B. W. Robinson

Malignant mesothelioma is an aggressive tumor of serosal surfaces, such as the pleura and the peritoneum. This tumor was once rare, but its incidence is increasing worldwide, probably as a result of widespread exposure to asbestos, a factor with which it is associated. The authors review advances made in the past 5 to 10 years in the understanding, diagnosis, and management of mesothelioma.

Abstract Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. Significance: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM. See related commentary by Aggarwal and Albelda, p. 1508. This article is highlighted in the In This Issue feature, p. 1494

Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapies have generated efficacious and durable responses in clinical trials and why this has reignited interest in this field. Cancer vaccines have also been explored in the past with marginal success. Identification of optimal candidate neoantigens may improve cancer vaccine efficacy and may pave the way to personalized immunotherapy, alone or in combination with other immunotherapy such as immune checkpoint blockade. Understanding the steps in immune recognition and eradication of cancer cells is vital to understanding why previous immunotherapies failed and how current therapies can be used optimally. We hold an optimistic view for the future prospect in lung cancer immunotherapy.

A total of 208 multiple trauma patients with head injury (HI) were investigated who had been treated in the period from 1990 to 1995. The average age was 35.2 +/- 17.7 years; the injury severity according to ISS was 30.2 +/- 8.6 points; 20.5% died as a result of the HI; the mortality of all patients was 26.5%. The Glasgow Coma Scale (GCS) was determined at an average of 22 min after trauma (8.0 +/- 4.3 points) at the scene of accident. The patients were classified according to GCS into minor HI (group 1: 14-15 points), moderate HI (group 2: 9-13 points) and severe HI (group 3: 3-8 points). Patient outcome was assessed by the Glasgow Outcome Scale (GOS) and was classified as good (GOS 4 and 5) and poor (GOS 1, 2 and 3) outcome. At the latest, 2 h after trauma, a CT scan of the head (CCT) was done. The HI groups are compared regarding frequency of types of injury. In all HI groups the fractures of the bony face occurred at the same frequency (36.0-38.9%). The frequency of calotte fractures (Kal-Fx) increased from group 1 (8.0%) to 2 (19.2%) and 3 (25.6%); fractures of the skull base significantly differed between group 1 (16.0%), 2 (7.8%) and 3 (33.4%). Epidural hemorrhage (EDB) appeared only in group 2 (7.8%) and 3 (6.7); subdural hemorrhage was found in group 1 (2.7%), 2 (7.8%) and 3 (10.0%). Subarachnoid hemorrhage (SAB) was significantly more frequently seen, dependent on HI severity, in group 3 (26.7%) compared to group 2 (11.7%) and 1 (8.0%). Intracerebral contusion (ICK) significantly increased from group 1 (12.0%) to 2 (27.3) and 3 (45.6%). Brain swelling (BS) also significantly increased from group 1 (8.0%) to 2 (19.5%) and 3 (49.0%) and lesions of ventricles (VL) from group 1 (2.7%) to 2 (11.7%) and 3 (20.0%). Midline shift (13.4%) and signs of herniation (4.5%) only occurred in group 3. The analysis of correlation/regression and receiver operating characteristics was able to predict 79% of patients' outcome accurately using GCS (r 0.54; P < 0.0001) alone, using CCT (r 0.65; P < 0.0001) 87% were correctly predicted with significant variables Cal-Fx, EDB, SAB and BS. CCT with GCS (r 0.74; P < 0.0001) were able to predict 88% accurately with significant variables Cal-Fx, EDB, BS and GCS. The combination of CCT with GCS, age and ISS (r 0.78; P < 0.0001) was able to predict only 87% correctly, although the r value was the highest; significant variable were Kal-Fx, EDB, BS, VL, GCS, age and ISS.