Tumour infiltrating lymphocytes and PD-L1 expression as potential predictors of outcome in patients with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of tumour. Some mesotheliomas have been proven to be highly immunogenic. Here, we investigated the correlation between tumour infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM. 62 Paraffin-embedded formalin fixed (PEFF) samples were analysed for TILs and PD-L1 expression. Patients were divided in 4 groups according to a cut-off of the percentage of TILs found per sample as measured by immunohistichemistry: "0" or absent (between 0 and 5%), "1" or low (between 6 and 25%), "2" or moderate (between 26 and 50%) and "3" or high (between 51 and 75%). OS was then correlated with different TILs' expression patterns. Moreover, PD-L1 expression was assessed within the tumour as well as in the adjacent stroma on the same samples. Higher expression of peritumoral TILs (Group 2 + 3) versus Group 0 and 1 correlated with improved OS (p-value = 0.02). On the contrary PD-L1 expression seemed to be inversely correlated with clinical outcomes, even in the absence of statistical significance (HR 1.76; p = 0.083 95% IC 0.92-3.36 in areas within the tumour; HR 1.60; p = 0.176 95%; IC 0.80-3.19 in areas within the stroma). No relationship between TILs and PD-L1 expression was identified. Our research supports the use of TILs and PD-L1 expression as potential outcome predictors in patients with MPM. The use of TILs and PD-L1 as biomarkers for checkpoint inhibitors' efficacy warrants future investigation.

Chemokines involved in the early inflammatory response and in pro-tumoral activity in asbestos-exposed workers from an Italian coastal area with territorial clusters of pleural malignant mesothelioma.

OBJECTIVES: Immune mediators are likely to be relevant for the biological response to asbestos exposure. The aim of this study was to investigate the association between immune mediators involved in inflammation, cell survival and angiogenesis, and asbestos-related diseases in workers from a coastal area of North-East Italy with a high incidence of pleural malignant mesothelioma (PMM). MATERIALS AND METHODS: A selected custom set of 12 soluble mediators was evaluated with a Luminex platform in sera, pleural fluid and mesothelioma biopsies from 123 asbestos-exposed workers (38 free from pleural-pulmonary disorders, 46 with non-malignant asbestos diseases, 39 with PMM) and in sera from 33 healthy controls from the same territorial area. RESULTS: Increased immune mediator concentrations were observed in the sera of the asbestos-exposed workers compared to controls for human fibroblast growth factor (FGF-b), vascular endothelial growth factor (VEGF), CCL5 (RANTES), CXCL10 (IP-10), CLEC11A (SCGF-b), CCL27 (CTACK), CCL11 (EOTAXIN), IL-5 and IL-6 (p<0.001). The chemokines IP-10 and RANTES were associated with the severity of asbestos-related diseases. In the workers with PMM, the immune proteins secreted by mesothelioma biopsies showed detectable levels of RANTES, VEGF, and IP-10. In the same workers with PMM, a significant relationship between serum and pleural fluid concentrations was found for RANTES alone. CONCLUSIONS: Occupational exposure to asbestos seems to drive the production of specific growth factors dually involved in the early inflammatory response and in pro-tumoral activity before clinical evidence of related disorders, suggesting that their over-expression may precede the onset of asbestos-related diseases. These findings suggest that some chemokines may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by non-malignant asbestos-related diseases.

High-frequency percussive ventilation during surgical bronchial repair in a patient with one lung.

We report the case of a patient that had undergone a left pneumonectomy during which a double-lumen tube was used and an undetected right bronchial laceration occurred. After diagnosis the patient underwent a second operation to repair the tear. The role of high-frequency percussive ventilation in enabling adequate gas exchange during the bronchial repair is described and discussed.

A renal metastasis from primary peripheral chondrosarcoma presenting as spontaneous retroperitoneal hematoma.

The authors describe a case of renal metastasis from chondrosarcoma originating from the rib, with acute clinical onset characterised by serious anaemia secondary to retroperitoneal perineal haemorrhage. No similar cases have been reported in the literature. The interest of this case lies in both the symptoms of onset and in the metastatic site. From a diagnostic point of view an intraoperative ultrasound scan was useful, revealing the presence of a roundish neoformation, irregularly hypogenic, with a different appearance from anything observed by the authors in the other intraoperative ultrasound examinations of renal masses.

[Role of CT assessment of mediastinal lymph nodes in the preoperative staging of T1 pulmonary carcinoma]. / Ruolo della valutazione TC dei linfonodi mediastinici nella stadiazione preoperatoria dei carcinomi polmonari T1.

The utility of the preoperative staging of T1 lung cancer is controversial. This is due to a lower prevalence of N2 metastases in tumors of small diameter. To assess the prevalence of N2 metastases in such tumors and the sensitivity and specificity of computed tomography in mediastinal sadiation, the authors reviewed CT scans and pathology reports of 56 patients who had undergone surgical resection of a T1 lung cancer so distributed: Adenocarcinoma 20 cases, adenosquamous carcinoma 14, Bronchioloalveolar carcinoma 7, Undifferentiated 7, Carcinoid 5, Small cells carcinoma 3. Mediastinal nodal metastases were present in 11 patients: 6 of them were correctly detected by CT scan. Some differences in terms of N2 prevalence and sensitivity were noted when the T1 were divided in two groups of diameter greater or smaller of 2 cm. Important considerations derived after dividing our patients according to the histological type. The prevalence of N2 metastases was greater in adenocarcinoma than in adenosquamous carcinoma but CT sensitivity was lower in adenocarcinoma (40% Vs 100%). The authors conclude that the prevalence of N2 metastases is high enough to request a preoperative sadiation, but the utility of CT in this purpose is limited by a low sensitivity.

[Endoscopic & histopathologic features of esophageal ulcers. Considerations in 13 cases]. / Caratteristiche endoscopiche ed istopatologiche delle ulcere esofagee. Considerazioni su di una casistica di 13 pazienti.

Chronic, severe reflux esophagitis can be complicated with an esophageal ulcer (EU), whose histomorphological characteristics change sensibly. Between 1983 and 1989, 18 EU were endoscopically identified in 13 (6%) out of 217 patients with chronic gastroesophageal reflux (GER). 2 groups were defined: EU and esophagitis, without columnar-lined esophagus and EU with localized columnar metaplasia or Barrett's esophagus. In the first, 4 Wolf's ulcers (WU) were present; in the second, there were 8 Barrett's ulcers (BU), 2 Savary's ulcers (SU) and 4 ulcers with intermediary characteristics (IU). The 24 h esophageal Ph monitoring demonstrated the reflux pathogenesis in all the patients (57%: alkaline reflux). The histomorphological findings of the EU could support the hypotesis that their variety is related to the different stage of the reflux disease. The EU, started as a peptic lesion on a stratified squamous mucosa (WU), due to an acid, alkaline or mixed reflux, would macroscopically turn into a BU, through intermediary entities (SU, IU), with a progressive extension of columnar metaplasia to the adjacent epithelium and walls. It's not possible to exclude the primitive development of the BU in a Barrett's mucosa, because of an alkaline reflux or because of a low mucosa's resistance (specialized columnar epithelium) to a prolonged acid exposure.

[An evaluation of the N parameter according to the system of the American Thoracic Society (ATS) in pulmonary carcinoma. A comparison between radiology, surgery and histological diagnosis]. / La valutazione del parametro "N" secondo il sistema dell'American Thoracic Society (ATS) nel carcinoma polmonare. Confronto tra radiologia, chirurgia e diagnosi istologica.

The hilar and mediastinal lymph nodes of 36 patients with bronchogenic carcinoma were evaluated with computed tomography (CT). The American Thoracic Society (ATS) mapping was employed, which defines nodal stations in terms of well-recognized anatomic landmarks which are easily identified with CT and during thoracotomy. The differences (30 cases) between CT and surgical measurements in the 124 nodal stations which could be analyzed are discussed in detail. A better correlation was found using a 2-cm threshold value to define a "positive" or "negative" lymph node with CT. The comparison of radiologic data and the presence of metastases showed how with the 2-cm size criterion sensitivity drops from 81% to 53%, whereas specificity rises from 53% to 84%, thus affecting the subsequent diagnosis and therapy positively.

[The role of the environment in postoperative infections]. / Ruolo dell'ambiente nelle infezioni postoperatorie.

The infections are a common complication after surgical procedures, ranging from wound to peritoneal infections. The authors compared the results, in terms of wound infection, of the same equipment in two hospitals, one of which of modern concept. They analysed 1202 operations equally distributed between the two hospitals classifying them in four kinds of operations: I (clean), II (clean-contaminated), III (contaminated), IV (septic). The difference, with less infections in the new hospital, appeared to be already evident if the global results were considered. Considering instead each kind of operations the difference was not statistically meaningful only in the clean operations. The role of antibiotic prophylaxis brought a modest improvement, also statistically not meaningful. Many authors in the past reported different results in terms of wound infections especially if the role of the environment was considered. Gillquist for instance, reported a reduction of wound infections after clean operations that was not present in the research of Bergman and Leissner. The great importance of the environment in preventing wound infections appear clearly in this research, together with the concept that many other factors play an important role.