Adenocarcinoma of Ascending Colon Associated with Sarcoid Reaction in Regional Lymph Nodes

Lymph node swelling in the setting of malignancy generally suggests metastasis of the primary tumor. A granulomatous reaction, i.e. sarcoid reaction, occurring within the lymph nodes draining carcinomas is a well-known but uncommon occurrence. The phenomenon is especially rarely seen in colon carcinoma. We herein report a rare case of a 56-year-old Japanese male with adenocarcinoma of the ascending colon associated with sarcoid reaction in the regional lymph nodes. A typical ileocecal resection and lymph node dissection were performed. Histopathological examination revealed moderately differentiated adenocarcinoma of the ascending colon, and the dissected lymph nodes included epithelioid granulomas with multinucleated giant cells. These findings suggest the existence of a sarcoid reaction associated with colon carcinoma; there was no metastasis in the dissected lymph nodes. The significance of this rare condition is discussed

Machine learning methods can more efficiently predict prostate cancer compared with prostate-specific antigen density and prostate-specific antigen velocity

BackgroundProstate-specific antigen (PSA)–based screening for prostate cancer has been widely performed, but its accuracy is unsatisfactory. To improve accuracy, building an effective statistical model using machine learning methods (MLMs) is a promising approach.MethodsData on continuous changes in the PSA level over the past 2 years were accumulated from 512 patients who underwent prostate biopsy after PSA screening. The age of the patients, PSA level, prostate volumes, and white blood cell count in urinalysis were used as input data for the MLMs. As MLMs, we evaluated the efficacy of three different techniques: artificial neural networks (ANNs), random forest, and support vector machine. Model performance was evaluated using area under the receiver operating characteristic curve (AUC) and compared with the PSA level and the conventional PSA–based parameters: PSA density and PSA velocity.ResultsWhen using two annual PSA testing, all receiver operating characteristic curves of the three MLMs were above the curve for the PSA level, PSA density, and PSA velocity. The AUCs of ANNs, random forest, and support vector machine were 0.69, 0.64, and 0.63, respectively. Those values were higher than the AUCs of the PSA level, PSA density, and PSA velocity, 0.53, 0.41, and 0.55, respectively. The accuracies of the MLMs (71.6% to 72.1%) were also superior to those of the PSA level (39.1%), PSA density (49.7%), and PSA velocity (54.9%). Among the MLMs, ANNs showed the most favorable AUC. The MLMs showed higher sensitivity and specificity than conventional PSA–based parameters. The model performance did not improve when using three annual PSA testing.ConclusionThe present retrospective study results indicate that machine learning techniques can predict prostate cancer with significantly better AUCs than those of PSA density and PSA velocity

Significance of antiprothrombin antibodies in patients with systemic lupus erythematosus: clinical evaluation of the antiprothrombin assay and the antiphosphatidylserine/prothrombin assay, and comparison with other antiphospholipid antibody assays

Antibodies against prothrombin are detected by enzyme immunoassays (EIA) in sera of patients with antiphospholipid syndrome (APS). However, there are two methods for antiprothrombin EIA; one that uses high binding plates (aPT-A), and another that utilizes phosphatidylserine bound plates (aPS/PT). We aimed to evaluate and compare aPT-A and aPS/PT in a clinical setting. We performed EIA for anti-PT, anti-PS/PT, IgG, and IgM anticardiolipin antibodies (aCL), and IgG β2-glycoprotein I-dependent aCL (aβ2GPI/CL) with serum samples from 139 systemic lupus erythematosus (SLE) patients (16 with history of at least one thrombotic episode) and 148 controls. We observed that: (1) although titers of anti-PT and anti-PS/PT were significantly related with each other (P < 0.0001, ρ = 0.548), titer of anti-PT and anti-PS/PT differed greatly in some samples; (2) odds ratio and 95% confidence interval for each assay was 3.556 (1.221–10.355) for aPT-A, 4.591 (1.555–15.560) for aPS/PT, 4.204 (1.250–14.148) for IgG aCL, 1.809 (0.354–9.232) for IgM aCL, and 7.246 (2.391–21.966) for aβ2GPI/CL. We conclude that, while all EIA performed in this study except IgM aCL are of potential value in assessing the risk of thrombosis, aPS/PT and aβ2GPI/CL seemed to be highly valuable in clinical practice, and that autoantibodies detected by anti-PT and anti-PS/PT are not completely identical

Gastric perforation caused by Candida infection：Report of a case

An 89-year-old female was admitted to our hospital because of fever and abdominal pain. The patient had used an antihypertensive agent, but had not used either antibiotics, steroids, or potent antacids. An abdominal CT scan revealed free air and ascites. An emergency operation was performed for acute peritonitis caused by a gastrointestinal perforation. A perforated ulcer was observed at the posterior wall of the gastric body. A distal gastrectomy with intraperitoneal drainage and a Billroth II reconstruction was performed. A histological examination demonstrated a perforated ulcer surrounded by Candida infection. The patient developed an abscess in the abdominal cavity, but was discharged on the 52nd postoperative day. Although gastrointestinal Candida infection is commonly seen in immunocompromised host with diabetics or malignant diseases, habitual use of strong antacids can also cause severe Candida infection of the stomach in healthy persons. In this case, it was thus concluded that there may have been a decrease in immunity in this patient because of her advanced age 89 years old and malnutrition

Potential Neuroprotective Effects of an LSD1 Inhibitor in Retinal Ganglion Cells via p38 MAPK Activity

Citation: Tsutsumi T, Iwao K, Hayashi H, et al. Potential neuroprotective effects of an LSD1 inhibitor in retinal ganglion cells via p38 MAPK activity. Invest Ophthalmol Vis Sci. 2016;57:6461-6473. DOI:10.1167/ iovs.16-19494 PURPOSE. The epigenetic mechanisms associated with ocular neurodegenerative diseases remain unclear. The present study aimed to determine the role of lysine-specific demethylase 1 (LSD1), which represses transcription by removing the methyl group from methylated lysine 4 of histone H3, in retinal ganglion cell (RGC) survival, and to investigate the details of the neuroprotective mechanism of tranylcypromine, a major LSD1 inhibitor. METHODS. The authors evaluated whether tranylcypromine contributes to neuronal survival following stress-induced damage using primary cultured rat RGCs and in vivo N-methyl-Daspartate (NMDA)-induced excitotoxicity. Additionally, the molecules associated with tranylcypromine treatment were assessed by microarray and immunoblot analysis. RESULTS. Tranylcypromine significantly suppressed neuronal cell death following glutamate neurotoxicity and oxidative stress. Microarray and immunoblot analyses revealed that p38 mitogen-activated protein kinase (MAPK)c was a key molecule involved in the neuroprotective mechanisms induced by tranylcypromine because the significant suppression of p38 MAPKc by glutamate was reversed by tranylcypromine. Moreover, although pharmacologic inhibition of the phosphorylation of the total p38 MAPKs interfered with neuroprotective effects of tranylcypromine, the specific inhibition of p38 MAPKa and p38 MAPKb did not influence RGC survival. This suggests that the non-p38 MAPKa/b isoforms have important roles in neuronal survival by tranylcypromine. Additionally, the intravitreal administration of tranylcypromine significantly saved RGC numbers in an in vivo glaucoma model employing NMDA-induced excitotoxicity. CONCLUSIONS. These findings indicate that tranylcypromine-induced transcriptional and epigenetic regulation modulated RGC survival via the promotion of p38 MAPKc activity. Therefore, pharmacologic treatments that suppress LSD1 activity may be a novel therapeutic strategy that can be used to treat neurodegenerative diseases

Regulation of PD-L1 expression in non–small cell lung cancer by interleukin-1β

IntroductionProgrammed cell death–ligand 1 (PD-L1) is a biomarker for prediction of the clinical efficacy of immune checkpoint inhibitors in various cancer types. The role of cytokines in regulation of PD-L1 expression in tumor cells has not been fully characterized, however. Here we show that interleukin-1β (IL-1β) plays a key role in regulation of PD-L1 expression in non–small cell lung cancer (NSCLC).MethodsWe performed comprehensive screening of cytokine gene expression in NSCLC tissue using available single-cell RNA-Sequence data. Then we examined the role of IL-1β in vitro to elucidate its induction of PD-L1 on NSCLC cells.ResultsThe IL-1β gene is highly expressed in the tumor microenvironment, particularly in macrophages. The combination of IL-1β and interferon-γ (IFN-γ) induced a synergistic increase in PD-L1 expression in NSCLC cell lines. IL-1β and IFN-γ also cooperatively activated mitogen-activated protein kinase (MAPK) signaling and promoted the binding of downstream transcription factors to the PD-L1 gene promoter. Furthermore, inhibitors of MAPK signaling blocked upregulation of PD-L1 by IL-1β and IFN-γ.DiscussionOur study reports high levels of IL-1β in the tumor microenvironment may cooperate with IFN-γ to induce maximal PD-L1 expression in tumor cells via activation of MAPK signaling, with the IL-1β–MAPK axis being a promising therapeutic target for attenuation of PD-L1–mediated suppression of antitumor immunity

A Metastatic Jejunal Tumor from Squamous Cell Carcinoma of the Lung Found in an Intestinal Perforation

An 85-year-old male with advanced squamous cell carcinoma of the lung, who was diagnosed about 10 years prior to his current presentation, suddenly complained of abdominal pain and underwent an abdominal computed tomography scan, which revealed free air and massive ascites. He was admitted to our hospital for acute peritonitis and emergency surgery was performed. During the surgical procedure, a perforation of the jejunum was diagnosed and repaired. He was diagnosed to have a metastatic tumor originating from a squamous cell carcinoma of the lung. He improved and was transferred to the former hospital on the 27th postoperative day. Jejunal metastasis from squamous cell carcinoma of the lung is rare, and the prognosis of peritonitis due to a perforated intestinal metastasis from lung cancer is poor. There have been 10 reports of jejunal metastasis of squamous cell carcinoma of the lung reported in Japan between 2000 and 2011. Therefore, when patients with advanced lung cancer present with acute abdomen, it is necessary to keep in mind the possibility of a gastrointestinal metastatic tumor

Feasibility of classical secondary hormonal therapies prior to docetaxel therapy in Japanese patients with castration-resistant prostate cancer: Multicenter retrospective study

BackgroundWe retrospectively analyzed castration-resistant prostate cancer (CRPC) patients treated with secondary hormonal therapies (SHTs) prior to docetaxel therapy.MethodsThe cases of 73 CRPC patients who underwent docetaxel therapy in 2005–2011 at four hospitals in Ibaraki, Japan were analyzed. We determined the cause-specific survival (CSS) from the start of docetaxel therapy and the time point of CRPC diagnosis, and we compared the CSS achieved with/without prior classical SHTs, which were defined as low-dose steroid and estramustine phosphate.ResultsOf the 73 enrolled patients, 26 underwent docetaxel therapy (DOC group), and 47 underwent SHTs (SHTs-DOC group) as the initial treatment for CRPC. In the docetaxel therapy, the rate of prostate-specific antigen responses were higher in the DOC group compared with the SHTs-DOC group (76.9% vs. 44.7%, P = 0.0066). The median CSS from the docetaxel therapy initiation was not significant but longer in the DOC group than in the SHTs-DOC group (23.4 months vs. 16.6 months, P = 0.0969). However, the median CSS from the time of CRPC diagnosis did not significantly differ between the DOC and SHTs-DOC groups (23.4 months vs. 24.7 months, P = 0.9233). In a univariate analysis, pain and visceral metastasis appeared to be risk factors for the CSS in the SHTs-DOC group. The patients with pain and/or visceral metastasis had significantly poorer survival than those without these factors in the SHTs-DOC group (31.5 months vs. 16.8 months, P = 0.0053).ConclusionThe induction of SHTs prior to docetaxel therapy is an acceptable treatment option with some survival benefits for CRPC patients without pain and visceral metastases