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Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess the recurrence risk and patient selection for adjuvant chemotherapy. We performed a meta-analysis of post-operative ctDNA in stage I-IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3568 patients with evaluable ctDNA in CRC patient post-curative-intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results showed that the pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA-positive versus -negative patients in all stages was 7.27 (95% CI 5.49-9.62), p < 0.00001. Subgroup analysis revealed pooled HRs of 8.14 (95% CI 5.60-11.82) and 4.83 (95% CI 3.64-6.39) for stages I-III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA-positive versus -negative patients in all stages was 10.59 (95% CI 5.59-20.06), p < 0.00001. Circulating tumor DNA (ctDNA) analysis has revolutionized non-invasive cancer diagnostics and monitoring, with two primary forms of analysis emerging: tumor-informed techniques and tumor-agnostic or tumor-naive techniques. Tumor-informed methods involve the initial identification of somatic mutations in tumor tissue, followed by the targeted sequencing of plasma DNA using a personalized assay. In contrast, the tumor-agnostic approach performs ctDNA analysis without prior knowledge of the patient's tumor tissue molecular profile. This review highlights the distinctive features and implications of each approach. Tumor-informed techniques enable the precise monitoring of known tumor-specific mutations, leveraging the sensitivity and specificity of ctDNA detection. Conversely, the tumor-agnostic approach allows for a broader genetic and epigenetic analysis, potentially revealing novel alterations and enhancing our understanding of tumor heterogeneity. Both approaches have significant implications for personalized medicine and improved patient outcomes in the field of oncology. The subgroup analysis based on the ctDNA method showed pooled HRs of 8.66 (95% CI 6.38-11.75) and 3.76 (95% CI 2.58-5.48) for tumor-informed and tumor-agnostic, respectively. Our analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.
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DNA Tumoral Circulante , Neoplasias Colorretais , Humanos , DNA Tumoral Circulante/genética , Neoplasia Residual/diagnóstico , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Biomarcadores Tumorais/genética , Recidiva Local de Neoplasia/patologiaRESUMO
Background: Radical excision (RE) for rectal cancer carries a higher risk of mortality and morbidity, while local excision (LE) could decrease these postoperative risks. However, the long-term benefit of LE is still debatable. Aim: To study the effectiveness of LE versus RE in T1 and T2 rectal cancer. Methods: A systematic review and meta-analysis was conducted using key databases like PubMed and ClinicalTrials.gov. Only cohort studies and randomized controlled trials were included. RevMan 5.4 tool was used for data analysis. Both clinical and statistical heterogeneity of the studies were assessed, and I2 >75% was considered as highly heterogeneous. The primary outcomes being measured were 5-year overall survival (OS) and 5-year disease free survival (DFS). A subgroup analysis of patients with T1-only was also conducted, without adjuvant chemo/radiotherapy. Results: A total of 18 studies were included for final meta-analysis. Four were RCTs, while the other 15 were retrospective cohort studies. One included study had data from both RCT and non-RCT study groups. Nine studies were multicentered or national studies while nine were unicentral.There was no difference in risk ratio (RR) between OS: RR 0.95, 95% Confidence Interval (CI) [0.91, 0.99] and DFS: RR 0.93, 95% CI [0.87, 1.01]. There were lower hazards ratios in OS: RR 1.41, 95% CI [1.14, 1.74] and DFS: RR 1.95, 95% CI [1.36, 2.78] with radical, as compared to LE. Lower recurrence rate was associated with RE. Random effect model was used due to clinical heterogeneity between studies (different surgical procedures, tumor staging, adjuvant chemo or radiotherapy). Conclusions: LE for early-stage rectal cancer has lower 5-year OS and DFS than RE, with higher local recurrence rate. However, LE is associated with lower early postoperative mortality, morbidity and length of stay as compared to RE.
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Adenoid cystic carcinoma (ACC) is a rare epithelial tumor of the salivary glands with an indolent course and usually bears a long-term survival rate even when metastasized. Spontaneous regression of such a resistant tumor is an even scarce event. We report a case of a patient with ACC of the parotid gland with pulmonary metastases, which spontaneously resolved following resection and post-surgical radiation of the primary tumor. Among the numerous theories proposed to explain such a phenomenon, immunogenic mechanisms and the abscopal effect are the most plausible explanations in this case.
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Heparin-induced skin necrosis (HISN) is a rare complication of heparin anticoagulation. The condition occurs in various situations, including in heparin-naive and exposed individuals, in areas local or distant from the heparin injection site, and with or without frank thrombocytopenia. We present a case in which a patient treated for a pulmonary embolism with therapeutic unfractionated heparin (UFH) develops this adverse event. Symptoms were reversed with cessation of UFH and transition to bivalirudin without surgical debridement. The patient initially had anti-PF4 antibodies present but subsequent testing showed borderline antibodies and a negative serotonin release assay. After starting bivalirudin, the patient was later switched to fondaparinux without further consequences. This case illustrates the pathogenesis of HISN and provides an example of inconsistently abnormal laboratory values. Additionally, it provides two novel exposures the mRNA-1273 vaccine and the immune checkpoint inhibitor pembrolizumab that, to our knowledge, have not been previously reported.
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Heparina , Trombocitopenia , Vacina de mRNA-1273 contra 2019-nCoV , Anticoagulantes/efeitos adversos , Heparina/efeitos adversos , Humanos , Necrose/induzido quimicamente , Trombocitopenia/induzido quimicamenteRESUMO
Background: It is well known that traditional smoking causes various types of cancer, leading to the current decline in traditional smoking among US adults from 20.9% in 2005 to 14.0% in 2019. Electronic cigarettes (e-cigarettes) are commonly marketed as a safe alternative and gaining popularity especially among never-smokers and adolescents. However, there is limited evidence of effects of e-cigarette on cancer. Hence, we aim to find the prevalence and association of e-cigarette and traditional smoking among cancer respondents. Methods: We conducted a retrospective cross-sectional study using the NHANES database from 2015 to 2018. We assessed history of cancer (MCQ220), type of cancers (MCQ230a), and smoking status (e-cigarette: SMQ900 or SMQ905 and traditional smoking: SMQ020) using questionnaires. We performed multivariable logistic regression models to find the association of e-cigarette use, traditional smoking, and no smoking with cancer after adjusting for confounding variables. Results: A total of 154,856 participants were included, of whom 5% were e-cigarette users, 31.4% were traditional smokers, and 63.6% were nonsmokers. There is a higher prevalence of e-cigarette use among younger participants, females (49 vs. 38) in comparison to traditional smokers (P < 0.0001). The e-cigarette users have lower prevalence of cancer compared to traditional smoking (2.3% vs. 16.8%; P < 0.0001), but they were diagnosed with cancer at a younger age. Among cancer subtypes, cervical cancer (22 vs. 2.6), leukemia (8.5 vs. 1.1), skin cancer (non-melanoma) (15.6 vs. 12.3), skin (other) (28 vs. 10) and thyroid (10.6 vs. 2.4) had higher prevalence of e-cigarette use compared to traditional smokers (P < 0.0001). Our regression analysis showed that e-cigarette users have 2.2 times higher risk of having cancer compared to non-smokers (odds ratio (OR): 2.2; 95% confidence interval (CI): 2.2 - 2.3; P < 0.0001). Similarly, traditional smokers have 1.96 higher odds of having cancer compared to nonsmokers (OR: 1.96; 95% CI: 1.96 - 1.97; P < 0.0001). Conclusion: In our study, e-cigarette users had an early age of cancer onset and higher risk of cancer. Hence, this is stepping stone for future research to evaluate the safety and effects of e-cigarettes in patients with cancer.
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The coronavirus (COVID-19) pandemic is claiming millions of lives and creating an additional burden on health care, which is already affected by the rise of non-communicable diseases (NCDs). The scientific community, on the other side, is enormously engaged with studies to best identify the characteristics of the virus and minimize its effect while supporting the fight to contain NCDs, mainly cardiovascular diseases (CVDs), which are contributing hugely to the global death toll. Hence, the roles of vitamin D in COVID-19 immunity and cardiovascular health are gaining traction recently. This literature review will mainly focus on summarizing pertinent studies and scientific publications which highlight the association of vitamin D levels with the various outcomes of COVID-19 and CVDs. It will also address how low vitamin D correlates with the epidemiology of CVDs and the inflammatory mechanisms attributed to COVID-19 severity. We believe that our review may open up hindsight perspectives and further discussions among the physicians in tapping the potential of vitamin D supplementation to tackle the morbidity, mortality, and health care cost of the two deadly diseases, COVID-19 and CVDs.
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We aimed to identify prevalence and association of comorbid chronic kidney disease (CKD), acute kidney injury (AKI) and utilization prevalence of continuous renal replacement therapy (CRRT) in COVID-19-hospitalized patients as a function of severity status. With the ongoing struggle across the globe to combat COVID-19 disease, published literature has described the role of kidney disease in COVID-19 patients based on single/multicenter experiences across the globe. We extracted data from observational studies describing comorbid CKD, AKI and CRRT and outcomes and severity of COVID-19-hospitalized patients from December 1, 2019-August 20, 2020 following PRISMA guidelines. Severity of COVID-19 includes intensive care unit admission, oxygen saturation < 90%, invasive mechanical ventilation utilization, in-hospital admission and mortality. Meta-analysis was performed using a random-effects model to calculate pooled estimates, and forest plots were created. In total, 29 studies with 15,017 confirmed COVID-19 patients were included. The overall prevalence of AKI was 11.6% [(430/3693)], comorbid CKD 9.7% [(1342/13,728)] and CRRT 2.58% [(102/3946)] in our meta-analysis. We also found higher odds of comorbid CKD (pooled OR: 1.70; 95%CI: 1.21-2.40; p = 0.002), AKI (8.28; 4.42-15.52; p < 0.00001) and utilization of CRRT (16.90; 9.00-31.74; p < 0.00001) in patients with severe COVID-19 disease. Conclusion Our meta-analysis suggests that comorbid CKD, AKI and utilization of CRRT were significantly associated with COVID-19 disease severity. Clinicians should focus on early triaging of COVID-19 patients with comorbid CKD and at risk for AKI to prevent complication and mortality.
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Injúria Renal Aguda , COVID-19 , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Humanos , Unidades de Terapia Intensiva , Estudos Multicêntricos como Assunto , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
Background: Ultrasound-based transient elastography (TE) is a non-invasive alternative to liver biopsy for the staging of hepatic fibrosis due to various chronic liver diseases. This meta-analysis aims to assess the diagnostic accuracy of TE for detecting liver cirrhosis (F4) and severe fibrosis (F3) in patients with chronic liver diseases, in comparison to the gold standard liver biopsy. Methods: A systematic search was performed using PubMed search engine following Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from inception to May 2021. The meta-analysis studies evaluating the diagnostic accuracy of TE for severe fibrosis and cirrhosis were identified. We conducted a meta-meta-analysis to generate pooled estimates of the sensitivity, specificity, and diagnostic odds ratios (ORs) for F3 and F4 fibrosis stage. Results: We included five studies with a total of 124 sub-studies and 20,341 patients in our analysis. Three studies have reported the diagnostic accuracy of TE in detecting F3/severe fibrosis stage and found 81.9% pooled sensitivity (95% confidence interval (CI): 79.9-83.7%; P < 0.001) (I2 = 0%), 84.7% pooled specificity (95% CI: 81.3-87.6%) (I2 = 81%; P = 0.02). All five studies reported the diagnostic accuracy of TE in detecting F4/liver cirrhosis stage. We found 84.8% pooled sensitivity (95% CI: 81.4-87.7%) (I2 = 86.4%; P < 0.001), 87.5% pooled specificity (95% CI: 85.4-89.3%) (I2 = 90%; P < 0.001) and pooled diagnostic OR (41.8; 95% CI: 3.9 - 56.5) (I2 = 87%; P < 0.001). Conclusions: Ultrasound-based TE has excellent diagnostic accuracy for identifying cirrhosis and liver fibrosis stages 3. Future studies should focus on estimating the diagnostic accuracy of other fibrosis stages in chronic liver disease patients. This will eventually decrease the risk associated with invasive liver biopsy.
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The use of social media continues to increase in health care and academia. Health care practice, particularly the oncologic field, is constantly changing because of new knowledge, evidence-based research, clinical trials, and government policies. Therefore, oncology trainees and professionals continue to strive to stay up-to-date with practice guidelines, research, and skills. Although social media as an educational and professional development tool is no longer completely new to medicine and has been embraced, it is still under-researched in terms of various outcomes. Social media plays several key roles in professional development and academic advancement. We reviewed the literature to evaluate how social media can be used for professional development and academic promotion of oncology professionals.
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Mídias Sociais , Atenção à Saúde , Humanos , OncologiaRESUMO
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by multiple episodes of venous and arterial thromboses or recurrent fetal losses in the presence of antiphospholipid antibodies against ß2GP1, frequently accompanied by moderate thrombocytopenia. Catastrophic APS (CAPS) is a severe manifestation of APS. COVID-19 may have an intense hypercoagulable state in critically ill patients. SARS-CoV2 may potentiate pathogenic APS effects, including the activation of endothelial cells, monocytes, platelets, and complement, resulting in a proinflammatory state and prothrombotic events. The endothelial tropism of SARS-CoV2 may also modify the clinical presentation of COVID-19 in susceptible individuals and trigger flares of underlying vascular diseases. We report a case of a 64-year-old woman with a history of triple-positive APS who had multiple thrombotic and bleeding episodes after being found to have a COVID-19 infection temporally associated with CAPS development that was successfully treated with eculizumab, preventing further macro- and microvascular thrombotic events at 1 month follow-up. Our case highlights the need for more research regarding the mechanism by which COVID-19 may potentiate APS and lead to the development of CAPS.
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A 54-year-old man with stage IV B metastatic colorectal cancer with liver and peritoneal metastasis was treated with cytoreductive surgery (extended left colectomy, right partial hepatectomy, resection of right diaphragm nodule) and perioperative oxaliplatin-based chemotherapy. The patient was cancer-free for 6 months, at which point a surveillance positron emission tomography-CT scan showed metabolically active hepatosplenic lesions and mediastinal and bilateral hilar lymph nodes. An endobronchial ultrasound bronchoscopy-guided fine needle aspiration of the mediastinal and hilar lymph nodes revealed non-necrotising granulomas. The workup was negative for bacterial, fungal or mycobacterial infection, cancer or autoimmune disease. Carcinoembryonic antigen and COLVERA (a circulating tumour DNA liquid biopsy test for the detection of recurrent colon cancer) tests were negative. Subsequently the rare diagnosis of a sarcoidosis-like reaction from oxaliplatin-based chemotherapy was made. Repeat imaging after 3 months showed resolution of the hepatosplenic lesions and lymphadenopathy, alike.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/terapia , Granuloma/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Oxaliplatina/efeitos adversos , Sarcoidose/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Antígeno Carcinoembrionário/sangue , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Colecistectomia , DNA Tumoral Circulante/sangue , Colectomia , Neoplasias do Colo/sangue , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Diagnóstico Diferencial , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Granuloma/induzido quimicamente , Granuloma/patologia , Hepatectomia , Humanos , Fígado/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sarcoidose/sangue , Sarcoidose/induzido quimicamente , Sarcoidose/patologia , Baço/diagnóstico por imagemRESUMO
Lymphangioleiomyomatosis (LAM) is a rare disease characterized by cystic lung lesions, lymphatic abnormalities, and angiomyolipomas. It can take a significant amount of time to diagnose LAM due to the vague symptoms of fatigue, progressive dyspnea, pneumothorax, and pleural effusion. We present a case of a 29-year-old woman with recurrent spontaneous pneumothorax and progressive dyspnea who was initially misdiagnosed with asthma and was later found to have LAM. As with all rare diagnoses, there needs to be a suspicion of the disease in order for a further workup to be initiated. In patients with a compatible High-resolution CT scan of the chest, a high vascular endothelial growth factor-D (VEGF-D) value is diagnostic for LAM, and no other confirmatory test is needed.
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BACKGROUND: Whether there is sex-bias within the adverse outcomes associated with COVID-19 in the cancer population is unknown. In this regard, several published studies have examined this question, but the results are inconclusive and inconsistent. To evaluate the sex-difference in the risk of adverse outcomes associated with COVID-19 in the cancer population, we have conducted a systematic review and meta-analysis. METHODS: Published articles evaluating adverse outcomes associated with COVID-19 in the cancer population from inception to June 2020 were identified by searching PubMed and EMBASE, ASCO 2020 Virtual Annual Conference, AACR 2020 COVID-19 and Cancer, ESMO conferences held from January to June 2020, and medRxiv and bioRxiv. Prospective or retrospective analyses in English, providing outcomes data with sex differences in the cancer population were included. The primary outcomes of interest were pooled ORs of severe illness, all-cause death, and the composite of severe illness and death attributable to COVID-19 in males versus females in cancer patients. FINDINGS: Overall, 3968 patients (17 studies) were analyzed in retrospective study settings. Overall, pooled ORs of the composite of severe illness and all-cause death in the setting of COVID-19 in males versus females was 1.60 (95% CI, 1.38-1.85). The risk of severe illness or death were both independently increased in males versus females. INTERPRETATION: Male sex was associated with a higher risk of severe illness and death attributable to COVID-19. This finding has implications in informing the clinical prognosis and decision making in the care of cancer patients. FUNDING: This study received no funding.
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INTRODUCTION: Ampullary cancers represent a subset of periampullary cancers, comprising only 0.2% all gastrointestinal cancers. Localized disease is primarily managed by a surgical intervention, called pancreaticoduodenectomy (PD), followed in many cases by the administration of adjuvant chemotherapy (CT) or chemoradiation therapy (CRT). However, there are no clear evidence-based guidelines to aid in selecting both the modality and regimen of adjuvant therapy for resected Ampullary carcinoma. METHODS: We retrospectively analyzed 54 patients at KU Cancer Center, who had undergone endoscopic resection or pancreaticoduodenectomy (PD) for Ampullary cancer from June 2006 to July 2016. We obtained patients' baseline characteristics, clinical presentation, pathology, treatment modality, recurrence pattern, and survival outcomes. The time-to-events data were compared using Kaplan-Meier methods. A univariate and multivariate Cox proportional hazards regression was performed to evaluate factors associated with overall survival (OS) and generate hazard ratios (HR). RESULTS: The mean age of the 54 patients was 68 (37-90). 38 (70%) were males and 16 (30%) were females. Most of the patients were Caucasian (76%). Approximately half of all patients had a history of smoking, 20% had alcohol abuse, and 13% had pancreatitis. Among the 54 patients with localized cancers, 9 (16%) were treated definitively with nonoperative therapies, usually due to a prohibitive comorbidity profile, performance status, or unresectable tumor. 45 out of 54 patients (83%) underwent surgery. Of the 45 patients who underwent surgery, 18 patients (40% of the study cohort) received adjuvant therapy due to concerns for advanced disease as determined by the treating physician. 13 patients (24%) received adjuvant CT and 5 patients (9.2%) received CRT. The remaining 27 patients (50%) underwent surgery alone. The median OS for the entire study cohort was 30 months. When compared to surgery alone, adjuvant therapy with either CT or CRT had no statistically significant difference in terms of progression-free survival (p=0.56) or overall survival (p=0.80). In univariate Cox proportional hazards regression analysis, high-risk features like peripancreatic extension (16%) and perineural invasion (26%) were found to be associated with poor OS. Lymph node metastasis (29%) did not significantly affect OS (HR 1.42, 95% CI [0.73-1.86]; p=0.84). Lymphovascular invasion (29%) was not associated with poor OS (HR 1.22, 95% CI [0.52, 2.96]; p=0.76). In multivariate Cox regression analysis, only age group>70 years was significantly associated with OS , while other factors, including the receipt of adjuvant therapy, lymph nodes, positive margin, and lymphovascular, perineural, and peripancreatic involvement, were not significantly associated with OS. These results are likely due to small sample size. CONCLUSIONS: Despite numerous advances in both cancer care and research, efforts in rare malignancies such as Ampullary cancer remain very challenging with a clear lack of an evidence-based standard of care treatment paradigm. Although adding adjuvant therapies such as chemotherapy or chemoradiotherapy is likely to improve survival in high-risk disease, there is no standardized regimen for the treatment of Ampullary cancer. More research is required to elucidate whether statistically and clinically relevant differences exist that may warrant a change in the current adjuvant treatment strategies.