Multilevel mechanism of immune checkpoint inhibitor action in solid tumors: History,present issues and future development

Immunotherapy with checkpoint inhibitors (antibodies that target and block immune checkpoints in the tumor microenvironment) is included in the standard of care for patients with different types of malignancy, such as melanoma, renal cell and urothelial carcinoma, lung cancer etc. The introduction of this new immunotherapy has altered the view on potential targets for treatment of solid tumors from tumor cells themselves to their immune microenvironment; this has led to a reconsideration of the mechanisms of tumor-associated immunity. However, only a subset of patients benefit from immunotherapy and patient response is often unpredictable, even with known initial levels of prognostic markers; the biomarkers for favorable response are still being investigated. Mechanisms of immune checkpoint inhibitors efficiency, as well as the origins of treatment failure, require further investigation. From a clinical standpoint, discrepancies between the theoretical explanation of inhibitors of immune checkpoint actions at the cellular level and their deployment at a tissue/organ level impede the effective clinical implementation of novel immune therapy. The present review assessed existing experimental and clinical data on functional activity of inhibitors of immune checkpoints to provide a more comprehensive picture of their mechanisms of action on a cellular and higher levels of biological organization.     

B超引导下多孔猪尾管置管引流的临床应用研究

目的　采用姑息性手段解除晚期恶性肿瘤病人的阻塞性黄疸 ,提高病人的生活质量。方法　 32例壶腹部占位、胆囊占位伴肝门部转移、胰头占位及胆总管占位病人 ,通过专用超声穿刺探头及 18号针将自制多孔猪尾管置入病人扩张的胆管内并保留。结果　 32例患者穿刺后 1周 ,肝内外胆管的直径分别由穿刺前的 0 6 5±0 10cm、1 85± 0 2 2cm下降为 0 35± 0 0 8cm、1 0 2± 0 12cm ;血清直接胆红素由穿刺前的 5 2 2 8± 5 93μmol L下降为10 6 8± 1 5 7μmol L。穿刺前后相比P <0 0 1。病人的临床症状明显改善。 结论　该方法简便 ,准确率高 ,无明显的副作用 ,而且经济实用 ,具有推广应用价值。     

核除术治疗儿童良性睾丸肿瘤

目的探讨睾丸肿瘤核除术治疗儿童良性睾丸肿瘤的可行性。方法22例患者在2000~2005年间行睾丸肿瘤核除术,复习他们的临床资料、组织病理学及随访数据。随访时间1~5年。结果睾丸肿瘤患者就诊时AFP和β-HCG水平在正常范围,术前均行睾丸超声及CT检查,每例患者术中均行腹股沟探查游离精索,肿瘤摘除后在修复睾丸前需行冰冻切片证实为良性,随访1~5年仅1例复发。在研究中所有睾丸组织均正常。结论睾丸肿瘤核除术能够保护睾丸组织,利于整形及功能的恢复,且术后复发率极低,因此是小儿良性睾丸肿瘤治疗中是一种有效的方法。     

Primary retroperitoneal cavernous hemangioma: An exceptional disease in adulthood

Primary retroperitoneal cavernous hemangioma is an extremely rare disease in clinical practice. It is classified as a vascular tumor. Only three cases have been reported in the literature. The diagnosis is uncommon due to the lack of specific radiological features. It becomes symptomatic as a consequence of its enormous size or complications like rupture or compression. We herein report a unique case of primary retroperitoneal cavernous hemangioma treated with conventional surgery in a 35‐year‐old male patient admitted to our department for chronic abdominal pain. Retroperitoneal cavernous hemangioma is an extremely rare vascular tumor in adulthood. Confirmation is made by histopathological examination after total surgical resection.     

幕上不同部位肿瘤的图形视觉诱发电位研究

对25例鞍区(A组)和27例幕上非鞍区肿瘤(B组)进行了P-VEP测试。结果A组异常率92%,B组异常率59.2%。VEP异常表现为P_100波波幅降低和/或潜伏期延迟.波形畸变乃至辨认困难或消失。A组VEP异常与视力、视野改变基本一致;B组VEP异常与视力、视野相关性差。资料表明,全视野P—VEP对鞍区枕叶肿痛的筛选诊断和视交叉或交叉后视通路损害的鉴别有参考价值,对早期发现幕上肿瘤患者的视功能损害和评价术后鞍区肿瘤患者的视功能恢复也有意义。     

危险区骨骼肌肉系统肿瘤的外科治疗

目的:介绍一种安全处理危险区骨骼肌肉系统良性或低度恶性肿瘤的外科治疗方法。方法:对骶2脊索瘤先施行前路经腹结扎双侧髂内动脉,然后再切除肿瘤,可减少出血。对腹股沟区或腘窝区较大肿瘤与股、腘大血管及神经紧密粘连者,先从肿瘤远近端血管、神经正常部分解剖出血管神经,再向病变区解剖,容易完整切除肿瘤。对锁骨上区肿瘤,先截除一段锁骨,然后从肿瘤远近端正常锁骨下动、静脉及臂丛神经处,向肿瘤部游离并保护好胸膜,可较安全地切除肿瘤。而对于腓骨头、颈及其周围部肿瘤,先解剖出腓总神经及其各肌支,尽可能保留肌支。结果:11例危险区(紧邻大血管、神经区域)良性或低度恶性骨骼肌肉系统肿瘤,采用先从肿瘤远近端正常血管、神经处游离出神经、血管,再向肿瘤部解剖,均顺利解剖出大血管及神经,并完整切除肿瘤。所有病例无复发,亦无肢体功能障碍。结论:对紧邻重要血管及神经的较大良性或低度恶性骨骼肌肉系统肿瘤,先从正常段血管、神经向肿瘤部解剖游离,既可彻底切除肿瘤,又可避免损伤血管、神经引起肢体功能障碍,是一种较好方法。     

Clinical Aspects of Feline Retroviruses: A Review

Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia), and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less commonly diagnosed than in the previous 20 years; prevalence has been decreasing in most countries. However, FeLV importance may be underestimated as it has been shown that regressively infected cats (that are negative in routinely used FeLV tests) also can develop clinical signs. FIV can cause an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. This article provides a review of clinical syndromes in progressively and regressively FeLV-infected cats as well as in FIV-infected cats.     

Comparing radiation toxicities across species: An examination of radiation effects in Mus musculus and Peromyscus leucopus

Abstract

Purpose: Life shortening and pathological complications in similarly irradiated cohorts of the laboratory mouse Mus musculus and the white-footed mouse Peromyscus leucopus were recorded in the course of the Janus studies conducted at Argonne National Laboratory from 1970–1992. This study examines how lifespan, tumor and non-tumor disease incidence, and tumor multiplicity are differentially affected by gamma-rays and neutron radiation exposure in two different animal species.

Materials and methods: Survival analyses examined differences in lifespan across species, while decision tree analyses examined statistically significant associations between lifespan, radiation exposure, and specific diseases. Logistic regression models were generated to examine the likelihood of disease incidence in these two species following gamma-ray or neutron radiation exposure.

Results: Life shortening in response to radiation was more significant in Peromyscus leucopus than in Mus musculus, irrespective of radiation quality. Many types of tumor and non-tumor diseases were found to be consistently species specific. Tumor multiplicity was observed in both species in response to radiation, although more pronounced in Mus musculus.

Conclusion: The response to radiation was highly species specific, highlighting the difficulty in extrapolating conclusions from one species to another, irrespective of their phenotypic similarities and ecologic niches.     

Fifteen years’ experience of intestinal and multivisceral transplantation in the Nordic countries

Abstract

Objective. Intestinal and multivisceral transplantation have gained acceptance as treatment modalities for patients with: intestinal failure and life-threatening complications of parenteral nutrition (PN), rare cases of vascular abdominal catastrophes and selected cases of low-grade neoplastic tumors such as neuroendocrine pancreatic tumors and desmoids involving the mesenteric root. The aim was to describe the survival and nutritional outcome in the transplanted Nordic patients and the complications attributed to this procedure. Method. The authors included all Nordic patients transplanted between January 1998 and December 2013. Information on patients transplanted outside the Nordic region was collected through questionnaires. Results. A total of 34 patients received different types of intestinal allografts. Currently, there are two Nordic transplant centers (n = 29) performing these procedures (Gothenburg, Sweden n = 24, Helsinki, Finland n = 5). The remaining five patients were transplanted in the USA (n = 3) and the UK (n = 2). Most patients were transplanted for life-threatening failure of PN (70%) caused primarily by intestinal motility diseases (59%). Allograft rejection was the most common complication and occurred in 79% of the patients followed by post-transplantation lymphoproliferative disorders (21%) and graft-versus-host disease (18%). The 1- and 5-year survival was 79% and 65% respectively for the whole cohort and nutritional autonomy was achieved in 73% of the adults and 57% of the children at 1 year after transplantation. Conclusion. This collective Nordic experience confirms that intestinal transplantation is a complex procedure with many complications, yet with the possibility to provide long-term survival in selected conditions previously considered untreatable.     

Pegfilgrastim for the prevention of chemotherapy-induced febrile neutropenia in patients with solid tumors

Introduction: Neutropenia and febrile neutropenia are the most common and most severe bone marrow toxicities of chemotherapy. Recombinant granulocyte-colony stimulating factors (G-CSFs), both daily (filgrastim and biosimilars, and lenograstim) and long-acting (pegfilgrastim and lipegfilgrastim) formulations, are currently available to counteract the negative consequences of these side effects.

Areas covered: The purpose of this article is to review the physiopathology of chemotherapy-induced febrile neutropenia and its consequences, and the current evidence regarding the pharmacological properties, clinical efficacy and cost-effectiveness of pegfilgrastim as a strategy to prevent chemotherapy-induced febrile neutropenia in patients with solid tumors.

Expert opinion: Chemotherapy-induced febrile neutropenia and its complications are still a major health-care concern, and the inappropriate employment of G-CSFs in clinical practice can partially explain its burden. Pegfilgrastim has pharmacological advantages over daily G-CSFs that makes it easily administrable, thus reducing the chance of incorrect delivery. The once-per-cycle administration might explain the findings derived from observational studies suggesting a possible superior efficacy of pegfilgrastim over daily G-CSFs. For patients at higher risk of failure with daily G-CSF prophylaxis (e.g. risk of non-compliance, difficulties on performing regular hemograms, high risk of developing febrile neutropenia), pegfilgrastim might be the most appropriate option.