宫颈癌顺铂耐药研究进展

顺铂（DDP）作为第一个被发现的金属抗癌药物，是目前最有潜力和应用最广泛的抗肿瘤药物。顺铂在宫颈癌的治疗中尤为重要，目前已被推荐为同步放化疗的首选药物。但随着广泛的使用，顺铂的耐药性逐渐显露出来，并成为限制临床疗效和部分患者肿瘤治疗进展的主要原因之一。顺铂的耐药机制复杂，发生环节较多，但具体耐药机制尚不明确，目前按照顺铂耐药发生的环节可分为:①顺铂在血液循环过程中产生耐药；②顺铂通过细胞膜的流入或流出产生耐药；③顺铂在胞质中产生耐药；④顺铂与DNA结合后产生耐药。本文综述了宫颈癌顺铂耐药可能发生的四个环节及克服耐药常用的手段，为提高顺铂对宫颈癌的疗效提供依据。     

Utility of teledermatopathology for intraoperative margin assessment of melanoma in situ,lentigo maligna type: A 6 year community practice experience

BackgroundAchieving negative margins for melanoma in situ, lentigo maligna type can be challenging, particularly on cosmetically sensitive areas.ObjectiveTo assess the utility of intraoperative frozen section margin assessment using a teledermatopathology system in the treatment of head and neck lentigo maligna.Methods and materialsOver a 6 year period, 96 patients with lentigo maligna had surgical excisions. The margins were assessed intraoperatively with frozen sections prepared in the manner used in Mohs surgery. The surgeon guided the frozen section slides around the margin while a dermatopathologist assessed the margin remotely.ResultsIn 2/96 (2.1%) cases, the safety margin was positive (frozen sections were false negative). In 1 further case (1%) there was a recurrence of the melanoma 13 months following the excision.ConclusionThe described method is effective in treating melanoma in situ, lentigo maligna type with clearance rates similar to previous studies for Mohs surgery.     

Laparoscopic versus open pancreatoduodenectomy: an individual participant data meta-analysis of randomized controlled trials

BackgroundRandomized trials have compared laparoscopic pancreatoduodenectomy (LPD) to open pancreatoduodenectomy (OPD) with conflicting results. An IPDMA may give more insight into the differences between LPD and OPD, and could identify high-risk subgroups.MethodsA systematic literature search was performed in the Pubmed, Embase, and the Cochrane library databases (October 2019). Out of 1410 studies, three randomized trials were identified. Primary outcome was major complications (Clavien-Dindo grade ≥ III). Subgroup analyses were performed for high-risk subgroups including patients with BMI of ≥25 kg/m2, pancreatic duct <3 mm, age ≥70 years, and malignancy.ResultsData from 224 patients were collected. After LPD, major complications occurred in 33/114 (29%) patients compared to 34/110 (31%) patients after OPD (adjusted odds ratio (OR) 0.62; 95% confidence interval (CI) 0.3–1.4, P = 0.257). No differences were seen for major complications and 90-day mortality LPD 8 (7%) vs OPD 4 (4%) (adjusted OR 0.2; 95% CI 0.02–1.3, P = 0.080). With LPD, operative time was longer (420 vs 318 min, p < 0.001) and hospital stay was shorter (mean difference ?6.97 days). Outcomes remained stable in the high-risk subgroups.ConclusionLPD did not reduce the rate of major postoperative complications as compared to OPD. LPD increased operative time and shortened hospital stay with 7 days.     

CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma

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Influenza vaccination-induced H3 stalk-reactive memory B-cell clone expansion

Current vaccine formulations elicit a recall immune response against viruses by targeting epitopes on the globular head of hemagglutinin (HA), and stalk-reactive antibodies are rarely found. However, stalk-specific memory B-cell expansion after influenza vaccination is poorly understood. In this study, B cells were isolated from individuals immunized with seasonal tetravalent influenza vaccines at days 0 and 28 for H7N9 stimulation in vitro. Plasma and supernatants were collected for the analysis of anti-HA IgG using ELISA and a Luminex assay. Memory B cells were positively enriched, and total RNA was extracted for B cell receptor (BCR) H-CDR3 sequencing. All subjects displayed increased anti-H3 antibody secretion after vaccination, whereas no increase in cH5/3-reactive IgG levels was detected. The number of shared memory B-cell clones among individuals dropped dramatically from 593 to 37. Four out of 5 subjects displayed enhanced frequencies of the VH3-23 and VH3-30 genes, and one exhibited an increase in the frequency of VH1-18, which are associated with the stalk of HA. An increase in H3 stalk-specific antibodies produced by B cells stimulated with H7N9 viruses was detected after vaccination. These results demonstrated that H3 stalk-specific memory B cells can expand and secrete antibodies that bind to the stalk in vitro, although no increase in serum H3 stalk-reactive antibodies was found after vaccination, indicating potential for developing a universal vaccine strategy.     

动态增强磁共振参数与局部晚期鼻咽癌患者预后相关性的前瞻性长期随访研究

目的 探讨动态增强磁共振（DCE-MRI）半定量参数与局部晚期鼻咽癌患者长期预后的关系,为局部晚期鼻咽癌患者预后寻找无创性的预测指标。方法 收集贵州省肿瘤医院2011年1月至2012年1月一项前瞻性临床研究的局部晚期鼻咽癌患者的临床信息,国际抗癌联盟（UICC）2010分期Ⅲ、Ⅳ_A、Ⅳ_B期,先行多西紫杉醇+顺铂+5''-氟尿嘧啶（TPF）方案时辰诱导化疗3周期;后予调强放疗（IMRT）同期紫杉醇化疗2周期。诱导化疗前均行DCE-MRI检查,并获取DCE-MRI相关半定量参数,将DCE-MRI相关半定量参数与同期放化疗结束的鼻咽病灶近期疗效进行相关性分析。结果 77例患者中,71例完成治疗并有长期完整随访信息,中位随访77个月（9~86个月）,3年、5年OS分别为80.2%、67.6%;3年、5年PFS分别为73.2%、60.5%;同步放化疗结束鼻咽病灶近期疗效评价完全缓解（CR）组与部分缓解（PR）组之间的造影剂到达组织时间的差异具有统计学意义（t=0.537,P<0.05）;单因素生存分析发现,造影剂到达组织时间短组的OS（χ²=3.982,P<0.05）和PFS（χ²=4.019,P<0.05）均高于造影剂到达组织时间长组;年龄≥ 45岁的患者OS（χ²=7.593,P<0.05）和PFS（χ²=5.624,P<0.05）明显低于年龄<45岁的患者。Cox多因素回归模型发现,临床分期晚（Ⅳ_A、Ⅳ_B期）（P=0.048）、年龄≥ 45岁（P=0.031）是鼻咽癌患者OS的独立不良预后因素;而造影剂到达组织时间长（P=0.018）、年龄≥ 45岁（P=0.004）、N（2~3期）分期晚（P=0.032）和强化峰值<3 000（P=0.005）则为鼻咽癌患者PFS的独立不良预后因素。结论 DCE-MRI参数造影剂到达组织时间可能作为局部晚期鼻咽癌患者预后可靠的影像学指标。     

Risk-based,response-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new-regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram-revised risk index (NRI). A comparative study was performed using propensity score-matched (PSM) analysis. Adding new-regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression-free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate-risk/high-risk patients, but not for low-risk patients. For intermediate-risk/high-risk patients, RT + CT and CT + RT resulted in non-significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk-based, response-adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate-risk/high-risk early-stage patients with ENKTCL in the modern treatment era.