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关键词： extracapsular extension   human papillomavirus   oropharyngeal cancer   survival   treatment paradigm  

摘要： Background The significance of extracapsular extension (ECE) and adjuvant treatment paradigm in patients with surgically managed human papillomavirus-positive (HPV+) oropharyngeal cancer (OPC) is debated. Methods National, hospital-based, retrospective cohort study of 2663 patients pN+ HPV+ OPC who underwent primary surgery. Results Patients with ECE had a 1.74-times risk of death (95% confidence interval [CI]: 1.26-2.40, p = 0.001) compared to patients without ECE. Among patients with pN1, ECE-positive disease, risk of overall mortality was similar across treatment paradigms (surgery alone: ref;adjuvant radiation therapy [RT]: aHR: 0.81;95% CI: 0.36-1.85;p = 0.62;adjuvant CRT: aHR: 0.66;95% CI: 0.34-1.32;p = 0.24). Patients with pN2 ECE-positive disease treated with adjuvant RT alone exhibited similar risk of all-cause mortality (hazard ratio: 1.04, 95% CI: 0.24-4.47, p = 0.96) compared to adjuvant chemoradiation (CRT). In patients with advanced, ECE-positive disease (e.g., pT3-T4pN2), adjuvant CRT did not reduce the risk of overall mortality relative to adjuvant RT. Conclusion Although pathologic ECE negatively predicts for survival in patients with HPV+ OPC, our analyses support expansion of postoperative de-intensification clinical trial eligibility criteria in patients with ECE-positive disease.

关键词： Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)   Coronavirus disease 2019 (COVID-19)   Infection   Pandemic stress   Pregnancy   Placenta  

摘要： Introduction: The reported effects of SARS-CoV-2 on pregnancy outcomes are conflicting;studies frequently overlook the placenta, which is critical for the health of the mother and infant(s). This study aimed to determine the effect of pandemic stress + SARS CoV-2 infection on placental histopathology. Methods: Women were recruited in Canada (n = 69);France (n = 21) or in the UK (n = 25), between March and October 2020. Historic controls (N = 20) were also included. Placenta and fetal membrane samples were collected rapidly after delivery and were fixed and stained for histopathological analysis. Maternal demo-graphical data and obstetric outcomes were recorded. Results: Over 80% of the placentas from SARS-CoV-2+ pregnancies had histopathological abnormalities: predominantly structural (71-86%) or inflammatory (9-22%), depending on geographical location. Excessive fibrin was seen in all sites, whereas deciduitis (Canada), calcifications (UK), agglutinations and chorangiosis (France) predominated in different locations. The frequency of abnormalities was significantly higher than in SARS-CoV-2 negative women (50%, p < 0.05). Demographic and obstetric data were similar in the SARS-CoV-2+ women across all sites - characterised by predominantly Black/Middle Eastern women, and women with elevated body mass index. Discussion: Overall, the frequency of placental abnormalities is increased in SARS-CoV-2+ women, but the incidence of placental abnormalities is also higher in SARS-CoV-2- women that gave birth during the pandemic, which highlights the importance of appropriate control groups to ascertain the roles of pandemic stress and SARS-CoV-2 infection on the placenta and pregnancy outcomes.

关键词： opportunistic testing   organized screening   prostate cancer   prostate-specific antigen  

摘要： Background In all the prefectures of Japan, with the exception of Shiga Prefecture, more than half of local governments have an organized prostate-specific antigen (PSA) screening system in place. However, in the Shiga Prefecture, only a single city performed PSA screening over the time period of this survey. The purpose of the present study was to determine the clinical, pathological, and therapeutic features of newly diagnosed prostate cancer in localities where a formally organized screening system was almost entirely absent. Methods A multicenter observational study was conducted in the Shiga Prefecture, which has the lowest rate of population-based PSA-screening in Japan. Patients' age, initial PSA, reasons for PSA testing, Gleason score, clinical stage, and primary treatments were surveyed. We stratified patients according to the reasons for PSA measurement, and compared the differences between groups subject to organized versus opportunistic screening. Results In the 2 years 2012 and 2017, 984 newly diagnosed prostate cancer patients were analyzed. Of these, 954 (97%) were opportunistically tested (i.e., not as part of an organized screening system), with the remaining 29 (3%) measured as part of an organized screening program. Patients in the former group exhibited a higher initial PSA value than in the organized screening group (median: 11.49 vs. 5.67 ng/ml). They also had worse clinical features, including higher Gleason score and TNM stage. More patients in the organized screening group were treated curatively than in the nonorganized screening group in terms of the primary treatment. The results were similar in a subanalysis of the patients of age 50-69 years. Conclusions Organized PSA screening contributes to increasing the number of patients diagnosed with early-stage cancer who can be treated curatively.

关键词： cancer genomic medicine   gene panel testing   next-generation sequencing   sample processing  

摘要： Clinical cancer genomic testing based on next-generation sequencing can help select genotype-matched therapy and provide diagnostic and prognostic information. Pathological tissue from malignant tumors obtained during routine practice are frequently used for genomic testing. This article is aimed to standardize the proper handling of pathological specimens in practice for genomic medicine based on the findings established in "Guidelines on the handling of pathological tissue samples for genomic medicine (in Japanese)" published by The Japanese Society of Pathology (JSP) in 2018. The two-part practical guidelines are based on empirical data analyses;Part 1 describes the standard preanalytic operating procedures for tissue collection, processing, and storage of formalin-fixed paraffin-embedded (FFPE) samples, while Part 2 describes the assessment and selection of FFPE samples appropriate for genomic testing, typically conducted by a pathologist. The guidelines recommend that FFPE sample blocks be used within 3 years from preparation, and the tumor content should be >= 30% (minimum 20%). The empirical data were obtained from clinical studies performed by the JSP in collaboration with leading Japanese cancer genome research projects. The Japanese Ministry of Health, Labour, and Welfare (MHLW) recommended to comply with the JSP practical guidelines in implementing cancer genomic testing under the national health insurance system in over 200 MHLW-designated core and cooperative cancer genome medicine hospitals in Japan.

关键词： Dysthyroid optic neuropathy   Tritan deficiency   Protan deficiency   Color vision test  

摘要： Purpose To investigate the sensitivity of the color vision test by Arden in patients with dysthyroid optic neuropathy (DON) to improve diagnosis. Methods In this observational, retrospective study, we included the medical records of 92 eyes (48 patients) with diagnosis of DON between 2008 and 2019 in order to evaluate the full spectrum of findings from the color vision test by Arden, and to determine potential importance of this test. Thirty-five patients were female, and 13 patients were male. The mean age was 58.0 years (range: 34-79) at the time of the DON diagnosis. Results Forty-one eyes displayed relatively good BCVA with <= 0.2 LogMAR. We found a protan value exceeding the threshold of >= 8% in 57 eyes (30 patients) at the time of the diagnosis. The sensitivity of protan was 61.9% (95% CI 51.2-71.8%), while that of tritan was a striking 98.9% (95% CI 94.1-99.9%). We discovered one pathological sign, tritan deficiency (based on a threshold of >= 8%) consistently in all eyes but one at the time of the diagnosis, regardless of the visual field defects or any changes in best-corrected visual acuity (BCVA). Conclusion We found blue-yellow (tritan) deficiency, to be a sensitive and reliable indicator of dysthyroid optic neuropathy. We conclude that, in cases with suspected DON, a color vision test that can detect tritan deficiency is an essential tool for the adequate assessment, diagnosis, and treatment of DON.

关键词： Breast cancer   Cancer sub-type   Classification   Deep learning   Grading   ResNet  

摘要： Breast cancer is an invasive tumor that develops in the breast tissue. It is the most common cancer and also the leading cause of cancer mortality among women worldwide. Survival from breast cancer can be increased through advances in screening methods and early diagnosis. Clinical examination, screening using imaging modalities and pathological assessment (biopsy test) are common methods of breast cancer diagnosis. Among these, pathological assessment is a gold standard due to its potential in identifying the cancer type, sub-type and stage. However, current diagnosis using this pathological assessment technique is commonly done through visual inspection microscopic images. This procedure is time consuming, tedious and subjective which may lead to misdiagnosis. In this paper, a multi-class classification system for breast cancer type, sub-type and grade is proposed based on deep learning technique. The system was trained and validated using histopathological images acquired from Jimma University Medical Center (JUMC) using digital camera (Optikam PRO5) mounted on Optika microscope by four levels of magnification (40x, 100x, 200x, 400x), and also from 'BreakHis' and 'zendo' online datasets. All images were pre-processed and enhanced prior to feeding to the ResNet 50 pre-trained model. The developed system is capable of classifying breast cancer into binary classes (benign and malignant) and multi-classes (sub-types). Identification of cancer grade was done for cancers that are classified as invasive ductal carcinomas. Test results showed that, the proposed method is 96.75%, 96.7%, 95.78%, and 93.86% accurate for binary classification, benign sub-type classification, malignant sub-type classification, and grade identification, respectively. The proposed method can be used as a decision support system for physicians especially in developing countries where both the means and the expertise are in scarce. Early and accurate detection of cancer type increases the chance

关键词： Breast cancer   Early stage   PMRT   Prognostic factors  

摘要： Purpose Postmastectomy radiation therapy (PMRT) in T1-T2 tumors with 1-3 positive axillary lymph nodes (ALNs) is controversial. This study was to identify prognostic factors of locoregional control (LRC) following mastectomy with or without PMRT for patients with T1-2N1 breast cancer and to discuss the selection of patients who might omit PMRT. Materials and methods Between January 2006 and December 2012, the data of 1474 postmastectomy patients staged pT1-2N1 were analyzed. PMRT was applied in 663 patients. LRC and disease-free survival (DFS) were calculated using the Kaplan-Meier method. Cox regression model was applied in the univariate and multivariate analyses to recognize the recurrence risk factors. Results With the median follow-up duration of 93 months (range, 5-168 months), 78 patients (5.3%) failed to secure LRC and 220 patients (14.9%) experienced any recurrence. The 7.7-year LRC and DFS was 94.9% and 85.4% respectively in the entire cohort. PMRT significantly improved 7.7-year LRC from 93.4% to 96.6% (p = 0.005), but not the DFS (p = 0.335). Multivariate analysis revealed that PMRT was an independent prognostic factor of LRC (p < 0.001), meanwhile, age <= 40 years (p = 0.012), histological grade 3 (p = 0.004), 2-3 positive nodes (p < 0.001) and tumor size of 3-5 cm (p = 0.045) were significantly associated with decreased LRC. The 7.7-year LRC for patients with 0, 1, and 2-4 risk factors was 97.7% / 98.9% (p = 0.233), 95.3% / 98.0% (p = 0.092), and 80.3% / 94.8% (p < 0.001) in the non-PMRT and PMRT group, respectively. Conclusions In patients with T1-2N1 breast cancer, clinical-pathological factors including young age, histological grade 3, 2-3 positive nodes, and tumor size of 3-5 cm were identified to be predictors of a poorer LRC following mastectomy. Patients with 0-1 risk factor might consider the omission of PMRT.

关键词： Frozen section   Soft tissue sarcoma   Unplanned excision  

摘要： Purpose An "unplanned excision" refers to soft tissue sarcomas excised without planning imaging studies and a diagnostic biopsy, resulting in the presence of residual disease and usually necessitating a re-excision procedure. We aimed to assess the impact of previous unplanned excisions on the intra-operative pathologic assessment at the time of re-excision, in terms of need to perform repeat assessments and the accuracy to predict margin status of the final pathologic specimen. Methods Data was collected for all patients with extremity soft tissue sarcoma who had undergone wide local excision limb salvage surgery or amputation between 2012 and 2017. Intra-operative pathologic assessment with frozen sections was performed in all cases and was classified as negative, negative but close (< 1 mm), and positive. Results A total of 173 patients with extremity soft tissue sarcoma were included, 54 in the unplanned excision group and 119 in the planned excision group. The accuracy of intra-operative pathologic assessment to predict the margin status on final pathology was similar between groups (87% unplanned vs. 90.7% planned excisions). However, the need for repeat intra-operative pathologic assessment and subsequent resection due to microscopically positive margins was found to be higher within the unplanned excision group ((p = 0.04), OR = 3.2 (95% CI: 1.1-9.1, p = 0.048)). Conclusions Intra-operative pathologic assessment of resection margins had a similar accuracy in planned and unplanned excisions;however, unplanned excisions showed a higher risk of re-resection during the same surgical setting.

关键词： cytoinclusion   dog   hematology   iliac crest   sternum  

摘要： Studies using the cell-block technique for bone marrow (BM) analysis are limited in the veterinary literature. This work assessed whether the histopathological analysis of canine BM was feasible using cell-block cytoin-clusions prepared from fine-needle sternal aspirate samples. Eight clinically healthy young-to-middle-aged dogs underwent both fine-needle sternal aspiration for BM cell-block (BM-Cb) processing and iliac-crest BM core biopsy (BM-B). Histopathologic parameters were compared between the 2 methods. There were no sta-tistically significant histopathological differences between hematopoietic tissue areas (P = .6294) in the BM-Cb and BM-B sections, and they had similar microscopic characteristics and microarchitecture. Cellularity and reticulin-fiber staining were equivalent in the BM-Cb and BM-B preparations in 87.5% (7/8) and 100% (8/ 8) of the sections, respectively. However, the quantitative results of the megakaryocytic series differed between BM-Cb and BM-B in 37.5% (3/8) of the sections, and the myeloid:erythroid (M:E) ratios differed between the 2 methods in 25% (2/8). These preliminary data indicate that cell-block preparations made from sternal fine-needle aspiration samples warrant continued evaluation in a larger number of animals, including those with various diseases affecting the bone marrow. (c) 2021 Elsevier Inc. All rights reserved.