From January 2020, COVID-19 is spreading around the world producing serious respiratory symptoms in infected patients that in some cases can be complicated by the severe acute respiratory syndrome, sepsis and septic shock, multiorgan failure, including acute kidney injury and cardiac injury. Cost and time efficient approaches to reduce the burthen of the disease are needed. To find potential COVID-19 treatments among the whole arsenal of existing drugs, we combined system biology and artificial intelligence-based approaches. The drug combination of pirfenidone and melatonin has been identified as a candidate treatment that may contribute to reduce the virus infection. Starting from different drug targets the effect of the drugs converges on human proteins with a known role in SARS-CoV-2 infection cycle. Simultaneously, GUILDify v2.0 web server has been used as an alternative method to corroborate the effect of pirfenidone and melatonin against the infection of SARS-CoV-2. We have also predicted a potential therapeutic effect of the drug combination over the respiratory associated pathology, thus tackling at the same time two important issues in COVID-19. These evidences, together with the fact that from a medical point of view both drugs are considered safe and can be combined with the current standard of care treatments for COVID-19 makes this combination very attractive for treating patients at stage II, nonsevere symptomatic patients with the presence of virus and those patients who are at risk of developing severe pulmonary complications.

BackgroundLocal relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4).Methods/DesignThe aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42–43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection.DiscussionWe assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma.Trial registrationNCT02614534 (clinicaltrial.gov) Nov-2015.

Hybrid transvaginal cholecystectomy is a good surgical model for minimally invasive surgery, a combination of NOTES and minilaparoscopy. It can be performed in surgical settings where laparoscopy is practised regularly, using the instruments normally used for endoscopy and laparoscopic surgery. Owing to the reproducibility of the intervention and the ease of vaginal closure, hybrid transvaginal cholecystectomy will permit further development of NOTES in the future.

Background: Sentinel node biopsy (SNB) is standard in assessing axillary lymph node status in patients with clinically node-negative breast cancer. The 5-year analysis of AMAROS trial showed that if locoregional treatment is advised after a tumor-positive axillary SNB, axillary radiotherapy (ART) is a reasonable alternative for an axillary lymph node dissection (ALND) with less side effects, though follow up was relatively short. Here we present the 10-year follow up data. Methods: From February 2001 to April 2010, patients with primary breast cancer stage cT1-2N0M0 were enrolled in the EORTC phase III non-inferiority AMAROS trial by 34 European sites. Patients were randomized between ALND and ART in case of a tumor-positive SNB. The primary endpoint, axillary recurrence rate (AxR) is now assessed at 10 years in the ITT population using Fine and Gray cumulative incidence method with deaths as competing risks, as well as secondary endpoints: overall survival (OS), distant metastasis free survival (DMFS), second primaries (including cancers other than breast cancers and contralateral DCIS) and locoregional recurrences (LRR). Little extra information beyond 5 years was available concerning Quality of Life and morbidity. Data collection is still ongoing and will be presented later. Results:Of the 4806 patients entered, 1425 patients had a tumor-positive SNB: 744 in the ALND-arm and 681 in the ART-arm, 60% with a macrometastasis. Both treatment-arms achieved a median 10-year follow-up and were comparable regarding age, tumor size, grade, tumor type and adjuvant systemic treatment. In the group who had ALND, the 5-year AxR was 0.41% (95%CI: 0.00;0.88) (4/744) and the 10-year AxR was 0.93% (95%CI:0.18;1.68) (7/744). In the group who had ART, the 5-year AxR was 1.04% (95%CI: 0.27;1.81) (7/681) and the 10-year AxR was 1.82% (95%CI: 0.74;2.94) (11/681) (HR 1.71, 95%CI: 0.67;4.39, p = 0.37). Sensitivity analysis, considering deaths and distant recurrences as competing risks, revealed consistent results. There were no significant differences between treatment arms regarding OS (ALND: 84.6% (95%CI: 81.5;87.1), ART: 81.4% (95%CI: 77.9;84.4), HR 1.17, 95%CI: 0.89;1.52, p= 0.26) and DMFS (ALND: 81.7% (95%CI: 78.5;84.4), ART: 78.2% (95%CI: 74.6;81.3), HR 1.18, 95%CI: 0.92;1.50, p=0.19). Cumulative incidence estimates of 10-year LRR are 3.59% (95%CI: 2.12;5.06) (ALND) versus 4.07% (95%CI: 2.49;5.65) (ART) (p= 0.69). More second primaries were observed after ART: 75/681 (21 contralateral breast) as compared to ALND: 57/744 (11 contralateral breast) (p = 0.035). All results are consistent in the per protocol analysis of patients with a tumor-positive SNB. Conclusion: Axillary recurrence after 10 years in patients with a tumor-positive SNB who were treated with ART is extremely rare and not significantly different from patients who were treated with ALND. OS, DMFS and locoregional control are also comparable. Second primaries including contralateral breast cancers are more frequently encountered after ART, but the difference is still low in absolute numbers. Thus, ART is a safe treatment for breast cancer patients with a tumor-positive SNB. Citation Format: Rutgers EJ, Donker M, Poncet C, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Blanken C, Orzalesi L, Klinkenbijl JH, van der Mijle HC, Veltkamp SC, van 't Riet M, Albregts M, Marinelli A, Rijna H, Tobon Morales R, Snoj M, Bundred N, Chauvet MP, Merkus JW, Petignat P, Schinagl DA, Coens C, Peric A, Bogaerts J, van Tienhoven G. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: 10 year follow up results of the EORTC AMAROS trial (EORTC 10981/22023) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-01.