Stomach Cancer And Stroke: Is There A Link?

Cancer-related stroke is an emerging subtype of ischemic stroke with unique pathomechanisms. Systemic cancer and ischemic stroke are common conditions and two of the most frequent causes of death among the elderly. The association between cancer and stroke has been reported worldwide. Stroke causes severe disability for cancer patients, while cancer increases the risk of stroke.

The risk factors for stroke in cancer patients are under investigation. Nguyen and DeAngelis systematically reviewed the literature of types of cancer patients with comorbid stroke, including data from the American Cancer Society, the Danish Hospital Discharge Registry, University of Massachusetts Medical Center, and Memorial Sloan Kettering Cancer Center. The authors report that patients with cancer are subject to the same stroke risk factors as the general population, and atherosclerosis remains the most common cause of stroke in cancer patients.

Further, they note that if stroke in cancer patients was caused by the same pathophysiological mechanisms as in the general population, the distribution of stroke should be identical to the population at large, and there would be a distribution of primary neoplasms proportional to the most common cancers (i.e., lung, breast, and prostate). In their review, there was a relatively wide variability of stroke among tumor types, e.g., data from Denmark and Massachusetts revealed comorbid stroke in 28 and 11% of gastrointestinal cancer patients, respectively.

Cancer-related stroke: An emerging subtype of ischemic stroke with unique pathomechanisms

Cancer is a leading cause of death and disability worldwide, and its incidence is increasing, particularly in younger age groups. Cancer and stroke share risk factors (such as smoking and obesity) and treatment of cancer can increase the risk of stroke (e.g., accelerated atherosclerosis after radiation therapy). The risk of stroke varies by cancer type and is highest with cancers most linked to venous thromboembolism risk, particularly lung and pancreatic cancer.

Cancer and Embolic Stroke of Undetermined Source

Cancer-associated stroke is an emerging subtype of ischemic stroke with unique pathomechanisms. It is a definable disease entity, as unique characteristics of this condition were reported among studies from different populations.

The risk of ischemic stroke increases during the first few months (up to 1 year) after cancer diagnosis. In a recent large population study, the increased risk of arterial thromboembolic events begins 5 months before cancer is officially diagnosed and peaks 1 month prior to the diagnosis.

The controversies regarding the characteristics of stroke in patients with cancer may be due to the involvement of both cancer-unrelated (by conventional stroke mechanisms) and cancer-related mechanisms in the development of stroke in cancer patients.

The underlying causes for the development of a stroke in cancer patients differ from those of non-cancer patients, and are associated with the cancer itself, as well as with the type of treatment.

In general, hypercoagulopathy or other coagulation disorders are most often related to the development of ischemic/embolic stroke.

Cancer and its treatment may accelerate conventional stroke mechanisms (i.e., atherosclerosis, small vessel disease, and cardiac thrombus).

In addition, active cancer and chemotherapy may enhance thrombin generation causing stroke related to coagulopathy.

Patients with stroke due to cancer-related coagulopathy showed the characteristics findings of etiologic workups, D-dimer levels, and infarct patterns.

Cancer and stroke: A complicated relationship

Cancer and stroke are two of the most frequent causes of death among the elderly. The association between cancer and stroke has been reported worldwide. Stroke causes severe disability for cancer patients, while cancer increases the risk of stroke.

The relationship between cancer and stroke

The risk of stroke in cancer patients is more than twice that of the general population and rises with longer follow-up time. The relative risk of fatal stroke, vs the general population, is highest in those with cancers of the brain and the upper gastrointestinal tract. The plurality of strokes occurs in patients >40 years of age with cancers of the prostate, breast, and colorectum. Patients of any age diagnosed with brain tumors and lymphomas are at risk for stroke throughout life.

Pathophysiology of ESUS with cancer

The potential underlying mechanisms of cancer-associated ESUS are broad and various heterogeneous pathophysiologies require consideration. These include mechanisms that develop from cancer-mediated hypercoagulability, an entity that increases the risk for not just venous thromboembolism, but also arterial events.

Clinical characteristics of cancer-associated ESUS

First, although conflicting data exist, most studies suggest that apart from smoking, patients with cancer-associated ESUS have fewer traditional stroke risk factors than those without cancer. Second, their strokes tend to be more severe, although their stroke severity scales can be confounded by preexisting disability from cancer. Third, cancer-related ESUS most commonly occurs with disseminated solid tumor adenocarcinomas; however, all cancer types, solid or hematologic, stage 1 through stage 4, are associated with an increased risk of ischemic stroke. Fourth, most will have increased D-dimer and inflammatory markers, although this profile is typical of cancer in general and with other stroke mechanisms (eg, cardioembolic). Fifth, anywhere from 30% to 70% demonstrate embolic-appearing infarcts in bilateral anterior and posterior circulations. Sixth, they face high rates of recurrent stroke, recurrent thromboembolism, early neurological deterioration, and mortality.

Treatment considerations for cancer-associated ESUS

There are strong theoretical considerations for anticoagulating patients with cancer and ESUS, and this is often empirically performed in practice, although data supporting this strategy are limited. Among 29 patients with cancer-related stroke with serial D-dimer measurements during their stroke hospitalization, anticoagulant use was associated with reduction in D-dimer, a surrogate for recurrent stroke risk. In the prospective OASIS-Cancer study, patients with cancer and stroke whose D-dimer decreased with anticoagulation had improved 1-year survival. In the pilot trial of TEACH (Trial of Enoxaparin Versus Aspirin in Patients With Cancer and Stroke), we conducted the only multicenter randomized clinical trial comparing anticoagulant therapy to antiplatelet therapy in patients with active cancer and acute ischemic stroke (n=20, 75% ESUS).

Cancer-associated stroke: Pathophysiology, detection and management (Review)

Cancer-associated strokes are a serious concern, with patients facing a high risk of mortality and recurrent stroke. The occurrence of cancer-associated strokes is typically seen in patients with active cancer and is characterised by multiple infarctions across multiple vascular territories, markedly elevated blood D-dimer levels, and metastasis. The presence of cardiac vegetations on echocardiography is a strong indicator of a cancer-associated stroke.

The risk of stroke in cancer patients is twice that of the general population, with the highest relative risk in those with brain and upper gastrointestinal tract cancers. The incidence of stroke is also high in patients over 40 with cancers of the prostate, breast, and colorectum. Patients of any age diagnosed with brain tumours are at risk of stroke throughout their lives. Lung/respiratory tract cancer has one of the strongest associations with death during a follow-up of patients under 49 years of age with ischemic stroke.

In addition, several tumour types have a relatively wide variability of stroke. For instance, data from Denmark and Massachusetts revealed comorbid stroke in 28 and 11% of gastrointestinal cancer patients, respectively. Cancers of the small intestine, pancreas, liver, kidneys, nervous system, thyroid gland, and endocrine glands, among others, also present a >2-fold higher risk of ischemic stroke in the first 6 months post-diagnosis.

The most common cause of stroke in cancer patients is NBTE, particularly in mucin-producing carcinomas of the lung or gastrointestinal tract. Thrombocytopenia may also be a contributing factor, resulting from either haematological cancers or chemotherapy.

Cancer and Embolic Stroke of Undetermined Source

Cancer-associated ESUS is a definable disease entity, as unique characteristics of this condition were reported among studies from different populations. Patients with stroke due to cancer-related coagulopathy showed the characteristics findings of etiologic workups, D-dimer levels, and infarct patterns.

In patients with stroke due to cancer-related coagulopathy, the principal lesion patterns on DWI are multiple small cortical lesions extending to multiple vascular territories and multi-staged acute and subacute ischemic lesions. The level of D-dimer, a plasmin-derived degradation product of cross-linked fibrin, is a direct measure of activated coagulation. In cancer-related stroke, hypercoagulability as assessed by serial D-dimer levels was associated with early neurological deterioration, stroke recurrence and poor survival after stroke in patients with active cancer, suggesting that D-dimer level can be used in monitoring the effect of anticoagulation therapy.

The Optimal Anticoagulation Strategy In Stroke related to cancer (OASIS-Cancer) study is ongoing to evaluate biological markers for intravascular coagulopathy causing stroke and for monitoring the effects of anticoagulation therapy in patients with active cancer and stroke.

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