Post-neoadjuvant strategies in breast cancer: From risk assessment to treatment escalation

The post-neoadjuvant setting in early breast cancer represents an attractive scenario for adjuvant clinical trials, offering the opportunity to test new drugs or combinations in high-risk patients who did not achieve pathologic complete response after primary treatment. No standard therapies are routinely proposed to patients with residual disease after neoadjuvant chemotherapy and few trials have explored this setting. To date, only one randomized phase III study showed the benefit of additional capecitabine after neoadjuvant chemotherapy, and international guidelines recommend at least to consider its use, particularly for triple negative breast cancer. Therefore, the management of these patients is still a clinical challenge, with limited data supporting the use of an additional adjuvant non-cross-resistant chemotherapy. Escalation strategies are currently under evaluation, with new agents proposed as supplementary post-neoadjuvant treatment (e.g. platinum salts, capecitabine, poly ADP-ribose polymerase inhibitors, immune checkpoint inhibitors, cyclin-dependent kinase 4/6 inhibitors). Based on these premises, selection criteria are critical to identify patients who may benefit from post-neoadjuvant therapies, through the validation of prognostic and predictive biomarkers for a reliable risk assessment and estimation of benefit.The present review summarizes the efforts in introducing new therapeutic options for patients with breast cancer and residual disease after neoadjuvant treatment, with a particular focus on the ongoing clinical trials and useful biomarkers for risk stratification.     

Factors influencing development of residual stresses during crystallization firing in a novel lithium silicate glass-ceramic

ObjectiveDevelopment of residual stresses is a potential source of premature fractures in glassy materials, being of special interest in novel lithium silicate glass-ceramics that require a crystallization firing to achieve their final mechanical properties. The aim of this work was to assess the influence of various firing tray systems and the application of different cooling protocols on the development of residual stresses in Suprinity PC crowns. Their effect on the in vitro lifetime of the restorations was also studied.MethodsThirty crowns were milled out of Suprinity PC blocks and crystallized using one of five different commercial firing tray systems (n = 6). Samples in each group were cooled following a fast (FC = 5.5 °C/s), a slow (SC = 0.4 °C/s) or the manufacturer’s reference cooling (REF ). Obtained crowns were sagittally or transversally sectioned and the magnitude and distribution of residual stresses was determined using the light birefringence method. Extra crowns of three of the subgroups (n = 8) were produced and submitted to chewing simulation for 10⁶ cycles or until fracture ensued.ResultsAverage residual stresses ranged between 0 and 1.5 MPa (peaks of 5 MPa). Highest stress magnitudes were observed at the support areas of groups using firing pins, leading to thermal cracks in FC samples and premature failures in the REF subgroup. The use of fibrous pads and firing pastes limited the development of residual stresses, whereas application of SC regimes extended the lifetime of the restorations.SignificanceDevelopment of residual stresses during crystallization firing in lithium silicate glass-ceramics results critical for their mechanical performance and should be therefore avoided by ensuring a homogenous cooling of the structures.     

牙冠延长术在残根残冠修复中的临床疗效

目的评价牙冠延长术在牙体缺损达龈下的残根残冠修复中的临床疗效。方法自2004年5月至2005年6月,对32例患者的36颗牙体缺损达龈下的患牙,术前按断端位于龈下最深距离分为A组(20颗患牙,距离<3.0mm)和B组(16颗患牙,3.0mm≤距离≤4.0mm),均采用牙冠延长术暴露龈下牙体断面,术后6周行桩冠修复。分别记录和比较手术前、后牙周探诊深度(PD)、菌斑指数(PLI)、龈沟出血指数(SBI)和牙齿松动度,以观察临床疗效。结果术后随访患者6个月,两组病例术后6周牙体断端均暴露较好、龈缘颜色正常,术后修复效果有效率为100%,满意率为77.78%。A组术后无松动,修复效果满意;B组术后50.00%出现Ⅰ度松动,修复效果欠佳,两组修复效果比较差异有显著意义(P<0.05)。术后各阶段两组的PD、PLI、SBI均明显优于术前(P<0.05),但两组术后牙周指数比较差异无显著意义(P>0.05)。结论牙冠延长术有利于残根残冠的保存和修复,但要注意适应证的选择。     

胆管残余结石的内镜治疗(附306例分析)

目的：探讨内镜治疗肝内外胆管残余结石的效果。方法：对1994年1月～2004年1月间306例胆道残余结石的治疗效果进行回顾性分析，采用十二指肠镜127例，胆道镜116例，经皮经肝胆道镜(PTCS)63例。结果：306例．1中有286例成功(93．46％)。十二指肠镜治疗127例成功125例；胆道镜经T管窦道治疗116例，成功109例；PTCS治疗肝内结石63例，成功52例。结论：内镜治疗肝内外胆道结石效果显著，可使绝大多数患者避免再次手术。     

78例胃窦癌的治疗分析

自１９８８年２月至１９９２年８月期间手术治疗的７８例胃窦癌患者进行了回顾性分析，手术后肿瘤复发的情况，与十二指肠断端有无癌细胞残存密切相关，并发现于幽门环下切断十二指肠少于３ｃｍ者有癌细胞残存达３４％，切除十二指肠达３ｃｍ者，无论肿瘤分化程度如何，恶性程度高低，切除断端均无癌细胞残存，手术后辅以化疗，对于病人的预后有一定提高。本组随访到的５９例病人中，接受化疗的３３例，在２年３个月至６年１个月内死亡７例（２１．２％），未接受化疗的２６例，在５个月至３年８个月内死亡的２６例，在５个月至３年８个月内死亡９例（３５％）。     

Incidence of Finding Residual Disease for Incidental Gallbladder Carcinoma: Implications for Re-resection

Re-resection for gallbladder carcinoma incidentally discovered after cholecystectomy is routinely advocated. However, the incidence of finding additional disease at the time of re-resection remains poorly defined. Between 1984 and 2006, 115 patients underwent re-resection at six major hepatobiliary centers for gallbladder carcinoma incidentally discovered during cholecystectomy. Data on clinicopathologic factors, operative details, TNM tumor stage, and outcome were collected and analyzed. Data on the incidence and location of residual/additional carcinoma discovered at the time of re-resection were also recorded. On pathologic analysis, T stage was T1 7.8%, T2 67.0%, and T3 25.2%. The median time from cholecystectomy to re-resection was 52 days. At the time of re-resection, hepatic surgery most often consisted of formal segmentectomy (64.9%). Patients underwent lymphadenectomy (LND) (50.5%) or LND + common bile duct resection (43.3%). The median number of lymph nodes harvested was 3 and did not differ between LND alone (n = 3) vs LND + common duct resection (n = 3) (P = 0.35). Pathology from the re-resection specimen noted residual/additional disease in 46.4% of patients. Of those patients staged as T1, T2, or T3, 0, 10.4, and 36.4%, respectively, had residual disease within the liver (P = 0.01). T stage was also associated with the risk of metastasis to locoregional lymph nodes (lymph node metastasis: T1 12.5%; T2 31.3%, T3 45.5%; P = 0.04). Cystic duct margin status predicted residual disease in the common bile duct (negative cystic duct, 4.3% vs positive cystic duct, 42.1%) (P = 0.01). Aggressive re-resection for incidental gallbladder carcinoma is warranted as the majority of patients have residual disease. Although common duct resection does not yield a greater lymph node count, it should be performed at the time of re-resection for patients with positive cystic duct margins because over one-third will have residual disease in the common bile duct. Presented at the 48th Annual Meeting of the Society for Surgery of the Alimentary Tract at Digestive Week 2007, Plenary Session, Washington, DC, March 23, 2007.     

肾衰合剂对维持性腹膜透析患者残余肾功能的影响

目的：观察肾衰舍剂对连续不卧床腹膜透析（CAPD）患者残余肾功能的影响，探讨中药治疗对CAPD患者残余肾功能的保护作用及其机制。方法：将56例脾肾气（阳）虚型的CAPD患者随机分为常规腹膜透析对照组，及加服中药肾衰合剂治疗组。治疗6个月，比较残余肾KT／V、残余肾CCr的变化及下降速率。结果：在维持总体透析效能的前提下，治疗组残余肾KT／V、残余肾CCr下降速度较对照组明显缓慢。结论：肾衰合荆能有效延缓PD患者的RRF的下降。     

七氟醚、异氟醚对阿曲库铵肌松恢复的影响

目的 观察七氟醚、异氟醚对阿曲库铵肌松恢复的影响.方法 选择75例Ⅰ或Ⅱ级成年择期全麻手术病人随机均分为三组.Ⅰ组丙泊酚4～10 mg·kg-1·h-1泵入;Ⅱ、Ⅲ组分别吸入呼气末浓度为1 MAC的七氟醚、异氟醚.诱导插管后阿曲库铵均以30μg·kg-1·min-1的速度静脉泵入.使用Biomter加速度仪监测肌松恢复情况,记录T1恢复至25%,75%及TOFr恢复至0.7的时间.结果 Ⅱ、Ⅲ组T1恢复至25%、75%的时间及TOFr恢复至0.7的时间均比Ⅰ组显著延长(P＜0.05).恢复指数(T1从25%至75%的时间)三组比较差异无统计学意义.结论 七氟醚、异氟醚均可增加阿曲库铵残余肌松作用.     

顶空气相色谱法测定醋酸烯诺孕酮埋植剂中环氧乙烷的残留量

用顶空气相色谱法测定醋酸烯诺孕酮埋植剂中环氧乙烷的残留量，结果表明，线性试验与精密度良好，平均回收率为99．8％，残留量为0．93％。样品在灭菌后，室温放置3天，其环氧乙烷残留量均在0．0001％以下，符合环氧乙烷残留量应不大于0．001％的规定。表明采用顶空气相色谱法测定醋酸烯诺孕酮理植剂中环氧乙烷残留量，方法简便，结果准确，适用于对该产品中环氧乙烷残留量的检测与控制。     

Interstitial Stress and Fluid Pressure Within a Growing Tumor

A solid tumor is composed of a population of cells that is expanding as a result of cell division. With dense cell packing, the solid matrix of the interstitial tissue is subject to residual stress. In addition, elevated interstitial fluid pressure (IFP) has been reported by researchers for a number of solid tumors. These features were incorporated into a mathematical model that predicts the mechanical response of a solid tumor within its host environment. A theoretical framework accounting for volumetric expansion, transvascular exchange and extravascular transport of fluids was developed using poroelastic theory, and applied to a spherical, vascularized, alymphatic tumor undergoing small growth increments. Simulations of tumor IFP were similar to those predicted by Jain and Baxter (Ref. 23), showing elevated IFP that is driven by microvascular fluid pressure. Tumor growth, tissue stiffness, and IFP contribute to the compressive stresses predicted in the solid tumor interior. Tensile and compressive stresses were predicted in adjacent host tissues corresponding to radial and circumferential directions, respectively. An application of this model includes a solid stress-based framework for predicting regions of vascular collapse within the tumor interior. © 2003 Biomedical Engineering Society. PAC2003: 8717Ee, 8710+e, 8719Rr, 8719Xx