一种基于线阵CCD成像的显微虚拟切片扫描系统

虚拟切片在数据存储、检索以及病理资料共享方面都显现出了常规切片所不具备的优势,正逐渐被病理医生所接受。本文基于线阵CCD相机和自动显微镜平台设计研发了一套虚拟切片扫描系统,这套系统能够实现：（1）自动对病理切片进行粗扫描; （2）定位病理关键区域; （3）对关键区域进行高倍物镜下的精扫描并拼接配准; （4）组织和管理图像数据并对其进行浏览。实验证明基于全自动显微镜平台和线阵CCD成像的显微虚拟切片扫描系统的可行性,该系统具有速度快、拼接处理数据量少等优点。     

Geant4-Simulations for cellular dosimetry in nuclear medicine

The application of unsealed radionuclides in radiobiological experiments can lead to intracellular radionuclide uptake and an increased absorbed dose. Accurate dose quantification is essential to assess observed radiobiological effects. Due to small cellular dimensions direct dose measurement is impossible. We will demonstrate the application of Monte Carlo simulations for dose calculation.Dose calculations were performed using the Geant4 Monte Carlo toolkit, wherefore typical experimental situations were designed. Dose distributions inside wells were simulated for different radionuclides. S values were simulated for spherical cells and cell monolayers of different diameter. Concomitantly experiments were performed using the PC Cl3 cell line with mediated radionuclide uptake. For various activity distributions cellular survival was measured.We yielded S values for dose distribution inside the wells. Calculated S values for a single cell are in good agreement to S values provided in the literature (ratio 0.87 to 1.07). Cross-dose is up to ten times higher for Y-90. Concomitantly performed cellular experiments confirm the dose calculation. Furthermore the necessity of correct dose calculation was shown for assessment of radiobiological effects after application of unsealed radionuclides. Thereby the feasibility of using Geant4 was demonstrated.     

A comparative study of a digital radiography system

The present study aimed to examine the efficiency of a new digital radiography system that was installed in the Royal Adelaide Hospital in September 1997, as compared to the existing conventional radiography system. A total of 55 examinations were observed over a 3-week period in January, and these consisted of 18 digital and 10 conventional chest examinations, and 27 conventional orthopaedic examinations. These were combined with 18 digital orthopaedic examinations recorded from a prior study. Total examination time was broken into several components, of which reporting time was of the most interest. The mean reporting times for digital and conventional chest examinations were 17 and 25 min, respectively, a significant (P < 0.1) 8-min difference. The orthopaedic examinations revealed mean reporting times of 8 and 26 min for digital and conventional systems, respectively; a significant (P < 0.001) 18-min difference. These results demonstrate that the digital system is a faster, more efficient system for the reporting of X-rays.     

A novel score system for predicting conversion to no evidence of Disease (C-NED) in initially unresectable colorectal cancer liver metastases

An estimated 70-80% of cases of colorectal cancer liver metastasis (CRLM) are defined as initially unresectable. “Converting” to no evidence of disease (NED) status may prolong survival. The current study aimed to develop a novel scoring system that predicts the conversion outcome for initially unresectable CRLM. A total of 215 consecutive CRLM patients who received first-line systemic therapy from December 2012 to January 2020 at Sun Yat-sen University Cancer Center were enrolled in the internal cohort. Forty CRLM patients from the database of the Chinese Colorectal Cancer Multidisciplinary Team Alliance were enrolled in the external cohort. A logistic regression model was applied to identify risk factors associated with the conversion outcome. The tumor-to-liver volume ratio (TLVR) was calculated as the total tumor volume divided by the total liver volume, and its cutoff value was 0.23. Three predictors of conversion failure were identified in the internal cohort and incorporated into the C-NED score: poor tumor differentiation (1 point), number of liver metastases > 8 (1 point) and TLVR ≥ 0.23 (1 point). The conversion rate was significantly negatively associated with the C-NED score (P < 0.001). The C-indexes of the C-NED score for predicting successful conversion outcome in the internal cohort and external cohort were 0.734 (95% confidence interval (CI), 0.668-0.800) and 0.736 (95% CIs, 0.566-0.907), respectively. Median progression-free survival (PFS) time (P = 0.001) and overall survival (OS) time (P = 0.003) were statistically significant different among different C-NED score groups. Our study demonstrated that the C-NED score is an effective scoring system that indicates the actual conversion probability for initially unresectable CRLM patients before treatment, which can serve as a tool that guides optimal first-line management strategies.     

A simple and reproducible scoring system for EGFR in colorectal cancer: application to prognosis and prediction of response to preoperative brachytherapy

The aim of this study was to determine the predictive and prognostic value of epidermal growth factor receptor (EGFR) expression in rectal cancers treated with preoperative high-dose rate brachytherapy and in mismatch-repair (MMR)-proficient colorectal cancers (CRCs), respectively. We validate the use of receiver operating characteristic (ROC) curve analysis to select cutoff scores for EGFR overexpression for the end points studied. Immunohistochemistry (IHC) for EGFR was performed on 82 rectal tumour biopsies and 1197 MMR-proficient CRCs using a tissue microarray. Immunoreactivity was scored as the percentage of positive tumour cells by three pathologists and the inter-observer reliability was assessed. ROC curve-derived cutoffs were used to analyse the association of EGFR overexpression, tumour response and several clinicopathological features including survival. The scoring method was found to be reproducible in rectal cancer biopsies and CRCs. The selected cutoff scores from ROC curve analysis for each clinicopathological feature were highly consistent among pathologists. EGFR overexpression was associated with response to radiotherapy (P-value <0.001) and with worse survival time (P-value <0.001). In multivariate analysis, EGFR overexpression was independently associated with adverse prognosis (P-value <0.001). Epidermal growth factor receptor is a predictive marker of response to preoperative radiotherapy and an independent adverse prognostic factor CRC.     

Search for germline alterations in CDKN2A/ARF and CDK4 of 42 Jewish melanoma families with or without neural system tumours

To gain insight into the molecular mechanisms involved in the inherited predisposition to melanoma and associated neural system tumours, 42 Jewish, mainly Ashkenazi, melanoma families with or without neural system tumours were genotyped for germline point mutations and genomic deletions at the CDKN2A/ARF and CDK4 loci. CDKN2A/ARF deletion detection was performed using D9S1748, an intragenic microsatellite marker. Allele dosage at the p14ARF locus was analysed by quantitative real-time PCR employing a TaqMan probe that anneals specifically to exon 1beta of the p14ARF gene. For detecting point mutations, dHPLC and direct sequencing of the coding sequences of CDKN2A/ARF and CDK4 was used. No germline alterations in any of the tested genes were detected among the families under study. We conclude that in the majority of Ashkenazi Jewish families, the genes tested are unlikely to be implicated in the predisposition to melanoma and associated neural system tumours.     

A fermentation system for filamentous fungi with special reference to dermatophytes. II. Evaluation of antimycotic substances1

To study the mode of action of antimycotic substances on dermatophytes during their growth, a fermentation assembly, earlier reported by us, was applied. Dermatophyte growth rate is here correlated to their alkalinisation of the substrate. A model experiment was performed with two antimycotic substances, hendecen-10-oic (undecylenic) acid and 5-chloro-7-iodo-8-hydroxyquinoline, in order to establish their effects on Epidermophyton floccosum. Even small changes in growth rate of dermatophytes, due to the presence of antimycotic substances, could be detected and quantitatively expressed, so that reliable comparisons of antifungal activity of the different test substances could be performed.

Zusammenfassung

Es wurde die Wirkungsart antimyzetischer Substanzen auf Dermatophyten während ihrer Wachstumsphase mit Hilfe eines selbstkonstruierten Fermenters, über den bereits früher berichtet wurde, untersucht. Die Dermatophytenwachstumsrate wurde mit der Alkalisierung des Nährsubstrates in Beziehung gesetzt. Dieser Modellversuch wurde in zwei Substanzen — Undecylensäure und 5-Chlor-7-Jod-8-Hydroxychinolin — um ihre antimyzetische Wirksamkeit auf Epidermophyton floccosum nachzuweisen, ausgeführt. Sogar geringe Änderungen der Dermatophytenwachstumsrate, die auf die Anwesenheit antimyzetischer Substanzen hinwies, konnten fetsgestellt und quantitativ erfaßt werden. Auf diese Weise konnte ein zuverlässiger Vergleich der antimyzetischen Wirkung von verschiedenen Testsubstanzen durhgeführt werden.     

A new prognostic score system in patients with advanced hepatocellular carcinoma not amendable to locoregional therapy: implication for patient selection in systemic therapy trials

BACKGROUND: Advanced hepatocellular carcinoma (HCC) patients who are not candidates for surgery or locoregional therapy are the focus of clinical trials of systemic therapy, as their overall prognosis remains poor. However, the current prognostic systems cannot reliably select appropriate candidates for systemic therapy trials based on the probability of 3-month survival. In this study, the authors constructed a new prognostic score system, the Advanced Liver Cancer Prognostic System (ALCPS), which can objectively predict the probability of 3-month survival. METHODS: Between 1990 and 2005, 1470 patients with advanced HCC who were not amendable to surgery or locoregional therapy were included in the analysis. The prognostic score system was developed from the multivariate Cox model through a point system and validated in an independent set. Okuda staging and Cancer of the Liver Italian Program (CLIP) score were also applied to the validation set to compare their predictive accuracy. RESULTS: The ALCPS was based on 11 prognostic factors with different weights: ascites, abdominal pain, weight loss, Child-Pugh grade, alkaline phosphatase, total bilirubin, alpha-fetal protein, urea, portal vein thrombosis, tumor size, and presence of lung metastases. It stratified patients in both training and validation sets to different prognostic groups with significant difference in 3-month overall survival (P < .0001). By using the patients in the validation set with known 3-month survival status, the ALCPS showed significantly better predictive power (area under the curve [AUC], 0.77) than Okuda score (AUC, 0.66; P < .001) and CLIP score (AUC, 0.71; P = .002). CONCLUSIONS: The new prognostic system can objectively help the clinicians to select appropriate candidates for evaluation of treatment efficacy in systemic therapy trials for advanced HCC.     

A new method to optimize resection area using a radiation treatment planning system and deformable image registration for breast-conserving surgery after neoadjuvant chemotherapy

BackgroundWe devised a breast-conserving surgery (BCS) utilizing a new image-processing and projection technique using a radiation treatment planning system (RTPS) and deformable image registration (DIR) for patients with breast cancer after neoadjuvant chemotherapy (NAC). RTPSs and DIR are commonly used in planning radiation treatment. The purpose of this pilot study was to evaluate the feasibility of our procedure.Patients and methodsTwenty-six patients diagnosed with breast cancer underwent NAC and BCS between November 2014 and May 2020. Multidetector-row computed tomography was performed in the same position used for surgery before and after NAC. In the DIR, CT before NAC was fused to CT after NAC. The RTPS simulated the design of tumor excision, and excision area was projected onto the breast skin utilizing an irradiation device.ResultsIn 26 patients with breast cancer after NAC, BCS was performed using the processing and projection technique of the RTPS with DIR. Only 1 of 26 patients showed carcinoma present in the surgical margins, and subsequently developed ipsilateral breast tumor recurrence. Mean excised volume was 33.5 cm³ (range, 12.8–62.8 cm³), and percent breast volume excised was 6.8% (range, 2.5–15.7%).ConclusionsThis pilot study confirmed the simplicity and utility of our procedure for minimally invasive BCS in patients with breast cancer after NAC. We will keep evaluating the safety and efficacy of our procedure in more patients.