Case Report: Spontaneous lung intercostal hernia series and literature review.

Spontaneous lung intercostal hernia (SLIH) is a rare condition potentially carrying severe morbidity. About 120 cases have been described so far, with an apparently increasing number of reports in recent years. The main presenting findings are chest pain and bulging, with ecchymosis in the affected area, hemoptysis, respiratory distress, and signs of infection or incarceration being described as well. The gold standard treatment has not been established, and conservative management has been advocated as first-line treatment for asymptomatic patients. Here, we report a case series of five patients, and surgical repair was deemed necessary for four of them either at first evaluation or after failure of conservative management. One patient remains under surveillance and conservative management. We believe that SLIH surgical repair should be considered as first-line treatment for fit patients, due to the uncertainty of its mid- and long-term impact and described pejorative trend/defect enlargement. A proposed algorithm for SLIH management is also presented.

Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment.

Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20-50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/-3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/-22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evolutionary clusters dictate MPM inflammation and immune evasion. These results reveal potentially drugable evolutionary bottlenecking in MPM, and an impact of clonal architecture on shaping the immune landscape, with potential to dictate the clinical response to immune checkpoint inhibition.

Women in thoracic surgery: European perspectives.

During the last decades, women have been discouraged from entering the medical career and in particular in the surgical specialties. This situation is changing across continents and national and international initiatives are supporting aspiring female surgeons in pursuing the surgical career through mentorship and fellowship programmes. Due to the differences in training programmes, Health Care systems and cultural backgrounds, it's not easy to describe unanimously the pathways and obstacles that junior female thoracic surgeons are experiencing in Europe. The development of female surgical associations, mentorship programmes and national initiatives will further champion the gender equality in this specialty across Europe. During the recent years, the European Society of Thoracic Surgeons (ESTS) has established initiatives like the first ESTS Women in Thoracic Surgery Scientific Session or the annual Women in Thoracic ESTS Reception during the Annual Conference, which are done in an effort to encourage all female colleagues to join this specialty and increase the opportunity to share their experience and meet potential mentors. In this article we will depict the situation in some of the European countries whose female thoracic surgeons have led their way. We aim to give the next generation the examples that can influence women's choice of surgical career, and the possible strategies and initiatives to reduce the gender discrimination within healthcare.

BRCA1/MAD2L1 Deficiency Disrupts the Spindle Assembly Checkpoint to Confer Vinorelbine Resistance in Mesothelioma.

Mesothelioma is a universally lethal cancer lacking effective therapy. The spindle poison vinorelbine exhibits clinical activity in the relapsed setting, and in preclinical models requires BRCA1 to initiate apoptosis. However, the mechanisms underlying this regulation and the clinical implications have not been explored. Here, we show that BRCA1 silencing abrogated vinorelbine-induced cell-cycle arrest, recruitment of BUBR1 to kinetochores, and apoptosis. BRCA1 silencing led to codepletion of MAD2L1 at the mRNA and protein levels consistent with its status as a transcriptional target of BRCA1 Silencing of MAD2L1 phenocopied BRCA1 and was sufficient to confer resistance to vinorelbine. This was recapitulated in cell lines selected for resistance to vinorelbine, which acquired loss of both BRCA1 and MAD2L1 expression. Following ex vivo vinorelbine in 20 primary tumor explants, apoptotic response rate was 59% in BRCA1/MAD2L1-positive explants compared with 0% in BRCA1/MAD2L1-negative explants. In 48 patients, BRCA1 and/or MAD2L1 loss of expression was not prognostic; however, in a subset of patients treated with vinorelbine, survival was shorter for patients lacking BRCA1/MAD2L1 expression compared with double-positive patients (5.9 vs. 36.7 months, P = 0.03). Our data implicate BRCA1/MAD2L1 loss as a putative predictive marker of resistance to vinorelbine in mesothelioma and warrant prospective clinical evaluation.

If Background Lung Abnormalities Do Not Affect the Presentation of Spontaneous Pneumothorax, Is Lung Resection Always Justified?

BACKGROUND: The suggestion that spontaneous pneumothorax (SP) may result from diffuse porosity rather than discrete anatomic abnormality challenges the practice of targeted bullectomy. We assessed whether underlying pulmonary abnormalities are correlated or could be predicted from the mode of presentation, with potential implications for treatment. METHODS: We analyzed 192 consecutive video-assisted thoracoscopic surgery resections for SP (139 primary, 53 secondary) in 171 patients (115 male, age 36, range, 16 to 81). Presentation was categorized as: recurrent never drained (RND), recurrent drained, persistent air leak (PAL). Resected lung pathology was categorized as: no bleb/bulla, ruptured bleb/bulla, unruptured bleb/bulla. RESULTS: No correlation between presentation and resected lung pathology was observed for primary (P=0.608) or secondary SP (P=0.597). A similar proportion of patients in each pathologic group presented with PAL or RND; ruptured bleb/bulla or no bleb/bulla was equally noted in PAL and RND group. CONCLUSIONS: There is lack of association between resected lung pathology and mode of presentation. This suggests that discrete anatomic abnormalities may not be responsible for the air leak leading to pneumothorax. In conjunction with favorable reported outcomes from medical thoracoscopy and talc pleurodesis alone, these findings challenge the current practice of routine video-assisted thoracoscopic surgery lung resection in these patients.

How does the timing of chemotherapy affect outcome following radical surgery for malignant pleural mesothelioma?

OBJECTIVES: There is little evidence regarding the use of chemotherapy as part of multimodality treatment of malignant pleural mesothelioma (MPM). We aimed to determine whether, in those patients fit for chemotherapy, a delay in this treatment affected survival. MATERIALS AND METHODS: We analysed postoperative variables of 229 patients undergoing either extrapleural pneumonectomy (EPP) (81 patients) or extended pleurectomy-decortication (EPD) (197 patients) for MPM at a single centre. There was no standard protocol for additional chemotherapy and varied with referral centre. Outcome was compared between 4 chemotherapy strategies: true adjuvant therapy, neo-adjuvant therapy, therapy reserved until evidence of disease progression in those otherwise fit in the post-operative setting, and those unfit for chemotherapy. RESULTS: There was no effect of the timing of chemotherapy on overall or progression free survival in patients fit enough for treatment (p=0.39 and p=0.33 respectively). However delaying chemotherapy until evidence of disease progression in patients with non-epithelioid disease had a detrimental effect on overall survival (OS), and on progression free survival (PFS) in lymph node positive patients (15.6 vs. 8.2 months p=0.001, and 14.9 vs. 6.0 months p=0.016). Further analysis of 169 patients receiving platinum/pemetrexed as first line treatment, showed similar results; there was no effect of the timing of chemotherapy on OS or PFS (p=0.80 and p=0.53 respectively) and an improved OS in patients with non-epithelioid disease, and improved PFS in those with lymph node metastases, if chemotherapy was given in the immediate adjuvant setting (p=0.001 and 0.038) when therapy was not delayed until disease progression. CONCLUSION: Our results suggest that the timing of additional chemotherapy may be important in those with a poorer prognosis on the basis of cell type and nodal stage. In these patients additional postoperative chemotherapy should not be delayed.

The management of the diaphragm during radical surgery for malignant pleural mesothelioma.

OBJECTIVES: Macroscopic complete resection with lung preservation is the objective of radical management of pleural mesothelioma (MPM). Total removal of visceral and parietal pleura (pleurectomy/decortication) almost invariably proceeds to an extended pleurectomy/decortication (EPD) to ensure macroscopic complete resection. We suspected this may not always be necessary. METHODS: We reviewed 314 patients, 86.0% male, median age 62 years (range 14-81 years) undergoing radical surgery for MPM from 1999 to 2014, by either EPD or extrapleural pneumonectomy. The extent of diaphragmatic muscle involvement was recorded from postoperative pathology. Patients were divided into three groups: no involvement, non-transmural, transmural diaphragmatic invasion. RESULTS: A total of 213 (68%) patients underwent EPD, 237 (75.5%) had epithelioid disease and 57.6% were node positive. There was no difference between the three groups in terms of age, cell type, laterality, neoadjuvant chemotherapy and operation. There was a higher degree of diaphragm involvement in females (P = 0.01) and in patients with positive lymph nodes (P = 0.01). No evidence of diaphragmatic involvement was found following pathological assessment of the resection specimen in 119 patients (37.9%). The incidence of abdominal disease progression was 23.9%. There was no correlation with degree of diaphragmatic invasion (ρ = 0.01 P = 0.88). Overall survival of those with abdominal progression was similar to those with progression elsewhere: 14.5 vs 13.0 months (P = 0.79), and with those with no progression (16.7 months, P = 0.189). There was no difference in survival when stratified by diaphragmatic involvement (P = 0.44). CONCLUSIONS: In our cohort, there was no evidence of diaphragmatic invasion in over 30% of patients, and we have also failed to find evidence that peritoneal disease progression affects overall survival following radical management. It may therefore theoretically be unnecessary to resect the diaphragm in all cases, and a pleurectomy-decortication could suffice. However, there is an unknown risk of R2 resection which would prejudice survival, and as such we would advocate resecting the diaphragm in all cases to avoid an R2 resection.

The effects of an intentional transition from extrapleural pneumonectomy to extended pleurectomy/decortication.

OBJECTIVES: For many years, extrapleural pneumonectomy (EPP) was the operation of choice for the radical management of pleural mesothelioma in the UK. However, doubts surrounding the efficacy of EPP, and the change in demographics of the affected population, have prompted a transition in our practice towards extended pleurectomy/decortication (EPD). The aim of this study was to determine the effects an intentional transition from EPP to EPD has had on patient outcome. METHODS: Data from 362 patients undergoing radical surgery (229 EPD, 133 EPP) during 1999-2014 were included. Demographics and outcome were compared between the two groups; EPP versus EPD. RESULTS: The median age of patients undergoing EPD was significantly higher than those undergoing EPP [57 years (range 14-70 years) vs 65 years (range 42-81 years), P < 0.001]. There was a significantly higher proportion of patients with performance status ≥1 in the EPD group (46.3 vs 35.4%, P = 0.047). There was no difference in the median length of hospital stay between the two groups [14 days (range 1-133 days) vs 13 days (range 0-93 days), P = 0.409]. There was also no difference between the groups in terms of in-hospital mortality (EPP 5.3% and EPD 6.6%, P = 0.389), 30-day mortality [EPP 8 (6.0%) and EPD 8 (3.5%), P = 0.294] or 90-day mortality [EPP 18 (13.5%) and EPD 21 (9.2%), P = 0.220]. There was a significantly higher early reoperation rate in the EPP group (15.0 vs 6.2%, P = 0.008) but a significantly higher late reoperation rate in the EPD group (0.8 vs 5.3%, P = 0.037). There was no significant difference in overall survival or disease-free interval between the two groups (P = 0.899 and P = 0.399, respectively). However, overall survival was significantly greater in patients over the age of 65 undergoing EPD (12.5 vs 4.7 months, P = 0.001). CONCLUSION: The transition from EPP to EPD in our standard practice has enabled us to operate on more elderly, frail patients with no significant increase in use of hospital resources, and without detriment to overall survival.

The successful use of octreotide in the treatment of traumatic chylothorax.

Chylothorax is a well-documented complication of thoracic trauma and is associated with mortality rates of up to 75%. The conservative treatment of chylothorax includes pleural drainage and a low-fat diet rich in medium-chain fatty acids, followed by total parenteral nutrition and nothing by mouth. If these measures fail and drainage continues to exceed 1 L/d, surgical thoracic duct ligation is usually recommended. However, many patients are unable to undergo this surgical procedure and require an alternative treatment. We present the cases of 2 adult patients, one of whom developed chylothorax after an elective surgical procedure, and the other after a traffic accident that caused multiple injuries. In both patients, conservative management with the addition of octreotide was successful and negated the need for surgical intervention.