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Best Practice & Research Clinical Anaesthesiology 27 (2013) 465480

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Best Practice & Research Clinical


Anaesthesiology
journal homepage: www.elsevier.com/locate/bean

Perioperative assessment of the cancer patient


Sunil Kumar Sahai, MD, FAAP, FACP, Medical Director,
Associate Professor a, b, *
a

The Internal Medicine Perioperative Assessment Center, The University of Texas MD Anderson Cancer
Center, Houston, TX, USA
b
Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston,
TX, USA

Keywords:
cancer
perioperative medicine
chemotherapy
radiation therapy
surgery
pre-anaesthesia clinic
medical evaluation

The perioperative evaluation of patients with cancer differs from


that of other patients in that the former may have received prior
chemotherapy or radiation therapy. These cancer treatments have
a wide range of side effects and complications that may affect
patients perioperative risks. The perioperative specialist who
evaluates the cancer patient prior to surgery must be familiar with
the effects of these treatments and their consequences for the
major organ systems. The perioperative specialist must also be
familiar with the natural history of cancer and have a basic understanding of how cancer affects the body. In this article, we review the perioperative concerns that are specic to the patient
with cancer.
! 2013 Elsevier Ltd. All rights reserved.

Introduction
It is estimated that in 2015, cancer will have a worldwide incidence of 15 million people and cause 9
million deaths [1]. Many of these people with cancer will need to undergo diagnostic, supportive,
curative or palliative surgical procedures. As cancer treatment evolves and survivors live longer, we will
face an increase in the number of survivors with new primary tumours or recurrences that require
surgical resection. These tumours may or may not be related to prior treatment. Cancer patients may
also undergo surgery that is unrelated to their cancer history. Thus, it is imperative that clinicians

* Department of General Internal Medicine, Unit 1465, The University of Texas MD Anderson Cancer Center, 1400 Pressler
Street, Houston, TX 77030, USA. Tel.: 1 713 745 4516; Fax: 1 713 794 1852.
E-mail address: ssahai@mdanderson.org.
1521-6896/$ see front matter ! 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bpa.2013.10.001

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S.K. Sahai / Best Practice & Research Clinical Anaesthesiology 27 (2013) 465480

recognise the unique challenges of perioperative assessment in patients with cancer and cancer
survivors.
Whereas surgery traditionally addresses organ-level dysfunctions that can be seen and can be
treated with a scalpel and sutures (fractures, vascular disease, bowel obstructions, etc.), the illness of a
cancer patient and neo-adjuvant treatment involve not only organ-level changes but also change at the
cellular and genetic levels. Traditional perioperative guidelines frequently describe surgeries as either
emergent or elective and thus advise physicians to proceed with medical evaluation along those lines;
for patients with cancer, however, surgery is rarely emergent, most often urgent and rarely elective.
Previous cancer therapies may cause or exacerbate medical co-morbidities, but delaying surgery to
optimise medical issues may allow the cancer to progress or metastasise. Therefore, the perioperative
evaluation and management of co-morbidities must take into account the natural history of the cancer.
Effective communication between all members of the surgical, oncologic, medical and anaesthesia
teams is necessary [2,3].
For all patients, regardless of diagnosis, a thorough medical evaluation is the primary source of
information for all care teams involved. Most cancer patients presenting for perioperative evaluation
have sufcient documentation of prior surgical procedures; however, complete documentation of the
presence and severity of co-morbidities and prior chemotherapy or radiation treatment regimens is
frequently absent. A careful history and physical examination accompanied by evidence-based targeted
testing before surgery are needed to reduce the likelihood of adverse perioperative outcomes [4,5].
Unfortunately, the literature lacks denitive evidence-based guidelines regarding many aspects of the
perioperative evaluation of cancer patients. This article aims to provide recommendations for the
perioperative assessment of patients with cancer who have undergone previous or neo-adjuvant
cancer therapy. Many of the following recommendations are based on extrapolation from nononcologic surgery and on practice patterns that have developed at our institution over time.
Preoperative evaluation
History and co-morbidities
In our practice, we assume nothing about a patient before beginning the evaluation. Despite prior
documentation by previous surgical and oncologic teams, we start from the beginning and perform a
comprehensive review of the patients medical history. In evaluating patients with cancer, particular
attention to medical co-morbidities is warranted; co-morbidities such as diabetes, cardiovascular
disease, pulmonary disease, cerebrovascular disease and renal disease are explored in depth. We clarify
and document details of cardiac interventions, especially with regard to bare metal and drug-eluting
cardiac stents. We document the presence of implantable devices such as pacemakers, debrillators
and pain pumps and the long-term use of anticoagulants or anti-platelet agents as well as the reasons
for such therapy. Cancer patients with current or previous venous thrombo-embolism are identied
and educated about the postoperative risk of recurrent thrombosis. We also clarify the details of any
previous major illnesses and hospitalisations. Each patients current medication list is compared with
the labels on the medications the patient is taking to ensure accuracy, prevent inadvertent omission of
combination medications and ensure compliance with medical therapy. When requesting records of
prior studies and interventions, we seek the primary source documents (e.g., an angiogram or operative report) rather than second- or third-party clinical notes, which may contain inaccuracies. In
addition, the physicians who supply us with patients medical records are sent copies of those patients
completed perioperative evaluations, as they are likely to see those patients in a post-discharge setting.
The organ systems of greatest concern that are identied during the history are then targeted during
the physical examination.
During the physical examination, particular attention is directed at those ndings that may
complicate surgery. For the patient who has a malignancy in the head and neck area, it is prudent to
thoroughly examine the airway and to anticipate the need for possible tracheostomy [6]. Head and
neck tumours may cause airway obstruction and recurrent laryngeal nerve damage. These tumours
may also result in superior vena cava obstruction, which may be exacerbated by positive pressure
ventilation during surgery. Additionally, for the patient who has received neo-adjuvant radiation

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467

therapy to the head and neck area, the anaesthetic team should have a high clinical suspicion for a
difcult airway [7,8]. Mediastinal masses may also cause compression of vascular and respiratory organs, and as such, induction of anaesthesia may result in a catastrophic reduction of cardiac output.
Tumours that present as massive abdominal masses also may compromise surrounding organs. Sarcomas and ovarian cancer may present with diaphragmatic splinting and massive ascites. Largevolume ascites will affect ventilation during surgery, and it may be prudent to perform a therapeutic paracentesis prior to surgery to relieve symptomology and prevent signicant volume shifts during
surgery.
Functional status
Chemotherapy and radiation therapy take a toll on functional ability; hence, particular attention is
directed to a patients functional status in the context of prior cancer treatments. For patients who have
undergone previous or neo-adjuvant therapy, a key question is whether they experienced any decline
of functional status and exercise tolerance before and during treatment. Additionally, the recovery of
functional status and exercise tolerance after neo-adjuvant treatment is assessed. These patients are
also asked about any side effects experienced during chemotherapy or radiation therapy, particularly
cardiovascular side effects.
The Eastern Cooperative Oncology Group (ECOG) performance status scale is among the most
widely used in cancer care, but its perioperative implications are not clear [9]. Evidence does show that
a variety of co-morbidity indices, including ECOG status, can be used to predict perioperative mortality
and morbidity in patients undergoing cystectomy, but further study is indicated [10].
Geriatrics
Geriatric patients with cancer require further discussion. Cancer has always affected older people
more often and to a greater extent than younger people. Additionally, older patients tend to have more
co-morbidities. Numerous studies have shown that advanced age in itself should not be considered a
risk factor for poor perioperative outcomes; co-morbidities, frailty and polypharmacy pose greater
perioperative challenges [1117]. Geriatric patients with cancer need to be educated about quality-oflife issues in the postoperative period, including the risk of delirium.
The long-term consequences of chemobrain, or chemotherapy-induced cognitive dysfunction, in
the elderly are still being debated. While cognitive dysfunction in the perioperative period is most
prevalent in the elderly, it is unknown whether chemobrain affects long-term prognosis in cancer
patients [18] or whether the presence of chemobrain before surgery affects the likelihood or severity of
postoperative delirium.
Patients are often concerned about the risk of immediate complications from surgery in light of the
geriatric patients life expectancy [19]. Although some elderly patients may have a chance at a curative
resection, the immediate perioperative risks may not be preferable to the natural progression of the
cancer. Family members and caregivers frequently underestimate the psychosocial and nancial burdens of taking care of a patient with cancer, especially a patient who experiences complications after
surgery [20].
Education and prevention
The preoperative evaluation is also an opportunity to educate patients about the importance of
managing their co-morbidities while being treated for cancer; emerging evidence shows that optimal
management of diabetes and other medical conditions may prevent cancer recurrence and prolong life
[21]. We also educate patients about the importance of exercise and other physical activity with regard
to not only surgical recovery but also overall survivorship [22,23]. To reduce the risks of perioperative
mortality and morbidity, we recommend that every patient start an exercise regimen prior to surgery.
The regimen may consist of simply walking daily, strength training with isometric rubber bands or
stretching exercises such as yoga. As in pulmonary medicine, the concept of prehabilitation prior to

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surgery is becoming more prevalent [2427]. Additionally, if needed, education is given on the
importance of stopping the use of tobacco products.
Adverse effects of previous cancer treatments
When evaluating a patient with cancer who presents for surgery, it is important to document any
prior treatment for cancer and its proximity to the time of surgery. Cancer survivors who have new
primary tumours years after their initial cancer may have long-term side effects that affect perioperative planning. Additionally, those who have just completed neo-adjuvant chemotherapy or radiation
therapy may have acute side effects that need to be addressed prior to surgery. Clinicians need to
identify any side effects from treatment that may affect perioperative outcomes. To date, over 100
chemotherapeutic drugs are available; fortunately, the side effects of chemotherapy tend to be similar
within the major classes of drugs (Table 1). However, these drugs are frequently combined in various
ways (Table 2), increasing the likelihood of multiple side effects. In the following sections, we will
review the major side effects of chemotherapy and radiation therapy.
Cardiovascular side effects
A primary concern for patients who have been treated for cancer is the presence of cardiovascular
complications in the perioperative period. In general, we follow the American College of Cardiology/
American Heart Association 2007 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery [28,29]. When assessing a patient with suspected cardiovascular disease, questions about
fatigue and shortness of breath are frequently asked. In a patient with cancer, fatigue and shortness of
breath may be due to pre-existing cardiovascular disease, chemotherapy-induced or radiation-induced
cardiovascular disease or simply fatigue and deconditioning from the cancer and its treatment; the
perioperative consultant needs to determine which of these aetiologies corresponds to the patients
symptoms. With the growing number of chemotherapeutic drugs that have cardiovascular side effects
(Table 3), it is helpful to approach the patient according to the schema in Fig. 1. Whether cardiovascular
symptoms are independent of or due to the chemotherapy needs to be determined on the basis of the
patients history. In certain situations, an infusion of chemotherapy that elicits chest pain due to coronary vasospasm may unmask signicant underlying coronary artery disease. Additionally, the risk of
developing a treatment-related cardiac toxicity depends on pre-existing cardiac factors, drug dosage
and the use of combination therapy and/or radiation therapy [30].
Radiation therapy also may affect the cardiovascular system in a variety of ways. Early complications
such as rash, itching and hair loss occur within 90 days of radiation therapy, affect tissues with high
cellular turnover (skin/mucosa) and tend to be transient, whereas late complications occur after 90
days and tend to be brotic in nature and irreversible. For the heart, late complications of radiation to
the mediastinum may include pericarditis, accelerated coronary artery disease, restrictive cardiomyopathy, valvular stenosis and conduction system defects [31,32]. Additionally, radiation to the head and
neck area may induce carotid stenosis, increasing the risk of perioperative stroke [33].
The use of vascular endothelial growth factor inhibitors such as monoclonal antibodies and tyrosine
kinase inhibitors in cancer therapy has raised concerns about their perioperative cardiovascular
complications, especially hypertension [34]. Vascular endothelial growth factor-induced hypertension
may be dramatic and difcult to manage. Generally, this hypertension needs to be treated with
angiotensin-converting enzyme inhibitors and calcium channel blockers [34].
During the physical examination, cardiovascular assessment begins with auscultation of the carotid
arteries followed by assessment of the heart and pulse. If bruits are heard, patients are asked about
prior Doppler ultrasonography or carotid ndings, and those records are acquired and documented. For
an asymptomatic patient with carotid bruits, we may elect to order Doppler ultrasonography.
Currently, controversy exists over how to manage severe carotid stenosis before surgery [3537]. At our
institution, we consult with vascular surgeons and then arrive at a decision once all of the care providers have presented their perspectives. Generally speaking, vessels with severe-to-critical radiationinduced carotid stenosis are revascularised prior to oncologic surgery if the critical stenosis lies within
the anticipated surgical eld or if we anticipate large intra-operative uid shifts that may adversely

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469

Table 1
Representative chemotherapy agents and perioperative concerns.
Class
Alkylating agent
Nitrosourea
Methylating agent

Agent

Common perioperative concerns

Carmustine
Lomustine
Procarbazine
Dacarbazine

Pulmonary brosis

Temozolomide
Platinum

Cisplatin
Carboplatin
Oxaliplatin

Nitrogen mustard

Cyclophosphamide
Ifosfamide

Melphalan
Chlorambucil
Antimetabolite
Anthracycline/anthraquinolone

Antitumour antibiotic:
natural product
Antimetabolite:
pyrimidine analogue

Antimetabolite:
purine analogue

Doxorubicin
Daunorubicin
Epirubicin
Idarubicin
Mitoxantrone
Valrubicin
Bleomycin
Mitomycin C
Capecitabine
Cytarabine (Ara-C)
5-Fluorouracil
Gemcitabine
Thioguanine
Pentostatin

Cladribine

Fludarabine

Mercaptopurine

Oedema, tachycardia
Hepatic necrosis and occlusion
Hepatic vein thrombosis
Seizure and gait abnormality
Peripheral oedema
Acute renal tubular necrosis
Magnesium wasting
Peripheral sensory neuropathy
Paraesthesia
Ototoxicity
Pericarditis
Pericardial effusions
Pulmonary brosis
Hemorrhagic cystitis
Water retention
Anaemia
SIADH
SIADH
Seizures
Cardiomyopathy
Electrocardiogram changes

Pulmonary brosis
Pneumonitis
Pulmonary hypertension
Myocardial ischaemia/infarction
Coronary vasospasm
Oedema
Proteinuria
Hepatotoxicity
Pulmonary toxicity
Deep vein thrombophlebitis
Chest pain
Oedema
Atrioventricular block
Arrhythmia
Hypotension or hypertension
Thrombosis
Tachycardia
Acute renal failure
Tumour lysis syndrome
Cerebrovascular
accident/transient
ischaemic attack
Angina
Thrombosis
Arrhythmia
Congestive heart failure
Acute renal failure
Tumour lysis syndrome
Intrahepatic cholestasis and focal
centrilobular necrosis
(continued on next page)

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Table 1 (continued )
Class

Agent

Common perioperative concerns

Antimetabolite: folate antagonist

Methotrexate

Substituted urea

Hydroxyurea

Elevated liver enzyme levels


Pulmonary oedema
Pleural effusions
Encephalopathy
Meningismus
Myelosuppression
Seizure
Oedema

Microtubule assembly inhibitor


Taxane

Alkaloid

Paclitaxel
Docetaxel
Vinblastine

Vincristine

Biologic agent
Monoclonal antibody

Alemtuzumab
Bevacizumab

Cetuximab
Rituximab
Trastuzumab

Daclizumab

Ibritumomab
Palivizumab
Muromonab-CD3
Biologic response modulator
Interleukin

Aldesleukin
Denileukin diftitox

Interferon

Interferon alfa-2b
Interferon alfacon-1

Peginterferon alfa-2a
Peginterferon alfa-2b

Peripheral neuropathy
Bradycardia
Autonomic dysfunction
Hypertension
Angina
Cerebrovascular accident
Coronary ischaemia
Electrocardiographic abnormalities
Raynaud phenomenon
SIADH
Gastrointestinal bleeding
Paraesthesia
Recurrent laryngeal nerve palsy
Autonomic dysfunction
Orthostasis
Hypotension and hypertension
SIADH
Dysrhythmia/tachycardia/supraventricular tachycardia
Hypotension or hypertension
Pulmonary bleeding
Hypertension
Thromboembolic events
Cardiopulmonary arrest
Tumour lysis syndrome
Electrolyte abnormality
Cardiomyopathy
Thrombus formation
Pulmonary toxicity
Tachycardia
Hypertension
Chest pain
Hypertension and hypotension
Thrombosis
Peripheral oedema
Arrhythmia
Tachycardia
Hypertension and hypotension
Capillary leak syndrome
Peripheral oedema
Hypotension
Electrocardiographic changes
Arrhythmia
Chest pain
Pulmonary pneumonitis
Ischaemic disorders
Hyperthyroidism
Hypothyroidism
Pulmonary inltrates
Ischaemic disorders
Hyperthyroidism
Hypothyroidism

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Table 1 (continued )
Class

Agent

Vascular endothelial growth factor inhibitor


Tyrosine kinase inhibitor
Imatinib
Sorafenib

Sunitinib

Dasatinib

Nilotinib

Epidermal growth factor receptor inhibitor


Erlotinib

Lapatinib

Panitumumab
Angiogenesis inhibitor
Immunomodulator

Common perioperative concerns


Oedema
Left ventricular dysfunction
Cardiac ischaemia and infarction
Hypertension
Thromboembolism
Cardiac ischaemia and infarction
Thromboembolism
Adrenal insufciency
Pulmonary haemorrhage
Hypertension
Hypothyroidism
Cardiomyopathy
QT prolongation
Torsades de pointes
Fluid retention
Cardiomyopathy
QT prolongation
Pulmonary haemorrhage
Platelet dysfunction
QT prolongation
Hypertension
Peripheral oedema
Deep venous thrombosis,
Arrhythmia
Pulmonary toxicity
Cerebrovascular accidents
Myocardial ischaemia
Syncope
Oedema
Cardiomyopathy
Pulmonary toxicity
QT prolongation
Pulmonary brosis
Peripheral oedema

Thalidomide
Lenalidomide

Thromboembolism
Oedema
Bradycardia

Asparaginase

Thrombosis
Glucose intolerance
Coagulopathy

Irinotecan
Topotecan
Rubitecan
Etoposide

Neutropenia
Diarrhoea
Cholinergic syndrome
Neutropenia
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Myocardial infarction
Congestive heart failure

Enzyme

Miscellaneous
Topoisomerase I inhibitor

Topoisomerase II inhibitor

SIADH, syndrome of inappropriate antidiuretic hormone.Adapted from Sahai et al. SK, Zalpour A, Rozner MA. Preoperative
evaluation of the oncology patient. Med Clin North Am. Mar 2010 2010;94(2):403419 with permission from Elsevier [77].

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Table 2
Common chemotherapeutic combinations.
Combination abbreviation

Chemotherapy components

A-CMF

Doxorubicin, cyclophosphamide,
methotrexate, 5-uorouracil
Bleomycin, doxorubicin, vinblastine, dacarbazine
Bleomycin, etoposide, cisplatin
Bleomycin, etoposide, vincristine,
cyclophosphamide, vincristine, procarbazine
Cyclophosphamide, doxorubicin, cisplatin
Capecitabine, oxaliplatin
Cyclophosphamide, doxorubicin, vincristine
Cyclophosphamide, doxorubicin,
etoposide, vincristine
Cyclophosphamide, doxorubicin,
vincristine, bleomycin
Cisplatin, cytarabine
Cisplatin, cytarabine, etoposide
5-uorouracil, cyclophosphamide, doxorubicin
5-uorouracil, cyclophosphamide, epirubicin
5-uorouracil, irinotecan, leucovorin
5-uorouracil, leucovorin, oxaliplatin
Course A: cyclophosphamide, doxorubicin,
methotrexate, vincristine (/" mesna)
Course B: cytarabine, leucovorin, methotrexate
Methotrexate, vinblastine, doxorubicin, cisplatin
Rituximab CHOP
Cyclophosphamide, docetaxel, doxorubicin
Paclitaxel, cisplatin, gemcitabine
Doxorubicin, vincristine
Etoposide, ifosfamide, methotrexate
Etoposide, ifosfamide, cisplatin, mesna

ABVD
BEP
BEACOPP
CAPP
CAPOX
CHOP /" rituximaba
CHOEP /" rituximaba
CHOP-Bleo
DHAP
ESHAP
FAC
FEC
FOLFIRI
FOLFOX
hyper-CVAD

M-VAC
R-CHOP
TAC
TCG
VAD
VIM
VIP

Steroids

Prednisone
Prednisone
Prednisone
Prednisone
Prednisone
Dexamethasone
Methylprednisolone

Dexamethasone
(Course A only)

Dexamethasone

Lexicomp Online". Available from www.crlonline.com, accessed on July 21, 2013.


Only generic names were used in this table. Commonly, the brand name Adriamycin is used for the drug doxorubicin. Another
generic name for doxorubicin is hydroxydaunorubicin, and this name is the source of the H in many abbreviations that include
this drug.
a
CHOP plus rituximab and CHOEP plus rituximab are often abbreviated R-CHOP and R-CHOEP, respectively.Adapted from
Sahai et al. SK, Zalpour A, Rozner MA. Preoperative evaluation of the oncology patient. Med Clin North Am. Mar 2010
2010;94(2):403419, with permission from Elsevier [77].

affect the patients blood pressure. Patients without critical disease are treated pharmacologically with
aspirin therapy.
With regard to non-invasive testing of the cardiovascular system using resting echocardiography, some controversy exists. In a large retrospective cohort study, Wijeysundera and colleagues
demonstrated no added benet for preoperative echocardiography with regard to postoperative
survival [38]. In our experience, a patient who has signicant fatigue and loss of functional status
due to neo-adjuvant treatment may present with a normal or near normal echocardiogram and yet
still be at risk for adverse cardiac outcomes due to loss of cardiac reserve in a physiologically
stressful situation such as surgery. For those patients who have had a series of echocardiograms
over time with changes in ejection fraction, it may be difcult to tell whether a cardiomyopathy has
developed or whether the differences are due to technique or reader interpretation. As a result, a
careful history and physical examination, along with judicious use of B-type natriuretic peptide,
may help guide risk assessment [39]. In several studies, cardiopulmonary exercise stress testing
(CPET) has been shown to predict the risk of adverse outcomes in the perioperative period,
including in those with oesophageal cancer [4042]. However, the impact of cancer and treatmentinduced fatigue, along with the presence of signicant co-morbidities such as advanced osteoarthritis, might prevent a patient from achieving an appropriate anaerobic thresholds, and further
study is needed.

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Table 3
Cardiac side effects of the major classes of chemotherapy [30,7884].
Anthracyclines

Taxanes

Cardiomyopathy
Daunorubicin
Paclitaxel
Doxorubicin
Docetaxel
Epirubicen
Idarubicin
Mitoxantrone
Valrubicin
Ischaemia
Paclitaxel
Docetaxel
Arrhythmias/QT prolongation
Epirubicen
Paclitaxel
Docataxel

Monoclonal
antibodies

Tyrosine kinase
inhibitors

Trastuzumab
Rituximab
Bevacizumab

Imatinib
Getinib
Sunitinib
Dasatinib
Erlotinib
Sorafenib

Bevacizumab

Erlotinib
Sorafenib

Sunitib
Vandetanib
Pazopanib
Sorafenib

Alkaloids

Antimetabolites

Alkylating
agents
Cyclophosphamide
Ifosfamide

Vinblastine
Vincristine
Vinorelbine

Capecitabine
Gemcitabine
5-Fluorouracil
5-Fluoruarcil

Ifosfamide

Pulmonary side effects


In addition to direct pulmonary complications from cancer such as obstructive disease and malignant pleural effusions, the lungs may be affected by prior cancer treatment. These side effects can
range from acute and delayed hypersensitivity reactions that are transient to long-term pulmonary
compromise due to interstitial lung disease and brosis. Bleomycin is the most well known of the
treatments that cause lung complications [43]. Additionally, controversy still exists regarding the use of
high oxygen concentrations during surgery as it may precipitate bleomycin-induced lung toxicity [44].
Despite the controversy, it is prudent to use the lowest concentration of inhaled oxygen that achieves
the desired oxygen saturation level. Monoclonal antibodies and tyrosine kinase inhibitors newer
agents also have some serious side effects, including pneumonitis and pleural effusions (Table 4).
Patients who have received chest irradiation are at an increased risk for pulmonary brosis. Additionally, cancer patients who have had prior lung resections are at an increased risk of developing
postoperative pulmonary complications and may need further evaluation by a pulmonologist.
When evaluating a patient for pulmonary toxicity in the perioperative period, the most important
diagnostic clues are symptoms such as coughing or shortness of breath. Asymptomatic patients rarely
require pulmonary evaluation beyond a physical examination. Chest radiographs are frequently
available from prior staging studies, and thus radiography is not indicated unless the patients
symptoms change. As with non-oncologic surgery, pulmonary function tests are rarely helpful in the
perioperative period for patients undergoing non-thoracic surgery [45]. However, patients with primary lung or oesophageal cancer who are facing resections should be evaluated using established
guidelines and recommendations [46,47]. For patients with pleural effusions, preoperative thoracentesis to improve lung expansion and function is indicated. Additionally, if time permits, pulmonary
rehabilitation prior to surgery may be helpful [48]. As is always the case, patients who are smoking or
using tobacco products should be encouraged to quit.
Renal side effects
The chemotherapeutic platinum compounds cisplatin and carboplatin are well known for causing renal
toxicity. Cisplatin-induced nephrotoxicity is due to disruption of the proximal tubules, which results in
electrolyte disturbances such as hypomagnesaemia [49]. The resulting abnormalities may persist for
several years after treatment. Newer agents such as oxaliplatin have a much lower incidence of renal
toxicity than these chemotherapeutic agents. The alkylating agents cyclophosphamide and ifosfamide
cause nephrotoxicity and haemorrhagic cystitis owing to their metabolites [49], and methotrexate is toxic
owing to its precipitation in the lumen. The nephrotoxicity from ifosfamide may persist for many years after
treatment [50], whereas methotrexate-induced nephrotoxicity is reversible upon cessation of treatment.

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Fig. 1. Schema for the perioperative cardiac evaluation of a cancer patient.

Patients who have received nephrotoxic chemotherapy or have exhibited renal dysfunction during
chemotherapy should have their electrolyte levels checked prior to surgery. Magnesium should be
replaced orally as indicated. As in the cardiovascular and pulmonary systems, there are no clear
evidence-based interventions that will help reduce the incidence and severity of perioperative acute
kidney injury [51]. Multiple scoring systems for kidney injury have been developed and validated for
both cardiac and non-cardiac surgery [52], but the utility of such scoring systems in oncologic surgery
has yet to be established. Patients with hydronephrosis and kidney dysfunction from obstructing lesions may benet from having nephrostomy tubes placed and waiting until their creatinine levels
normalise before they undergo abdominal or pelvic surgery. Renal cancer patients with chronic kidney
disease need to be educated and informed about the possibility of renal replacement therapy after
surgery.

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Table 4
Pulmonary side effects of the major classes of chemotherapy [30,7885].
Anthracyclines

Taxanes

Monoclonal
antibodies

Bronchospasm/hypersensitivity reactions
Doxorubicin
Paclitaxel
Docetaxel
Rituximab
Panitumumab
Cetuximab
Interstitial lung disease (pneumonitis/brosis)
Epirubicen
Bevacizumab
Trastuzumab
Ofatumumab
Pleural effusions
Epirubicen
Paclitaxel
Docataxel

Tyrosine kinase
inhibitors

Alkaloids

Antimetabolites

Alkylating agents

Vinblastine
Vincristine
Vinorelbine

Fludarabine

Cyclophosphamide
Busulfan
Procarbazine

Sorafenib
Sunitinib

Capecitabine
Gemcitabine
5-Fluorouracil

Ifosfamide
Oxaliplatin

Dasatinib
Imatinib

5-Fluoruarcil

Ifosfamide

Gastrointestinal and hepatic side effects


Chemotherapy-induced nausea and vomiting, mucositis and diarrhoea lead to malabsorption in the
gastrointestinal tract and result in cancer cachexia and malnutrition. Radiation to the abdomen or
pelvis may also result in malabsorption and malnutrition. Oncologic patients who are nutritionally
compromised have poorer outcomes and must be evaluated by a health-care team familiar with the
treatment of cancer cachexia [53]. Evidence shows that extensive pre- and postoperative nutritional
supplementation via enteral and parenteral routes improves surgical outcomes [54,55].
Hepatic complications of cancer treatment also pose unique perioperative challenges. Interestingly,
chemotherapy is associated with the reactivation of hepatitis B in patients, especially those with
haematologic malignancies [56]. Patients with unexplained abnormal liver function prior to surgery
should be screened for hepatitis B and their liver function should be observed in the perioperative
period. A devastating complication of high-dose chemotherapy is hepatic veno-occlusive disease.
Perioperative patients presenting with unexplained jaundice and ascites should be evaluated for hepatic veno-occlusive disease, and the appropriate consultation should be obtained [57]. Radiation
therapy and combination chemotherapy (concurrently and individually) raise the risk of hepatic
dysfunction in cancer patients.
The perioperative management of hepatic dysfunction depends on its aetiology and severity. Mild
dysfunction can usually be managed with observation and the avoidance of hepatotoxic agents during
the perioperative period. More severe derangements in liver function may require evaluation by a
specialist prior to surgery. In general, for patients with cancer and cirrhosis, the ChildTurcottePugh
and Model for End-Stage Liver Disease scores can be used to guide perioperative risk assessment [58,59].
Endocrine side effects
Patients with cancer and diabetes require a nuanced approach. Frequently, steroids are used in
cancer care as part of a chemotherapy regimen to reduce inammation, as immunosuppressants, to
reduce nausea and vomiting or to boost appetite; however, short- or long-term steroid use can induce a
hyperglycaemic state, resulting in a clinical picture similar to that of diabetes [60]. Steroid use in the
neo-adjuvant period may unmask previously undiagnosed diabetes or make known diabetes more
difcult to treat and manage. In the perioperative setting, management of steroid-induced or -exacerbated diabetes is similar to that of diabetes in non-oncologic patients. Additionally, patients with
cancer on long-term steroids may be at risk for adrenal insufciency in the postoperative period.
Stress-dose-steroid use in the perioperative period remains controversial but is generally considered
acceptable for patients at risk of adrenal insufciency due to suppression of the hypothalamicpituitaryadrenal axis [61,62].
For cancer patients who have received radiation to the head and neck area, it is imperative to inquire
about thyroid function testing within the past year. Hypothyroidism after radiation treatment may

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develop 4 weeks to several years after treatment [63]. Patients with suboptimal thyroid function who
are asymptomatic generally begin thyroid replacement therapy and then proceed to surgery as
scheduled. Delaying surgery is prudent in patients who are experiencing symptoms of hypothyroidism,
but only if the delay will not compromise oncologic treatment outcomes [61].
Hyponatraemia in the form of the syndrome of inappropriate antidiuretic hormone secretion is
frequently seen in cancer patients as a paraneoplastic process and must be managed appropriately.
Generally, patients who are mildly hyponatraemic and stable may proceed with surgery without
further intervention. Patients who have developed acute hyponatraemia need to have surgery
delayed until appropriate diagnostic testing is done and an aetiology uncovered. In addition to
hyponatraemia, numerous other paraneoplastic syndromes such as Cushings syndrome, Eaton
Lambert syndrome and hypercalcaemia of malignancy that may affect the patient with cancer undergoing surgery.
Obesity presents a special challenge in the perioperative period, especially for patients undergoing
radiation therapy. Frequently, these patients are counselled not to lose weight because weight loss will
necessitate replanning the radiation therapy [64,65]. However, from the perspective of the perioperative physician and surgeon, directed weight loss during the neo-adjuvant period for the obese patient
may reduce the likelihood of postoperative complications. Resolving this impasse depends on close
communication between all teams involved.
Haematologic side effects
Special consideration must be given to patients with leukaemia or lymphoma who are undergoing
surgery. These patients have signicant abnormalities in their haematologic cells. The range of perioperative complications in these patients includes severe infections, bleeding and thrombosis. The
literature on the management of these conditions in the perioperative period is sparse. Leukaemic
patients with signicant leucocytosis (white blood cell count >100,000/ml) should receive treatment
(chemotherapy or leukapheresis) to reduce the leucocyte count because hyperleucocytosis is associated with high rates of mortality and morbidity [66]. Patients with hyperleucocytosis who are undergoing surgery are at risk for leucostasis syndrome, acute respiratory failure, cerebrovascular
occlusions and bleeding due to increased blood viscosity and disturbed microvascular perfusion [67].
Two case series of patients with haematologic malignancies undergoing cardiac surgery reported high
perioperative mortality due to infection and bleeding in the postoperative setting [68,69]. Additionally,
thrombocytopaenia due to the cancer itself or to its treatment is common in patients with leukaemia or
lymphoma. For cancer patients, platelet transfusion thresholds may be higher owing to platelet
dysfunction; however, platelet transfusion must be balanced against the prothrombotic state that
cancer induces. Indeed, thrombocytosis is often seen in the cancer population. Patients with chronic
myeloid leukaemia, primary myelobrosis, polycythaemia vera, myelodysplastic syndrome or acute
myeloid leukaemia sometimes present with thrombocytosis, frequently with platelet counts
<1,000,000/ml. If time permits, the platelet count can be lowered by administering myelosuppressive
agents such as anagrelide or hydroxyurea. Otherwise, for urgent or emergent surgery, plateletpheresis
is indicated [70,71].
The use of granulocyte colony-stimulating factors for neutropenic patients who are undergoing
surgery is controversial [72,73] and is not recommended at our institution. Similarly, although
erythropoiesis-stimulating agents are approved for the treatment of anaemic patients scheduled to
undergo elective, non-cardiac, non-vascular surgery to reduce the need for allogeneic blood transfusions, their use is also controversial [74]. We recommend that erythropoiesis-stimulating agents be
considered only in patients at high risk for signicant blood loss, especially patients who are anaemic
but unable to receive blood transfusions for various reasons (including religious reasons).
Postoperative care
Cancer patients are at higher risk for a postoperative venous thrombotic event than the general
surgical population. As a result, both the American College of Chest Physicians and the American Society of Clinical Oncology recommend extending venous thrombotic event prophylaxis for up to 4

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477

weeks after surgery for the highest-risk patients [75,76]. The highest-risk patients are generally
considered to be those undergoing major abdominal or pelvic surgery who have high-risk features
such as restricted mobility, obesity or a history of venous thrombotic events.
Summary
The perioperative evaluation of the cancer patient must take into account the effects of any
prior cancer treatments and the cancer itself in a systematic, evidence-based manner. The
multidisciplinary nature of cancer care frequently involves preoperative, neo-adjuvant treatment,
which may cause unforeseen side effects that may unmask or exacerbate signicant co-morbidities
that affect perioperative outcomes. Clinicians and patients need to be aware of these side effects
and the short- and long-term consequences they may entail. Previous treatment with chemotherapeutic agents, which tend to have similar toxic effects within pharmacologic classes, may
affect perioperative risks. Additionally, prior radiotherapy to vital organs has predictable side effects that may need to be evaluated prior to surgery. A key challenge is separating the fatigue and
malaise that accompany cancer treatment from underlying or undiagnosed coronary artery disease
or heart failure. On the whole, it is important to recognise whether organ dysfunction discovered
during the perioperative evaluation is due to prior cancer treatment or to some other underlying
cause.
Practice points
# The patient who has received cardiotoxic chemotherapy needs to be assessed for underlying
cardiomyopathy, which may be masked by malaise and fatigue from the cancer itself.
# Cardiovascular evaluation generally follows established American College of Cardiology/
American Heart Association guidelines.
# Chemotherapy and radiation therapy may lead to pulmonary brosis many years after initial
treatment.
# Perioperative renal issues in cancer patients usually involve electrolyte disturbances that
need to be corrected before surgery.
# Patients who have received steroids should be assessed for steroid-induced diabetes before
surgery.
# Nutritional status plays a key role in perioperative outcomes; hence, nutritional optimisation
before surgery is strongly recommended.
# Functional status is also very important; hence, patients should be educated about the need
for exercise and weight loss prior to surgery.
# Extended venous thrombotic event prophylaxis is now recommended for patients at highest
risk of postoperative venous thrombo-embolism.

Research agenda
# Further research into all elds of perioperative cancer medicine is needed.
# The role of cardiopulmonary exercise stress testing in cancer therapy and risk stratication
for surgery should be investigated.
# The relationship between chemotherapy-induced cognitive dysfunction and postoperative
delirium needs to be elucidated, especially as the general population ages.
# Long-term studies into the risks of vascular endothelial growth factors, including their cardiovascular side effects, are needed.
# Exploration of the role of prehabilitation during the neo-adjuvant treatment phase and its
effects on outcomes is needed.

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Statement of conict of interest


None.
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