单孔加一孔联合ERAS在高位直肠及乙状结肠癌中的应用

目的 探讨单孔加一孔腹腔镜手术联合 ERAS 治疗高位直肠及乙状结肠癌的近期疗效。方法 回顾性分析 2017 年 11 月至2018 年 10 月在福建省肿瘤医院胃肠肿瘤外科进行加速康复外科干预的 92 例高位直肠及乙状结肠癌患者资料，根 据手术方式的不同，分为单孔加一孔手术联合快速康复外科组39 例及常规腹腔镜手术联合ERAS 组 53 例，对比两组围术 期情况。结果 两组患者基线资料无明显统计学差异（P ＞ 0.05），且在手术时间、出血量、上下切缘、清扫淋巴结数量及 并发症方面无明显统计学差异（P ＞ 0.05）。但单孔加一孔手术联合ERAS 组较常规手术联合ERAS 组，总切口长度更短 [（6.7±1.1）cm 比（8.5±1.3）cm，P=0.000]，术后首次下床时间更早 [（22.2±5.2）h 比（27.1±7.9）h，P=0.001]，首次排便 时间更早[（70.2±19.8）h比（83.1±20.4）h，P=0.005]，术后第一天C反应蛋白值更低[（43.5±28.6）mg/L比（57.2±33.2） mg/L，P=0.038]，术后住院时间更短 [（7.0±1.7）d 比（8.1±2.1）d，P=0.010]，且术后 2~4 天疼痛评分更低（P ＜ 0.05）。 结论 经验丰富的腔镜医师采用单孔加一孔手术治疗高位直肠及乙状结肠癌并联合 ERAS 干预是安全可行的，且单孔加一孔 手术可减低操作难度，具有疼痛轻、术后恢复快等优势，值得临床推广。     

Resistin is elevated in cystic fibrosis sputum and correlates negatively with lung function

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Risk factors and management of stoma-related obstruction after laparoscopic colorectal surgery with diverting ileostomy

BackgroundStoma-related obstruction (SRO) is defined as small bowel obstruction occurring around the limbs of diverting ileostomy (DI). This study was aimed to investigate the incidence, risk factors, and management of SRO after laparoscopic colorectal surgery with DI creation.MethodsThis study included 155 patients who underwent laparoscopic colorectal surgery with DI creation for rectal cancer (n = 138), ulcerative colitis (UC) (n = 14), and familial adenomatous polyposis (FAP) (n = 3) between 2011 and 2019. Univariate and multivariate analyses were performed to identify the risk factors of SRO.ResultsThe incidence of SRO was 7.7% (n = 12), and it was significantly lower (P < 0.01) in patients with lower anterior resection or intersphincteric resection (4.3%) than in those with ileal-pouch anal anastomosis (IPAA) (35.2%). The multivariate analysis revealed that IPAA was independently associated with the development of SRO (P = 0.001; odds ratio, 9.4; 95% confidence interval, 2.5–35.4). Eleven of 12 patients (92%) with SRO required trans-stomal tube decompression, and 8 of those (67%) underwent early stoma closure.ConclusionIPAA was an independent risk factor of SRO in laparoscopic colorectal surgery with DI creation. Early stoma closure was needed in most cases of SRO.     

Motivation for participating in phase 1 vaccine trials: Comparison of an influenza and an Ebola randomized controlled trial

Introduction/Hypothesis

Recruitment of participants into phase 1 vaccine clinical trials can be challenging since these vaccines have not been used in humans and there is no perceived benefit to the participant. Occasionally, as was the case with a phase 1 clinical trial of an Ebola vaccine in Halifax, Canada, during the 2014–2016 West African Ebola virus outbreak, recruitment is less difficult. In this study, we explored the motivations of participants in two phase 1 vaccine trials that were concurrently enrolling at the same centre and compared the motivations of participants in a high-profile phase 1 Ebola vaccine trial to those in a less high-profile phase 1 adjuvanted seasonal influenza vaccine study.

Use of the Covera Stent Graft for the Treatment of Dysfunctional or Thrombosed Arteriovenous Grafts: A Retrospective Analysis of 64 Patients

PurposeTo retrospectively evaluate the safety and effectiveness of the Covera stent graft (SG) for the treatment of dysfunctional or thrombosed arteriovenous grafts (AVGs).Materials and MethodsWithin 29 months (February 2016–August 2018), 79 patients underwent Covera SG placement in the authors’ department for the treatment of dysfunctional AVGs. Data were available for 64 patients who underwent 64 procedures, using 64 devices. Minimum follow-up was 6 months, unless reintervention occurred. Mean follow-up was 277 days (6–923 days). Treatment characteristics were 51 cases with venous-graft anastomosis (VGA) stenosis (79.7%), 13 cases of puncture zone stenosis (20.3%), 14 cases of in SG stenosis (21.9%), 8 cases of pseudoaneurysm treatment (12.5%) (1 treatment area might have had more than 1 characteristic). Thirty-six patients presented with thrombosis (56.2%), and 31 of 64 case were de novo treatment areas (48.4%). Primary outcome measurements were technical success and post-intervention primary patency (PIPP) at 6 months, whereas secondary outcome measurements included factors influencing primary outcome.ResultsTechnical success was 100%. Median PIPP was 336 days, and 73.6% of treatment areas were patent at 6 months. There were no significant differences in terms of PIPP when de novo treatment areas were compared with restenotic areas (519 vs. 320 days, respectively; P = .1); patients who presented with versus those who presented without thrombosis (320 vs. 583 days, respectively; P = .07); puncture zone stenosis or elsewhere (329 vs. 686 days, respectively; P = .52); and VGA stenosis or elsewhere (336 vs. 335 days, respectively; P = .9).ConclusionsUse of the Covera SG for AVG treatment was safe and effective in every type of treatment area presented in this retrospective analysis.     

Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III,randomized, observer-blind,multicenter, parallel-group study

BackgroundBroad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1 year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013.MethodsWe compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM₁₉₇) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria–tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM₁₉₇ or PRP-T vaccines. The primary endpoint was the “long-term seroprotection rate”, defined as the group proportion with anti-PRP antibody titers ⩾1.0 μg/mL, after the primary series.ResultsLong-term seroprotection rates were 99.3% in the PRP-CRM₁₉₇ group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM₁₉₇ group – PRP-T group) was 3.7% (95% confidence interval: 0.099–7.336), demonstrating that PRP-CRM₁₉₇ vaccine was non-inferior to PRP-T vaccine (p < 0.0001). Furthermore, the “short-term seroprotection rate” (anti-PRP antibody titer ⩾0.15 μg/mL) before booster vaccination was higher in the PRP-CRM₁₉₇ group than in PRP-T. Concomitant administration of PRP-CRM₁₉₇ vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM₁₉₇ vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles.ConclusionThe immunogenicity of PRP-CRM₁₉₇ vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1 year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns.Clinical trial registry: Registered on ClinicalTrials.gov: NCT01379846     

Phase 1 Study of Erlotinib and Metformin in Metastatic Triple-Negative Breast Cancer

BackgroundEpidermal growth factor receptor (EGFR) is frequently overexpressed in metastatic triple-negative breast cancer (mTNBC). One strategy for overcoming resistance to EGFR inhibition is concomitant inhibition of downstream signaling. The antidiabetic drug metformin inhibits both MAPK and PI3K/mTOR pathway signaling. We evaluated the combination of erlotinib and metformin in a phase 1 study of patients with mTNBC.Patients and MethodsPatients with mTNBC who had received at least one prior line of therapy for metastatic disease were eligible. Erlotinib dose was fixed at 150 mg daily. Metformin dose escalation was planned according to a 3 + 3 design. Dose-limiting toxicities (DLT) were assessed during the first 5 weeks of therapy. The primary objective was to determine the maximum tolerated dose of metformin with fixed-dose erlotinib. Secondary endpoints were response rate, stable disease rate, and progression-free survival.ResultsEight patients were enrolled. The median number of prior therapies for metastatic disease was 2.5 (range, 1-6). No DLT events were reported during the DLT assessment period. Most adverse events were grade 1/2. Grade 3 diarrhea despite maximum supportive care required dose reduction of metformin in one patient. Grade 3 rash led to study withdrawal in one patient. No grade 4 adverse events were reported. The best observed response was stable disease in 2 patients (25%). Median progression-free survival was 60 days (range, 36-61 days).ConclusionErlotinib and metformin were well tolerated in a population of pretreated mTNBC patients but did not demonstrate efficacy in this population.