Impact of Ambulation Status in Patients with End-stage Renal Disease on Hemodialysis due to Diabetic Nephropathy : The PREDICT Study

Article信州医学雑誌 68(3): 131-138(2020)journal articl

Sarcoidosis of mediastinal lymph nodes mimicking distant metastasis of oral squamous cell carcinoma : a case report and review of literature

Sarcoidosis is a systemic, chronic inflammatory disease with unknown cause and is characterized by formation of epithelioid granulomas in various organs, mainly the lungs and lymphatic system as mediastinal lymph nodes (LNs). Lymphadenopathy is common in sarcoidosis. Subsequent cancer also tends to occur in patients with the disease, and the most frequent is lymphoma and cancer of the lung. Head and neck cancer is uncommon but possible. We report a 70-year-old woman with squamous cell carcinoma (SCC) of the mandibular gingiva concomitant with mediastinal multiple lymphadenopathy, and a medical history of chronic sarcoidosis. Mediastinal LNs showed increased uptake of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) with positron emission tomography (PET). Subsequent to lymphadenectomy, the histological diagnosis was lymphadenopathy caused by sarcoidosis. Next, we performed wide local excision of the gingival tumor. During follow-up, a pulmonary lesion was detected by computed tomography at 3 years and 11 months after surgery, and diagnosed as pulmonary sarcoidosis, which had been stable without treatment until now. After follow-up of 5 years, the patient was alive without signs of local recurrence or metastasis. The combination of oral SCC and sarcoidosis of the mediastinal LNs in a sarcoidosis patient has not been previously reported. FDG-PET was not able to distinguish LN metastasis from lymphadenopathy caused by sarcoidosis. In our case, her chronic inflammatory condition with sarcoidosis as well as ill-fitting dentures could have increased the risk of oral cancer. We suggest that clinicians should carefully check for the development of subsequent oral cancer in patients with a past history of sarcoidosis. To avoid inaccurate staging and incorrect therapy, LN biopsy should be promptly performed following a diagnosis of cancer and multiple lymphadenopathies in patients with a history of sarcoidosis. Lymphadenopathy with sarcoidosis patients have malignant potential, especially those who develop subsequent cancer. Misdiagnosis of LN malignancy and sarcoidosis may lead to unnecessary adjuvant therapy or worse prognosis

Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain

Messenger RNA (mRNA) medicine has become a new therapeutic approach owing to the progress in mRNA delivery technology, especially with lipid nanoparticles (LNP). However, mRNA encapsulated-LNP (mRNA-LNP) cannot spontaneously cross the blood-brain barrier (BBB) which prevents the expression of foreign proteins in the brain. Microbubble-assisted focused ultrasound (FUS) BBB opening is an emerging technology that can transiently enhance BBB permeability. In this study, FUS/microbubble-assisted BBB opening was investigated for the intravenous delivery of mRNA LNP to the brain. The intensity of FUS irradiation was optimized to 1.5 kW/cm2, at which BBB opening occurred efficiently without hemorrhage or edema. Exogenous protein (luciferase) expression by mRNA-LNP, specifically at the FUS-irradiated side of the brain, occurred only when FUS and microbubbles were applied. This exogenous protein expression was faster but shorter than that of plasmid DNA delivery. Furthermore, foreign protein expression was observed in the microglia, along with CD31-positive endothelial cells, whereas no expression was observed in astrocytes or neurons. These results support the addition of mRNA-LNP to the lineup of nanoparticles delivered by BBB opening