BACKGROUND There is limited randomized evidence on the comparative outcomes of early-stage lung cancer resection by video-assisted thoracoscopic surgery (VATS) versus open resection. METHODS We conducted a parallel-group multicenter randomized trial that recruited participants with known or suspected early-stage lung cancer and randomly assigned them to open or VATS resection of their lesions. The primary outcome was physical function at 5 weeks as a measure of recovery using the European Organisation for Research and Treatment of Cancer core health-related quality of life questionnaire (QLQ-C30)(scores range from 0 to 100, with higher scores indicating better function; the clinical minimally important difference for improvement is 5 points). We followed the patients for an additional 47 weeks for other outcomes.RESULTS A total of 503 participants were randomly assigned (247 to VATS and 256 to open lobectomy). At 5 weeks, median physical function was 73 in the VATS group and 67 in the open surgery group, with a mean difference of 4.65 points (95% confidence interval, 1.69 to 7.61). Of the participants allocated to VATS, 30.7% had serious adverse events after discharge compared with 37.8% of those allocated to open surgery (risk ratio, 0.81 [95% confidence interval, 0.66 to 1.00]). At 52 weeks, there were no differences in cancer progression-free survival (hazard ratio, 0.74 [0.43 to 1.27]) or overall survival (hazard ratio, 0.67 [0.32 to 1.40]).CONCLUSIONS VATS lobectomy for lung cancer is associated with a better recovery of physical function in the 5 weeks after random assignment compared with open surgery. Long-term oncologic outcomes will require continued follow-up to assess.

We provide evidence of how RAD51AP1 can be of importance as potential biomarker since it is overexpressed in both tissue and peripheral blood of ovarian and lung cancer patients. Silencing of the gene can also lead to decrease in cell proliferation in vitro, so a potential therapeutic target.

Severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV2) is the cause of a new disease (COVID-19) which has evolved into a pandemic during the first half of 2020. Older age, male sex and certain underlying diseases, including cancer, appear to significantly increase the risk for severe COVID-19. SARS-CoV-2 infection of host cells is facilitated by the angiotensin-converting enzyme 2 (ACE-2), and by transmembrane protease serine 2 (TMPRSS2) and other host cell proteases such as cathepsin L (CTSL). With the exception of ACE-2, a systematic analysis of these two other SARS-CoV2 infection mediators in malignancies is lacking. Here, we analysed genetic alteration, RNA expression, and DNA methylation of TMPRSS2 and CTSL across a wide spectrum of tumors and controls. TMPRSS2 was overexpressed in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), uterine corpus endometrial carcinoma and uterine carcinosarcoma, with PRAD and READ exhibiting the highest expression of all cancers. CTSL was upregulated in lymphoid neoplasm diffuse large B-cell lymphoma, oesophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, lower grade glioma, pancreatic adenocarcinoma, skin cutaneous melanoma, stomach adenocarcinoma, and thymoma. Hypo-methylation of both genes was evident in most cases where they have been highly upregulated. We have expanded on our observations by including data relating to mutations and copy number alterations at pan-cancer level. The novel hypotheses that are stemming out of these data need to be further investigated and validated in large clinical studies.

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Nuclear grading system for epithelioid malignant pleural mesothelioma (MPM) has been proposed but 2 it remains uncertain if they could be applied in a biopsy-heavy setting. Using the proposed system, we 3 conducted an independent, external validation study using 563 consecutive cases of epithelioid MPM 4 diagnosed at our institution between 2003 and 2017, of which 87% of patients underwent biopsies 5 only. The median number of sites sampled was 1, with median maximum tissue dimension of 17mm 6 (Biopsy) and 150mm (Resection). The median overall survival (OS) was 14.7 months. The 7 frequencies of Grade I, II and III tumors were 31% (132/563), 52% (292/563) and 17% (94/563). 8Grade I tumors were associated with the most favorable median OS (24.7 months) followed by grade 9 II (12.7 months) and III (7.2 months). 2-tier nuclear grade separated tumors into low grade (19.3 10 months) and high grade (8.9 months). In multivariate analysis, 3-tier nuclear grade, 2-tier nuclear 11 grade and mitosis-necrosis score predicted OS independent of age, procedural type, solid-predominant 12 growth pattern, necrosis and atypical mitosis (all p<0.001 except 2-tier nuclear grade, p=0.001). In the 13 scenario of a single site biopsy with tissue dimension less than or equal to 10mm, none but age 14 (p=0.002) were independently predictive. Our data also suggested sampling 3 sites or a maximum 15 tissue dimension of at least 20mm from a single site is optimal for nuclear grade assessment. In 16 conclusion our study confirmed the utility of nuclear grade in epithelioid MPM using a biopsy-heavy 17 cohort provided the tissue sample met minimum dimensional criteria.

Severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2), the causative viral agent for the ongoing COVID-19 pandemic, enters its host cells primarily via the binding of the SARS-CoV-2 spike (S) proteins to the angiotensin-converting enzyme 2 (ACE2). A number of other cell entry mediators have also been identified, including neuropilin-1 (NRP1) and transmembrane protease serine 2 (TMPRSS2). More recently, it has been demonstrated that transmembrane protease serine 4 (TMPRSS4) along with TMPRSS2 activate the SARS-CoV-2 S proteins, and enhance the viral infection of human small intestinal enterocytes. To date, a systematic analysis of TMPRSS4 in health and disease is lacking. In the present study, using in silico tools, the gene expression and genetic alteration of TMPRSS4 were analysed across numerous tumours and compared to controls. The observations were also expanded to the level of the central nervous system (CNS). The findings revealed that TMPRSS4 was overexpressed in 11 types of cancer, including lung adenocarcinoma, lung squamous cell carcinoma, cervical squamous cell carcinoma, thyroid carcinoma, ovarian cancer, cancer of the rectum, pancreatic cancer, colon and stomach adenocarcinoma, uterine carcinosarcoma and uterine corpus endometrial carcinoma, whilst it was significantly downregulated in kidney carcinomas, acute myeloid leukaemia, skin cutaneous melanoma and testicular germ cell tumours. Finally, a high TMPRSS4 expression was documented in the olfactory tubercle, paraolfactory gyrus and frontal operculum, all brain regions which are associated with the sense of smell and taste. Collectively, these data suggest that TMPRSS4 may play a role in COVID-19 symptomatology as another SARS-CoV-2 host cell entry mediator responsible for the tropism of this coronavirus both in the periphery and the CNS.

Background Lung cancer is the leading cause of cancer death. Surgery remains the main method of managing early-stage disease. Minimal-access video-assisted thoracoscopic surgery results in less tissue trauma than open surgery; however, it is not known if it improves patient outcomes. Objective To compare the clinical effectiveness and cost-effectiveness of video-assisted thoracoscopic surgery lobectomy with open surgery for the treatment of lung cancer. Design, setting and participants A multicentre, superiority, parallel-group, randomised controlled trial with blinding of participants (until hospital discharge) and outcome assessors conducted in nine NHS hospitals. Adults referred for lung resection for known or suspected lung cancer, with disease suitable for both surgeries, were eligible. Participants were followed up for 1 year. Interventions Participants were randomised 1 : 1 to video-assisted thoracoscopic surgery lobectomy or open surgery. Video-assisted thoracoscopic surgery used one to four keyhole incisions without rib spreading. Open surgery used a single incision with rib spreading, with or without rib resection. Main outcome measures The primary outcome was self-reported physical function (using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) at 5 weeks. Secondary outcomes included upstaging to pathologic node stage 2 disease, time from surgery to hospital discharge, pain in the first 2 days, prolonged pain requiring analgesia at > 5 weeks, adverse health events, uptake of adjuvant treatment, overall and disease-free survival, quality of life (Quality of Life Questionnaire Core 30, Quality of Life Questionnaire Lung Cancer 13 and EQ-5D) at 2 and 5 weeks and 3, 6 and 12 months, and cost-effectiveness. Results A total of 503 patients were randomised between July 2015 and February 2019 (video-assisted thoracoscopic surgery, n = 247; open surgery, n = 256). One participant withdrew before surgery. The mean age of patients was 69 years; 249 (49.5%) patients were men and 242 (48.1%) did not have a confirmed diagnosis. Lobectomy was performed in 453 of 502 (90.2%) participants and complete resection was achieved in 429 of 439 (97.7%) participants. Quality of Life Questionnaire Core 30 physical function was better in the video-assisted thoracoscopic surgery group than in the open-surgery group at 5 weeks (video-assisted thoracoscopic surgery, n = 247; open surgery, n = 255; mean difference 4.65, 95% confidence interval 1.69 to 7.61; p = 0.0089). Upstaging from clinical node stage 0 to pathologic node stage 1 and from clinical node stage 0 or 1 to pathologic node stage 2 was similar (p ≥ 0.50). Pain scores were similar on day 1, but lower in the video-assisted thoracoscopic surgery group on day 2 (mean difference –0.54, 95% confidence interval –0.99 to –0.09; p = 0.018). Analgesic consumption was 10% lower (95% CI –20% to 1%) and the median hospital stay was less (4 vs. 5 days, hazard ratio 1.34, 95% confidence interval 1.09, 1.65; p = 0.006) in the video-assisted thoracoscopic surgery group than in the open-surgery group. Prolonged pain was also less (relative risk 0.82, 95% confidence interval 0.72 to 0.94; p = 0.003). Time to uptake of adjuvant treatment, overall survival and progression-free survival were similar (p ≥ 0.28). Fewer participants in the video-assisted thoracoscopic surgery group than in the open-surgery group experienced complications before and after discharge from hospital (relative risk 0.74, 95% confidence interval 0.66 to 0.84; p < 0.001 and relative risk 0.81, 95% confidence interval 0.66 to 1.00; p = 0.053, respectively). Quality of life to 1 year was better across several domains in the video-assisted thoracoscopic surgery group than in the open-surgery group. The probability that video-assisted thoracoscopic surgery is cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year is 1. Limitations Ethnic minorities were under-represented compared with the UK population (< 5%), but the cohort reflected the lung cancer population. Conclusions Video-assisted thoracoscopic surgery lobectomy was associated with less pain, fewer complications and better quality of life without any compromise to oncologic outcome. Use of video-assisted thoracoscopic surgery is highly likely to be cost-effective for the NHS. Future work Evaluation of the efficacy of video-assisted thoracoscopic surgery with robotic assistance, which is being offered in many hospitals. Trial registration This trial is registered as ISRCTN13472721. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 48. See the NIHR Journals Library website for further project information.