Intrahepatic cholangiocarcinoma: current management and emerging therapies

Introduction: Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with an increasing incidence and a high-case fatality. While surgery offers the best hope at long-term survival, only one-third of tumors are amenable to surgical resection at the time of the diagnosis. Unfortunately, conventional chemotherapy offers limited survival benefit in the management of unresectable or metastatic disease. Recent advances in understanding the molecular pathogenesis of iCCA and the use of next-generation sequencing techniques have provided a chance to identify ‘target-able’ molecular aberrations. These novel molecular therapies offer the promise to personalize therapy for patients with iCCA and, in turn, improve the outcomes of patients.

Area covered: We herein review the current management options for iCCA with a focus on defining both established and emerging therapies.

Expert commentary: Surgical resection remains as an only hope for cure in iCCA patients. However, frequently the diagnosis is delayed till advanced stages when surgery cannot be offered; signifying the urge for specific diagnostic tumor biomarkers and targeted therapies. New advances in genomic profiling have contributed to a better understanding of the landscape of molecular alterations in iCCA and offer hope for the development of novel diagnostic biomarkers and targeted therapies.     

Progress towards the treatment of Ebola haemorrhagic fever

Being highly pathogenic for human and nonhuman primates and the subject of former weapon programmes makes Ebola virus one of the most feared pathogens worldwide today. Due to a lack of licensed pre- and postexposure intervention, the current response depends on rapid diagnostics, proper isolation procedures and supportive care of case patients. Consequently, the development of more specific countermeasures is of high priority for the preparedness of many nations. Over the past years, enhanced research efforts directed to better understand virus replication and pathogenesis have identified potential new targets for intervention strategies. The authors discuss the most promising therapeutic approaches for Ebola haemorrhagic fever as judged by their efficacy in animal models. The current development in this field encourages discussions on how to move some of the experimental approaches towards clinical application.     

Advances in the diagnosis and management of diabetic distal symmetric polyneuropathy

Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of diabetes mellitus. The pathogenesis of DSPN is not fully elucidated, but it is certainly multifactorial in nature and attributable to metabolic and microvessel disorders related to chronic hyperglycemia, diabetes duration, and several cardiovascular risk factors. Early diagnosis and appropriate management are extremely important, since up to 50% of DSPN cases may be asymptomatic, and patients are unaware of foot injury leading to foot ulcers and amputation. Simple, validated tests such as the Neuropathy Disability Score and/or Vibration Perception Threshold may be used to diagnose DSPN. Similarly, neurological dysfunction screening questionnaires should be used to assess the quality and severity of DSPN symptoms. Using both methods enables prediction of the prognosis of diabetic patients with DSPN. No causative treatment of DSPN is known, but the results of clinical trials indicate that several treatment options are highly effective in symptomatic treatment of painful DSPN. The appropriate treatment of DSPN may improve the outcome, preventing or delaying the development of numerous diabetic complications.     

从瘀热辨治子痈的临证思路与经验——周仲瑛教授瘀热病机男科运用

国医大师周仲瑛教授结合多年的临床经验对"瘀热"病机理论进行较为系统的论述。在周仲瑛教授指导下,通过文献分析,结合临床实践,初步探讨子痈瘀热的病机概念、临床表现、辨证思路、组方用药特点,并举案例说明,以更好丰富"瘀热"理论,也为子痈的辨证施治提供新的思路。     

中医外治法在高血压病治疗中的应用

高血压病是世界性常见病和多发病，是我国脑卒中和冠心病的主要致病因素，传统西医治疗有明显副作用，中医外治法在高血压病治疗护理方面效果良好，无毒副作用，价格低廉，患者易于接受，便于推广。     

不同评价方法对介入放射工作人员个人剂量监测结果的影响

结核分枝杆菌（Mycobacterium tuberculosis, MTB）感染人体后，有两种不同的发病类型，即原发性结核病和原发后（继发性）结核病。本文重点回顾近几年结核病发病学的重要进展，包括以肺泡巨噬细胞、脂质体、泡沫巨噬细胞、肉芽肿等为结构特点的原发性结核病，在结核发病过程中所起到的保护性免疫作用，以及结核空洞等继发性结核病所造成的组织破坏性免疫反应，导致MTB释放、逃离并播散。局部组织MTB抗原持续存在与宿主高致敏淋巴细胞游走，是形成结核免疫独具特色koch现象的基础，决定潜伏性MTB感染向活动性结核病的转化。当前MTB潜伏感染人群很大，因此加强筛查仍是结核病防控的首要措施。     

Breast implant-associated ALK-negative anaplastic large cell lymphoma: a case report and discussion of possible pathogenesis

Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized clinical entity, with only 39 well-documented cases reported worldwide, including 3 fatalities. Because of its rarity, the clinical and pathologic features of this malignancy have yet to be fully defined. Moreover, the pathogenesis of ALCL in association with textured silicone gel breast implants is poorly understood. Here we report a case of BIA-ALCL arising in a 67-year-old woman with a mastectomy due to breast cancer followed by implantation of textured silicone gel breast prosthesis. The patient presented with breast enlargement and tenderness 8 years following reconstructive surgery. MRI revealed a fluid collection surrounding the affected breast implant. Pathologic examination confirmed the presence of malignant ALCL T cells that were CD30+, CD8+, CD15+, HLA-DR+, CD25+ ALK- and p53. A diagnosis of indolent BIA-ALCL was made since tumor cells were not found outside of the capsule. Interestingly, an extensive mixed lymphocytic infiltrate and ectopic lymphoid tissue (lymphoid neogenesis) adjacent to the fibrous implant capsule were present. The patient was treated with capsulectomy and implantation of new breast prostheses. Six months later, the patient was found to have BIA-ALCL involvement of an axillary lymph node with cytogenetic evolutionof the tumor. To our knowledge, this is the sixth reported case of aggressive BIA-ALCL. Unique features of this case include the association with lymphoid neogenesis and the in vivo cytogenetic progression of the tumor. This case provides insight into the potential role of chronic inflammation and genetic instability in the pathogenesis of BIA-ALCL.     

Practical analysis of pars flaccida cholesteatoma with classification and staging system proposed by Japan Otological Society: a comparative study

Abstract

Background: The Japan Otology Society (JOS) proposed the classification and staging system for middle ear cholesteatoma. However, there was little analysis of the pathology of cholesteatoma using this staging system.

Aims/objectives: To analyze the pathology of pars flaccida cholesteatoma using the staging system by JOS.

Material and methods: A total of 183 cases of fresh pars flaccida cholesteatoma treated between January 2009 and December 2015 were included. We used the staging system recommended by JOS (2015). The association of the following variables in each stage of pars flaccida cholesteatoma was examined: age, gender, preoperative hearing level, staging, statuses of mastoid cell growth and stapes, tympanic sinus invasion.

Results: Stage II disease showed the highest degree of progression, and peak incidence was observed in the third and fourth decades of life. Stage III significantly increased after the age of 40 years. The progression of the disease stage was significantly associated with deterioration of hearing level. Cholesteatoma invasion to tympanic sinus was recognized in 14.2% of cases. The state of the stapes is increasingly likely be to fracture as stage progresses.

Conclusions: The JOS Staging System appropriately reflects the disease state, and it was found to be clinically meaningful in this study.