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It has been reported that various kinds of immune checkpoint inhibitors (iCIs) could induce immune-related liver damage. We should focus on the programmed cell death-receptor-1 (PD-1) antibody and non-small cell lung cancer (NSCLC) to analyze the characteristics of hepatitis related to iCIs and find factors that could be useful biomarkers for the diagnosis. A single-center retrospective study of 252 NSCLC patients who received PD-1 antibody (nivolumab or pembrolizumab). Some of the biochemical markers and immunological markers were analyzed during PD-1-antibody treatment with or without ALT elevation. Histopathological features were reviewed by a single expert of hepatic pathology focusing on the following features: fibrosis, portal inflammation, lobular inflammation, lobular necrosis. The formation of macro- and micro-granulomas was also evaluated. The frequency of liver damage induced by nivolumab including grade 1 to 4 (ALT) was 41.9% (78/186 patients). The positive rate of anti-nuclear antibody in the nivolumab group with iCIs-related hepatitis was significantly higher than that in the nivolumab group without iCIs-related hepatitis (p = 0.00112). Granulomatous changes were significantly increased in patients with iCIs-related hepatitis compared with DILI and AIH patients (p < 0.05). The ratios of inflammatory cells CD4/CD8, and CD138/CD3 in ICIs-related hepatitis were significantly lower than those in AIH or DILI patients (p < 0.05). We demonstrated that the pre-existing ANA and characteristic liver histology including CD8+ cells dominancy and granulomatous hepatitis could be biomarkers for the diagnosis of iCIs-related hepatitis in the NSCLC with anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

Immunotherapy is considered one of the most important therapeutic strategies for patients with lung adenocarcinoma after the development of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) resistance. However, useful predictors of immunotherapy for these patients has not been examined well, although the status of the tumor immune microenvironment (TIME), including programmed death‐ligand 1 expression and lymphocyte infiltration, has been generally known to provide predictive markers for the efficacy of immunotherapy. This study aimed to clarify novel predictors of immunotherapy following EGFR‐TKI resistance in lung adenocarcinoma, especially regarding micro RNA (miRNA). We evaluated the correlation between EGFR‐TKI resistance and lymphocyte infiltration, before and after acquiring EGFR‐TKI resistance, in 21 cases of lung adenocarcinoma, and further explored this by in vitro studies, using miRNA PCR arrays. Subsequently, we transfected miRNA‐1 (miR‐1), the most variable miRNA in this array, into three kinds of lung cancer cells, and examined the effects of miR‐1 on EGFR‐TKI sensitivity, cytokine expression and lymphocyte migration. Histopathological examination demonstrated that infiltration levels of CD8‐positive T cells were significantly decreased after development of EGFR‐TKI resistance. In vitro studies revealed that miR‐1 significantly inhibited EGFR‐TKI effect and induction of cytokines, such as C‐C motif chemokine ligand 5 and C‐X‐C motif chemokine ligand 10, causing inhibition of monocyte migration. These results indicate that the upregulated miR‐1 might suppress the TIME, following development of EGFR‐TKI resistance. Therefore, miR‐1 could be a clinically useful marker to predict therapeutic efficacy of immunotherapy in lung adenocarcinoma patients with EGFR‐TKI resistance. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin G4-related disease is increasingly recognized as a systemic autoimmune disorder characterized by immunoglobulin G4-positive lymphocyte infiltration. Organ biopsy and histopathology are the most important diagnostic methods; however, the significance of a cytological examination in immunoglobulin G4-related disease cases is still unclear.Case Presentation: A 73-year-old Asian man who was a former tobacco smoker presented with progressive exertional dyspnea, systemic edema, and pericardial effusion. A cytological examination of his pericardial effusion detected three or four plasma cells per high-power field by Giemsa staining. Moreover, immunoglobulin G4-positive plasma cells were detected by immunostaining. Cardiac catheterization after pericardiocentesis revealed that both ventricular pressure traces showed an early diastolic dip and plateau. Positron-emission tomography with 18F-fluorodeoxyglucose imaging revealed inflammatory foci in his pericardium. A surgical pericardiectomy was performed and the resultant specimen showed significant immunoglobulin G4-positive plasma cell infiltration and marked fibrous thickening of his pericardium; therefore, a diagnosis of constrictive pericarditis due to immunoglobulin G4-related disease was made. Oral administration of 0.6-mg/kg/day prednisolone resolved his heart failure and he was discharged on foot 1 week later.Conclusion: Our experience with this case indicates that cytological examination of pericardial effusion was useful in the diagnosis of immunoglobulin G4-related disease. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the utility of a 12-core prostate biopsy protocol including apical anterior peripheral zone (AAPZ) cores. Methods: Between February 2002 and October 2006, 10-core and 12-core initial transrectal prostate biopsies were performed on 164 and 549 men, respectively. Two AAPZ-directed biopsies were included in the 12-core biopsy. During the same period, 12-core repeat biopsies including six AAPZ sites were performed on 118 men. Results: Cancer was found in 66 cases (40.2%) in the 10-core biopsy group and in 252 (45.9%) in the 12-core biopsy group. In this latter group, 13 (5.2%) of the 252 men with positive biopsy had cancer exclusively in the AAPZ cores. When the cancer detection rate at initial biopsy in AAPZ alone was compared according to the digital rectal examination (DRE) findings, it was significantly higher in men with normal rather than abnormal DRE: 12/250 (3.4%) vs 1/185 (0.5%) ( P < 0.01). In repeat 12-core biopsies, cancer was detected in 25 (21.2%) men and 9 of them (36.0%) had cancer exclusively in the AAPZ cores. The cancer detection rate from AAPZ sites was significantly higher in repeat biopsy than that in initial biopsy ( P < 0.01). Conclusions: Addition of the AAPZ site-directed biopsy had greater utility in men with normal DRE and particularly in patients with a prior negative biopsy. [ABSTRACT FROM AUTHOR]

Fibrous dysplasia is a condition in which normal skeletal bone changes into fibroblastic stroma and immature bone. We report our experience of a unilateral external fixator applied for the treatment of polyostotic fibrous dysplasia arising in the elbow. The patient was a 38 year-old man. His main complaint was left elbow pain and a mass, which increased in size. The histological diagnosis from the needle biopsy was fibrous dysplasia. An articulated unilateral external fixator was used for immobilization. The lesions in the left distal humerus and proximal ulna were curetted and cancellous bone was packed into the cavity. An external fixator (Elbow Fixator, Orthofix Inc., McKinney, USA) was applied from the proximal humeral shaft to the distal ulnar shaft for postoperative tentative immobilization and preservation of the affected elbow joint movement. At two years after the operation, the range of motion of the affected elbow was 90 degrees in flexion and -35 degrees in extension. The range of motion in pronation and supination of the left forearm was normal. No evidence of recurrence was noted at two years after surgery. The merits of using an external fixator were: an earlier start of range of motion exercises, and a decrease in the risk of tumor dissemination. [ABSTRACT FROM AUTHOR]

Sarcomatoid renal cell carcinoma (SRCC) is associated with an aggressive course, high incidence of bone metastasis, and an extremely poor prognosis. There are a few case reports concerning the effectiveness of chemotherapy on metastasis in SRCC. To our knowledge, however, there are no reports describing its effectiveness on bone metastasis. We report a 22-year-old woman with an 8-cm × 7-cm left renal mass. Left nephrectomy was done. The pathological diagnosis was SRCC, INF-β, pT3aN2. Although, she received continuous infusion of interferon α-2a (INFα-2a) and interleukin-2 (IL-2) as adjuvant therapy, liver metastasis appeared 2 months later. Resection of the liver metastasis was done. After resection of the metastasis, multiple bone metastases appeared, in both humeri, the left chest wall, the left fourth rib, and the left iliac bone. The patient was treated with gemcitabine, 1000 mg/m2 (days 1, 8), docetaxel 80 mg/m2 (day 1), and carboplatin 300 mg/m2 (day 1). A computed tomography (CT) scan after the first cycle revealed that the multiple osteolytic bone tumors had significantly decreased in size. Her ability of daily life (ADL) improved and this continued for almost 2 months. A second course of chemotherapy, with gemcitabine and IL-2 was given, but it was ineffective, and the patient died approximately 16 months after the initial diagnosis of SRCC. Combination chemotherapy with gemcitabine, docetaxel, and carboplatin was effective for the bone metastasis of SRCC. [ABSTRACT FROM AUTHOR]

Tyramide signal amplification–avidin–biotin complex (TSA-ABC) method is a powerful technique used to detect antigens that are not detectable by ordinary immunohistochemistry. It is worth trying in cases where localization of antigens by the conventional method has failed and antibodies are precious. [ABSTRACT FROM AUTHOR]