Negative Pseudo Labeling Using Class Proportion for Semantic Segmentation in Pathology

16th European Conference, Glasgow, UK, August 23–28, 2020. Part of the Lecture Notes in Computer Science book series (LNCS, volume 12360). Also part of the Image Processing, Computer Vision, Pattern Recognition, and Graphics book sub series (LNIP, volume 12360).In pathological diagnosis, since the proportion of the adenocarcinoma subtypes is related to the recurrence rate and the survival time after surgery, the proportion of cancer subtypes for pathological images has been recorded as diagnostic information in some hospitals. In this paper, we propose a subtype segmentation method that uses such proportional labels as weakly supervised labels. If the estimated class rate is higher than that of the annotated class rate, we generate negative pseudo labels, which indicate, “input image does not belong to this negative label, ” in addition to standard pseudo labels. It can force out the low confidence samples and mitigate the problem of positive pseudo label learning which cannot label low confident unlabeled samples. Our method outperformed the state-of-the-art semi-supervised learning (SSL) methods

Lung metastasis from breast cancer combined with primary lung cancer: Report of a case

We herein report a case of lung metastasis from breast cancer combined with primary lung cancer. A 59-year-old female had received mastectomy 5 years ago, and underwent adjuvant chemotherapy with trastuzumab and anastrozole. Chest computed tomography revealed nodules in right lobe of lung. She underwent partial resection through video-assisted thoracoscopic surgery, and metastatic breast cancer and primary lung cancer were recognized on pathological diagnosis. Two years later after chemotherapy and exemestane with trastuzumab, she was pointed out lung cancer recurrence and has been receiving chemotherapy. When nodules are removed and diagnosed as lung metastasis combined with primary lung cancer, additional treatment should be considered depending on the prognosis of each disease

Prognostic significance of cribriform adenocarcinoma of the lung: validation analysis of 1,057 Japanese patients with resected lung adenocarcinoma and a review of the literature

Background: Cribriform-predominant adenocarcinoma of the lung (Cribri-ADC) is a recently described tumor growth pattern. However, its prognostic impact has not been clearly determined. We analyzed the data of a series of 1, 057 Japanese patients with resected lung adenocarcinoma to identify the clinical significance of Cribri-ADC. Methods: Cribriform pattern (Cribri-p) is defined as invasive back-to-back fused tumor glands with poorly formed glandular spaces or invasive tumor nests comprising tumors cells that produced glandular lumina. We investigated the correlations of Cribri-p and Cribri-ADC with clinicopathological factors as well as disease-free survival (DFS) and overall survival (OS). Results: Cribri-p was present in 217 patients (20.5%) and Cribri-ADC was determined in 25 patients (2.4%). Cribri-p was associated with larger tumor size, pleural invasion, vascular invasion, lymphatic invasion, and spreading through air spaces (STAS) (all, P<0.0001). Cribri-ADC was associated with younger age (P=0.019), vascular invasion (P=0.0025), STAS (P<0.0001), and ALK rearrangement (P=0.012). The DFS curve of patients with Cribri-ADC was identical to that of patients with solid adenocarcinoma; however, the OS curve was located between that of patients with papillary and acinar adenocarcinoma. Of the 10 patients who had tumor recurrences, eight had EGFR mutations or ALK rearrangement, six of whom achieved relatively long survival (median, 64.6, range, 37.4–113 months) following treatment with tyrosine kinase inhibitors (TKIs). In multivariate analysis, Cribri-ADC was not an independent prognostic factor of either recurrence or death. Conclusions: Cribri-ADC is associated with a higher risk of recurrence; however, most patients can be successfully treated with TKIs

Phosphorylated Platelet-Derived Growth Factor Receptor-Positive Cells With Anti-apoptotic Properties Accumulate in the Synovium of Patients With Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease caused by inflammation of the synovium and characterized by chronic polyarthritis that destroys bone and cartilage. Fibroblast-like synoviocytes (FLSs) in the synovium of patients with RA can promote cartilage and bone destruction by producing proteins such as matrix metalloproteinases and receptor activator of NF-κB ligand, thereby representing an important therapeutic target for RA. FLSs have several phenotypes depending on which cell surface proteins and adhesion factors are expressed. Identifying the cellular functions associated with different phenotypes and methods of controlling them are considered essential for developing therapeutic strategies for RA. In this study, synovial tissue was collected from patients with RA and control subjects who required surgery due to ligament injury or fracture. Immunohistological analysis was used to investigate the rates of positivity for phosphorylated platelet-derived growth factor receptor-αβ (pPDGFRαβ) and cadherin-11 (CDH11) expression, and apoptosis-related markers were assessed for each cell phenotype. Next, FLSs were isolated in vitro and stimulated with tumor necrosis factor-α (TNF-α) in addition to a combination of PDGF and transforming growth factor (2GF) to investigate pPDGFRαβ and CDH11 expression and the effects of the inhibition of TNF and cyclin-dependent kinase (CDK) 4/6 on FLSs. Immunohistological analysis showed a large percentage of pPDGFRαβ+CDH11– cells in the sub-lining layer (SL) of patients with RA. These cells exhibited increased B-cell lymphoma-2 expression, reduced TNF receptor-1 expression, resistance to cell death, and abnormal proliferation, suggesting a tendency to accumulate in the synovium. Further, in vitro 2GF stimulation of FLSs lowered, whereas 2GF + TNF stimulation increased the pPDGFRαβ/CDH11 ratio. Hypothesizing that FLSs stimulated with 2GF + TNF would accumulate in vivo in RA, we determined the therapeutic effects of TNF and CDK4/6 inhibitors. The TNF inhibitor lowered the pPDGFRαβ/CDH11 ratio, whereas the CDK4/6 inhibitor suppressed cell proliferation. However, a synergistic effect was not observed by combining both the drugs. We observed an increase in pPDGFRαβ+CDH11– cells in the SL of the RA synovium and accumulation of these cells in the synovium. We found that the TNF inhibitor suppressed FLS activity and the CDK4/6 inhibitor reduced cell proliferation

Identification of a Vitamin-D Receptor Antagonist, MeTC7, which Inhibits the Growth of Xenograft and Transgenic Tumors In Vivo

Vitamin-D receptor (VDR) mRNA is overexpressed in neuroblastoma and carcinomas of lung, pancreas, and ovaries and predicts poor prognoses. VDR antagonists may be able to inhibit tumors that overexpress VDR. However, the current antagonists are arduous to synthesize and are only partial antagonists, limiting their use. Here, we show that the VDR antagonist MeTC7 (5), which can be synthesized from 7-dehydrocholesterol (6) in two steps, inhibits VDR selectively, suppresses the viability of cancer cell-lines, and reduces the growth of the spontaneous transgenic TH-MYCN neuroblastoma and xenografts in vivo. The VDR selectivity of 5 against RXRα and PPAR-γ was confirmed, and docking studies using VDR-LBD indicated that 5 induces major changes in the binding motifs, which potentially result in VDR antagonistic effects. These data highlight the therapeutic benefits of targeting VDR for the treatment of malignancies and demonstrate the creation of selective VDR antagonists that are easy to synthesize

前立腺癌pT3a期における前立腺外進展および膀胱頸部浸潤の臨床的意義―新たなpT3aサブクラスの提案

京都大学新制・課程博士博士(医学)甲第24317号医博第4911号新制||医||1062(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 小林 恭, 教授 溝脇 尚志, 教授 松田 道行学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Sarcopenia effect on convalescent rehabilitation outcomes

Sarcopenia is widely believed to be linked to poorer outcomes in inpatient rehabilitation. This study aimed to assess the impact of sarcopenia on functional outcomes and dietary intake during hospitalization in adults undergoing convalescent rehabilitation. We conducted a retrospective cohort analysis at a single rehabilitation institution. The Asian Working Group Consensus Criteria for Sarcopenia was used to diagnose. The Functional Independence Measure (FIM) score was used at hospital discharge to measure the primary functional outcome. Energy and protein intakes during hospitalization were calculated as part of the nutritional assessment. There were 126 patients in the research (median age, 73 yr; 54% women). Stroke (n = 73; 53.4% sarcopenia) and musculoskeletal disorders (n = 53; 56.6% sarcopenia) were among the admission diagnoses. Multiple linear regression analysis revealed that the FIM total score at discharge was modestly associated with sarcopenia only in stroke patients (β = −0.1872, P = 0.09), as well as significantly and independently associated with protein intake during admission only in stroke patients (β = 0.3217, P < 0.05). In hospitalized stroke patients undergoing convalescent therapy, sarcopenia is related to lower functional results. Early identification of sarcopenia and treatment with rehabilitation nutrition should be implemented in this population