Unlike the commonly seen uphill esophageal varices in clinical practice, downhill esophageal varices are caused by obstruction of the superior vena cava and azygous venous system. The predominant causes of downhill esophageal varices are hemodialysis in end-stage renal disease patients and mediastinal malignancies. The cornerstone of the treatment for downhill esophageal varices is to address the underlying primary causes. Without this, patients may suffer from recurrent bleeding, and the bleeding can be fatal.

This review is primarily summarized through previous case reports. Meanwhile, it emphasizes the significance of case reports.

Clinicians should be conscious that esophageal varices are not necessarily caused by liver cirrhosis or non-cirrhotic portal hypertension.

Specifically, when varices are only observed in the upper and middle esophagus, and the patient presents with evidence of superior vena cava obstruction, clinicians should be particularly vigilant for downhill esophageal varices. Moreover, a thorough investigation and definitive treatment of the underlying primary causes should be implemented.

Thrombophilia, characterized by an imbalance between fibrinolysis and coagulation leading to inappropriate blood clotting, is a significant medical condition. The CDC has designated it as an underdiagnosed, serious, and potentially preventable disorder, contributing to an estimated 600,000-900,000 cases and 100,000 deaths annually in the United States. These figures surpass the combined annual mortality of AIDS, breast cancer, and motor vehicle accidents. The pathogenesis of thrombophilia involves complex interactions between genetic predispositions, such as mutations in Factor V Leiden, Factor II, MTHFR, and Serpine-1, and environmental factors, including unhealthy lifestyles, prolonged hospitalization, obesity, and cancer. Prevalence of specific genetic mutations varies across populations. Additional risk factors include age, family history, and pregnancy, with recent attention to increased susceptibility in SARS-CoV-2 infection. While molecular diagnostic techniques are available, there remains a need for robust, cost-effective, and accurate screening methods for large populations. This systematic review provides an updated overview of thrombophilia, encompassing pathophysiology, epidemiology, genetic and environmental risk factors, coagulation cascade, population-specific mutation prevalence, and diagnostic approaches. By synthesizing clinical and molecular evidence, this review aims to guide researchers, hematologists, and clinicians in the diagnosis and management of thrombophilia.

Edoxaban, a direct oral anticoagulant (DOAC), is a first-line treatment for venous thromboembolism (VTE) and the suppression of VTE recurrence. In patients with cancer, however, recurrent VTE after DOAC treatment may be more common than in noncancer patients. To evaluate our hypothesis that the anticoagulation effect of edoxaban is lower in VTE patients with cancer than in noncancer patients.

This study was a prospective, multicenter, observational study including patients treated with edoxaban for VTE in Japan. The primary outcome was the difference in the prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer level at 5 h after initial edoxaban administration between the cancer and noncancer groups. An additional outcome was the longitudinal change in PT and APTT from 5 h to overnight after edoxaban administration. The incidence of adverse events was further investigated.

PT and APTT at 5 h after initial edoxaban administration were not significantly different between the cancer (n = 84) and noncancer groups (n = 138) (e.g., log-transformed APTT 3.55 vs. 3.55, p = 0.45). However, D-dimer in the cancer groups was significantly greater than that in the noncancer groups (log-transformed 1.83 vs. 1.79, p = 0.009). PT and APTT significantly decreased from 5 h to overnight after edoxaban, but a similar pattern was observed in each group. All adverse events after edoxaban administration were also similar between patients with cancer and noncancer.

PT and APTT after edoxaban administration were similar between VTE patients with cancer and noncancer groups, suggesting that edoxaban has anticoagulation effects on cancer-associated VTE similar to those of noncancer patients.

UMIN000041973; Registration Date: 2020.10.5.

A 51-year-old female patient presented with abdominal distension. Computed tomography revealed a right ovarian tumor suspicious for clinical stage IC ovarian cancer, along with a considerable inferior vena cava (IVC) thrombus extending to the Th2 level, accompanied by a deep vein thrombus and a peripheral left pulmonary embolism (PE). Preoperative IVC filter placement was deemed unfavorable due to the short distance between the renal vein and the thrombus. On the second day of hospitalization, ovarian tumor extraction, thrombectomy, and IVC filter placement were performed. Pathology of the excised tumor revealed endometrioid carcinoma. Postoperatively, anticoagulation therapy with edoxaban 30 mg/day resulted in improvement of the deep vein thrombus and PE. The concomitant adnexal resection and thrombectomy rendered the safe placement of an IVC filter feasible despite the preoperative placement being unfeasible. Open thrombectomy remains a valid treatment strategy despite advances in endovascular therapy.

Cholangiocarcinoma (CCA) is an uncommon cancer, with limited data available on the incidence of cancer-associated thrombosis in CCA patients. This was a single-center, retrospective study conducted in a university-based hospital in Thailand. We included consecutive patients newly diagnosed with CCA between January 2019 and December 2022. The study outcomes focused on the incidence of venous thromboembolism (VTE) and all-cause mortality within 12 months of diagnosis. A total of 450 patients were included in the study, with a median follow-up time of 212 days, and 61.8% of participants were male. The one-year incidence of VTE was 15.3%, with a median time to VTE occurrence of 6 days (Q1-Q3: 1-86 days). Multivariable analysis indicated that age ≤ 55 years (hazard ratio 2.34, 95% confidence interval [CI] 1.40-3.88, p = 0.001), ECOG performance status ≥ 2 (HR 2.53, 95% CI 1.41-4.53, p = 0.002), stage IV cancer (HR 1.84, 95% CI 1.14-3.00, p = 0.013), and total bilirubin ≤ 13 mg/dL (HR 4.11, 95% CI 1.67-10.15, p = 0.002) were associated with VTE occurrence. During follow-up, all-cause mortality was 57.3%, and VTE presence increased the risk of all-cause mortality, with an HR of 1.41 (95% CI 1.02-1.94, p = 0.035). The incidence of VTE following a diagnosis of CCA was notably high. CCA patients who developed VTE were observed to be at a heightened risk of all-cause mortality. Therefore, VTE should be recognized as one of the significant complications among CCA patients.

Coagulation status is closely related to the progression of malignant tumors. In the era of neoadjuvant immunochemotherapy (NICT), the prognostic utility of coagulation indicators in patients with locally advanced gastric cancer (LAGC) undergoing new treatments remains to be determined.

To determine whether hypercoagulation is an effective prognostic indicator in patients with LAGC who underwent radical resection after NICT.

A retrospective analysis of clinical data from 104 patients with LAGC, who underwent radical resection after NICT between 2020 and 2023, was performed. D-dimer and fibrinogen concentrations were measured one week before NICT, and again one week before surgery, to analyze the association between these two indicators and their combined indices [non-hypercoagulation (D-dimer and fibrinogen concentrations within the upper limit of normal) vs hypercoagulation (D-dimer or fibrinogen concentrations above the upper limit of normal)] with prognosis. After radical resection, patients were followed-up periodically. The median follow-up duration was 21 months.

Data collected after NICT revealed that the three-year overall survival (OS) and disease-free survival (DFS) rates the non-hypercoagulation group were significantly better than those in the hypercoagulation group [94.4% vs 78.0% (P = 0.019) and 87.0% vs 68.0% (P = 0.027), respectively]. Multivariate analysis indicated that hypercoagulation after NICT was an independent factor for poor postoperative OS [hazard ratio (HR) 4.436, P = 0.023] and DFS (HR 2.551, P = 0.039). Pre-NICT data demonstrated no statistically significant difference in three-year OS between the non-hypercoagulation and hypercoagulation groups (88.3% vs 84.1%, respectively; P = 0.443).

Hypercoagulation after NICT is an effective prognostic indicator in patients with LAGC undergoing radical gastrectomy.

The reported incidence of arterial thromboembolism (ATE) and venous thromboembolism (VTE) after cancer varies. A meta-analysis was performed to define the incidence of thromboembolism (TE) in cancer patients. Articles were searched in PubMed and Embase from inception to November 1, 2023. Studies reporting the incidence data or data from which incidence could be estimated among patients with cancer and the explicit follow-up duration were included. Seventy-four studies involving 5,059,134 cancer patients were identified. The incidence rate per 1000 person-years was 11.60 (95% CI 7.62-15.58) for ATE, 6.11 (95% CI 3.70-8.53) for myocardial infarction, 9.07 (95% CI 7.48-10.66) for ischemic stroke, 2.11 (95% CI 0.89-3.31) for another ATE, 26.32 (95% CI 24.46-28.18) for VTE, 12.69 (95% CI 11.51-13.87) for deep vein thrombosis, 5.94 (95% CI 5.29-6.59) for pulmonary embolism, and 13.18 (95% CI 9.93-16.42) for another VTE. In addition, the highest incidence of ATE was observed in patients with gastrointestinal cancer, while patients with pancreatic cancer had the highest incidence of VTE. The risk of ATE and VTE increased at the initial stage of cancer, and then declined and became non-significant. This meta-analysis provided overall estimates of ATE and VTE incidence in cancer patients, adding an important insight into the trajectory of the development of TE in cancer patients, which could help the early detection of TE in cancer patients in the future.

Cancer-associated venous thromboembolism (CAT) is a frequent and serious complication in cancer patients. Resveratrol, a natural compound with reported anti-tumor effects, is not fully understood in its role regarding CAT in lung cancer. This study aims to explore resveratrol's potential to diminish platelet activation induced by lung adenocarcinoma cells and uncover the underlying mechanisms.

Clinical data on coagulation function in non-small cell lung cancer (NSCLC) patients were gathered. A549 human lung cancer cells and Lewis mouse lung cancer cells were employed to assess tumor-induced platelet activation and the impact of resveratrol on this process. Western blotting analyzed protein expression, electron microscopy examined extracellular vesicle (EV) morphology, flow cytometry measured platelet activation, reactive oxygen species (ROS), and exocrine protein expression, while ELISA quantified secretory proteins. Tumor control and platelet function were studied in tumor-bearing mice.

We identified that hematological profiles of NSCLC patients frequently manifest a hypercoagulable state relative to healthy controls and lung cancer cells could instigate platelet activation, yet resveratrol could attenuate this phenomenon induced by lung cancer. Resveratrol stimulates lung cancer cells to release HMGB1-enriched EVs, promoting platelet ferroptosis and inhibiting platelet activation through increased ROS, lipid peroxidation, and disrupted cystine transporters. In vivo studies confirm that resveratrol inhibits lung cancer cell growth and suppresses tumor-induced platelet activation in mice.

Our studies revealed that resveratrol alleviated lung cancer-induced ferroptosis associated platelet activation. This suggests a potential pharmacological approach for preventing and treating both lung cancer and CAT.

To assess the currently applied regimens of antithrombotic therapy after microvascular reconstruction.

A systematic literature review was performed using the MEDLINE/PubMed Database for work published until September 2022. Data synthesis and risk of bias were reported in accordance with NIH Study Quality Assessment Tools guidelines.

204 articles were found including the keywords either in the abstract or in the title. After screening their abstracts and titles, 41 articles were identified as suitable and the full texts were retrieved. 23 studies were included in this review. No gold standard could be shown; on the contrary, the applied antithrombotic regimens varied widely. A broad consensus could be obtained that Dextran should no longer be used after an increased complication rate was proven. The most commonly used agents are unfractionated (UFH) as well as low molecular weight (LMWH) heparin and acetylsalecylic acid (ASA), although the literature results are partly contradictory.

A consensus could be found that it is useful to perform thromboprophylaxis when the patient is immobilized, but there is no evidence for a survival advantage of the flap by chemical prophylaxis. On the contrary, it has been shown that there is an increased rate of bleeding complications and flap loss combined with the simultaneous use of multiple chemical anticoagulants. In conclusion the generalized use of anticoagulation is explained less by microvascular grafting than by general medical risk factors. Thus, large prospective RCTs will be needed to establish a gold standard therapeutic regimen.

Prevention of death from in-hospital pulmonary thromboembolism (PE) is crucial, but research exploring the risk factors for this event remains limited.

This retrospective analysis evaluated PE data among hospitalized patients, focusing on the diseases present on admission to hospital with the highest number of patients with in-hospital PE events, using the Medical Data Vision database (January 2017-December 2021). Endpoints included the incidence rate of in-hospital PE, patient characteristics, and PE prophylactic procedures. Overall, 4,684,659 patients (in-hospital PE cohort, n=5,007; non-PE cohort, n=4,679,952) were eligible: heart failure (n=208; n=87,160), femoral fracture (n=478; n=139,049), pneumonia (n=309; n=222,257), stroke (n=351; n=248,805), and cancer (n=934; n=764,413). The incidence rate of in-hospital PE in the overall population was 20.6/1,000 person-years: heart failure (34.6), femoral fracture (35.3), pneumonia (21.4), stroke (15.9), and cancer (25.6). History of venous thromboembolism (VTE) was a risk factor for in-hospital PE in >50% of patients in all subgroups. Prophylactic PE procedures were implemented in 33.8% of the overall population: femoral fracture (79.5%), cancer (49.7%), stroke (24.2%), heart failure (12.7%), and pneumonia (6.2%).

The incidence of in-hospital PE was not high overall but was higher in patients with a history of VTE and those with hospitalization due to heart failure or femoral fracture. Risk assessment for in-hospital PE, including medical history and diagnosis at admission, is preferred in hospitalized patients.

Splanchnic vein thrombosis (SVT) in pancreatic disease has a 20%-30% incidence rate, leading to increased mortality and complication rates. Therefore, the aim of this review is to summarize recent evidence about the incidence, risk factors, and management of pancreatic cancer, pancreatic cystic neoplasm-, and pancreatitis-related SVT. Doppler ultrasound should be the first imaging choice, followed by contrast-enhanced computed tomography or magnetic resonance imaging. Data regarding SVT treatment in acute pancreatitis and pancreatic cancer are scarce; however, for venous thromboembolism treatment, direct oral anticoagulants and low molecular weight heparin have been effective. Further trials must investigate the length of anticoagulant treatment and the need for interventional radiological procedures.

Stroke leads to significant disability in most patients, whereas cancer elevates the occurrence of stroke. The incidence of cancer-associated stroke (CAS) is projected to rise as a result of improvements in cancer therapies. Various forms of cancer have been demonstrated to be linked to ischemic stroke. Cancer might influence stroke pathophysiology either directly or through coagulation that creates a hypercoagulative state, in addition to infections. Treatment methods for cancer, including chemotherapy, radiotherapy, and surgery, have all been demonstrated to increase the risk of stroke as well. This review discusses the subtypes, epidemiology, pathophysiology, mechanisms of stroke within cancer patients, biomarkers, and signaling pathways of stroke in cancer while providing vital information on the involved transcription factors, treatment, and management of patients with cancer-associated ischemic stroke. Atherosclerosis, extracellular vesicles (EVs), and signaling biomolecules can also affect CAS. Overall, stroke is a significant and not uncommon complication of cancer, and there is an immediate demand for neurologists and oncologists to create strategies for screening and preventing strokes in cancer patients.

The relationship between the concomitant use of immune checkpoint inhibitors (ICIs) and elevated prothrombin time-to-international standard ratio (PT-INR) in patients receiving warfarin remains unclear. In the present study, 26 patients treated with ICIs during warfarin therapy were examined for increases in PT-INR within 60 d of ICI administration. Of these patients, 13 developed Grade 2 or higher PT-INR elevations, 5 of which required the immediate administration of vitamin K. The increased risk of bleeding and the impact on the continuation of cancer drug therapy are significant burdens for patients. Immune-related adverse events caused by ICIs have been suggested as one of the reasons for increases in PT-INR, and patients taking warfarin and ICIs need to be managed in consideration of the risk of elevated PT-INR by frequently checking the blood coagulation capacity.

Venous thromboembolism, a common complication associated with cancer, causes increased morbidity and mortality. D-dimer levels are often increased non-specifically in cancer which limits their use to diagnose venous thromboembolism. The current study aimed to investigate the role of the serum soluble suppression of tumorigenicity 2 (sST2) as a new biomarker to diagnose venous thromboembolism in cancer.

Eighty-eight patients with different types of cancer were enrolled and divided into two groups: Group I: 44 cancer patients with confirmed diagnosis of venous thromboembolism and Group II: 44 age- and sex-matched cancer patients without any thrombotic complications. The D-dimer test and sST2 measurement were performed for all study subjects.

Serum sST2 levels were significantly higher in Group I than in Group II (p-value < 0.001); the median serum sST2 was 13.02 ng/mL (range: 7.65-117.9 ng/mL) in Group I versus 8.56 ng/mL (range: 5.59-10.33 ng/mL) in Group II. There was a significant positive correlation between serum sST2 and the D-dimer level. Using a receiver operating characteristic curve, sST2 had a greater area under the curve than the D-dimer test (0.974 versus 0.869, respectively). Although the D-dimer test was more sensitive, sST2 had a greater specificity than D-dimer (95.45 % versus 27.3 %, respectively) and a higher positive predictive value (95.3 % versus 56.8 %, respectively).

The results of the current study support a potential role of soluble ST2 to aid in diagnosing venous thromboembolism in cancer patients.

This case report explores the management of a 56-year-old female oncology patient presenting with acute ST-elevation myocardial infarction (STEMI) and an incidental atrial septal defect (ASD). The patient, with a history of rectal cancer and hypothyroidism, experienced acute chest pain and dyspnea. She was diagnosed with an inferior STEMI and underwent percutaneous coronary intervention (PCI) with the placement of three medicated stents in the right coronary artery. During hospitalization, an echocardiogram revealed a significant ostium secundum ASD. Angiography indicated thrombi, suggesting a potential paradoxical embolism. Percutaneous ASD closure was performed during the same hospital stay, leading to a favorable clinical course without immediate complications. This case highlights the importance of a multidisciplinary approach and comprehensive evaluation in managing complex cardiovascular conditions, particularly in patients with increased thrombotic risk due to malignancy.

Previous studies have investigated cardiovascular disease (CVD) risks in cancer patients, but there is limited knowledge concerning the CVD risk in adult and young adolescent (AYA) survivors of gastric cancer.

This study aims to investigate the incidence of CVD in AYA gastric cancer survivors, analyzing it by treatment type and identifying associated risk factors.

We conducted a retrospective cohort study using Korean National Health Insurance Service data collected from 2006 to 2019. Propensity score matching (1:3, caliper < 0.1) was performed using the variables age, sex, income, residential area, and presence of comorbidities, and we classified participants into gastric cancer (n = 6562) and non-cancer control (n = 19,678) groups. Cox regression models were used to calculate hazard ratios (HRs) for CVD incidence. The study assessed CVD incidence by cancer treatment and identified risk factors through multivariable Cox regression.

During a median 6.5-year follow-up, AYA gastric cancer survivors consistently exhibited greater CVD incidence. Their risk of CVD was significantly elevated compared to that of controls (HR, 1.18; 95% confidence interval [CI] 1.05-1.33). In particular, deep vein thrombosis (HR, 3.93; 95% CI 3.06-14.67) and pulmonary embolism (HR, 6.58; 95% CI 3.06-14.67) risks were notably increased. Chemotherapy was associated with an increased risk of stroke, heart failure, atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Hypertension (HR, 1.58; 95% CI 1.10-2.26) and dyslipidemia (HR, 1.46; 95% CI 1.06-2.20) emerged as risk factors for CVD development.

This study reports elevated risks of CVD in AYA gastric cancer survivors and emphasizes the need for vigilant monitoring of CVD in this population.

This study aimed to develop a machine learning (ML) model for predicting pulmonary embolism (PE) in patients with gastrointestinal cancers, a group at increased risk for PE. We conducted a retrospective, multicenter study analyzing patients who underwent computed tomographic pulmonary angiography (CTPA) between 2010 and 2020. The study utilized demographic and clinical data, including the Wells score and D-dimer levels, to train a random forest ML model. The model's effectiveness was assessed using the area under the receiver operating curve (AUROC). In total, 446 patients from hospital A and 139 from hospital B were included. The training set consisted of 356 patients from hospital A, with internal validation on 90 and external validation on 139 patients from hospital B. The model achieved an AUROC of 0.736 in hospital A and 0.669 in hospital B. The ML model significantly reduced the number of patients recommended for CTPA compared to the conventional diagnostic strategy (hospital A; 100.0% vs. 91.1%, P < 0.001, hospital B; 100.0% vs. 93.5%, P = 0.003). The results indicate that an ML-based prediction model can reduce unnecessary CTPA procedures in gastrointestinal cancer patients, highlighting its potential to enhance diagnostic efficiency and reduce patient burden.

Non-Hodgkin's Lymphoma (NHL) is the most common subtype of lymphoma. The incidence of venous thromboembolism (VTE) in aggressive NHL was estimated recently to be 11%. Several risk assessment scores and factors are available to help identify cancer patients at risk for developing VTE. Patients with a pathologically confirmed diagnosis of NHL were identified at the Oncology Center of Mansoura University. The study included 777 patients: 719 with DLBCL-NOS, 26 with Anaplastic-B-cell, and 32 with T-cell-rich-NHL. Data were retrospectively collected from electronic medical records, including clinical, radiological, and laboratory information related to VTE and NHL. The median age at NHL diagnosis was 53 years, (range: 18-98). There was a male predominance, 51.4% of the cases. At initial lymphoma diagnosis, VTE was identified in 46 (5.9%) patients, and 61 (7.9%) patients experienced VTE while undergoing chemotherapy. According to logistic regression analysis, a PS (performance status) ≥ 2, bulky lesions, and mediastinal masses were significant predictors of VTE at presentation, with P-values of 0.022, 0.002, and < 0.001, respectively. Meanwhile, NHL patients who developed VTE during chemotherapy had significantly poorer PS, higher absolute neutrophilic counts (ANC), neutrophil/lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lactate dehydrogenase (LDH) levels than lymphoma patients without VTE, with P-values of 0.003,  0.034, 0.049, 0.01 and 0.007, respectively, as determined by multivariate analysis. The ROC curve identified the cut-off values of 4.875 × 109/L for ANC, 2.985 for NLR, 144.85 for PLR, and 417.5 U/L for LDH as potential markers for predicting VTE in NHL patients. Patients with a PS ≥ 2 and values exceeding these cut-offs for ANC, NLR, and PLR experienced significantly higher incidences of VTE than other groups, with P-values of 0.003, < 0.001, < 0.001, and < 0.001, respectively. At the end of the follow-up, the overall survival was significantly shortened by VTE occurring during chemotherapy, hypoalbuminemia,  intermediate-high and high international prognostic index (IPI) scores (intermediate-high and high), responses other than CR and relapse, all with P-values < 0.05. ECOG PS and Inflammatory markers such as NLR, PLR, and neutrophilic count could serve as predictors of the development of thrombotic events in patients with NHL-DLBCL. Additionally, the occurrence of VTE during chemotherapy is an independent poor prognostic marker for overall survival (OS).

Thromboembolism is a significant cause of mortality and morbidity in cancer patients. While the link between cancer and venous thrombosis is well known, the recognition of arterial thrombosis as a serious complication of cancer and chemotherapeutic agents is a recent development. One of the chemotherapy agents frequently linked to acute vascular events is cisplatin. We discuss a rare case of cisplatin-related brachial arterial thrombosis in a 50-year-old man who was treated for cholangiocarcinoma with cisplatin and gemcitabine. Although rare, cisplatin-related arterial thrombosis demands careful monitoring, a high index of suspicion, and prompt management to prevent serious complications and mortality.

Calcified amorphous tumor of the heart is a rare non-neoplastic cardiac mass composed of calcified nodules over amorphous fibrous tissue with degeneration and some chronic inflammation. Calcified amorphous tumor is often associated with mitral annular calcification in patients with end-stage renal disease on dialysis. However, the exact etiology of calcified amorphous tumors remains uncertain.

A 77-year-old female with lung cancer showed a tumor with large mobility in the left ventricular outflow tract on transthoracic echocardiography. She had mitral annular calcification, although her renal function was normal. The tumor was excised surgically. Pathologically, the extracted specimen consisted of a calcified lesion without tumor tissue and was diagnosed as a calcified amorphous tumor.

As the patient had no other risk factors for calcified amorphous tumor except mitral annular calcification, we considered the association of blood coagulation abnormalities due to cancer-related thrombosis. This case suggests that calcified amorphous tumors may be associated with malignant tumors.

Incidental diffuse-weighted imaging (DWI)-positive subcortical and cortical lesions, or acute incidental cerebral microinfarcts (CMIs), are a common type of brain ischemia, which can be detected on magnetic resonance DWI for approximately 2 weeks after occurrence. Acute incidental CMI was found to be more common in patients with cancer. Whether acute incidental CMI predicts future ischemic stroke is still unknown. We aimed to examine the association between acute incidental CMI in patients with cancer and subsequent ischemic stroke or transient ischemic attack (TIA).

This is a retrospective cohort study. We used Clalit Health Services records, representing over half of the Israeli population, to identify adults with lung, breast, pancreatic, or colon cancer who underwent brain MRI between January 2014 and April 2020. We included patients who underwent scan between 1 year before cancer diagnosis and 1 year after diagnosis. Primary outcome was ischemic stroke or TIA using International Classification of Diseases, Ninth Revision codes. Secondary outcomes were intracranial hemorrhage (ICH) and mortality. Records were followed from first MRI until primary outcome, death, or end of follow-up (January 2023). Cox proportional hazards models were used to calculate hazard ratio (HR) for patients with and without acute incidental CMI, as a time-dependent covariate.

The study cohort included 1,618 patients with cancer, among whom, 59 (3.6%) had acute incidental CMI on at least 1 brain MRI. The median (interquartile range) time from acute incidental CMI to stroke or TIA was 26 days (14-84). On multivariable analysis, patients with acute incidental CMI had a higher stroke or TIA risk (HR 2.97, 95% CI 1.08-8.18, p = 0.035) compared with their non-CMI counterparts. Acute incidental CMIs were also associated with mortality after multivariable analysis (HR 2.76, 95% CI 2.06-3.71, p < 0.001); no association with ICH was found.

Acute incidental CMI on brain MRI in patients with active cancer is associated with an increased risk of near-future ischemic stroke or TIA and mortality. This finding might suggest that randomly detected acute incidental CMI in patients with cancer may guide primary cerebrovascular risk prevention and etiologic workup.

Peripherally inserted central catheters are commonly used in cancer patients and provide vascular access for the administration of chemotherapy, antibiotics, or parenteral nutrition. Besides many advantages, they represent a source of possible complications such as catheter related blood stream infection, catheter occlusion, or thrombosis. In this study, the catheter-related complication rate between oncologic and non-oncologic patients was compared.

This retrospective cohort-study included 411 patients who underwent their first catheter placement at the Vienna General Hospital-Medical University of Vienna from January 2013 to June 2018. Patient demographics and catheter-related parameters were collected and statistically analyzed using a competing risk model.

Mean catheter dwell time was 27.75 days. The overall complication rate was 7.54% (2.72 per 1000 catheter days). Underlying malignant disease (hazard ratio: 0.351, 95% confidence interval [CI]: 0.133-0.929, P = .035) and chemotherapy administration (hazard ratio: 2.837, 95% CI: 1.088-7.394, P = .033) were significantly associated with the occurrence of any kind of complication. Catheter related blood stream infection was observed among 11 (2.68%) patients and again significantly associated with chemotherapy administration (hazard ratio: 4.545, 95% CI: 1.178-17.539; P = .028). Thrombosis was found in 7 (1.70%) patients and occlusion in 13 (3.16%) cases.

Choice of venous access is an interdisciplinary decision with emphasis on patient participation. In oncologic patients, our data suggests that the benefits of peripherally inserted central catheters regarding costs, invasiveness, and accessibility might be outweighed by the higher rate of complications associated with the device. This becomes even more important in a community care setting, where standardized handling procedures and patient education play a pivotal role in device safety.

Direct oral anticoagulants are the established drugs for treating pulmonary thromboembolism. The advantage of direct oral anticoagulants over conventional therapy for clot lysis and right ventricular unloading in the acute phase remains unclear. This study aimed to evaluate the effect of acute treatment with direct oral anticoagulants on clot dissolution and right ventricular unloading in intermediate high-risk pulmonary thromboembolism.

Thirty patients with intermediate high-risk pulmonary thromboembolism admitted between November 2012 and December 2018 were included; 21 and 9 were treated with direct oral anticoagulants and conventional therapy, respectively. We compared the efficacy of clot dissolution and right ventricular unloading for intermediate high-risk pulmonary thromboembolism between direct oral anticoagulant and conventional therapy in the acute phase. Efficacy was assessed by computed tomography obstruction index, right/left ventricular ratio, and brain natriuretic peptide levels between baseline and at discharge.

Computed tomography obstruction index, right ventricular/left ventricular ratio, and brain natriuretic peptide levels were significantly lower at discharge than at admission in both groups. The rate of improvement in computed tomography obstruction index was significantly higher in the direct oral anticoagulant therapy group than in the conventional therapy group (64 ± 15% vs. 47 ± 16%; p = 0.01). There were no significant differences in the rate of improvement in right ventricular/ left ventricular ratio and brain natriuretic peptide levels between the two groups.

Compared with conventional therapy, direct oral anticoagulants significantly reduced pulmonary artery clot burden conventional therapy in the acute treatment of intermediate high-risk pulmonary thromboembolism.

Cancer-associated thrombosis (CAT) has been identified as the second most prevalent cause of death after cancer itself. Moreover, the risk of thrombotic events in cancer patients increases due to anticancer drugs, such as tyrosine kinase inhibitors (TKIs). Venous thromboembolism (VTE) as well as arterial thromboembolic (ATE) events are present in CAT. Although VTE occurs more frequently, ATE events are very significant and in some cases are more dangerous than VTE. Guidelines for preventing thrombosis refer mainly VTE as well as the contribution of ATE events. Several factors are involved in thrombosis related to cancer, but the whole pathomechanism of thrombosis is not clear and may differ between patients. The activation of the coagulation system and the interaction of cancer cells with other cells including platelets, endothelial cells, monocytes, and neutrophils are promoted by a hypercoagulable state caused by cancer. We present an update on the pathomechanisms of CAT and the effect of anticancer drugs, mainly targeted therapies with a focus on TKIs. Considering the risk of bleeding associated with anticoagulation in each cancer patient, the anticoagulation strategy may involve the use of FXIa inhibitors, direct oral anticoagulants, and low-molecular-weight heparin. Further research would be valuable in developing strategies for reducing CAT.

As a kind of proteolytic enzyme extracted from earthworms, lumbrokinase has been used as an antithrombotic drug clinically. Nevertheless, its potential in anti-cancer, especially in anti-non-small cell lung cancer (NSCLC), as a single form of treatment or in combination with other therapies, is still poorly understood. In this study, we explored the anti-tumor role and the responsive molecular mechanisms of lumbrokinase in suppressing tumor angiogenesis and chemoresistance development in NSCLC and its clinical potential in combination with bevacizumab and chemotherapeutics. Lumbrokinase was found to inhibit cell proliferation in a concentration-dependent manner and caused metastasis suppression and apoptosis induction to varying degrees in NSCLC cells. Lumbrokinase enhanced the anti-angiogenesis efficiency of bevacizumab by down-regulating BPTF expression, decreasing its anchoring at the VEGF promoter region and subsequent VEGF expression and secretion. Furthermore, lumbrokinase treatment reduced IC50 values of chemotherapeutics and improved their cytotoxicity in parental and chemo-resistant NSCLC cells via inactivating the NF-κB pathway, inhibiting the expression of COX-2 and subsequent secretion of PGE2. LPS-induced NF-κB activation reversed its inhibition on NSCLC cell proliferation and its synergy with chemotherapeutic cytotoxicity, while COX-2 inhibitor celecoxib treatment boosted such effects. Lumbrokinase combined with bevacizumab, paclitaxel, or vincristine inhibited the xenograft growth of NSCLC cells in mice more significantly than a single treatment. In conclusion, lumbrokinase inhibited NSCLC survival and sensitized NSCLC cells to bevacizumab or chemotherapeutics treatment by targeted down-regulation of BPTF/VEGF signaling and inactivation of NF-κB/COX-2 signaling, respectively. The combinational applications of lumbrokinase with bevacizumab or chemotherapeutics are expected to be developed as promising candidate therapeutic strategies to improve the efficacy of the original monotherapy in anti-NSCLC.

Abnormal activation of the coagulation system is associated with malignant tumor progression. Although neoadjuvant treatment (NAT) for resectable esophageal squamous cell carcinoma (ESCC) is the standard of care, the correlation between coagulation status and prognosis of patients undergoing preoperative treatment is insufficiently understood.

Patients (n = 200) who underwent radical subtotal esophagectomy after preoperative treatment for ESCC between January 2012 and December 2021were included in the analysis. Plasma D-dimer and fibrinogen levels and their combined indices (non-hypercoagulation; D-dimer and fibrinogen levels within the upper normal limit, or hypercoagulation; D-dimer or fibrinogen levels above the upper normal limit) were determined before and after NAT and correlated to clinicopathological factors and prognosis.

The nonhypercoagulation group achieved superior overall survival (OS) than the hypercoagulation group (5-year OS rates = 89% vs. 55%; hazard ratio 3.62, P = 0.0008) when determined according to coagulation status after NAT. Multivariate analysis showed that hypercoagulation after NAT served as an independent factor for poor postoperative OS (hazard ratio 3.20; P = 0.0028). The nonhypercoagulation group achieved significantly better disease-free survival (76% vs. 54%; P = 0.0065) than the hypercoagulation group that experienced a significantly higher rate of hematogenous metastasis as an initial recurrence (P = 0.0337).

Hypercoagulation state after NAT served as a valid indicator correlating with postoperative outcomes of patients with ESCC who underwent NAT followed by radical subtotal esophagectomy.

Patients with cancer have a higher risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), compared to the general population. Cancer-associated thrombosis (CAT) is a thrombotic event that occurs as a complication of cancer or cancer therapy. Major factors determining VTE risk in cancer patients include not only treatment history and patient characteristics, but also cancer type and site. Cancer types can be broadly divided into three groups based on VTE risk: high risk (pancreatic, ovarian, brain, stomach, gynecologic, and hematologic), intermediate risk (colon and lung), and low risk (breast and prostate). This implies that the mechanism of VTE differs between cancer types and that specific VTE pathways may exist for different cancer types. This review summarizes the specific pathways that contribute to VTE in cancer patients, with a particular focus on leukocytosis, neutrophil extracellular traps (NETs), tissue factor (TF), thrombocytosis, podoplanin (PDPN), plasminogen activator inhibitor-1 (PAI-1), the intrinsic coagulation pathway, and von Willebrand factor (VWF).

The coexistence of venous thromboembolism (VTE) within patients with cancer, known as cancer-associated thrombosis (CAT), stands as a prominent cause of mortality in this population. Over recent years, the incidence of VTE has demonstrated a steady increase across diverse tumor types, influenced by several factors such as patient management, tumor-specific risks, and treatment-related aspects. Furthermore, mutations in specific genes have been identified as potential contributors to increased CAT occurrence in particular cancer subtypes. We conducted an extensive review encompassing pivotal historical and ongoing studies on CAT. This review elucidates the risks, mechanisms, reliable markers, and risk assessment methodologies that can significantly guide effective interventions in clinical practice.

The aim of this study was to record and assess the efficacy and safety ofthromboprophylaxis with an intermediate dose of Tinzaparin in lung cancer patients with high thrombotic risk.

This was a non-interventional, single-arm, prospective cohort study of lung cancer patients who received thromboprophylaxis with Tinzaparin 10.000 Anti-Xa IU in 0.5 mL, OD, used in current clinical practice. Enrolled ambulatory patients signed informed consent. Anti-Xa levels were tested.

In total, 140 patients were included in the study, of which 81.4% were males. The histology of the tumor was mainly adenocarcinoma. Lung cancer patients with high thrombotic risk based on tumor, patient, treatment, and laboratory-related factors were enrolled. Only one patient experienced a thrombotic event (0.7%), and 10 patients had bleeding events (7.1%), including only one major event. Anti-Xa levels measured at 10 days and 3 months did not differ significantly between patients who developed hemorrhagic events and those who did not (p = 0.26 and p = 0.32, respectively).

Thromboprophylaxis with an intermediate Tinzaparin dose in high thrombotic-risk lung cancer patients is a safe and effective choice for the prevention of VTE.

Cancer remains a major cause of mortality worldwide, and urological cancers are the most common cancers among men. Several therapeutic agents have been used to treat urological cancer, leading to improved survival for patients. However, this has been accompanied by an increase in the frequency of survivors with cardiovascular complications caused by anticancer medications. Here, we propose the novel discipline of uro-cardio-oncology, an evolving subspecialty focused on the complex interactions between cardiovascular disease and urological cancer. In this comprehensive review, we discuss the various cardiovascular toxicities induced by different classes of antineoplastic agents used to treat urological cancers, including androgen deprivation therapy, vascular endothelial growth factor receptor tyrosine kinase inhibitors, immune checkpoint inhibitors, and chemotherapeutics. In addition, we discuss possible mechanisms underlying the cardiovascular toxicity associated with anticancer therapy and outline strategies for the surveillance, diagnosis, and effective management of cardiovascular complications. Finally, we provide an analysis of future perspectives in this emerging specialty, identifying areas in need of further research.

Cerebral microinfarcts (CMIs) are the most common type of brain ischemia; however, they are extremely rare in the general population. CMIs can be detected by magnetic resonance diffusion-weighted imaging (MRI-DWI) only for a very short period of approximately 2 weeks after their formation and are associated with an increased stroke risk and cognitive impairment. We aimed to examine CMI detection rate in patients with lung cancer (LC), which is strongly associated with ischemic stroke risk relative to other cancer types.

We used the Clalit Health Services record (representing more than 5 million patients) to identify adults with LC and breast, pancreatic, or colon cancer (non-lung cancer, NLC) who underwent brain magnetic resonance diffusion (MRI) scan within 5 years following cancer diagnosis. All brain MRI scans were reviewed, and CMIs were documented, as well as cardiovascular risk factors.

Our cohort contained a total of 2056 MRI scans of LC patients and 1598 of NLC patients. A total of 143 CMI were found in 73/2056 (3.5%) MRI scans of LC group compared to a total of 29 CMI in 22/1598 (1.4%) MRI scans of NLC (p < 0.01). Cancer type (e.g. LC vs NLC) was the only associated factor with CMI incidence on multivariate analysis. After calculating accumulated risk, we found an incidence of 2.5 CMI per year in LC patients and 0.5 in NLC.

CMIs are common findings in cancer patients, especially in LC patients and therefore might serve as a marker for occult brain ischemia, cognitive decline, and cancer-related stroke (CRS) risk.

Intestinal Ischemia: Etiology and Foundational ConceptsThe authors provide an overview of the intestinal anatomy and the pathophysiology and etiology of intestinal ischemia.

There is a paucity of data on real-world management strategies and clinical outcomes of cancer-associated venous thromboembolism (VTE) in the direct oral anticoagulants (DOACs) era.

To investigate the status of cancer-associated VTE in the DOAC era.

This multicenter, retrospective cohort study among 31 centers in Japan between 2015 and 2020 enrolled 5197 consecutive patients with acute symptomatic VTE, who were divided into 1507 patients (29 %) with active cancer and 3690 patients (71 %) without.

The cumulative 3-year rate of anticoagulation discontinuation was significantly higher in patients with active cancer than in those without (62.7 % vs. 59.1 %, P < 0.001). The cumulative 5-year incidence of recurrent VTE was higher in patients with active cancer than in those without (10.1 % vs. 9.1 %, P = 0.01), however, after adjusting for the confounders and competing risk of mortality, the excess risk of the active cancer group relative to the no active cancer group was no longer significant (HR: 0.95, 95 % CI: 0.73-1.24). The cumulative 5-year incidence of major bleeding was much higher in the active cancer group (20.4 % vs. 11.6 %, P < 0.001). Even after adjusting for the confounders and competing risk of mortality, the risk of the active cancer group relative to the no active cancer group remained significant (HR: 1.36, 95 % CI: 1.11-1.66).

The current large real-world registry revealed that the risk of major bleeding was still higher in patients with active cancer than in those without, leading to the frequent anticoagulation discontinuation, which has been still a huge challenge to overcome in the DOAC era.

Patients with active cancer frequently develop venous thromboembolism (VTE). However, there is little data about VTE in patients with advanced cholangiocarcinoma (CCA). Therefore, we investigated the clinical significance of VTE in patients with advanced CCA.

We analyzed the data of a total of 332 unresectable CCA patients diagnosed between 2010 and 2020 in this retrospective study. We investigated the incidence and risk factors for VTE, and its effect on survival in patients with advanced CCA.

During a median follow-up of 11.6 months, 118 patients (35.5%) developed VTE. The cumulative incidence of VTE was 22.4% (95% confidence interval [CI], 0.18 to 0.27) at 3 months and 32.8% (95% CI, 0.27 to 0.38) at 12 months. Major vessel invasion was an independent risk factor for VTE (hazard ratio, 2.88; 95% CI, 1.92 to 4.31; p<0.001). Patients who developed VTE during follow-up had shorter overall survival than patients who did not (11.50 months vs 15.83 months, p=0.005). In multivariable analysis, VTE (hazard ratio, 1.58; 95% CI, 1.23 to 2.02; p<0.001) was associated with poor overall survival.

Major vessel invasion is related to the occurrence of VTE in advanced CCA. The development of VTE significantly decreases the overall survival and is an important unfavorable prognostic factor for survival.

Cancer patients represent a growing population with drastically difficult care and a lowered quality of life, especially due to the heightened risk of vast complications. Thus, it is well established so far that one of the most prominent complications in individuals with cancer is venous thromboembolism. Since there are various improved methods for screening and diagnosing cancer and its complications, the incidence of cancer-associated thrombosis has been on the rise in recent years. Therefore, the high mortality and morbidity rates among these patients are not a surprise. Consequently, there is an excruciating need for understanding the mechanisms behind this complex process, as well as the imperative for adequate analysis and application of the most suitable steps for cancer-associated thrombosis prevention. There are various and numerous mechanisms offering potential answers to cancer-associated thrombosis, some of which have already been elucidated in various preclinical and clinical scenarios, yet further and more elaborate studies are crucial to understanding and preventing this complex and harsh clinical entity. This article elaborates on the growing incidence, mortality, morbidity, and risk factors of cancer-associated thrombosis while emphasizing the pathophysiological mechanisms in the light of various types of cancer in patients and summarizes the most novel therapy and prevention guidelines recommendations.

Cancer is associated with an increased risk of developing venous thromboembolism, due to its direct influence on the three pillars of Virchow's triad (e.g., compression on the blood vessels by the tumour, blood vessels invasion, and cytokine release), together with the effect of exogenous factors (such as chemotherapy, radiotherapy, surgery). In cancer patients, the risk of thrombosis at unusual sites, such as splanchnic, ovarian and renal vein thrombosis, is also increased. Abdominal vein thromboses are frequently incidental findings on abdominal imaging performed as part of the diagnostic/staging workup or the follow-up care of malignancies. There is little evidence on the management of unusual site venous thromboembolism in cancer patients since there are only a few specific recommendations; thus, the management follows the general principles of the treatment of cancer-associated deep vein thrombosis and pulmonary embolism. This narrative review summarises the latest evidence on cancer-associated abdominal vein thrombosis, i.e., thrombosis of the splanchnic, ovarian and renal veins.