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Genetic Analysis of Small Well-differentiated Pancreatic Neuroendocrine Tumors Identifies Subgroups With Differing Risks of Liver Metastases.

小的高分化胰腺神经内分泌肿瘤的遗传学分析确定了肝转移风险不同的亚组。

  • 影响因子:4.91
  • DOI:10.1097/SLA.0000000000003022
  • 作者列表:"Pea A","Yu J","Marchionni L","Noe M","Luchini C","Pulvirenti A","de Wilde RF","Brosens LA","Rezaee N","Javed A","Chianchiano P","Gobbo S","Regi P","Salvia R","Bassi C","He J","Weiss MJ","Cameron JL","Offerhaus GJA","Hruban RH","Lawlor RT","Scarpa A","Heaphy CM","Wood LD","Wolfgang CL
  • 发表时间:2020-03-01
Abstract

OBJECTIVE:The aim of this study was to investigate the key molecular alterations in small primary pancreatic neuroendocrine tumors (PanNETs) associated with the development of liver metastases. BACKGROUND:Well-differentiated PanNETs with small size are typically indolent; however, a limited subset metastasize to the liver. METHODS:A total of 87 small primary PanNETs (<3 cm), including 32 metastatic cases and 55 nonmetastatic cases after a 5-year follow-up, were immunolabeled for DAXX/ATRX and analyzed for alternative lengthening of telomeres (ALT) by Fluorescence In Situ Hybridization. A subset of these cases, 24 that metastasized and 24 that did not metastasize, were assessed by targeted next-generation sequencing and whole-genome copy number variation. RESULTS:In the entire cohort, high Ki-67 (OR 1.369; 95% CI 1.121-1.673; P = 0.002), N-stage (OR 4.568; 95% CI 1.458-14.312; P = 0.009), and ALT-positivity (OR 3.486; 95% CI 1.093-11.115; P = 0.035) were independently associated with liver metastases. In the subset assessed by next-generation sequencing and copy number variation analysis, 3 molecular subtypes with differing risks of liver metastases were identified. Group 1 (n = 15; 73% metastasized) was characterized by recurrent chromosomal gains, CN-LOH, DAXX mutations, and ALT-positivity. Group 2 (n = 19; 42% metastasized, including 5 G1 tumors) was characterized by limited copy number alterations and mutations. Group 3 (n = 14; 35% metastasized) were defined by chromosome 11 loss. CONCLUSIONS:We identified genomic patterns of small PanNETs associated with a different risk for liver metastases. Molecular alterations, such as DAXX mutations, chromosomal gains, and ALT, are associated with an increased risk of metastasis in small PanNETs. Therefore, targeted sequencing and/or ALT analysis may help in the clinical decisions for these small PanNETs.

摘要

目的: 本研究的目的是探讨与肝转移相关的原发性胰腺神经内分泌小肿瘤 (PanNETs) 的关键分子改变。 背景: 大小较小的高分化PanNETs通常是惰性的; 然而,有限的子集转移到肝脏。 方法: 经 5 年随访,共 87 例小原发PanNETs (<3 cm),包括 32 例转移病例和 55 例非转移病例,对DAXX/ATRX进行免疫标记,并通过荧光原位杂交分析端粒 (ALT) 的替代延长。这些病例的一个子集,24 例转移,24 例未转移,通过靶向新一代测序和全基因组拷贝数变异进行评估。 结果: 在整个队列中,高Ki-67 (OR 1.369; 95% CI 1.121-1.673; P = 0.002),N分期 (OR 4.568; 95% CI 1.458-14.312; P = 0.009) 和ALT阳性 (OR 3.486; 95% CI 1.093-11.115; P = 0.035) 与肝转移独立相关。在通过新一代测序和拷贝数变异分析评估的子集中,确定了 3 种具有不同肝转移风险的分子亚型。组 1 (n = 15; 73% 转移) 的特征为复发性染色体增益、CN-LOH、DAXX突变和ALT阳性。组 2 (n = 19; 42% 例转移,包括 5 例G1 期肿瘤) 的特征是拷贝数有限的改变和突变。组 3 (n = 14; 35% 转移) 由 11 号染色体丢失定义。 结论: 我们确定了与不同肝转移风险相关的小PanNETs的基因组模式。分子改变,如DAXX突变、染色体增益和ALT,与小pannets转移风险增加相关。因此,靶向测序和/或ALT分析可能有助于这些小pannets的临床决策。

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影响因子:4.91
发表时间:2020-03-01
来源期刊:Annals of surgery
DOI:10.1097/SLA.0000000000003022
作者列表:["Pea A","Yu J","Marchionni L","Noe M","Luchini C","Pulvirenti A","de Wilde RF","Brosens LA","Rezaee N","Javed A","Chianchiano P","Gobbo S","Regi P","Salvia R","Bassi C","He J","Weiss MJ","Cameron JL","Offerhaus GJA","Hruban RH","Lawlor RT","Scarpa A","Heaphy CM","Wood LD","Wolfgang CL"]

METHODS:OBJECTIVE:The aim of this study was to investigate the key molecular alterations in small primary pancreatic neuroendocrine tumors (PanNETs) associated with the development of liver metastases. BACKGROUND:Well-differentiated PanNETs with small size are typically indolent; however, a limited subset metastasize to the liver. METHODS:A total of 87 small primary PanNETs (<3 cm), including 32 metastatic cases and 55 nonmetastatic cases after a 5-year follow-up, were immunolabeled for DAXX/ATRX and analyzed for alternative lengthening of telomeres (ALT) by Fluorescence In Situ Hybridization. A subset of these cases, 24 that metastasized and 24 that did not metastasize, were assessed by targeted next-generation sequencing and whole-genome copy number variation. RESULTS:In the entire cohort, high Ki-67 (OR 1.369; 95% CI 1.121-1.673; P = 0.002), N-stage (OR 4.568; 95% CI 1.458-14.312; P = 0.009), and ALT-positivity (OR 3.486; 95% CI 1.093-11.115; P = 0.035) were independently associated with liver metastases. In the subset assessed by next-generation sequencing and copy number variation analysis, 3 molecular subtypes with differing risks of liver metastases were identified. Group 1 (n = 15; 73% metastasized) was characterized by recurrent chromosomal gains, CN-LOH, DAXX mutations, and ALT-positivity. Group 2 (n = 19; 42% metastasized, including 5 G1 tumors) was characterized by limited copy number alterations and mutations. Group 3 (n = 14; 35% metastasized) were defined by chromosome 11 loss. CONCLUSIONS:We identified genomic patterns of small PanNETs associated with a different risk for liver metastases. Molecular alterations, such as DAXX mutations, chromosomal gains, and ALT, are associated with an increased risk of metastasis in small PanNETs. Therefore, targeted sequencing and/or ALT analysis may help in the clinical decisions for these small PanNETs.

关键词: 暂无
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影响因子:0.50
发表时间:2020-02-01
DOI:10.1080/00015458.2018.1538283
作者列表:["Aksel B","Güven HE"]

METHODS::Background: This retrospective comparative case series study aims to analyze the pancreatic fistula rates of internal and external stenting of the pancreatojejunostomy (PJ) anastomosis in patients who underwent pancreatoduodenectomy (PD) for periampullary tumors.Methods: Ninety-eight patients with periampullary tumors who were operated between 2010 and 2017 were enrolled in this study. A classic open PD with Roux-en-Y PJ reconstruction was performed in all cases.Results: The PJ anastomosis of 53 patients (54%) were stented internally whereas in 45 patients (46%) external stenting was preferred. Pancreatic fistula was observed in 29 patients (29.6%). Internal stenting and soft pancreatic tissue were found to be related to higher pancreatic fistula rates with odds ratios of 3.27 (p = .024) and 3.4 (p = .017), respectively. When only grade B and grade C fistulas were taken into account, the type of stenting has lost its significance but the texture of the remnant pancreas was still associated with 'clinically important' pancreatic fistula.Conclusions: We concluded that the external stenting of the PJ anastomosis may be considered as an effective approach for reducing postoperative pancreatic leaks in PD-planned patients for periampullary tumors. Although our study was retrospectively designed, we used standard charts to gather patient data and compared two stenting methods among homogeneous patient groups.

关键词: 暂无
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影响因子:1.74
发表时间:2020-01-01
DOI:10.1016/j.jfma.2019.01.015
作者列表:["Yang SH","Guo JC","Hsu C","Kuo SH","Tien YW","Cheng AL","Yeh KH"]

METHODS:BACKGROUND:Heavily pretreated pancreatic cancer patients have a grave prognosis. In this case series study, we evaluated the safety and efficacy of nab-paclitaxel-based chemotherapy for such patients. METHODS:The data of pancreatic adenocarcinoma patients (n = 40) treated with nab-paclitaxel after the failure of gemcitabine or fluoropyrimidines at our institution in 2013-2015 were reviewed. RESULTS:The median number of prior chemotherapy regimens was two (range, 1-6). Eighteen patients had an Eastern Cooperative Oncology Group performance status of ≥2. The regimens comprised nab-paclitaxel combined with the following drugs: gemcitabine (n = 28), gemcitabine and fluoropyrimidine (n = 3), platinum and fluoropyrimidine (n = 4), fluoropyrimidine (n = 4), and irinotecan and fluoropyrimidine (n = 1). The median dose of nab-paclitaxel was 63 (range, 51-72) mg/m2/dose, with the schedule of D1/15, D1/8, and D1/8/15 followed in 23, 14, and 3 patients, respectively. The median overall survival was 5.1 (95% CI, 4.6-5.7) months. Among 32 evaluable patients, two partial responses and six stable diseases were observed. The median progression-free survival was 2.6 (95% CI, 1.9-3.2) months. Grade 3/4 leucopenia or neutropenia was observed in three and two patients, respectively. Grade 3/4 anemia was observed in four patients. Other significant (grade 3 or more) nonhematological toxicities were not frequent, except for sepsis/infection (n = 7). However, more severe anemia or sepsis/infection was significantly associated with disease control. CONCLUSION:In heavily pretreated pancreatic adenocarcinoma patients, low-dose nab-paclitaxel-based chemotherapy was fairly tolerable with modest efficacy.

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胰腺疾病方向

胰腺疾病是发生在胰腺的病理过程,包括胰腺先天性疾病、胰腺损伤性疾病、胰腺炎症性疾病、胰腺囊性病变和胰腺分泌性肿瘤等。

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