Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination.

Inhibition of immune checkpoints using anti-programmed cell death-1 (PD-1) or anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibodies has revolutionized the management of patients with advanced-stage melanoma and is among the most promising treatment approaches for many other cancers. Use of CTLA-4 and PD-1 inhibitors, either as single agents, or in combination, has been approved by the US FDA for the treatment of metastatic melanoma. Treatment with these novel immunotherapies results in a unique and distinct spectrum of adverse events, which are mostly related to activation of the immune system and are, therefore, an unwanted consequence of their mechanisms of action. Adverse effects of CTLA-4 and/or PD-1 inhibition are most commonly observed in the skin, gastrointestinal tract, liver and endocrine systems and include pruritus, rash, nausea, diarrhoea and thyroid disorders. In this Review, the authors describe the adverse event profile of checkpoint inhibitors targeting CTLA-4 and PD-1, used both as monotherapies and in combination and aim to provide some general guidelines, based upon the mechanisms of action of these therapies and on the management of these immune-related adverse events.

[Surgical treatment of chronic thromboembolic pulmonary hypertension]. / Traitement chirurgical de l'hypertension pulmonaire post-embolique.

Chronic thromboembolic pulmonary hypertension is a rare but underdiagnosed disease. The development of imaging played a crucial role for the screening and the decision of operability over the past few years. Indeed, chronic thromboembolic pulmonary hypertension is the only type of pulmonary hypertension with a potential curative treatment: pulmonary endarterectomy. It is a complexe surgical procedure performed under cardiopulmonary bypass with deep hypothermia and circulatory arrest. The aim of the procedure is to completely remove the scar tissue inside the pulmonary arteries down to the segmental and sub-segmental levels. Compared to lung transplantation, which carries a postoperative mortality of 15-20% and a 5-year survival of 50%, pulmonary endarterectomy is a curative treatment with a postoperative mortality of less than 3%. However, lung transplantation remains an option for young patients with inoperable distal disease or after pulmonary endarterectomy failure. Considering that medical history of deep venous thrombosis or pulmonary embolism is lacking in 25 to 50%, the diagnosis of chronic thromboembolic pulmonary hypertension remains challenging. The lung V/Q scan is useful for the diagnosis showing ventilation and perfusion mismatches. Lesions located at the level of the pulmonary artery, the lobar or segmental arteries may be accessible to surgical removal. The pulmonary angiogram with the lateral view and the pulmonary CT scan help to determine the level of the intravascular lesions. If there is a correlation between the vascular obstruction assessed by imaging and the pulmonary resistance, pulmonary endarterectomy carries a postoperative mortality of less than 3% and has a high rate of success. If the surgery is performed at a later stage of the disease, pulmonary arteriolitis developed mainly in unobstructed territories and participated in the elevated vascular resistance. At this stage, postoperative risk is higher.

Is sacrifying the phrenic nerve during thymoma resection worthwhile?

OBJECTIVES: Locally advanced thymoma can often involve the phrenic nerve (PN) due to its location on the mediastinal pleura. However, en bloc resection including the PN may cause severe postoperative complications, especially in myasthenia gravis patients. The aim of the study was to determine whether a PN involved could be spared during thymoma resection. METHODS: A retrospective study was conducted on patients who underwent resection of Masaoka Stage III and IV thymomas adherent, on digital palpation, to at least one PN in our institution between 1998 and 2012. An en bloc resection of the tumour with the invaded PN was performed unless patients with no preoperative PN paralysis had: both PN involved, compromised preoperative lung function, severe myasthenia gravis, severe comorbidities or minimal PN involvement (PN adherent to the edge of the tumour). All patients received postoperative radiation therapy. RESULTS: There were 114 patients with a mean age of 57 years (range, 28-84). PN was spared in 73 patients (64%) and removed in 41 (36%). Sixty-five patients had Masaoka Stage III (57%) and 49 had Stage IV (43%); these were similar between both groups. On permanent histology, 6 (15%) of the resected PN were not involved, whereas a permanent postoperative PN palsy was found in 4 (5.4%) patients where the PN was spared. Postoperative mortality and morbidity were 0 and 15% in the spared group and 2.4 and 9.7% in the resected group, respectively (P = 0.56). Recurrence rate was significantly higher in the spared group (39.5 vs 19.5%; P = 0.02) but the 5-year disease-free survival rates (53.6 vs 66.8%, P = 0.14) and overall 5-year survival (85 vs 88%, P = 0.6) were not significantly different between the spared- and resected-PN groups, respectively. CONCLUSIONS: Sparing the PN during thymoma resection achieved good long-term and disease-free survivals in high-risk patients comparable with en bloc PN resection. However, it carried a higher risk of recurrence despite adjuvant radiation therapy.