Preoperative evaluation and management of patients with cancer

INTRODUCTION — The preoperative management of the patient with cancer can be complex. While patients with cancer are similar in many ways to those without cancer, the direct and indirect (systemic) effects of the cancer and the side effects of cancer therapy can influence perioperative evaluation and management. Here we will provide an overview of issues that are relevant to patients with current or past cancer. General preoperative evaluation and estimation of cardiac risk from surgery are discussed elsewhere. (See "Preoperative medical evaluation of the healthy adult patient" and "Evaluation of cardiac risk prior to noncardiac surgery".)

The preoperative medical evaluation of cancer patients should include an assessment of nutritional status, functional status, and symptom control (particularly regarding cancer-related pain) in addition to an assessment of general medical issues. The natural history of the cancer and effects of any prior chemotherapy or radiation therapy should also be considered. The short- and long-term outcomes of cancer surgery in older patients can be equivalent to those in younger patients. Treatment considerations should be based on functional status, not on chronological age [1]. (See "Comprehensive geriatric assessment for patients with cancer".)

The timing and purpose of the cancer surgery can affect perioperative evaluation. While rarely an emergency, cancer surgery is usually not elective, and therefore the amount of time available to medically optimize a patient may be limited.

There is growing recognition that a patient's physiologic fitness for surgery plays a role in reducing perioperative complications. Patients with cancer tend to be deconditioned due to numerous factors. In this situation, where patients are taking numerous insults to their overall functional status, it may be beneficial to enroll patients into a prehabilitation program as soon as a cancer diagnosis is made (figure 1).

In addition to managing coexisting medical conditions, the internist may also play an important role in coordinating the many complex levels of care provided by surgeons, medical oncologists, radiation oncologists, and others.

NUTRITION — If possible, we recommend consultation with a nutritionist for all cancer patients for whom surgery is being contemplated, regardless of time to operation.

Patients with cancer may become significantly malnourished for a variety of reasons. Eating and drinking can be impaired by pain, nausea, stomatitis, or tumors involving the oropharynx or gastrointestinal tract. Furthermore, metabolic aberrations may induce anorexia and weight loss. (See "Pathogenesis, clinical features, and assessment of cancer cachexia".)

The indiscriminate use of enteral or parenteral nutrition is not indicated in well-nourished patients or those with mild malnutrition. Although many studies have failed to demonstrate a survival benefit from preoperative nutritional support in patients undergoing cancer surgery, some have found fewer operative complications and a shorter length of hospital stay in severely malnourished patients receiving nutritional support prior to major surgery for cancers of the digestive tract and the head and neck. (See "The role of parenteral and enteral/oral nutritional support in patients with cancer", section on 'The perioperative setting'.)

On the other hand, nutrition optimization is an important component of enhanced recovery programs for surgical patients. (See "Overview of prehabilitation for surgical patients", section on 'Nutritional supplementation'.)

Thus, preoperative nutritional support for cancer patients may be reasonable in the following circumstances:

●Seven to 10 days of preoperative parenteral nutritional support for severely malnourished cancer patients prior to major visceral surgery

●One to two weeks of enteral nutritional support via a gastrostomy or jejunostomy feeding tube for severely malnourished patients prior to major head and neck cancer surgery

PAIN — Patients with cancer often require medication for pain control. Those who have been receiving opioid analgesics can be expected to have some degree of tolerance and may require dose escalation in the postoperative period to attain adequate pain control. Many patients will be receiving long-acting forms of opioids and may require conversion to short-acting forms of analgesia in the perioperative period. Conversion tables are available (table 1). (See "Assessment of cancer pain" and "Cancer pain management with opioids: Optimizing analgesia".)

As in other surgical patients, medications used for pain control in patients with cancer can have important side effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause bleeding, gastritis, and impaired renal function, and opioids can cause nausea, constipation, sedation, and delirium. (See "Prevention and management of side effects in patients receiving opioids for chronic pain".)

NSAIDs may be contraindicated in patients with thrombocytopenia from cancer or its treatment, and in patients with impaired renal function. Selective COX-2 inhibitors (eg, celecoxib) do not increase nongastrointestinal bleeding risk, but as with other NSAIDs, they do increase the risk of renal failure. (See "Overview of COX-2 selective NSAIDs" and "Cancer pain management: Use of acetaminophen and nonsteroidal anti-inflammatory drugs".)

Patients may have concerns about postoperative pain control. These should be addressed as part of the preoperative evaluation. The subject of managing acute pain in the patient on chronic opioid therapy is addressed elsewhere. (See "Management of acute pain in the patient chronically using opioids for non-cancer pain".)

CARDIOVASCULAR STATUS

Cardiac assessment — The clinician must integrate information from the history, physical examination, and electrocardiogram (ECG) in order to develop an initial estimate of perioperative cardiac risk.

An algorithmic approach to assessment of cardiac risk prior to noncardiac surgery is provided (algorithm 1). This subject is addressed elsewhere. (See "Evaluation of cardiac risk prior to noncardiac surgery".)

The following sections address specific issues that arise in patients with cancer.

Pericardial disease — Patients with cancer are at risk for malignant and non-malignant pericardial disease. Metastases to the pericardium can cause effusions, tamponade, and constrictive pericarditis. (See "Pericardial disease associated with cancer: Clinical presentation and diagnosis".)

Radiation therapy to the mediastinum can also cause constrictive pericarditis or effusions with or without tamponade. Pericarditis can present months to years after radiation treatment [2]. (See "Constrictive pericarditis: Diagnostic evaluation" and "Cardiac tamponade".)

Echocardiography should be performed if physical examination reveals findings consistent with tamponade or constriction (eg, hypotension, jugular venous distension, narrowed pulse pressure, distant heart sounds, or excessive respiratory variation in blood pressure) or if electrocardiography or imaging suggests a significant pericardial effusion.

Tamponade and constrictive pericarditis must be treated prior to surgery whenever possible. Patients with asymptomatic malignant pericardial effusions should be carefully monitored for the development of tamponade in the perioperative period.

Coronary, electrical, and valvular heart disease — Radiation therapy to fields that include the heart can lead to premature coronary heart disease (CHD). Radiation to the heart may also be associated with conduction abnormalities [3]. Therefore, younger patients who might not otherwise be expected to be at risk for CHD, but who have a history of thoracic radiation therapy for cancer, should be assessed for symptomatic CHD as part of the preoperative history and review of systems, and should have a preoperative screening ECG. (See "Cardiotoxicity of radiation therapy for breast cancer and other malignancies".)

Radiation therapy has also been associated with valvular heart disease, particularly of the mitral and aortic valves [4-6]; therefore, careful cardiac auscultation is an important part of the preoperative examination. (See "Cardiotoxicity of radiation therapy for Hodgkin lymphoma and pediatric malignancies", section on 'Valvular heart disease'.)

However, antibiotic endocarditis prophylaxis is not necessarily indicated. The 2007 American Heart Association guideline for the prevention of infective endocarditis (which was updated in 2008) narrowed the indications for bacterial endocarditis prophylaxis, compared with prior versions, in recognition of the absence of strong supportive evidence [7,8]. Antimicrobial prophylaxis is not indicated unless the patient has a history of endocarditis. Guidelines from the combined American Heart Association/American College of Cardiology and the European Society of Cardiology are largely in agreement with this approach [9,10].

Carotid artery disease — Survivors of head and neck cancers who have received radiation therapy to the neck are at risk for radiation-induced carotid stenosis and, as such, may need review and documentation of the most recent carotid ultrasound. [11]. (See "Management of late complications of head and neck cancer and its treatment", section on 'Carotid artery injury' and "Overview of approach to long-term survivors of head and neck cancer", section on 'Damage to the carotid arteries'.)

Cardiac toxicity from chemotherapy — Certain chemotherapeutic agents, particularly trastuzumab and the anthracyclines, cause significant cardiotoxicity. Dose-dependent cardiomyopathy and heart failure may be seen in patients who have received cumulative doses of over 550 mg/m² of doxorubicin or 600 mg/m² of daunorubicin [12]. Pre-existing heart disease, radiation therapy, and exposure to other chemotherapeutic agents (eg, taxanes, trastuzumab) can lower the cumulative anthracycline dose threshold at which cardiomyopathy develops. (See "Clinical manifestations, diagnosis, and treatment of anthracycline-induced cardiotoxicity" and "Risk and prevention of anthracycline cardiotoxicity" and "Cardiotoxicity of cancer chemotherapy agents other than anthracyclines, HER2-targeted agents, and fluoropyrimidines" and "Cardiotoxicity of trastuzumab and other HER2-targeted agents".)

Electrocardiographic abnormalities such as sinus tachycardia, premature atrial or ventricular contractions, nonspecific ST and T wave changes, and low-voltage QRS complexes may be early signs of cardiotoxicity, but are insensitive indicators of myocardial dysfunction. Assessment of left ventricular function before surgery should be considered in patients who are at risk for cardiomyopathy since they are at increased risk for heart failure [13]. Follow-up screening guidelines for childhood cancer survivors at risk for treatment-related heart failure are available from the Children's Oncology group and discussed in more detail elsewhere. (See "Clinical manifestations, diagnosis, and treatment of anthracycline-induced cardiotoxicity" and "Risk and prevention of anthracycline cardiotoxicity".)

Perioperative management of these patients is similar to that of other patients with heart failure who require surgery. (See "Perioperative management of heart failure in patients undergoing noncardiac surgery".)

Several chemotherapy drugs are associated with prolongation of the QT interval, particularly crizotinib, dasatinib, eribulin, ivosidenib, vemurafenib, and small molecule inhibitors of the vascular endothelial growth factor, including pazopanib, sorafenib, sunitinib, lenvatinib, and vandetanib. Patients receiving these drugs are at risk for potentially fatal arrhythmias. Risk factors for torsades de pointes include concurrent use of other drugs that can prolong the QT interval (table 2) or that slow drug metabolism due to inhibition of cytochrome P450 (CYP) enzymes, such as CYP3A4 (table 3), and electrolyte disturbances (hypokalemia, hypomagnesemia). Correction of electrolyte disturbances and avoidance of other QT-prolonging drugs or strong inhibitors of CYP3A4 should be considered in patients who are already taking a QT-prolonging drug. (See "Cardiovascular toxicities of molecularly targeted antiangiogenic agents", section on 'Prolongation of the QTc interval and cardiac arrhythmias'.)

In addition, checkpoint inhibitor immunotherapy may be associated with immune-mediated myocarditis. (See "Toxicities associated with immune checkpoint inhibitors", section on 'Cardiovascular toxicity'.)

Medication management — Recommendations for management of medications for cardiovascular risk (eg, aspirin and other antiplatelet therapy, beta-blockers) prior to noncardiac surgery are addressed in detail elsewhere. (See "Management of cardiac risk for noncardiac surgery".)

CARDIOPULMONARY MASS EFFECTS — Patients with tumors in or adjacent to the central airway are at risk for airway obstruction. Stridor, or other signs or symptoms of upper airway obstruction, should be assessed preoperatively by laryngoscopy. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults" and "Malignancy-related superior vena cava syndrome".)

Anterior and middle mediastinal masses can compress the lower airways, heart, and major vessels. This can lead to life-threatening airway obstruction or to cardiopulmonary arrest during any phase of general anesthesia [14]. Therefore, the preoperative evaluation of a patient with an anterior or middle mediastinal mass should include a detailed review for respiratory symptoms including stridor, dyspnea, wheezing, and orthopnea, and examination for evidence of neck or chest vein engorgement or swelling restricted to the face and neck. Imaging of the chest with computed tomography (CT) or magnetic resonance imaging (MRI) and echocardiography should be performed to look for central airway, cardiac, or vascular compression. Flow volume loops should also be obtained to look for central airway compromise. (See "Flow-volume loops" and "Approach to the adult patient with a mediastinal mass".)

Patients with any evidence of central airway, cardiac, or major vessel compression may require special anesthetic care and precautions, including but not limited to the following [15]:

●Fiberoptic intubation while awake

●Spontaneous ventilation throughout surgery

●Quick repositioning of the patient to the lateral, prone, or sitting position as needed

●Rigid bronchoscopy in the event of a collapsed airway

●Femoral-femoral cardiopulmonary bypass in the event of cardiovascular collapse

If surgery is being performed for the purpose of pathologic diagnosis of a mediastinal tumor that is causing compression, serious consideration should be given to alternate diagnostic strategies that would not require general anesthesia, such as lymph node biopsy or pleural or sputum cytology. However, in patients with superior vena cava syndrome, invasive procedures such as bronchoscopy and thoracoscopy can be safely carried out under general anesthesia with minimal risk of complications. (See "Malignancy-related superior vena cava syndrome", section on 'Histologic diagnosis' and "Malignancy-related superior vena cava syndrome", section on 'Urgency of diagnosis and treatment'.)

PULMONARY ISSUES

Treatment-related pulmonary toxicity — Both chemotherapy and radiation therapy can produce pulmonary toxicity, which may be intensified when they are administered concomitantly. (See "Radiation-induced lung injury" and "Pulmonary toxicity associated with systemic antineoplastic therapy: Clinical presentation, diagnosis, and treatment" and "Pulmonary toxicity associated with antineoplastic therapy: Cytotoxic agents" and "Pulmonary toxicity associated with antineoplastic therapy: Molecularly targeted agents".)

Bleomycin is associated with significant pulmonary toxicity in up to 10 percent of patients, and treatment with supplemental inhaled oxygen (as might occur during general anesthesia) may induce pulmonary toxicity several years after bleomycin treatment. For bleomycin-exposed patients who undergo subsequent surgery, supplemental oxygen during surgery should be carefully titrated and intravenous fluids should be administered sparingly to avoid volume overload and perioperative pulmonary edema. (See "Bleomycin-induced lung injury", section on 'Supplemental oxygen and future perioperative management'.)

In addition, patients undergoing checkpoint inhibitor immunotherapy may have an immune-mediated pneumonitis. (See "Toxicities associated with immune checkpoint inhibitors", section on 'Pneumonitis'.)

As with other preoperative patients who may have pulmonary deficits, patients exposed to chest radiation therapy or chemotherapy should undergo a thorough history, review of systems, physical examination, and a preoperative chest radiograph. (See "Radiation-induced lung injury", section on 'Diagnostic evaluation' and "Evaluation of perioperative pulmonary risk".)

Pulmonary function testing and measurement of oxygen saturation may be appropriate for selected patients with unexplained symptoms or abnormal examination findings. Patients at risk of postoperative pulmonary complications can benefit from special perioperative care [16]. (See "Strategies to reduce postoperative pulmonary complications in adults".)

Pleural effusions — Patients who have a pleural effusion that is large enough to be symptomatic may benefit from therapeutic thoracentesis prior to surgery. (See "Management of malignant pleural effusions".)

ENDOCRINE AND ELECTROLYTE STATUS

Glucocorticoids — Many chemotherapeutic regimens include glucocorticoids, either as a therapeutic agent or as a component of premedication to prevent chemotherapy-induced nausea and vomiting or an infusion reaction. Glucocorticoids may unmask occult diabetes or exacerbate previously controlled blood sugar levels. (See "Prevention of chemotherapy-induced nausea and vomiting in adults" and "Infusion reactions to systemic chemotherapy" and "Infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy".)

Standard recommendations for perioperative management of diabetes are available elsewhere. (See "Perioperative management of blood glucose in adults with diabetes mellitus".)

Patients who are taking 5 mg/day of prednisone or its equivalent for more than three weeks may have suppression of the hypothalamic-pituitary-adrenal axis (HPA) and may be at risk for insufficient adrenal response to the stress of surgery. (See 'Adrenal insufficiency' below.)

Hyponatremia — Preoperative hyponatremia can occur in cancer patients, and may be attributed to paraneoplastic effects of the tumor or be caused by treatments. (See "Pathophysiology and etiology of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)".)

Preoperative hyponatremia may be associated with increased risk for postoperative complications. In a cohort study of 964,263 adults undergoing major surgery at one of 200 hospitals over a five-year period, a preoperative serum sodium concentration below 135 mmol/L was associated with significantly higher postoperative 30-day mortality (adjusted odds ratio [aOR] 1.44), and significantly higher rates of major adverse cardiac events (aOR 1.21), surgical site infection (aOR 1.24), and pneumonia (aOR 1.17), as well as a longer postoperative hospitalization (by a median of one day) [17]. Because the association was actually stronger for lower-risk surgeries and for younger patients, and was independent of the time prior to surgery that the serum sodium was measured, hyponatremia is likely not the direct cause of postoperative complications, but instead a marker for impaired fluid and electrolyte homeostasis associated with chronic conditions, such as chronic heart failure.

Therefore, the best approach to the patient with preoperative hyponatremia may be to identify the underlying impairment(s), avoid exacerbating the hyponatremia with hypotonic intravenous solutions, and to closely monitor and carefully manage the patient in the postoperative period [18]. (See "Overview of the treatment of hyponatremia in adults" and "Manifestations of hyponatremia and hypernatremia in adults" and "Pathophysiology and etiology of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)".)

Hypercalcemia — Hypercalcemia is a common complication of cancer, occurring in up to 15 percent of patients [19]. Therefore, a preoperative screening serum calcium measurement is often appropriate. If hypercalcemia is identified, then the patient's hydration should be optimized and calcium levels normalized prior to surgery, if feasible. (See "Hypercalcemia of malignancy: Mechanisms" and "Treatment of hypercalcemia".)

Adrenal insufficiency — Adrenal insufficiency can occur in cancer patients as a result of adrenal suppression from chronic glucocorticoid treatment, or less commonly, from metastatic disease to both adrenal glands. Adrenal insufficiency is also described as a rare complication of immunotherapy with immune checkpoint inhibitors. (See "Toxicities associated with immune checkpoint inhibitors", section on 'Endocrinopathies'.)

The presence or absence of adrenal suppression, and therefore the need for perioperative "stress-dose" glucocorticoid coverage, can usually be predicted from the dose and duration of the patient's glucocorticoid therapy (see "Pharmacologic use of glucocorticoids" and "The management of the surgical patient taking glucocorticoids"):

●HPA axis suppression should be assumed to be present in patients taking prednisone at a dose greater than 20 mg/day for three weeks or more, and in patients with a Cushingoid appearance.

●In general, patients who have taken any dose of glucocorticoids for fewer than three weeks or who have taken chronic alternate day therapy are unlikely to have a suppressed HPA axis and should continue on their usual dose of glucocorticoids perioperatively.

●Patients on intermediate doses of glucocorticoids should undergo testing, although many clinicians prefer empiric treatment with "stress-dose" glucocorticoids.

Adrenal insufficiency should be considered in postoperative patients with hypotension that is unresponsive to intravenous fluid boluses. (See "The management of the surgical patient taking glucocorticoids" and "Treatment of adrenal insufficiency in adults".)

Hypothyroidism — Radiation therapy to the neck can cause hypothyroidism (see "Disorders that cause hypothyroidism", section on 'External neck irradiation' and "Management of late complications of head and neck cancer and its treatment", section on 'Thyroid disease'):

●In one study, 41 percent of patients with Hodgkin lymphoma who received 15 to 40 Gy to the cervical lymph nodes had hypothyroidism 20 years after treatment [20].

●In another study, almost 60 percent of patients with Hodgkin lymphoma who had received mantle field irradiation had an elevated level of thyroid stimulating hormone (TSH) 10 to 18 years after treatment [21].

●A systemic review of radiation-induced hypothyroidism in head and neck cancer patients suggests that rates range from 23 to 53 percent [22].

Hypothyroidism may also complicate long-term treatment with the tyrosine kinase inhibitors sunitinib and (to a lesser extent) sorafenib. (See "Non-cardiovascular toxicities of molecularly targeted antiangiogenic agents", section on 'Thyroid dysfunction'.)

Thyroid disorders are also common in patients undergoing immunotherapy with immune checkpoint inhibitors. (See "Toxicities associated with immune checkpoint inhibitors", section on 'Endocrinopathies'.)

Because hypothyroidism is associated with poor surgical site healing, serum TSH and free T4 concentrations should be measured prior to surgery in patients who have received more than a 10 Gy total dose to the neck or are receiving treatment with sunitinib, sorafenib, or an immune checkpoint inhibitor and who are not already being treated for hypothyroidism. Patients found to be hypothyroid should receive supplemental thyroid hormone prior to surgery. (See "Nonthyroid surgery in the patient with thyroid disease" and "Treatment of primary hypothyroidism in adults".)

Carcinoid crisis — Carcinoid crisis is a life-threatening form of carcinoid syndrome that develops in patients with serotonin-producing well-differentiated neuroendocrine tumors, primarily those arising in the gastrointestinal tract (carcinoid tumors), and may be triggered by tumor manipulation (palpation at the bedside, biopsy, or during surgery) or by induction of anesthesia. Carcinoid crisis presumably arises because of the release of an overwhelming amount of biologically active compounds, such as catecholamines, that are produced by the tumor. Symptoms include flushing, diarrhea, tachycardia, arrhythmias, hypertension or hypotension, bronchospasm, and delirium. (See "Clinical features of carcinoid syndrome".)

For patients undergoing surgery for metastatic neuroendocrine tumors who have a history of carcinoid syndrome, prophylactic preoperative use of octreotide is optional, especially in those who are already receiving a long-acting somatostatin analog, and almost certainly unnecessary in patients without carcinoid syndrome. However, octreotide should be readily available during any surgical procedure for use on an "as needed" basis in the event of hemodynamic compromise. (See "Treatment of the carcinoid syndrome", section on 'Carcinoid crisis: prevention and management'.)

Pheochromocytoma/paraganglioma surgery — Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic ganglia (sometimes referred to as extra-adrenal catecholamine-secreting paragangliomas or extra-adrenal pheochromocytomas). Some form of preoperative pharmacologic preparation is indicated for all patients with catecholamine-secreting neoplasms, including pheochromocytomas and paragangliomas. Preoperative medical therapy (typically starting with pharmacologic alpha-adrenergic followed by beta-adrenergic blockade) is aimed at controlling hypertension (including preventing a hypertensive crisis during surgery) and ensuring adequate intravascular volume prior to surgery. (See "Treatment of pheochromocytoma in adults", section on 'Medical preparation for surgery' and "Paragangliomas: Treatment of locoregional disease", section on 'Medical preparation for surgery'.)

HEMATOLOGIC STATUS

Hypercoagulability — A hypercoagulable state is common in patients with cancer, particularly those with advanced disease and primary brain tumors, and may be due to increased plasma levels of clotting factors, cytokines, or cancer procoagulant A, or to increased release of tissue plasminogen activator. (See "Cancer-associated hypercoagulable state: Causes and mechanisms".)

Hypercoagulability (leading to arterial [myocardial infarction and stroke] as well as venous thrombosis) is also a potential side effect of cancer treatment with certain drugs (eg, bevacizumab and other drugs that target the vascular endothelial growth factor, thalidomide, lenalidomide) and drug combinations (such as bleomycin, cisplatin, and vinblastine). (See "Multiple myeloma: Prevention of venous thromboembolism" and "Cardiovascular toxicities of molecularly targeted antiangiogenic agents", section on 'Arterial and venous thromboembolism' and "Treatment-related toxicity in testicular germ cell tumors", section on 'Thromboembolic events' and "Cancer-associated hypercoagulable state: Causes and mechanisms", section on 'Therapy-related factors'.)

Perioperative venous thromboembolism (VTE) is more frequent in patients with known cancer than in the general population, occurring in up to 40 percent of patients in clinical trials employing venography for diagnosis. As a result, individuals with cancer should be considered high risk for development of perioperative VTE. This increased risk is reflected in the Caprini score for VTE in surgical patients, which assigns two points for the presence of malignancy (table 4). (See "Risk and prevention of venous thromboembolism in adults with cancer", section on 'Surgical patients' and "Treatment and prevention of venous thromboembolism in patients with brain tumors", section on 'Primary prevention (VTE prophylaxis)'.)

Options for prophylaxis include mechanical methods (eg, pneumatic boots), low-dose unfractionated heparin, low-molecular-weight heparin, or fondaparinux. Specific recommendations for prophylactic treatment are available from expert groups and are discussed elsewhere. (See "Risk and prevention of venous thromboembolism in adults with cancer", section on 'Surgical patients' and "Treatment and prevention of venous thromboembolism in patients with brain tumors", section on 'Incidence and risk factors'.)

Recommendations for patients who require anticoagulation and are also thrombocytopenic are provided elsewhere. (See "Anticoagulation in individuals with thrombocytopenia", section on 'Cancer-associated VTE'.)

Anemia — Anemia is common in cancer patients, and it is frequently undertreated. Anemia is associated with impaired performance status and poorer postoperative outcomes. In addition, anemia is an independent predictor of poor prognosis in cancer patients [23-30]. Therefore, patients who have undergone cancer treatment or who are at risk for anemia due to their cancer should have a complete blood count with differential/platelets before surgery.

Iron deficiency commonly contributes to anemia in cancer patients, particularly in patients with gastrointestinal malignancies [31]. If present, iron deficiency should be treated before surgery to improve the patient's strength, endurance, and, possibly, quality of life, although it is unclear whether or not treatment will reduce perioperative transfusion requirements [32-38]. In addition to encouraging iron-rich foods (table 5), oral iron supplementation and intravenous iron replacement should be considered on an individual basis. Intravenous iron replacement has become safer and is likely to more rapidly replete iron stores than oral iron [33,39-41]. There are no guidelines regarding which patients are most likely to benefit from intravenous rather than only oral iron replacement. Additional clinical trials are needed in this area. (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults" and "Treatment of iron deficiency anemia in adults", section on 'Perioperative'.)

The optimal approach for preoperative management of anemic patients who are not iron deficient is debated. The use of erythropoietin-stimulating agents in the preoperative period may increase thrombotic complications. Such agents may also stimulate neoplastic growth, thereby increasing the risk of recurrence and of secondary cancers, such as transitional cell cancers of the urinary tract. (See "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer", section on 'Issues related to thromboembolic risk' and "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer", section on 'Should use be avoided in patients treated with curative intent?'.)

Blood transfusion might be appropriate for a severely anemic patient at risk for demand ischemia of the heart, brain, or kidneys due to the expected physiologic stress of surgery [42,43]. However, in patients undergoing cancer surgery, blood transfusions have been independently associated with worse cancer outcomes and more postoperative complications in many [30,44-50], but not all [23,51], studies. Whether this reflects an independent effect of the transfusion or anemia severe enough to necessitate transfusion is simply a marker of the severity of the underlying disease remains uncertain. Concerns about blood transfusion have also included potential immunosuppression and the risk of transmitting or inducing cancer. At least some data suggest that restricted transfusion practices may be associated with better outcomes [52,53]. If the patient receives a blood transfusion prior to surgery, the goal should be to transfuse the fewest possible units to achieve a hemoglobin level ≥7 g/dL.

Although autologous blood transfusion has the benefit of reducing the risk of an immune reaction, it is more expensive, administratively more complicated and therefore more likely to create an error in the process, and unlikely to be a consideration in cancer patients because there is seldom time before surgery to allow the patient to recover from autologous donation.

Neutropenia and lymphopenia — Patients who are myelosuppressed as a result of chemotherapy or hematologic malignancy are at increased risk of infection. The risk is higher with longer durations of neutropenia and lymphopenia. (See "Overview of neutropenic fever syndromes" and "Overview of neutropenia in children and adolescents".)

Whenever possible, nonemergency surgery should be postponed in neutropenic patients. Postoperative fever is common, and if it develops in the setting of neutropenia, aggressive diagnostic and therapeutic interventions are necessary. As discussed in more detail separately, neutropenic fever in any setting requires the prompt administration of broad spectrum antimicrobials. Even when neutropenia has resolved, patients receiving myelosuppressive chemotherapy remain relatively immunocompromised for a period of time. (See "Fever in the surgical patient" and "Treatment of neutropenic fever syndromes in adults with hematologic malignancies and hematopoietic cell transplant recipients (high-risk patients)" and "Treatment and prevention of neutropenic fever syndromes in adult cancer patients at low risk for complications".)

Patients with hematologic cancers such as chronic lymphocytic leukemia have abnormal cellular and humoral-mediated immune responses due to defects in immune effector cells, and they are predisposed to infection, particularly if they are treated with purine analogs (eg, fludarabine), chlorambucil, and alemtuzumab. These issues should be considered in the perioperative period. (See "Risk of infections in patients with chronic lymphocytic leukemia" and "Prevention of infections in patients with chronic lymphocytic leukemia".)

Thrombocytopenia — Thrombocytopenia can occur in cancer patients either as a result of the malignancy or from treatment. In general, a platelet count of at least 50,000/microL is adequate for most surgical procedures, but the specific procedure and the platelet function must also be considered. Consider postponing surgery until the platelet count has recovered if the thrombocytopenia is treatment related.

Drugs that can interfere with platelet function (aspirin, clopidogrel, nonsteroidal anti-inflammatory agents) should be discontinued long enough prior to surgery to allow for adequate recovery of platelet function. This period will depend on the specific antiplatelet agent, the surgery, and the patient's other clinical conditions and medications. (See "Preoperative assessment of bleeding risk" and "Platelet transfusion: Indications, ordering, and associated risks", section on 'Platelet function disorders'.)

NEUROLOGIC STATUS

Paraneoplastic syndromes — Paraneoplastic syndromes that affect neuromuscular function are relatively rare, but are of particular concern in the perioperative period because treatment with anesthetic agents can exacerbate neuromuscular dysfunction, leading to respiratory failure or delayed extubation. Although a wide variety of tumor types may be responsible, many of these neuromuscular paraneoplastic syndromes arise in the setting of small cell lung cancer. Treatment of the cancer may occasionally mitigate these symptoms. (See "Paraneoplastic syndromes affecting spinal cord, peripheral nerve, and muscle".)

Screening for brain metastases — Routine imaging of the central nervous system is not mandatory in patients with cancer prior to surgery. However, radiographic imaging of the brain may be warranted in the setting of unexplained symptoms referable to the central nervous system (CNS). Furthermore, if prophylactic anticoagulation is planned, radiographic screening for brain metastases (preferably with magnetic resonance imaging [MRI]) should be pursued in those patients whose tumors have a propensity to spread to the CNS and spontaneously bleed, including melanoma, small cell carcinoma of the lung, choriocarcinoma, renal cell, breast, adenocarcinoma of the lung, or thyroid cancer. Patients with other systemic cancers should also be imaged if there are any symptoms suggesting brain metastasis (eg, headache, mental status changes, seizures, other neurologic symptoms). The presence of untreated CNS metastases represents a relative contraindication to systemic anticoagulation in this setting, while active intracranial bleeding is an absolute contraindication. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients" and "Treatment and prevention of venous thromboembolism in patients with brain tumors", section on 'Pre-anticoagulation risk assessment'.)

Stroke risk in patients undergoing neck irradiation — Ischemic stroke can be a late complication of neck irradiation, with multiple factors contributing to this risk, including carotid artery stenosis, increased deposition of plaque, and pre-existing risk factors for cerebrovascular disease, such as smoking. A high index of suspicion for carotid artery disease should be maintained in patients who have received neck irradiation, particularly in conjunction with chemotherapy for head and neck cancer. (See "Management of late complications of head and neck cancer and its treatment", section on 'Carotid artery injury'.)

OTHER EFFECTS OF CHEMOTHERAPY

Hepatotoxicity — Several chemotherapeutic agents are potentially hepatotoxic. Although most hepatotoxic effects are transient, if signs or symptoms suggest the development of hepatotoxicity, then measure the prothrombin time as a test of adequate hepatic synthetic function prior to surgery. (See "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Conventional cytotoxic agents".)

Reactivation of viral hepatitis (particularly hepatitis B virus [HBV]) is a potential complication of myelosuppressive chemotherapy, particularly in patients receiving rituximab and ofatumumab. Patients who are positive for HBV surface antigen or for antibodies against HBV core antigen (anti-HBc) should have liver biochemical tests measured prior to surgery. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy".)

Nephrotoxicity — Several chemotherapeutic agents are potentially nephrotoxic, particularly cisplatin. For virtually all patients who have recently undergone chemotherapy, measure serum blood urea nitrogen, creatinine, and electrolyte concentrations before surgery. (See "Cisplatin nephrotoxicity" and "Nephrotoxicity of chemotherapy and other cytotoxic agents" and "Nephrotoxicity of molecularly targeted agents and immunotherapy".)

Wound healing — Impaired wound healing is a well-described complication of certain chemotherapy agents, particularly antiangiogenic agents targeting the vascular endothelial growth factor. Because of the long half-life of bevacizumab (20 days), it is generally recommended that at least 28 days (preferably six to eight weeks) should elapse between a dose of bevacizumab and major surgery when feasible. Because of their shorter half-lives, some suggest that orally active small molecular antiangiogenic tyrosine kinase inhibitors (eg, sunitinib, sorafenib, pazopanib, vandetanib, cabozantinib) be stopped for at least one week (48 hours for agents with a short half-life such as axitinib) before surgery and not reinitiated until adequate wound healing has occurred. (See "Non-cardiovascular toxicities of molecularly targeted antiangiogenic agents", section on 'Delayed wound healing' and "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy", section on 'Issues related to bevacizumab'.)

IMMUNIZATIONS PRIOR TO SPLENECTOMY — The spleen is the dominant site for the production of immunoglobulin M (IgM) antibodies required for opsonizing encapsulated pathogens. Thus, for patients in whom concomitant splenectomy is anticipated (eg, during resection of a distal pancreatic cancer), patients should undergo appropriately timed preoperative immunization against Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae type b. If vaccination was not possible prior to surgery, or unanticipated splenectomy was performed, the patient should be vaccinated postoperatively. Vaccination recommendations for asplenic patients are presented elsewhere (table 6). (See "Prevention of infection in patients with impaired splenic function" and "Elective (diagnostic or therapeutic) splenectomy", section on 'Vaccinations'.)

SUMMARY — The surgical risk for most cancer patients is comparable to that of patients without cancer and should be managed similarly. However, the following should be considered in the preoperative evaluation of patients with cancer:

●Nutrition – Optimize nutritional status prior to surgery. For all cancer patients for whom surgery is being contemplated, regardless of time to operation, consultation with a nutritionist should be obtained if possible. (See 'Nutrition' above.)

●Pain control – Address postoperative pain control during the preoperative evaluation of patients who chronically take opioids because these patients are likely to require greater than usual doses of medication for postoperative pain control. (See 'Pain' above.)

●Cardiopulmonary issues

•Patients who have received radiation therapy (RT) to fields that include the heart are at increased risk for premature coronary artery disease, cardiac conduction disease, and valvular heart disease, and should be screened for heart disease clinically and with a 12-lead electrocardiogram (ECG). Obtain additional cardiac testing if indicated. (See 'Cardiovascular status' above.)

•Patients who have received anthracycline or trastuzumab chemotherapy are at risk for heart failure, and should be screened for heart failure clinically and with a 12-lead ECG. Obtain additional cardiac testing if indicated. (See 'Cardiac toxicity from chemotherapy' above.)

•Several chemotherapy drugs prolong the QT interval, which may increase the risk for potentially fatal arrhythmias (table 2). Correct electrolyte abnormalities preoperatively and avoid other QT-prolonging drugs or strong inhibitors of cytochrome P450 3A4 (CYP3A4) (table 3).

•Patients with symptomatic pericardial effusions, cardiac tamponade, or constrictive pericarditis should be managed prior to surgery. (See 'Pericardial disease' above.)

•Patients with mass lesions that could compromise the upper central airway are at increased risk for perioperative respiratory failure, and should have airway patency assessed preoperatively. (See 'Cardiopulmonary mass effects' above.)

Patients with a mediastinal mass are also at increased risk for perioperative cardiopulmonary failure. Before surgery, obtain chest cross-sectional imaging echocardiography, and flow-volume loop measurements. Those with evidence of cardiac, vascular, or airway compression require special perioperative management. (See 'Cardiopulmonary mass effects' above.)

•Treatment with supplemental inhaled oxygen several years after bleomycin therapy can also cause lung damage. Before surgery, carefully assess the pulmonary function of patients who have ever received bleomycin, and minimize the use of supplemental inhaled oxygen and intravenous fluids both during and after surgery. (See "Strategies to reduce postoperative pulmonary complications in adults".)

●Endocrine and electrolyte issues

•If time and facilities permit, assess patients at risk for adrenal insufficiency with measurement of an early morning serum cortisol concentration or an adrenocorticotropin stimulation test. Otherwise, consider treating high-risk patients with an empiric perioperative stress-dose glucocorticoid. (See 'Adrenal insufficiency' above and "The management of the surgical patient taking glucocorticoids" and "Treatment of adrenal insufficiency in adults".)

•Measure serum thyroid stimulating hormone and free T4 concentrations in patients who have ever received neck RT or who have received sunitinib or sorafenib for more than a few weeks, and correct hypothyroidism prior to surgery. Maintain a high clinical index of suspicion for radiation-induced carotid artery stenosis. (See 'Hypothyroidism' above and 'Stroke risk in patients undergoing neck irradiation' above.)

•Preoperative pharmacologic preparation is indicated for all patients with catecholamine-secreting neoplasms, such as well-differentiated metastatic neuroendocrine neoplasms of the gastrointestinal tract (carcinoids) or pheochromocytoma/paraganglioma. (See 'Carcinoid crisis' above and 'Pheochromocytoma/paraganglioma surgery' above.)

•Before surgery, screen all patients who have systemic malignancy with serum blood urea nitrogen, creatinine, sodium, and calcium concentrations, and with a complete blood count. Preoperative hyponatremia is associated with worse outcomes; avoid hypotonic intravenous solutions, and closely monitor the patient in the postoperative period. (See 'Hyponatremia' above.)

•Patients with cancer often have a hypercoagulable state (which may be due to the cancer or its treatment), and they are at high risk for perioperative venous thromboembolism; prophylaxis is warranted for most patients in the perioperative period. (See 'Hypercoagulability' above.)

●Hematologic issues

•When feasible, postpone surgery to allow recovery from chemotherapy-induced neutropenia and thrombocytopenia. (See 'Neutropenia and lymphopenia' above.)

•If present, treat iron deficiency before surgery. Depending on the cause and the timing of surgery, it might be necessary to give the patient a blood transfusion to at least achieve a hemoglobin level of 7 g/dL, although blood-sparing techniques are preferable. (See 'Anemia' above.)

●Other

•Reactivation of viral hepatitis (particularly hepatitis B virus [HBV]) is a potential complication of myelosuppressive chemotherapy, particularly rituximab and ofatumumab. Patients who are positive for HBV surface antigen or for antibodies against HBV core antigen should have liver biochemical tests measured prior to surgery. (See 'Hepatotoxicity' above.)

•Impaired wound healing is a well-described complication of certain chemotherapy agents, particularly antiangiogenic agents At least 28 days (preferably six to eight weeks) should elapse between a dose of bevacizumab and major surgery, when feasible. Orally active small molecular antiangiogenic tyrosine kinase inhibitors should be stopped at least one week before surgery. (See 'Wound healing' above.)

•For patients in whom concomitant splenectomy is anticipated (eg, resection of a distal pancreatic cancer), preoperative immunization against S. pneumoniae (pneumococcus), N. meningitidis (meningococcus), and H. influenzae type b is indicated. (See 'Immunizations prior to splenectomy' above.)