Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.
Breast cancer can be classified based on the expression or lack of expression of protein receptors including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (Her2). The basal molecular subtype is mostly made up of breast cancers that do not express ER/PR or Her2, triple-negative breast cancers (TNBC) (Bertucci et al. in Int J Cancer 123(1):236, 2008). TNBC tends to be more aggressive as there are no approved targeted treatments and the only treatment option currently is cytotoxic chemotherapy. Recent data show that some chemotherapies, specifically anthracyclines, not only have cytotoxic effects but also use the immune system by activating CD8+ T cell responses to kill cancer cells (Stagg et al. in Ther Adv Med Oncol 5(3):169-181, 2013), and thus, tumor-infiltrating lymphocytes respond well to chemotherapy. Currently, systemic immunotherapy which utilizes the patient's own immune system directly to eradicate and target neoplastic cells is being explored as treatment for TNBC as this type of breast cancer has been shown to be immunogenic (Yu et al. in Int J Environ Res Public Health 14:68, 2017). According to the Cancer Genome Atlas, TNBC has higher PD-L1 mRNA expression (Mittendorf et al. Cancer Immunol Res 2(4):361-370, 2014). Higher rates of CD8+ T cell infiltration were also found in TNBC according to a study by Liu et al. (Breast Cancer Res 14:R48, 2012). In TNBC patients, Pembrolizumab, a monoclonal antibody that targets programmed cell death protein 1 (PD-1), and Atezolizumab, a monoclonal antibody that targets its ligand, have been investigated to assess dose tolerability and side effects. Further studies involving vaccines, immunotherapy that targets cytotoxic T lymphocyte-associated protein-4 and PD-L1, are currently being investigated for treatment of TNBC. This review outlines the systemic immunotherapies that are currently being investigated for patients with TNBC.
SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1-6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1-2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2-3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9-3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality ). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.
In the United States, the estimated number of new cases of renal cell carcinoma (RCC) is approximately 65,000 case with about 15,000 deaths in the year of 2018 (Siegel et al. in CA Cancer J Clin 68(1):7, 2018). RCC as an immunogenic malignancy is supported by many theories and facts which include tumor richness of lymphocytes infiltrate, the occurrence of spontaneous tumor regression, and the proved effect of traditional immunotherapy (Finke et al. in J Immunother 11(1):1-11, 1992), all these factors support the potential therapeutic effect of the novel immunotherapeutic agents in RCC. Historically, complete tumor regression in metastatic RCC is achievable in a minority of patients through traditional immunotherapies such as high-dose interleukin-2 (IL-2) (Fyfe et al. in J Clin Oncol 13(3):688, 1995) and interferon-alfa (IFNa) (Negrier et al. in N Engl J Med 338(18):1272, 1998); however due to the significant rate of toxicities and low efficacy; accordingly the targeted therapy with tyrosine kinase inhibitors (TKIs) and vascular endothelial growth factor-antibodies (VEGF) became the standard and prevalent treatment approach for advanced RCC both in front and subsequent lines of therapy (Escudier et al. in Ann Oncol. 25(Suppl 3):iii49-iii56, 2014). A new avenue of immunotherapy utilizing novel strategy to block immune checkpoints has emerged in a new era for RCC treatment (Ascierto et al. in J Transl Med 12:291, 2014). Results from clinical trials are encouraging in both front-line and second-line settings, in a phase III trial (CheckMate 025) nivolumab compared to everolimus improved overall survival in previously treated metastatic RCC who had progressed on prior treatment with targeting agents (Motzer et al. in N Engl J Med 373:1803, 2015). CheckMate 214, a phase III trial, demonstrated superior overall survival and objective response with combined checkpoint inhibitors compared to sunitinib in Treatment-Naïve Advanced RCC among intermediate- and poor-risk group (Motzer et al. in N Engl J Med. 378(14):1277-1290, 2018). In this review, we discuss the systemic Immunotherapy with checkpoint inhibitors that have been approved or are currently being investigated in RCC, clinical experience with these agents, and its future development.
Bladder cancer is the most common malignancy involving the genitourinary system (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). In the USA, it is the fifth most common cancer and approximately 79,000 new cases will be diagnosed in 2017 (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). The mortality from bladder cancer is approximately 17,000 deaths each year (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). The incidence rate for bladder cancer is higher in men compared to women. Risk factors are predominantly related to tobacco smoking, although infection with Schistosoma haematobium is another risk factor in selected populations (Antoni et al. in Eur Urol, 71:96-108, 2017). Cisplatin-based systemic chemotherapy regimens remain the standard of care in both the neoadjuvant and metastatic setting for muscle-invasive bladder cancer (Gupta et al. in Cancer, 9(15):1-14, 2017; Von der Maase et al. in J Clin Oncol, 23:4602-4608, 2005; De Santis et al. in J Clin Oncol, 30:191-199, 2012; Bellmunt et al. in J Clin Oncol, 27: 4454-4461, 2009). There is an estimated overall survival of 9-15 months in metastatic bladder cancer in those who receive the standard of care platinum-based chemotherapy (Von der Maase et al. in J Clin Oncol, 23:4602-4608, 2005; De Santis et al. in J Clin Oncol, 30:191-199, 2012). The median survival, however, is significantly reduced after relapse in patient treated with platinum chemotherapy to less than 7 months (Bellmunt et al. in J Clin Oncol, 27: 4454-4461, 2009). Thus, this approach is preferred for patients who can tolerate this treatment as first-line chemotherapy (Gupta et al. in Cancer, 9(15):1-14, 2017). Until recently, there were few treatment options for those patients with poor performance status who are ineligible to receive cisplatin including renal insufficiency and multiple comorbidities or had disease progression after receiving platinum-based chemotherapy (Gupta et al. in Cancer, 9(15):1-14, 2017). With further understanding of tumor immune evasion, systemic immunotherapy which utilizes the patient's own immune system directly to eradicate and target neoplastic cells, has now been approved for urothelial bladder cancer. Monoclonal antibodies that target programmed cell death protein 1 (PD-1), including Nivolumab and Pembrolizumab, and its ligand, PD-L1, including Atezolizumab, Durvalumab, Avelumab, have all been investigated and approved in the setting of metastatic refractory urothelial cancer (Gupta et al. in Cancer, 9(15):1-14, 2017; Von der Maase et al. in J Clin Oncol, 23:4602-4608, 2005; Zilchi et al. in BioMed Res Int, 2017, 2017, doi: 10.1155/2017/5618174 ). Atezolizumab and Pembrolizumab have also been approved as first-line therapy in the setting of cisplatin-ineligible metastatic bladder cancer (Gupta et al. in Cancer, 9(15):1-14, 2017; Zilchi et al. in BioMed Res Int, 2017, 2017, doi: 10.1155/2017/5618174 ). Those that target cytotoxic T-lymphocyte-associated protein 4, including Ipilimumab and Tremelimumab, have also been investigated and further studies are ...
This review article focuses on all pulmonary adverse effects of programmed death-1 (PD-1) inhibitors (nivolumab). These complications include dyspnea, pneumonitis, pleural effusion, pulmonary sarcoidosis, pulmonary tuberculosis, acute fibrinous organizing pneumonia, organizing pneumonia, eosinophilic pneumonia, adult respiratory distress syndrome, and lung cavitation.
We found that elderly patients with pancreatic cancer receive treatment less frequently compared with younger patients. However, elderly patients receiving chemotherapy derive similar benefits. Randomized clinical trials are needed to evaluate pancreatic cancer treatment in the elderly patients, particularly given the increasing occurrence of pancreatic cancer in later life.
Chronic lymphocytic leukemia, the most common adult leukemia worldwide, is considered an indolent but incurable non-Hodgkin lymphoma. Leukemia cutis is an uncommon manifestation of chronic lymphocytic leukemia. We present a case of an adult patient who presented with skin lesion of bilateral ears, which led to the diagnosis of chronic lymphocytic leukemia. We also reviewed the cases of auricular involvement in chronic lymphocytic leukemia patients reported in the literature. Local treatment is indicated in case of leukemia cutis; however, systemic treatment is recommended when there are systemic signs and symptoms. Better awareness of disease evolution and prompt diagnosis of this leukemia cutis of chronic lymphocytic leukemia will improve the effectiveness and outcome of its management.
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