Two Cases of Nivolumab Re-Administration after Pneumonitis as Immune-Related Adverse Events

Nivolumab is a recently approved medication for the treatment of unresectable malignant melanoma. Many immune-related adverse events (irAEs) associated with nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how or if nivolumab should be administered to patients after they have experienced an irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1 demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2 had a diffuse alveolar damage (DAD) pattern. Oral corticosteroids improved chest shadow of CT scan in both cases. However, when nivolumab was re-administrated, case 1 demonstrated no symptoms, but case 2 demonstrated pneumonia again. From our cases, it is difficult to re-administrate nivolumab for the patients with pneumonitis which shows a DAD pattern in CT, even if oral corticosteroids improve their symptoms

Sudden Onset of Brain Metastasis despite the Use of Vemurafenib for Another Metastatic Lesion in Malignant Melanoma Patients

Vemurafenib is an inhibitor of the BRAF mutation and has been approved by the Food and Drug Administration as a treatment option for patients with unresectable melanoma without brain metastasis. In the literature, vemurafenib has been reported to be also effective against brain metastasis. We encountered 3 cases with brain metastasis on vemurafenib therapy. In these cases, vemurafenib was clinically effective against metastatic lesions other than those in the brain. The brain lesions developed after the metastatic lesion had occurred. Therefore, we assume that the melanomas of the patients acquired resistance against vemurafenib. The brain metastases were treated with the cyberknife. Patients 1 and 2 without LDH elevation are still alive, but patient 3 with abnormal LDH elevation died despite the treatment. We need to carefully follow patients on vemurafenib therapy because brain metastasis can suddenly occur even if the metastatic lesion has decreased clinically. The therapeutic effect of vemurafenib against brain metastasis is poor in cases with LDH elevation

Successful Treatment of Sudden Hepatitis Induced by Long-Term Nivolumab Administration

Immune checkpoint inhibitors have drastically changed in the treatment of many kinds of malignancies, especially malignant melanoma. The focus of the recent experiments has not only been on their efficacy but also immune-related adverse events (irAEs). We report a case of fulminant hepatitis due to nivolumab. In this case, the patient had undergone long-term nivolumab therapy. He did not complain of any symptoms but his liver enzyme levels were extremely elevated (grade 4). We promptly decided to start oral corticosteroids in the patient. His liver function rapidly improved. The dose of corticosteroids was gradually reduced. Our case demonstrates that sudden onset fulminant hepatitis can occur despite the safe use of long-term nivolumab therapy. The irAE can improve rapidly with proper corticosteroid treatment. This report will be useful for the physicians who always use immune checkpoint inhibitors

Successful Treatment of Sudden Hepatitis Induced by Long-Term Nivolumab Administration

Immune checkpoint inhibitors have drastically changed in the treatment of many kinds of malignancies, especially malignant melanoma. The focus of the recent experiments has not only been on their efficacy but also immune-related adverse events (irAEs). We report a case of fulminant hepatitis due to nivolumab. In this case, the patient had undergone long-term nivolumab therapy. He did not complain of any symptoms but his liver enzyme levels were extremely elevated (grade 4). We promptly decided to start oral corticosteroids in the patient. His liver function rapidly improved. The dose of corticosteroids was gradually reduced. Our case demonstrates that sudden onset fulminant hepatitis can occur despite the safe use of long-term nivolumab therapy. The irAE can improve rapidly with proper corticosteroid treatment. This report will be useful for the physicians who always use immune checkpoint inhibitors

Fluid Lubrication and Cooling Effects in Diamond Grinding of Human Iliac Bone

Background and Objectives: Although there have been research on bone cutting, there have been few research on bone grinding. This study reports the measurement results of the experimental system that simulated partial laminectomy in microscopic spine surgery. The purpose of this study was to examine the fluid lubrication and cooling in bone grinding, histological characteristics of workpieces, and differences in grinding between manual and milling machines. Materials and Methods: Thiel-fixed human iliac bones were used as workpieces. A neurosurgical microdrill was used as a drill system. The workpieces were fixed to a 4-component piezo-electric dynamometer and fixtures, which was used to measure the triaxial power during bone grinding. Grinding tasks were performed by manual activity and a small milling machine with or without water. Results: In bone grinding with 4-mm diameter diamond burs and water, reduction in the number of sudden increases in grinding resistance and cooling effect of over 100 °C were confirmed. Conclusion: Manual grinding may enable the control of the grinding speed and cutting depth while giving top priority to uniform torque on the work piece applied by tools. Observing the drill tip using a triaxial dynamometer in the quantification of surgery may provide useful data for the development of safety mechanisms to prevent a sudden deviation of the drill tip