Two hundred thirty-seven patients with cancer of the breast treated with radical mastectomy were reviewed. Coefficients of correlation between patient's and doctor's delay vs. survival were not significant at p smaller than 0.05. No significant relationship between delay and time of recurrence was found.
Pathological diagnosis of drowning remains a challenge for forensic science, because of a lack of pathognomonic findings. We analyzed microbiota and surfactant protein in the lungs for a novel diagnosis of drowning. All rats were divided into drowning, postmortem submersion, and control groups. The water, lungs, closed organs (kidney and liver), and cardiac blood in rats were assayed by targeting 16S ribosomal RNA of Miseq sequencing. Lung samples were analyzed by immunohistochemical staining for surfactant protein A. The closed organs and cardiac blood of drowned group have a lot of aquatic microbes, which have not been detected in postmortem submersion group. Furthermore, intra-alveolar granular staining of surfactant protein A (SP-A) was severely observed in the drowned group than the postmortem submersion and control groups. The findings suggested that the presence of aquatic microbiota in the closed organs and increased expression of SP-A could be markers for a diagnosis of drowning.
Angiosarcoma is a rare malignant tumor of the skin and soft tissue, and commonly metastasizes to the lungs, showing multiple nodules. The metastatic lung lesions rarely cavitate(1-5), though a angiosarcoma with cavitary metastasis can be complicated by hemopneumothorax(1-5). Metastatic lung lesions showing both cavities and pulmonary hemorrhage on high resolution CT have not, however, been reported. We describe a case of angiosarcoma of the scalp which rapidly developed cavitary lung metastasis, bilateral pneumothoraces, and diffuse pulmonary hemorrhage, and led to the patient s death.
Case ReportAn 85-year-old non-smoking man was admitted with dyspnea; its onset had been sudden, it persisted for a week and was accompanied by a cough, fresh hemoptysis and chest pain. Fifteen days before admission he had undergone excision biopsy of a soft tissue mass in the parietal area of the scalp. The histologic findings of the lesion were consistent with angiosarcoma involving the dermis and subcutaneous fat.The results of a pulmonary function test, performed on admission were normal. Cytologic examination of the sputum revealed no malignant cells, and sputum culture showed no bacterial growth.Initial chest radiograph showed increased interstitial markings and numerous thin-walled cavitary lesions in both lungs, small amount of pneumothorax was seen in the left pleural space. The chest radiograph obtained six days later showed an area of ground-glass opacity in the We describe a case of cavitary metastasis to the lungs from a small angiosarcoma of the scalp, in which the metastatic lesions were complicated by pneumothorax and pulmonary hemorrhage. On high-resolution CT, the lesions simulated the findings of Langerhans cell histiocytosis. Thin-walled cavitary metastatic lesions were similar to those of thin walled air cysts in Langerhans cell histiocytosis. Ground-glass opacity simulated the findings of smoke r s respiratory bronchiolitis in Langerhans cell histiocytosis but histologically represented hemorrhage during metastasis of the angiosarcom a .
Primary Objective: To assess the efficacy of MK-3475 as a single agent in patients with MIBC and non-IBC TNBC. The primary endpoint is disease control rate at the end of 4 months after receiving the treatment. We will also investigate the association between biomarkers in the peripheral blood and tumor tissue, safety and efficacy.
Background: The extensive invasion of lymphatic vessels by tumor emboli in patients with IBC suggests that the host immune surveillance system is suboptimal or that the tumor cells have decreased immunogenicity through immune editing to avoid detection by the host. In the immune-competent host, tumor cells must overcome both innate and adaptive immunologic defenses of the host. The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress immune control. MK-3475 is a potent and highly selective humanized mAb designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. MK-3475 strongly enhances T lymphocyte immune responses in cultured blood cells from healthy human donors, cancer patients, and primates. Mouse anti-PD-1, as a monotherapy, demonstrated efficacy in several syngeneic mouse tumor models. To date, no specific targeted therapeutic options exist for the treatment of MIBC and TNBC. After patients achieving a clinical response to systemic therapy, the maintenance of disease control is not guaranteed. Further, our recent publication suggests that IBC has immune dysfunction. Chemotherapies can debulk the disease volume but cannot be used for maintenance due to their toxicities. Using an anti PD-1 monoclonal antibody is a promising approach for this patient population.
Study Design and Treatment Plan: This is a single arm phase II study. Up to 35 patients with HER2 negative MIBC or metastatic TN-IBC (MTNBC) who have achieved clinical response or stable disease after receiving any prior systemic therapy for metastatic/recurrent disease, and meet all other criteria will be eligible. Patients will receive MK-3475 200 mg IV every 3 weeks for up to 2 years.
Statistical Considerations: The trial will be conducted using Simon's optimal two-stage design and the rate of disease control will be estimated accordingly. It is assumed that the MK-3475 single agent will have a disease control rate of 30%. A disease control rate of 10% or lower will be considered treatment failure and the regimen will be rejected under this circumstance.
Status of the study:
Activation Date: June 2015. 13 patients have been enrolled. Enrollment continues.
Sponsor: Merck Sharp & Dohme Corp.
State of Texas appropriation for rare and aggressive breast cancer research.
Citation Format: Willey JS, Parker CA, Valero V, Lim B, Reuben JM, Krishnamurthy S, Gong Y, Scoggins ME, Dryden MJ, Liu DD, Woodward WA, Ueno NT. A phase II study of anti-PD-1 (MK-3475) therapy in patients with metastatic inflammatory breast cancer (MIBC) or non-IBC triple negative breast cancer (non-IBC TNBC) who have achieved clinical response or stable disease to prior chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-02-01.
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