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。     

Occupational hydrocarbon exposure and chronic nephropathy

This review aims at discussing the questions raised by the hydrocarbon-related chronic nephropathy and its possible consequence, the hydrocarbon-related chronic renal failure. It has been attempted to adopt the point of view of the clinician. Therefore, the most important part of the review is devoted to a presentation and an analysis of the available data on humans. The main features of the available studies on human subjects are presented, their conclusions discussed in the light of the possible methodological flaws, and practical conclusions drawn. After a discussion of the main difficulties encountered for selecting the suitable exposure indicator, the studies are discussed in order of decreasing quality of the study design (cohort, case-control, cross-sectional studies, and the case reports). It is concluded that a great deal of controversies about chronic hydrocarbon-related nephropathy is explained by differences in the study design and that hydrocarbon-induced nephropathy is probably more than a mere hypothesis, although a causal relationship has not yet been proven. Finally, some practical consequences for dealing with a hydrocarbon-exposed patient diagnosed with a kidney disease and the need for further research are discussed.     

The use of experimental studies to reveal suspected neurotoxic chemicals as occupational hazards: acute and chronic exposures to organic solvents.

The nervous system differs from many other body organs by its central control of vital functions and its low regeneration capacity. Organic solvents have, as a group, been suspected to have neurotoxic effects. Because of their similar physical properties and the fact that in industrial uses, they are often present in various mixtures, organic solvents have also been regarded, unfortunately, to induce common neurotoxic effects. However, it is evident from experimental studies using specified exposure conditions that different organic solvents have very diverse neurotoxic effects and also that the toxic mechanism may differ between acute and chronic exposure. No specific method used to describe a neurotoxic effect or single toxic response can be used for the overall occupational risk assessment of all organic solvents. Each solvent has to be considered as having its own unique toxic effects.     

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。     

A review of the effect of pesticide formulations on male fertility

Experimental studies suggest that large numbers of chemicals, environmental and industrial pollutants affect the male reproductive system. At present, almost no information is available on the effects of these adverse agents on human reproduction. Recent reports, however, suggest that in the past 50 years male fertility has declined based on qualitative and quantitative measurements of normal sperm. This study identifies‐among the active ingredients and solvents included in pesticide formulations registered in Italy‐the chemical agents with experimental evidence of male reproductive toxicity. Documents produced by international agencies and organizations such as IARC, EPA, WHO, and original papers from the international literature were systematically reviewed. The results indicate that several pesticide products notified in the Italian Registry contain active ingredients and/or solvents severely affecting testicular function and sperm morphology in laboratory animals. Therefore, exposure to reproductive toxicants occurring among manufacturers and users of pesticide formulations registered in Italy suggest further epidemiologic surveys should be conducted in this area.     

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％）。