% [-35.5 to 54.1] vs -38.4% [-71.5 to -19.3]; P = 0.001). Laparoscopic myomectomies in women pretreated with UPA were subjectively judged more difficult than in women pretreated with GnRHa. CONCLUSIONS:Non-inferiority of UPA in terms of intraoperative blood loss could not be established, possibly due to the preliminary termination of the study. Pretreatment with GnRHa was more favorable than UPA in terms of fibroid volume reduction, intraoperative blood loss, hemoglobin drop directly postoperatively, suturing time of the first fibroid and several subjective surgical ease parameters.

影响因子:2.67
发表时间:2020-02-01
来源期刊:Histopathology
DOI:10.1111/his.14007
作者列表:["Liu C","Dillon J","Beavis AL","Liu Y","Lombardo K","Fader AN","Hung CF","Wu TC","Vang R","Garcia JE","Xing D"]

METHODS:AIMS:Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is caused by germline mutations in the Fumarate hydratase (FH) gene. In young women, the syndrome often presents with symptomatic uterine leiomyomas, leading to myomectomy or hysterectomy. In this study, we aimed to investigate the incidence and mutational profiles of FH-negative leiomyomas from young patients, thus allowing for early identification and triage of syndromic patients for surveillance. METHODS AND RESULTS:We evaluated 153 cases of uterine leiomyomas from women aged up to 30 years for loss of FH expression by tissue microarray (TMA)-based immunohistochemical staining. Mutational analysis of tumours with loss of FH was carried out by polymerase chain reaction (PCR) amplification of 10 exons within the FH gene and subsequent Sanger sequencing. The status of promoter methylation was assessed by bisulphite sequencing. Loss of FH protein expression was detected in seven (4.6%) of 153 tested uterine leiomyomas from young patients. All FH-negative leiomyomas displayed staghorn vasculature and fibrillary/neurophil-like cytoplasm. We found that six (86%) of seven FH-negative tumours detected by immunohistochemistry harboured FH mutations, 50% of which contained germline mutations. In particular, the germline mutational rate in FH gene was 2.0% (three of 153 cases). Bisulphite sequencing analysis failed to detect promoter methylation in any of the seven tumours. CONCLUSION:Our study showed a relatively high rate of FH germline mutation in FH-negative uterine leiomyomas from patients aged up to 30 years. While genetic mutations confer protein expression loss, epigenetic regulation of the FH gene appears to be unrelated to this phenotype.

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