A Prospective, Multi-Center Phase I Study of Postoperative Enoxaparin Treatment in Patients Undergoing Curative Hepatobiliary-Pancreatic Surgery for Malignancies.
- 作者列表："Eguchi H","Kawamoto K","Tsujie M","Yukawa M","Kubota M","Asaoka T","Takeda Y","Noda T","Shimizu J","Nagano H","Doki Y","Mori M
BACKGROUND:Venous thromboembolism (VTE) is one of the critical complications that can occur after surgery. A positive association between cancer and VTE risk is well established; however, the safety and efficacy of VTE prophylaxis have not been established in hepatobiliary-pancreatic surgery, especially in surgery for malignancies. METHODS:A prospective, multi-center Phase I study to determine the safety of enoxaparin was performed. Subcutaneous injection of enoxaparin was initiated 48-72 h after surgery and repeated for 8 days. The primary endpoint was the incidence of bleeding events. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000007761). RESULTS:A total of 154 patients was registered and 133 patients including 74 hepatectomies and 35 pancreaticoduodenectomies were analyzed. Three patients (2.3%) exhibited major bleeding events postoperatively, while 7 (5.2%) had minor bleeding. No Symptomatic VTE was observed. CONCLUSIONS:Our study indicated that enoxaparin was well tolerated and safe for patients who received hepatobiliary-pancreatic surgery for malignancies.
背景: 静脉血栓栓塞症 (VTE) 是手术后可能发生的严重并发症之一。癌症和VTE风险之间的正相关已被确定; 然而，在肝胆胰手术中，特别是在恶性肿瘤手术中，VTE预防的安全性和有效性尚未确定。 方法: 进行了一项前瞻性、多中心I期研究，以确定依诺肝素的安全性。术后48-72 h开始皮下注射依诺肝素，重复8天。主要终点是出血事件的发生率。本研究在大学医院医学信息网临床试验注册中心 (UMIN000007761) 注册。 结果: 共登记了154例患者，分析了133例患者，包括74例肝切除术和35例胰十二指肠切除术。3例患者 (2.3%) 术后出现大出血事件，7例 (5.2%) 出现轻微出血。未观察到有症状的VTE。 结论: 我们的研究表明，对于接受肝胆胰手术治疗恶性肿瘤的患者，依诺肝素具有良好的耐受性和安全性。
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.
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.
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.