ABSTRACT

Adenocarcinomas of the ampulla of Vater represent only 0.2% of all gastrointestinal cancers. Due to the low incidence no large clinical trials evaluating efficacy of treatments are available. Adjuvant therapy is often administered in patients with stage IB or higher. Oxaliplatin is considered as an effective and well tolerated therapeutic option. Adverse events associated with this therapy include cardio-, neuro-, nephrotoxicity and myelosuppression. Previously granulomatous pulmonary and liver manifestations have been described in oxaliplatin-based chemotherapy. In this report peritoneal manifestation of granulomatous disease associated with oxaliplatin is described for the first time. Sarcoidlike reactions may be misinterpreted as tumour progression or metastatic disease, and may consequently result in over-treatment.

PMID:37814569 | DOI:10.51821/86.3.11323

04:10

PubMed articles on: Cancer & VTE/PE

Obstructive Sleep Apnea and Venous Thromboembolism: Unraveling the Emerging Association

Cureus. 2023 Aug 30;15(8):e44367. doi: 10.7759/cureus.44367. eCollection 2023 Aug.

ABSTRACT

Oxidative stress has emerged as a significant contributor to skeletal muscle atrophy, influencing cellular processes that underlie muscle wasting. This review article delves into the intricate interplay between oxidative stress and muscle atrophy, shedding light on its mechanisms and implications. We begin by outlining the fundamental concepts of oxidative stress, delineating reactive oxygen species (ROS) and reactive nitrogen species (RNS), their sources, and the ensuing oxidative damage to cellular components. Subsequently, we delve into skeletal muscle atrophy, elucidating its diverse forms, molecular pathways, key signaling cascades, and the role of inflammation in exacerbating muscle wasting. Bridging these concepts, we explore the connections between oxidative stress and muscle atrophy, unveiling how oxidative stress impacts muscle protein synthesis and breakdown, perturbs cellular signaling pathways, and contributes to mitochondrial dysfunction. The review underscores the complexity of quantifying and interpreting oxidative stress markers, highlighting the challenges posed by the dynamic nature of oxidative stress and the presence of basal ROS levels. Addressing the specificity of oxidative stress markers, we emphasize the importance of selecting markers pertinent to muscle tissue and considering systemic influences. Standardization of experimental protocols emerges as a critical need to ensure consistency and reproducibility across studies. Looking ahead, we discuss the implications of oxidative stress in diverse scenarios, encompassing age-related muscle loss (sarcopenia), muscle wasting in chronic diseases like cancer cachexia, and disuse-induced muscle atrophy. Additionally, we delve into potential therapeutic strategies, including antioxidant supplementation, exercise, pharmacological interventions, nutritional approaches, and lifestyle modifications, as avenues to mitigate oxidative stress-driven muscle atrophy. The review concludes by outlining promising future directions in this field, calling for deeper exploration of specific oxidative stress markers, understanding the temporal dynamics of oxidative stress, validation through translational studies in humans, and the development of targeted therapeutic interventions. By advancing our understanding of the intricate relationship between oxidative stress and skeletal muscle atrophy, this review contributes to paving the way for innovative strategies to address muscle wasting and improve muscle health.

PMID:37779809 | PMC:PMC10540504 | DOI:10.7759/cureus.44367

04:10

PubMed articles on: Cancer & VTE/PE

Hypoxia-induced exosomes facilitate lung pre-metastatic niche formation in hepatocellular carcinoma through the miR-4508-RFX1-IL17A-p38 MAPK-NF-κB pathway

Int J Biol Sci. 2023 Sep 4;19(15):4744-4762. doi: 10.7150/ijbs.86767. eCollection 2023.

ABSTRACT

Background: Hypoxia plays an important role in the lung metastasis of hepatocellular carcinoma (HCC). However, the process by which hypoxia promotes the formation of a pre-metastatic niche (PMN) and its underlying mechanism remain unclear. Methods: Exosomes derived from normoxic and hypoxic HCC cells were collected to induce fibroblast activation in vitro and PMN formation in vivo. The micro RNA (miR) profiles of the exosomes were sequenced to identify differentially expressed miRNAs. Gain- and loss-of-function analyses were performed to investigate miR-4508 function. Dual-luciferase, western blotting, and real-time reverse transcription-PCR analyses were used to identify the direct targets of miR-4508 and its downstream signaling pathways. To demonstrate the roles of hypoxic tumor-derived exosomes (H-TDEs) and miR-4508 in the lung metastasis of liver cancer, H22 tumor cells were injected through the tail vein of mice. Blood plasma-derived exosomes from patients with HCC who underwent transarterial chemoembolization (TACE) were applied to determine clinical correlations. Results: We demonstrated that H-TDEs activated lung fibroblasts and facilitated PMN formation, thereby promoting lung metastasis in mice. Screening for upregulated exosomal miRNAs revealed that miR-4508 and its target, regulatory factor X1 (RFX1), were involved in H-TDE-induced lung PMN formation. Moreover, miR-4508 was significantly upregulated in plasma exosomes derived from patients with HCC after TACE. We confirmed that the p38 MAPK-NF-κB signaling pathway is involved in RFX1 knockdown-induced fibroblast activation and PMN formation. In addition, IL17A, a downstream target of RFX1, was identified as a link between RFX1 knockdown and p38 MAPK activation in fibroblasts. Conclusion: Hypoxia enhances the release of TDEs enriched with miR-4508, thereby promoting lung PMN formation by targeting the RFX1-IL17A-p38 MAPK-NF-κB pathway. These findings highlight a novel mechanism underlying hypoxia-induced pulmonary metastasis of HCC.

PMID:37781522 | PMC:PMC10539707 | DOI:10.7150/ijbs.86767

04:10

PubMed articles on: Cardio-Oncology

Allogeneic mitochondrial transplantation ameliorates cardiac dysfunction due to doxorubicin: An in vivo study

Biomed Pharmacother. 2023 Oct 7;168:115651. doi: 10.1016/j.biopha.2023.115651. Online ahead of print.

ABSTRACT

Damage to the mitochondria may lead to serious conditions that are difficult to treat. Doxorubicin is one of the most widely used chemotherapeutic drugs for the treatment of malignancies in children and adults, and reportedly causes damage to the mitochondria. Unfortunately, the dangerous cardiac side effects of doxorubicin appear when the patient is in the midst of a vigorous fight against the disease, either by taking doxorubicin alone or in combination with other drugs. This study aimed to determine whether exogenous healthy and functional mitochondria are internalized by cells, can it help the survival of these cells, and can reduce cardiotoxicity. For this purpose, isolated, pure, and functional exogenous mitochondria were injected into the tail vein of a rat model of doxorubicin-induced cardiotoxicity. After that, the heart function of the rats and their antioxidant status, inflammatory markers, and histopathological examination were investigated. Our findings show that intravenous mitochondrial transplantation provided efficient mitochondrial uptake and reduced cardiotoxicity by reducing ROS production, lipid peroxidation, and inflammation. In addition, the levels of ATP and antioxidant enzymes increased after mitochondrial transplantation; therefore all of these complex processes resulted in the reduction of apoptosis and necrosis in rat heart tissue. These promising results open the way to more effective cancer treatment without the side effects of related drugs. Transplanting exogenous mitochondria probably enhances the cell's mitochondrial network, potentially treating mitochondria-related disorders such as cardiovascular and neurodegenerative diseases, although the exact relationship between mitochondrial damage and these conditions remains unclear.

PMID:37812888 | DOI:10.1016/j.biopha.2023.115651

04:10

PubMed articles on: Cardio-Oncology

Multimodal Imaging of Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer-A State-of-the-Art Review

J Clin Med. 2023 Sep 29;12(19):6295. doi: 10.3390/jcm12196295.

ABSTRACT

BACKGROUND: This review focuses on multimodality imaging of cardiotoxicity in cancer patients, with the aim of evaluating the effectiveness of different techniques in detecting and monitoring cardiac changes associated with cancer therapy.

METHODS: Eight studies were included in the review, covering various imaging modalities such as cardiac magnetic resonance imaging, echocardiography, and multigated acquisition scanning.

RESULTS: Cardiac magnetic resonance imaging emerged as the most definitive modality, offering real-time detection, comprehensive assessment of cardiac function, the ability to detect early myocardial changes, and superior detection of cardiotoxicity when compared to the other imaging modalities. The studies also emphasize the importance of parameters such as left ventricular ejection fraction and global longitudinal strain in assessing cardiac function and predicting cardiotoxicity.

CONCLUSION: Due to the common use of HER2 agents and anthracyclines within the breast cancer population, the LVEF as a critical prognostic measurement for assessing heart health and estimating the severity of left-sided cardiac malfunction is a commonly used endpoint. CTRCD rates differed between imaging modalities, with cardiac MRI the most sensitive. The use of multimodal cardiac imaging remains a nuanced area, influenced by local availability, the clinical question at hand, body habits, and medical comorbidities. All of the imaging modalities listed have a role to play in current care; however, focus should be given to increasing the provision of cardiac MRI for breast cancer patients in the future to optimize the detection of CTRCD and patient outcomes thereafter.

PMID:37834939 | PMC:PMC10573256 | DOI:10.3390/jcm12196295

04:10

PubMed articles on: Cardio-Oncology

Atypical Presentation of Acute Pericarditis Secondary to Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report

Cureus. 2023 Sep 7;15(9):e44868. doi: 10.7759/cureus.44868. eCollection 2023 Sep.

ABSTRACT

Cardiotoxicity linked with hematopoietic stem cell transplantation (HSCT) is a well-described phenomenon associated with an increased mortality risk; however, the majority of cardiac events present over 100 days following transfusion and are often attributed to graft-versus-host disease or pre-treatment conditioning by chemotherapy with or without radiation therapy. Here, we present the case of a 60-year-old female with a medical history of chronic lymphocytic leukemia complicated by a myelodysplastic syndrome that progressed to acute myeloid leukemia who developed chest pain immediately following an allogeneic HSCT. Electrocardiogram showed dynamic ST-depressions in leads V3-5 without evidence of reciprocal changes. Transthoracic echocardiography revealed pericardial effusion without signs of tamponade. The patient was thought to have acute pericarditis and was subsequently treated with high-dose intravenous methylprednisolone with a taper for two weeks. Her symptoms promptly subsided, and the pericardial effusion resolved on repeat echocardiography, which confirmed the diagnosis. Acute pericarditis is a rarely described complication of HSCT that is fatal if left untreated and prompts urgent management. This atypical case of acute pericarditis in the early post-transplant phase highlights the importance of cardiac stratification in patients with active malignancy undergoing treatment. It would suggest a potential benefit in closely monitoring high-risk individuals who have a history of coronary artery disease, smoking, or pericarditis in the pre-engraftment phase of transplantation.

PMID:37818511 | PMC:PMC10561524 | DOI:10.7759/cureus.44868

04:10

PubMed articles on: Cancer & VTE/PE

Extended Venous Thromboembolism Prophylaxis after Robotic Staging for Endometrial Cancer

South Med J. 2023 Oct;116(10):790-794. doi: 10.14423/SMJ.0000000000001611.

ABSTRACT

OBJECTIVES: Our objectives were to estimate the incidence of venous thromboembolism (VTE) after robotic staging for endometrial cancer and to compare the incidence of VTE in patients who received a single dose of preoperative prophylaxis of enoxaparin with those who received extended postoperative prophylaxis.

METHODS: This study is a retrospective chart review of patients who underwent robot-assisted surgical staging for endometrial cancer. Patients were categorized into two groups: preoperative prophylaxis (PP), patients who received a single dose of enoxaparin preoperatively, and extended prophylaxis (EP), patients who received 28 days of enoxaparin postoperatively.

RESULTS: In total, 148 patients were included, with 117 patients in the PP group and 31 patients in the EP group. The overall incidence of VTE within 30 days postoperatively was 0.67%. No significant difference was found between the PP and the EP groups (0.9% and 0%, respectively; P = 1.00). Most patients in the cohort had endometrioid adenocarcinoma (78%) with low-grade disease (70%), although there were a greater number of patients in the PP group with uterine serous carcinoma compared with the EP group (17% vs 10%; P = 0.034). The PP group had higher estimated blood loss (106 vs 81 mL; P = 0.009) and longer operative times (178 vs 151 min; P = 0.028) compared with the EP group. Significantly more patients in the PP group underwent lymph node dissection compared with the EP group (32% vs 7%; P = 0.008).

CONCLUSIONS: The incidence of VTE following robot-assisted surgical staging for endometrial cancer in this study was 0.67%. No significant difference was found in VTE incidence between the PP group compared with the EP group. Mechanical prophylaxis plus a single dose of preoperative pharmacologic prophylaxis may suffice for low-risk patients following robotic surgical staging for endometrial cancer.

PMID:37788812 | DOI:10.14423/SMJ.0000000000001611

04:10

PubMed articles on: Cancer & VTE/PE

Machine-Learning-Assisted Procoagulant Extracellular Vesicle Barcode Assay toward High-Performance Evaluation of Thrombosis-Induced Death Risk in Cancer Patients

ACS Nano. 2023 Oct 4. doi: 10.1021/acsnano.3c04615. Online ahead of print.

ABSTRACT

Venous thromboembolism (VTE) is the most fatal complication in cancer patients. Unfortunately, the frequent misdiagnosis of VTE owing to the lack of accurate and efficient evaluation approaches may cause belated medical intervention and even sudden death. Herein, we present a rapid, easily operable, highly specific, and highly sensitive procoagulant extracellular vesicle barcode (PEVB) assay composed of TiO2 nanoflower (TiNFs) for visually evaluating VTE risk in cancer patients. TiNFs demonstrate rapid label-free EV capture capability by the synergetic effect of TiO2-phospholipids molecular interactions and topological interactions between TiNFs and EVs. From ordinary plasma samples, the PEVB assay can evaluate potential VTE risk by integrating TiNFs-based EV capture and in situ EV procoagulant ability test with machine-learning-assisted clinical data analysis. We demonstrate the feasibility of this PEVB assay in VTE risk evaluation by screening 167 cancer patients, as well as the high specificity (97.1%) and high sensitivity (96.8%), fully exceeding the nonspecific and posterior traditional VTE test. Together, we proposed a TiNFs platform allowing for highly accurate and timely diagnosis of VTE in cancer patients.

PMID:37791763 | DOI:10.1021/acsnano.3c04615

04:10

PubMed articles on: Cancer & VTE/PE

Ruptured Baker's cyst presenting with a palpable popliteal mass and crescent sign

BMJ Case Rep. 2023 Oct 4;16(10):e257869. doi: 10.1136/bcr-2023-257869.

NO ABSTRACT

PMID:37793850 | PMC:PMC10551967 | DOI:10.1136/bcr-2023-257869

04:10

PubMed articles on: Cancer & VTE/PE

Real-world data emulating randomized controlled trials of non-vitamin K antagonist oral anticoagulants in patients with venous thromboembolism

BMC Med. 2023 Sep 29;21(1):375. doi: 10.1186/s12916-023-03069-1.

ABSTRACT

BACKGROUND: Emulating randomized controlled trials (RCTs) by real-world evidence (RWE) studies would benefit future clinical and regulatory decision-making by balancing the limitations of RCT. We aimed to evaluate whether the findings from RWE studies can support regulatory decisions derived from RCTs of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE).

METHODS: Five landmark trials (AMPLIFY, RE-COVER II, Hokusai-VTE, EINSTEIN-DVT, and EINSTEIN-PE) of NOACs were emulated using the South Korean nationwide claims database (January 2012 to August 2020). We applied an active comparator and new-user design to include patients who initiated oral anticoagulants within 28 days from their VTE diagnoses. The prespecified eligibility criteria, exposure (each NOAC, such as apixaban, rivaroxaban, dabigatran, and edoxaban), comparator (conventional therapy, defined as subcutaneous heparin followed by warfarin), and the definition of outcomes from RCTs were emulated as closely as possible in each separate emulation cohort. The primary outcome was identical to each trial, which was defined as recurrent VTE or VTE-related death. The safety outcome was major bleeding. Propensity score matching was conducted to balance 69 covariates between the exposure groups. Effect estimates for outcomes were estimated using the Mantel-Haenszel method and Cox proportional hazards model and subsequently compared with the corresponding RCT estimates.

RESULTS: Compared to trial populations, real-world study populations were older (range: 63-69 years [RWE] vs. 54-59 years [RCT]), with more females (55-60.5% vs. 39-48.3%) and had a higher prevalence of active cancer (4.2-15.4% vs. 2.5-9.5%). The emulated estimates for effectiveness outcomes showed superior effectiveness of NOAC (AMPLIFY: relative risk 0.81, 95% confidence interval 0.70-0.94; RE-COVER II: hazard ratio [HR] 0.60, 0.37-0.96; Hokusai-VTE: 0.49, 0.31-0.78; EINSTEIN-DVT: 0.54, 0.33-0.89; EINSTEIN-PE: 0.50, 0.34-0.74), when contrasted with trials that showed non-inferiority. For safety outcomes, all emulations except for AMPLIFY and EINSTEIN-DVT yielded results consistent with their corresponding RCTs.

CONCLUSIONS: This study revealed the feasibility of complementing RCTs with RWE studies by using claims data in patients with VTE. Future studies to consider the different demographic characteristics between RCT and RWE populations are needed.

PMID:37775786 | PMC:PMC10542685 | DOI:10.1186/s12916-023-03069-1

04:10

PubMed articles on: Cardio-Oncology

Deep learning-assisted high-content screening identifies isoliquiritigenin as an inhibitor of DNA double-strand breaks for preventing doxorubicin-induced cardiotoxicity

Biol Direct. 2023 Oct 9;18(1):63. doi: 10.1186/s13062-023-00412-7.

ABSTRACT

BACKGROUND: Anthracyclines including doxorubicin are essential components of many cancer chemotherapy regimens, but their cardiotoxicity severely limits their use. New strategies for treating anthracycline-induced cardiotoxicity (AIC) are still needed. Anthracycline-induced DNA double-strand break (DSB) is the major cause of its cardiotoxicity. However, DSB-based drug screening for AIC has not been performed possibly due to the limited throughput of common assays for detecting DSB. To discover new therapeutic candidates for AIC, here we established a method to rapidly visualize and accurately evaluate the intranuclear anthracycline-induced DSB, and performed a screening for DSB inhibitors.

RESULTS: First, we constructed a cardiomyocyte cell line stably expressing EGFP-53BP1, in which the formation of EGFP-53BP1 foci faithfully marked the doxorubicin-induced DSB, providing a faster and visible approach to detecting DSB. To quantify the DSB, we used a deep learning-based image analysis method, which showed the better ability to distinguish different cell populations undergoing different treatments of doxorubicin or reference compounds, compared with the traditional threshold-based method. Subsequently, we applied the deep learning-assisted high-content screening method to 315 compounds and found three compounds (kaempferol, kaempferide, and isoliquiritigenin) that exert cardioprotective effects in vitro. Among them, the protective effect of isoliquiritigenin is accompanied by the up-regulation of HO-1, down-regulation of peroxynitrite and topo II, and the alleviation of doxorubicin-induced DSB and apoptosis. The results of animal experiments also showed that isoliquiritigenin maintained the myocardial tissue structure and cardiac function in vivo. Moreover, isoliquiritigenin did not affect the killing of HeLa and MDA-MB-436 cancer cells by doxorubicin and thus has the potential to be a lead compound to exert cardioprotective effects without affecting the antitumor effect of doxorubicin.

CONCLUSIONS: Our findings provided a new method for the drug discovery for AIC, which combines phenotypic screening with artificial intelligence. The results suggested that isoliquiritigenin as an inhibitor of DSB may be a promising drug candidate for AIC.

PMID:37807075 | PMC:PMC10561451 | DOI:10.1186/s13062-023-00412-7

04:10

PubMed articles on: Cardio-Oncology

Alterations in Left Atrial Strain in Breast Cancer Patients Immediately Post Anthracycline Exposure

Heart Lung Circ. 2023 Oct 6:S1443-9506(23)04291-9. doi: 10.1016/j.hlc.2023.06.864. Online ahead of print.

ABSTRACT

AIMS: With improved diagnosis and treatments, a greater percentage of breast cancer patients are achieving long-term survival. Consequently, long-term cardiotoxicity secondary to chemotherapy has become more prevalent, warranting improved cardiac surveillance. We evaluated changes in left atrial (LA) strain in breast cancer patients immediately post anthracycline (AC) therapy to assess its utility as a marker of diastolic dysfunction.

METHODS: This was a prospective cohort study of 128 consecutive human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who underwent transthoracic echocardiography prior to and immediately post AC treatment. Traditional left ventricular (LV) systolic and diastolic parameters and LA volumes were evaluated; additionally, LV global longitudinal strain (LV GLS) and LA phasic strain were measured.

RESULTS: All patients had normal LV ejection fraction (>53%) post AC, though LV GLS was significantly reduced. Peak E and é velocities were reduced post AC, with no change in LA volumes. LA reservoir strain (LASRES 34.8% vs 31.5%, p<0.001)CD 17.2% vs 14.4%, p<0.001)RES from baseline) (32%) compared to alteration in systolic function (≥15% reduction in LV GLS) (23%).

CONCLUSIONS: LA strain is a promising marker of early diastolic dysfunction. We demonstrate its potential utility in surveillance of breast cancer patients treated with AC.

PMID:37806911 | DOI:10.1016/j.hlc.2023.06.864

04:10

PubMed articles on: Cancer & VTE/PE

A case report: A patient rescued by VA-ECMO after cardiac arrest triggered by trigeminocardiac reflex after nasal surgery

Medicine (Baltimore). 2023 Sep 29;102(39):e35226. doi: 10.1097/MD.0000000000035226.