Efficacy and safety of mycophenolate mofetil in treating immune-related hepatitis induced by immune checkpoint inhibitor use: A retrospective study.

Background and Aim: To investigate the outcomes in eight Japanese patients with cancer treated with mycophenolate mofetil (MMF) and corticosteroids for immune checkpoint inhibitor treatment-induced severe immune-related hepatitis (ir-hepatitis) and the efficacy and safety of MMF. Methods: We retrospectively examined patient background, treatment course, as well as examination and imaging data using electronic medical records. Results: The ratio of male to female patients was 7:1, and the median age was 60 years (27-72 years). There were five and two cases of kidney cancer and malignant melanoma, respectively, and one case of lung cancer. The median number of days until MMF administration in addition to systemic corticosteroid therapy after the onset of ir-hepatitis was 14.5 (2-42). The patients were categorized as four "good responders" who showed an improvement in the liver function tests following MMF treatment and four "poor responders" who did not. Furthermore, the time from the onset of ir-hepatitis to initial MMF administration was significantly shorter in good responders (median 3 days, range 2-15 days) than in poor responders (median 25.5 days, range 14-42 days) (P = 0.042). No significant intergroup difference was observed in other clinical factors. No serious adverse events caused by MMF were observed in any case. Conclusions: According to these findings, early recognition of corticosteroid refractoriness and the use of MMF may be beneficial in patients with ir-hepatitis.

Efficacy and safety of Infliximab for steroid-resistant immune-related adverse events: A retrospective study.

The present study investigated outcomes of infliximab (IFX) treatment among 8 Japanese patients with various types of cancer (4 with malignant melanoma, 3 with lung cancer and 1 with renal cancer) who developed severe steroid-resistant immune-related adverse events (irAEs) in association with immune checkpoint inhibitors (ICIs) to determine its efficacy and safety. Information, including patient background, treatment progress, examination data and imaging data, was collected retrospectively from electronic medical records. Adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Specific ICIs used were anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibody preparations in 7, 2 and 5 patients, respectively. Specific irAEs included grade 3 diarrhea/colitis in 7 patients and disseminated intravascular coagulation and myocarditis attributed to autoimmune activation in 1 patient. The median duration between systemic steroid and IFX treatments was 9 (range, 2-39) days. A total of 3 patients responded to IFX, 1 of whom responded after one dose and 2 responded after two doses. Respective diseases improved to grade 0 after a median of 18 (range, 9-32) days. No AEs were attributable to IFX. Additionally, anti-cytomegalovirus (CMV) and antibacterial agents were administered in parallel given the presence of CMV and Clostridium difficile (CD) infections in all patients, except in 1 exhibiting a marked IFX response after one dose. The combination of highly immunosuppressive IFX and high-dose systemic steroid administration over a long period presumably predisposed the patients to opportunistic enteric infections. Accordingly, early initiation of IFX treatment in conjunction with systemic steroid therapy should be considered for severe diarrhea/colitis and other irAEs. However, the possibility for CMV and CD infections should be recognized, and for these the treatment strategy may need to be modified at an early stage.

[Effect of Relative Dose Intensity(RDI)-Guided Dose Adjustments of Palbociclib on Duration of Treatment in Patients with Severe Neutropenia].

The study subjects consisted of 54 patients with inoperable or recurrent breast cancer who were administered a combination of palbociclib plus endocrine therapy. We examined the onset of neutropenia during the first course of treatment and evaluated the influence that various risk factors had on treatment continuity. Patients with neutropenia Grade≥3 had significantly lower relative dose intensity(RDI) values during the first course of treatment than did patients with neutropenia Grade ≤2. Patients with neutropenia Grade≥3 showed significantly longer treatment to failure than did patients with neutropenia Grade≤2. These results suggest that the degree of neutropenia during the first course of treatment might contribute to treatment continuity and that it is important to improve the curative effect by maintaining appropriate RDI and by continuously administering palbociclib in patients with neutropenia Grade≥3.

Video-assisted thoracic surgery for lung cancer: is it a feasible operation for stage I lung cancer?

OBJECTIVE: The objective of this study was to confirm the safety and feasibility of video-assisted thoracic surgery (VATS) for primary lung cancer and to compare prognoses with that of conventional procedures, and then to examine whether VATS would supplant a conventional thoracotomy for stage I lung cancer. METHODS: From September 1995 through March 2002, 144 patients with primary lung cancer, included 118 patients with postoperative stage I, underwent VATS lobectomy. We reviewed the previous cases whether they could be candidates for VATS lobectomy according to present indications. 166 cases were supposed to be candidates for VATS, and 121 cases of postoperative stage I disease were recruited into the "conventional thoracotomy" group. RESULTS: There was no mortality or major complication except one case, and mean follow-up was 31.8 months in VATS. The number of removed lymph nodes was not significantly less than the number by conventional thoracotomy (p=0.061). Five-year survival for patients with pathological stage IA adenocarcinoma was 92.4% (n=66) in VATS and 86.9% (n=50) in conventional thoracotomy, and a statistical significance could not be recognized (p=0.980). The length of hospital stay was significantly short in VATS lobectomy (p<0.0001). CONCLUSIONS: VATS lobectomy for stage I lung cancer can be performed safely with minimal morbidity, satisfying survival comparable with that of lobectomy through conventional thoracotomy. VATS approach is a feasible surgical technique for patients with stage I lung cancer.

[A case of multicentric Castleman's disease with multiple pulmonary nodules].

A 55-year-old woman visited our hospital for further examination of abnormal shadows on chest radiographs. Her routine chest radiograph showed two nodular shadows in the right lower lung field. A chest CT scan revealed other nodules, small patchy shadows in both lung fields, and enlargement of the mediastinal lymphnodes (#2, 3). Laboratory data showed polyclonal hyperimmunoglobulinemia. This case was initially considered on the basis of a transbronchial lung biopsy to be a plasma cell granuloma. However, serum gammaglobulin levels gradually increased, and video-assisted thoracoscopic surgery was performed to aid in making a definite diagnosis. Biopsy specimens revealed lymphoid follicles with plasma cells which were stained with both anti-kappa chain and anti-lambda chain antibodies. The patient was treated with prednisolone (50 mg/day), and the serum gammaglobulin level and the shadows on the chest CT were temporarily slightly improved. During the clinical course, her laboratory data and histological specimens were re-examined, and the final diagnosis was multicentric Castleman's disease.