Histopathology Image Analysis in Two Long‐Term Animal Experiments with Helical Flow Total Artificial Heart

Histopathological analysis can provide important information in long‐term experiments with total artificial heart (TAH). Recently, a new type of blood pump, the helical flow total artificial heart (HF‐TAH) was developed. This study aimed to investigate the changes in selected vital organs in animal experiments with implanted HF‐TAH. Samples from lung, liver, and kidneys from two female goats (No. 1301 and No. 1304) with implanted HF‐TAH were analyzed. Tissue samples were fixed in 10% formaldehyde and 4 µm thick transverse sections were stained with hematoxylin‐eosin (HE). Additional staining was done for detection of connective tissue (Masson‐Goldner stain) and for detection of iron (hemosiderin) deposits (Perls stain). Sections were scanned at 100× and 500× magnification with a light microscope. Experiment no. 1301 survived 100 days (cause of termination was heavy damage of the right pump); experimental goat no.1304 survived 68 days and was sacrificed due to severe right hydrodynamic bearing malfunction. Histopathological analysis of liver samples proved signs of chronic venostasis with limited focal necrotic zones. Dilated tubules, proteinaceous material in tubular lumen, and hemosiderin deposits were detected in kidney samples. Contamination of the organs by embolized micro‐particles was suspected at the autopsy after discovery of visible damage (scratches) of the pump impeller surface (made from titanium alloy) in both experiments. Sporadic deposits of foreign micro‐particles (presumably titanium) were observed in most of the analyzed parenchymal organs. However, the described deposits were not in direct connection with inflammatory reactions in the analyzed tissues. Histopathological analysis showed the presence of minimal contamination of the lung, kidney, and liver tissue samples by foreign material (titanium very likely). The analysis showed only limited pathological changes, especially in liver and kidneys, which might be attributed to the influence of artificial perfusion often observed in chronic TAH experiments.     

Melatonin protects against epirubicin-induced cardiotoxicity

We investigated the cytoprotective effect of melatonin in epirubicin-induced cardiotoxicity using four experimental groups of male Wistar rats: untreated control rats, epirubicin-treated rats, epirubicin+melatonin-treated rats, and melatonin-treated rats. We examined the histopathological and biochemical effects of melatonin on the epirubicin-induced changes and measured the levels of the lipid peroxidation end-product (malondialdehyde, MDA), an indicator of nitric oxide (NO) synthesis (nitrite/nitrate production), and reduced glutathione (GSH) in the heart. We also studied the extracellular matrix components (fibronectin, laminin) in the heart. Vacuole formation, mitochondrial deformation and degeneration, and disordered myofibrillary structures were detected ultrastructurally in the epirubicin-treated group. The degeneration was reduced in the heart tissues of the epirubicin+melatonin group. Epirubicin increased the nitrite/nitrate production, but did not change the MDA and GSH levels significantly. Melatonin treatment lowered the nitrite/nitrate concentrations, while increasing the GSH levels, which exceeded the levels in epirubicin+melatonin-treated rats. We conclude that the epirubicin increased the nitrozative stress, not the oxidative stress, in heart tissue, and the cardioprotective effect of melatonin was partially attributed to the suppression of epirubicin-induced nitrozative stress. These results suggest that melatonin partially protects against epirubicin-induced cardiotoxicity.     

癌伴引流区淋巴结结节病样肉芽肿反应病理学观察

目的讨论癌伴引流区淋巴结结节病样肉芽肿反应(SGR)，避免诊断为结核及其他肉芽肿病变。方法对2例肺癌、3例食管癌和2例乳腺癌伴引流区淋巴结SGR和癌组织进行组织学分析，并与典型肺门和颈部淋巴结结核进行组织学对比。结果7例淋巴结SGR中，伴食管鳞癌2例、腺癌1例，肺腺癌、腺鳞癌各1例，乳腺浸润性导管癌2例。引流区均无结核、结节病及其他肉芽肿病变。SGR结节均无干酪样坏死。结论癌伴引流区淋巴结SGR可见于鳞癌及腺癌。此病变为机体对异源性抗原物质的一种免疫反应。     

合并室间隔缺损及粗大体肺侧支的肺动脉闭锁的选择性侧支融合术及粗大体肺侧支的再认识

目的探讨选择性侧支融合术或单源化治疗(unifocalization,UF)在室间隔缺损(VSD)及粗大体肺侧支(MAPCAs)的肺动脉闭锁(PA)患儿中的应用,并从组织病理学角度深入剖析不同解剖形态的MAPCAs。方法2017年6月至2018年12月,6例合并粗大体肺侧支及室间隔缺损的肺动脉闭锁(MAPCAs/VSD/PA)患儿实施选择性UF术加一期根治术,男4例,女2例;年龄6~96个月;体质量5.0~23.0 kg。术前均行心导管、选择性体肺侧支造影及心脏CTA检查,明确体肺侧支种类及解剖分布。对造影提示参与肺"气血交换"的粗大体肺侧支实行选择性UF,对不参与肺"血气交换"的功能性体肺侧支术中结扎或不处理。术中留取不同种类粗大体肺侧支的组织行病理检查,根据组织病理学结果明确侧支类型。结果围术期及随访期间无死亡。术前心导管、选择性侧支检查及术中组织病理学检查证实,参与肺"血气交换"的功能性MAPCAs具有肺动脉壁结构,属于弹性动脉;不参与肺"血气交换"的非功能性MAPCAs为小动脉壁结构,属于肌型动脉。结论术前可通过选择性MAPCAs造影检查明确参与肺"血气交换"功能性侧支,功能性侧支属于弹性动脉,具有肺动脉壁结构,术中对功能性侧支进行UF术可取得良好的手术效果。     

Novel Tools to Improve Patient Selection and Monitoring on Active Surveillance for Low-risk Prostate Cancer: A Systematic Review

Context

Active surveillance (AS) is an alternative to initial radical treatment of low-risk prostate cancer (PCa). Current criteria for selection and follow-up incorrectly exclude some patients eligible for AS and misclassify some who actually harbour significant disease. Better prediction of cancer behaviour at diagnosis would allow less strict monitoring and may improve acceptance of AS.

Objective

To review and critically analyse the literature on the value of novel clinical tools for patient selection and monitoring on AS.

Evidence acquisition

A comprehensive search of the PubMed database until July 10, 2013, was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement guidelines. Studies assessing novel markers and diagnostics for patient selection for AS and follow-up during AS were included. Studies analysing only classic clinical parameters used in current protocols (prostate-specific antigen, prostate volume, number of (positive) prostate biopsies, percentage malignant tissue, Gleason score) were excluded. This review focuses only on the AS setting and not on predicting insignificant disease in general.

Evidence synthesis

Of 787 studies on AS, 30 were included in this review: 14 on magnetic resonance imaging (MRI), 5 on serum markers, 5 on urinary markers, 4 on histopathology markers, and 2 on germline genetic markers. Several of these markers improve the prediction of tumour volume, tumour grade, or time to active treatment. MRI has a high specificity for low-risk PCa; new serum markers are associated with unfavourable disease. In none of the studies was the new marker used as the primary decision tool. Long-term outcome measures such as mortality were not assessed. The definition of indolent PCa is disputable.

Conclusions

Imaging and serum markers may improve future patient selection for AS and follow-up during AS. Prospective studies should aim to further evaluate the clinical utility of these new markers with respect to longer term outcomes of AS.

Patient summary

We searched the literature for articles reporting new ways to safely monitor low-risk prostate cancer for patients who have not had radical treatment. We found 30 articles. The most promising tools appear to be magnetic resonance imaging scans and various new blood markers. These may be used in the future within active surveillance regimens.     

Applicability of rat precision-cut lung slices in evaluating nanomaterial cytotoxicity,apoptosis, oxidative stress,and inflammation

The applicability of rat precision-cut lung slices (PCLuS) in detecting nanomaterial (NM) toxicity to the respiratory tract was investigated evaluating sixteen OECD reference NMs (TiO₂, ZnO, CeO₂, SiO₂, Ag, multi-walled carbon nanotubes (MWCNTs)). Upon 24-hour test substance exposure, the PCLuS system was able to detect early events of NM toxicity: total protein, reduction in mitochondrial activity, caspase-3/-7 activation, glutathione depletion/increase, cytokine induction, and histopathological evaluation. Ion shedding NMS (ZnO and Ag) induced severe tissue destruction detected by the loss of total protein. Two anatase TiO₂ NMs, CeO₂ NMs, and two MWCNT caused significant (determined by trend analysis) cytotoxicity in the WST-1 assay. At non-cytotoxic concentrations, different TiO₂ NMs and one MWCNT increased GSH levels, presumably a defense response to reactive oxygen species, and these substances further induced a variety of cytokines. One of the SiO₂ NMs increased caspase-3/-7 activities at non-cytotoxic levels, and one rutile TiO₂ only induced cytokines. Investigating these effects is, however, not sufficient to predict apical effects found in vivo. Reproducibility of test substance measurements was not fully satisfactory, especially in the GSH and cytokine assays. Effects were frequently observed in negative controls pointing to tissue slice vulnerability even though prepared and handled with utmost care. Comparisons of the effects observed in the PCLuS to in vivo effects reveal some concordances for the metal oxide NMs, but less so for the MWCNT. The highest effective dosages, however, exceeded those reported for rat short-term inhalation studies. To become applicable for NM testing, the PCLuS system requires test protocol optimization.     

Effect of Methotrexate on Collagen-Induced Arthritis Assessed by Micro-Computed Tomography and Histopathological Examination in Female Rats

We tested the hypothesis that micro-computed tomography (micro-CT) analysis provides a better quantitative readout of the therapeutic potential of methotrexate (MTX) for treating collagen-induced arthritis (CIA) in rats and compared to conventional histopathological examination. Rats were divided into three groups: Group 1 (G1) was treated with 0.9% saline, whereas groups 2 (G2) and 3 (G3) were boosted with type II collagen at days 0 and 7. Following the first collagen immunization, rats in G1 and G2 were treated with 0.9% saline and those in G3 were treated with 1.5 mg/kg MTX from day 14 to 28. All rats were sacrificed on day 28, at which point and all hind knee joints were analyzed by micro-CT and histopathological examination. Micro-CT analyses showed that bone volume and trabecular number were significantly decreased in G2 and G3 compared to G1 (p<0.01), as was percent bone volume (p<0.05 and p<0.01, respectively). However, bone surface/bone volume was significantly increased in G2 and G3 compared to G1 (p<0.05 and p<0.01, respectively). Trabecular separation was significantly increased in G3 compared to G1 (p<0.05). Histopathological examination showed that knee joints of rats in G2 and G3 showed severe joint destruction with inflammatory cell infiltration. However, cartilage destruction was slightly reduced in G3 compared to G2. Taken together, these results suggest that MTX treatment reduced cartilage destruction in rats with CIA, and micro-CT analyses made it possible to quantify arthritic bony lesion.     

慢性粒细胞白血病的骨髓组织病理学研究

应用国产塑料包埋剂对23例慢粒慢性期患者进行了骨髓塑包切片的组织病理学研究,证明慢粒属于异质性疾病,分两类组织学亚型:即以粒系细胞极度增殖为主的粒细胞(GRAN)型和以粒系细胞—巨核细胞混合性增殖,且伴巨核细胞多形性与异位的粒细胞/巨核细胞(GRAN/MEG)型。本文对两型的其它组织学特点一并进行了讨论。