Abstract

EDITOR’S PERSPECTIVE
What We Know about This Topic

IV anesthesia may impair anticancer immunity less than volatile anesthesia and therefore reduce recurrence risk

What This Article Tells Us That Is New

In a large propensity-matched retrospective cohort analysis, the authors compared total IV and volatile anesthesia for breast cancer surgery

Recurrence hazard was similar with each approach

Selection of IV or volatile anesthesia should be based on factors other than cancer recurrence

Background

The association between type of anesthesia used and recurrence of cancer remains controversial. This retrospective cohort study compared the influence of total IV anesthesia and inhalation anesthesia on the primary outcome of recurrence-free survival after breast cancer surgery.

Methods

The authors reviewed the electronic medical records of patients who had breast cancer surgery at a tertiary care teaching hospital between January 2005 and December 2013. The patients were grouped according to whether IV or inhalation anesthesia was used for surgery. Propensity score matching was used to account for differences in baseline characteristics. Kaplan–Meier survival curves were constructed to evaluate the influence of type of anesthesia on recurrence-free survival and overall survival. The risks of cancer recurrence and all-cause mortality were compared between each type of anesthesia.

Results

Of 7,678 patients who had breast cancer surgery during the study period, data for 5,331 patients were available for analysis (IV group, n = 3,085; inhalation group, n = 2,246). After propensity score matching, 1,766 patients remained in each group. Kaplan–Meier survival curves showed that there was no significant difference in recurrence-free survival or overall survival between the two groups, with 5-yr recurrence-free survival rates of 93.2% (95% CI, 91.9 to 94.5) in the IV group and 93.8% (95% CI, 92.6 to 95.1) in the inhalation group. Inhalation anesthesia had no significant impact on recurrence-free survival (hazard ratio, 0.96; 95% CI, 0.69 to 1.32; P = 0.782) or overall survival (hazard ratio, 0.96; 95% CI, 0.69 to 1.33, P = 0.805) when compared with total IV anesthesia.

Conclusions

The authors found no association between type of anesthesia used and the long-term prognosis of breast cancer. The results of this retrospective cohort study do not suggest specific selection of IV or inhalation anesthesia for breast cancer surgery.

Disease recurrence after cancer surgery is a major fear for patients. Several factors affect the risk of recurrence, including residual cancer cells at the surgical margin, the characteristics of the cancer cells, and host immune function. Paradoxically, surgery itself may facilitate distant metastasis of circulating cancer cells by inducing an inflammatory response and immunosuppression.1–3  Furthermore, anesthetic drugs can have an unfavorable effect on the immune system.4,5  Both surgery and anesthesia suppress cell-mediated immunity and increase angiogenesis and can therefore promote proliferation and metastasis of cancer cells during the perioperative period.6  Decreased levels of circulating antiinflammatory cytokines and change in the functioning of natural killer cells have been reported to be mechanisms by which anesthetic techniques can affect immune function.7–10 

Anesthetic agents vary in their ability to induce immunomodulation and potentiation of tumorigenic growth factors, including hypoxia-inducible factor-1 and insulin-like growth factor.10–13  Several studies have reported that propofol has a more favorable immunomodulatory effect than inhalation agents.8,9,14  Some clinical studies have shown that survival after cancer surgery is better in patients who receive total IV anesthesia than in those who receive inhalation anesthesia.15–19  However, the data are presently inadequate, and more evidence is needed.

Breast cancer is the most common type of malignancy in women. There has been some debate regarding the influence of anesthetic agents on the recurrence of breast cancer.16,20  To address this controversy, we undertook a retrospective cohort study that included a large number of patients and was adjusted for strong prognostic factors, such as subtype of breast cancer and the chemotherapeutic modalities used. We hypothesized that there would be differences in recurrence-free survival and overall survival between patients who receive total IV anesthesia and those who receive inhalation anesthesia during breast cancer surgery. The primary purpose of this study was to assess the relationship between type of anesthesia and long-term outcomes after breast cancer surgery, using propensity score-matched analyses. The secondary purpose was to identify potential risk factors for cancer recurrence and all-cause mortality—including type of anesthesia—in patients with breast cancer, using multivariable Cox regression analyses.

Materials and Methods

The study was approved by the institutional review board of Seoul National University Hospital (approval number 1711-058-899). The requirement for informed consent was waived in view of the retrospective design of the study.

Study Population

We reviewed the electronic medical records of all patients who had breast cancer surgery at a tertiary care teaching hospital between January 2005 and December 2013. The exclusion criteria were as follows: bilateral breast cancer, immediate breast reconstruction surgery, metastatic breast cancer, other malignancy, history of breast surgery, administration of both IV and inhalation anesthetics, male sex, benign breast tumor or carcinoma in situ, American Society of Anesthesiologists (ASA) physical status greater than or equal to IV, and unknown type of anesthesia.

Patients were grouped according to whether they received total IV anesthesia (IV group) or inhalation anesthesia (inhalation group) for breast cancer surgery. The type of anesthesia was determined according to the preference of the attending anesthesiologists. Patients in the IV group received continuous administration of propofol and remifentanil via a target-controlled infusion pump, and those in the inhalation group received a volatile anesthetic agent (enflurane, isoflurane, sevoflurane, or desflurane). Those who received the same type of anesthesia for multiple surgeries during the study period remained eligible. None of the patients received additional regional anesthesia for postoperative pain control.

Variables and Outcome Measurements

We recorded the following data from the electronic medical records: age, height, weight, ASA physical status, date of surgery, anesthetic time, type of surgery (breast-conserving surgery or total mastectomy), perioperative use of opioids, use of ketorolac for postoperative analgesia, transfusion, tumor size, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 expression, Ki-67 expression, and whether postoperative adjuvant chemotherapy, radiation therapy, or hormone therapy was used. Based on estrogen receptor and progesterone receptor status and levels of human epidermal growth factor receptor 2 and Ki-67 expression, we determined the subtype of breast cancer in each patient as luminal A, luminal B, human epidermal growth factor receptor 2–enriched, or basal.21  We also identified whether each patient adhered to standard cancer therapy. Nonadherence to standard cancer therapy was defined as not receiving anticancer treatment, including adjuvant chemotherapy, radiation therapy, and hormone therapy, as recommended in the National Comprehensive Cancer Network guideline for each type of cancer.22  However, time to administration of standard cancer therapy was not considered.

The primary endpoint of the study was recurrence-free survival, which was defined as the interval between the date of surgery and the date of recurrence of breast cancer or death. Recurrence of breast cancer was determined as locoregional or systemic, and confirmed by radiologic or histologic examination. The secondary endpoint was overall survival, defined as the interval from the date of surgery to the date of death. The dates of death were obtained from the Korean Ministry of the Interior and Safety, using the resident registration number for each patient. Follow-up was concluded on December 31, 2015; therefore, the duration of follow-up ranged from 2 to 11 yr. Patients who were lost to follow-up during the study period were censored at the date of last follow-up.

Statistical Analysis

The sample size was based on the available data from all patients who had breast cancer surgery at our institution from January 2005 to December 2013. No statistical power calculation was performed before the study.

The study results are presented as the number (percentage) for categorical variables and as the mean ± SD or median [interquartile range] for continuous variables, as appropriate. The normality of the data distribution was assessed using the normal quantile–quantile plot. The independent samples t test or Mann–Whitney U test were used to compare continuous variables and the chi-square test to compare categorical variables between groups.

Propensity score matching was used to reduce the potential confounding effect of each variable and the differences in baseline characteristics between the groups. The propensity score was defined as the probability of receiving inhalation anesthesia by logistic regression analysis. The variables used for matching were age, height, weight, ASA physical status, anesthetic time, postoperative use of ketorolac, transfusion, type of surgery, subtype of breast cancer, nonadherence to standard cancer therapy, and year of surgery. Perioperative use of opioids was excluded from the model because all patients in the IV group received an opioid (remifentanil) intraoperatively. We matched patients at a ratio of 1:1 using the nearest neighbor method with a caliper of 0.05 SD of the logit of the propensity score. The balance of the matched patients was assessed using the standardized mean difference for each contributor.

In the propensity-matched cohort, recurrence-free survival and overall survival were estimated for up to 11 yr using the Kaplan–Meier method, and the groups were compared using the log-rank test. Cox proportional hazards models were used to compare hazard ratios for the two groups and to identify risk factors for recurrence of cancer and all-cause mortality; potential risk factors included type of anesthesia, age, anesthetic time, ASA physical status, type of surgery, perioperative use of opioids, postoperative use of ketorolac, transfusion, subtype of breast cancer, nonadherence to standard cancer therapy, and year of surgery. All variables were adjusted in multivariable Cox regression analysis using the enter method to assess the association of type of anesthesia with long-term outcome after breast cancer surgery. Patients with missing data were excluded from the analysis. Proportional hazard assumptions for categorical variables were assessed using log-minus-log survival plots, and restricted cubic splines were used for continuous variables, such as age and anesthetic time.23,24  The log hazard was not linear for age, so the patients were categorized into the following groups based on age: less than 40 yr, 40 to 50 yr, and greater than or equal to 50 yr.

We performed an additional analysis using a Cox regression with inverse probability of treatment weighting to adjust for the propensity score, which differs from the model-based adjustment because it can deal with the possibility that patients with better prognosis are assigned to a particular group.25  Perioperative use of opioids and type of anesthesia were included in the weighted Cox proportional hazards model because use of opioids was not adjusted for in the aforementioned model used for calculation of the propensity score.

All analyses were performed using R software version 3.4.4 (R Foundation for Statistical Computing, Austria). We used the package “survival” for the Cox regression analysis and “MatchIt” for the propensity score matching. The inverse probability of treatment weighting was conducted by using “weights” argument in “coxph” function. A two-tailed P < 0.05 was considered statistically significant.

Results

Of 7,678 patients who had breast cancer surgery between January 2005 and December 2013 at Seoul National University Hospital, 5,331 patients (IV group, n = 3,085; inhalation group, n = 2,246) were finally included in the analyses (fig. 1). The distribution of patients who received IV or inhalation anesthesia according to the year of surgery is shown in Figure 1 (Supplemental Digital Content 1, http://links.lww.com/ALN/B807).

Fig. 1.

Flow diagram of the study population. ASA, American Society of Anesthesiologists.

Fig. 1.

Flow diagram of the study population. ASA, American Society of Anesthesiologists.

All patients in the IV group received propofol, and those in the inhalation group received sevoflurane (1,537 of 2,246; 68.4%), desflurane (700 of 2,246; 31.2%), enflurane (8 of 2,246; 0.35%), or isoflurane (1 of 2,246; 0.05%) for maintenance of general anesthesia. Table 1 shows the characteristics for the total study cohort and those for the propensity-matched cohort.

Table 1.

Patient Characteristics for the Total Study Cohort and for the Propensity-matched Cohort

Patient Characteristics for the Total Study Cohort and for the Propensity-matched Cohort
Patient Characteristics for the Total Study Cohort and for the Propensity-matched Cohort

The median follow-up duration was 62 (interquartile range, 39 to 85) months for all patients, 67 (interquartile range, 48 to 86) months for the IV group, and 53 (interquartile range, 35 to 84) months for the inhalation group.

After propensity score matching, 1,766 patients remained in each group, with a good matching balance. All standardized mean differences for the study variables were less than 0.1 (table 1), and their distributions are shown in figure 2 (Supplemental Digital Content 1, http://links.lww.com/ALN/B807).

Fig. 2.

Kaplan–Meier survival curve for recurrent-free survival and overall survival in propensity score-matched patients.

Fig. 2.

Kaplan–Meier survival curve for recurrent-free survival and overall survival in propensity score-matched patients.

The Kaplan–Meier survival curves demonstrated 5-yr recurrence-free survival rates of 93.2% (95% CI, 91.9 to 94.5) in the IV group and 93.8% (95% CI, 92.6 to 95.1) in the inhalation group and respective 5-yr overall survival rates of 94.2% (95% CI, 92.9 to 95.5) and 94.5% (95% CI, 93.3 to 95.8). There was no significant difference in recurrence-free survival (P = 0.491) or overall survival (P = 0.365) between the IV group and the inhalation group in the propensity-matched cohort (fig. 2).

In the propensity-matched cohort, the Cox proportional hazards model for recurrence-free survival was constructed to evaluate the association between type of anesthesia and recurrence-free survival, the primary outcome of this study, and is shown in table 2. Multivariable Cox regression revealed no significant association between inhalation anesthesia and poorer recurrence-free survival (hazard ratio, 0.96; 95% CI, 0.69 to 1.32; P = 0.782; table 2) when compared with the IV anesthesia group.

Table 2.

Univariable and Multivariable Cox Regression Analysis for Recurrence-free Survival in the Propensity-matched Cohort

Univariable and Multivariable Cox Regression Analysis for Recurrence-free Survival in the Propensity-matched Cohort
Univariable and Multivariable Cox Regression Analysis for Recurrence-free Survival in the Propensity-matched Cohort

Table 3 shows the Cox proportional hazards model for overall survival after breast cancer surgery in the propensity-matched cohort. After adjustment, inhalation anesthesia was not associated with a difference in overall survival (hazard ratio, 0.96; 95% CI, 0.69 to 1.33, P = 0.805; table 3).

Table 3.

Univariable and Multivariable Cox Regression Analysis for Overall Survival in the Propensity-matched Cohort

Univariable and Multivariable Cox Regression Analysis for Overall Survival in the Propensity-matched Cohort
Univariable and Multivariable Cox Regression Analysis for Overall Survival in the Propensity-matched Cohort

We also conducted the Cox regression analyses for the total study cohort to determine risk factors for cancer recurrence and all-cause mortality, the secondary outcome of this study. Age younger than 40 yr, ASA physical status, total mastectomy, subtype of breast cancer other than luminal-A, and nonadherence to standard cancer therapy were found to be associated with higher risks of cancer recurrence and all-cause mortality. The Cox proportional hazards models for recurrence-free survival and overall survival in the total study cohort are tabulated in tables 1 and 2 (Supplemental Digital Content 1, http://links.lww.com/ALN/B807), respectively.

The Cox regression analysis with inverse probability of treatment weighting also demonstrated that there was no significant association between type of anesthesia and recurrence-free survival (hazard ratio, 0.86; 95% CI, 0.65 to 1.14; P = 0.293) or overall survival (hazard ratio, 0.79; 95% CI, 0.59 to 1.04; P = 0.091).

Discussion

In this study, there was no influence of total IV anesthesia or inhalation anesthesia on recurrence-free survival or overall survival in patients who had breast cancer surgery. We found no significant association between type of anesthesia used and the prognosis after breast cancer surgery.

Numerous studies have investigated the influence of anesthetic technique on the prognosis in patients with cancer. Use of regional analgesia, including epidural and paravertebral block, was reported to be effective in reducing inflammation and preventing immunosuppression in patients undergoing cancer surgery.26  Epidural analgesia for postoperative pain was found to be associated with an improved prognosis in patients with colon,27  prostate,28  rectal,29  and gastric cancer.30  Paravertebral analgesia was also reported to have a beneficial effect on the risk of recurrence of breast cancer.31  In contrast, other studies reported that epidural analgesia did not have any clear impact on oncologic outcomes, such as disease recurrence, in patients with prostate cancer32  or ovarian cancer.33  Moreover, post hoc analysis of a prospective randomized controlled trial revealed no significant association between use of an epidural block and cancer-free survival,34  and the same result was found in recent meta-analyses.26,35 

Recently, the impact of the anesthetic agent used on the prognosis of various cancers has been evaluated. One study found that use of total IV anesthesia during surgery for esophageal cancer was associated with a better postoperative survival rate than inhalation anesthesia.18  Another study that compared the 5-yr disease recurrence rate in patients with breast cancer who received propofol-based total IV anesthesia or sevoflurane-based inhalation anesthesia demonstrated that total IV anesthesia could reduce the risk of recurrence.16  However, the statistical power of that study seemed to be low because of a small sample size. Another study reported no significant difference in cancer-free survival or overall survival according to the type of anesthesia used.20  However, that study included only 56 patients in the IV group. Our present study included a larger population with similar numbers of patients in both groups to strengthen its statistical power. Furthermore, we obtained clinically relevant results by adjusting for subtype of breast cancer, which is determined based on the gene expression profile and known to be closely associated with the clinical prognosis of breast cancer.21,36  The molecular subtypes of breast cancer have been incorporated into the latest edition of the American Joint Committee on Cancer staging system.37  We also included details of whether each patient adhered to the standard cancer therapy recommended in the recent guideline of the National Comprehensive Cancer Network as a covariate in our regression analyses to adjust for the interaction between use of adjuvant chemotherapy or radiation therapy and tumor, node, and metastasis disease stage classification.

The mechanism through which anesthesia affects the prognosis of cancer is thought to be the immunomodulatory effect of anesthetic agents. Cell-mediated immunity plays an important role in preventing dissemination and implantation of cancer cells, which are facilitated by the stress response and tissue damage induced by surgery.3,38  Both in vitro and in vivo studies have found that volatile anesthetic agents suppress the functioning of natural killer cells,14,39,40  which is critical in preventing growth of cancer cells. In contrast, propofol, a widely used IV anesthetic agent, was found to preserve the activity of natural killer cells and to have a protective anticancer effect.9  Furthermore, several studies have demonstrated that volatile anesthetic agents induce upregulation of tumorigenic growth factors, including hypoxia-inducible factor-1 and vascular endothelial growth factor.11,41  Anesthesia-related immunomodulation has also been proposed as the mechanism by which regional anesthesia may improve survival in patients with cancer.26  Although a number of studies suggest a favorable impact of regional anesthesia on the prognosis of cancer, the evidence for such a benefit remains inadequate.26,42  Similarly, conflicting results have been reported with regard to the association between use of total IV anesthesia and a decrease in the risk of recurrence of cancer.43,44  Any conclusions regarding this association must await the results of the prospective randomized controlled trials currently in progress around the world.

Opioids have also been suggested to promote proliferation and angiogenesis of cancer cells by inhibiting cell-mediated immunity.45,46  In our study, all patients in the IV group had received remifentanil, but not those in the inhalation group, so there was a difference in opioid use between the two groups. However, given that we found no significant association between use of opioids and outcomes after breast cancer surgery, the clinical impact of perioperative opioid administration on the long-term prognosis does not seem to be significant. Indeed, a recent large prospective population-based cohort study reported that use of opioids was not associated with recurrence of breast cancer.47 

Our study confirmed a strong association between the subtype of breast cancer and the risks of cancer recurrence and death. Nonadherence to standard cancer therapy was also found to be associated with worse outcomes after breast cancer surgery, as would be expected. However, several factors, including postoperative complications, multiple neoadjuvant chemotherapy, and comorbidities, can impede a patient’s ability to complete the intended oncologic treatment and are independently associated with poor long-term oncologic outcomes.48  Although there was a strong association between ASA physical status and overall mortality in this study, this parameter, which reflects how frail a patient is, may also have had an impact on nonadherence to standard cancer therapy. Other studies have also identified poor ASA physical status to be an independent risk factor for decreased long-term survival in patients with cancer.17,49  We determined all-cause mortality rather than cancer-related mortality as an outcome variable in this study, and it is obvious that patients with multiple complicated comorbidities have a higher mortality rate.

Several limitations should be considered when interpreting the results of this study. First, a number of patients were excluded because of missing variables relating to their gene expression profiles and use of adjuvant chemotherapy and radiation therapy that were necessary to determine the subtype of breast cancer and nonadherence to standard cancer therapy. These exclusions may have introduced a degree of selection bias. Second, we could not take into account the medical advances that took place during our relatively long study period; changes in insurance coverage for trastuzumab in particular may have confounded the results. Third, because we determined the sample size on the basis of the data available during the study period rather than by a priori calculation, we cannot exclude the possibility that the lack of statistical significance may have resulted from inadequate statistical power to detect a potential difference between the two groups. Fourth, the time lapse until administration of standard cancer therapy, such as trastuzumab, was not considered. Finally, because of the retrospective study design, it was not possible to measure levels of inflammatory biomarkers that could explain the causal relationship between type of anesthesia used and recurrence of cancer.

In conclusion, we found no significant impact of total IV anesthesia or inhalation anesthesia on recurrence of breast cancer and overall survival in patients with the disease. Both anesthetic techniques can be used for breast cancer surgery, and the choice of anesthetic agent should be made according to the characteristics of the individual patient.

Acknowledgments

The authors thank the Medical Research Collaboration Center of Seoul National University Hospital for their support with the statistical analysis.

Research Support

Support for this research was provided solely from institutional and departmental sources (Seoul National University grant No. 800-20180131).

Competing Interests

The authors declare no competing interests.

References

References
1.
Lennard
TW
,
Shenton
BK
,
Borzotta
A
,
Donnelly
PK
,
White
M
,
Gerrie
LM
,
Proud
G
,
Taylor
RM
:
The influence of surgical operations on components of the human immune system.
Br J Surg
1985
;
72
:
771
6
2.
Ogawa
K
,
Hirai
M
,
Katsube
T
,
Murayama
M
,
Hamaguchi
K
,
Shimakawa
T
,
Naritake
Y
,
Hosokawa
T
,
Kajiwara
T
:
Suppression of cellular immunity by surgical stress.
Surgery
2000
;
127
:
329
36
3.
Hiller
JG
,
Perry
NJ
,
Poulogiannis
G
,
Riedel
B
,
Sloan
EK
:
Perioperative events influence cancer recurrence risk after surgery.
Nat Rev Clin Oncol
2018
;
15
:
205
18
4.
Byrne
K
,
Levins
KJ
,
Buggy
DJ
:
Can anesthetic–analgesic technique during primary cancer surgery affect recurrence or metastasis?
Can J Anaesth
2016
;
63
:
184
92
5.
Stollings
LM
,
Jia
LJ
,
Tang
P
,
Dou
H
,
Lu
B
,
Xu
Y
:
Immune modulation by volatile anesthetics.
Anesthesiology
2016
;
125
:
399
411
6.
Kim
R
:
Anesthetic technique and cancer recurrence in oncologic surgery: Unraveling the puzzle.
Cancer Metastasis Rev
2017
;
36
:
159
77
7.
O’Riain
SC
,
Buggy
DJ
,
Kerin
MJ
,
Watson
RW
,
Moriarty
DC
:
Inhibition of the stress response to breast cancer surgery by regional anesthesia and analgesia does not affect vascular endothelial growth factor and prostaglandin E2.
Anesth Analg
2005
;
100
:
244
9
8.
Ke
JJ
,
Zhan
J
,
Feng
XB
,
Wu
Y
,
Rao
Y
,
Wang
YL
:
A comparison of the effect of total intravenous anaesthesia with propofol and remifentanil and inhalational anaesthesia with isoflurane on the release of pro- and anti-inflammatory cytokines in patients undergoing open cholecystectomy.
Anaesth Intensive Care
2008
;
36
:
74
8
9.
Melamed
R
,
Bar-Yosef
S
,
Shakhar
G
,
Shakhar
K
,
Ben-Eliyahu
S
:
Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: Mediating mechanisms and prophylactic measures.
Anesth Analg
2003
;
97
:
1331
9
10.
Buckley
A
,
McQuaid
S
,
Johnson
P
,
Buggy
DJ
:
Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: A pilot study.
Br J Anaesth
2014
;
113
:
i56
62
11.
Huang
H
,
Benzonana
LL
,
Zhao
H
,
Watts
HR
,
Perry
NJ
,
Bevan
C
,
Brown
R
,
Ma
D
:
Prostate cancer cell malignancy via modulation of HIF-1α pathway with isoflurane and propofol alone and in combination.
Br J Cancer
2014
;
111
:
1338
49
12.
Rohwer
N
,
Lobitz
S
,
Daskalow
K
,
Jöns
T
,
Vieth
M
,
Schlag
PM
,
Kemmner
W
,
Wiedenmann
B
,
Cramer
T
,
Höcker
M
:
HIF-1α determines the metastatic potential of gastric cancer cells.
Br J Cancer
2009
;
100
:
772
81
13.
Luo
X
,
Zhao
H
,
Hennah
L
,
Ning
J
,
Liu
J
,
Tu
H
,
Ma
D
:
Impact of isoflurane on malignant capability of ovarian cancer in vitro.
Br J Anaesth
2015
;
114
:
831
9
14.
Dubowitz
JA
,
Sloan
EK
,
Riedel
BJ
:
Implicating anaesthesia and the perioperative period in cancer recurrence and metastasis.
Clin Exp Metastasis
2018
;
35
:
347
58
15.
Soltanizadeh
S
,
Degett
TH
,
Gögenur
I
:
Outcomes of cancer surgery after inhalational and intravenous anesthesia: A systematic review.
J Clin Anesth
2017
;
42
:
19
25
16.
Lee
JH
,
Kang
SH
,
Kim
Y
,
Kim
HA
,
Kim
BS
:
Effects of propofol-based total intravenous anesthesia on recurrence and overall survival in patients after modified radical mastectomy: A retrospective study.
Korean J Anesthesiol
2016
;
69
:
126
32
17.
Wigmore
TJ
,
Mohammed
K
,
Jhanji
S
:
Long-term curvival for patients undergoing volatile versus IV anesthesia for cancer surgery: A retrospective analysis.
Anesthesiology
2016
;
124
:
69
79
18.
Jun
IJ
,
Jo
JY
,
Kim
JI
,
Chin
JH
,
Kim
WJ
,
Kim
HR
,
Lee
EH
,
Choi
IC
:
Impact of anesthetic agents on overall and recurrence-free survival in patients undergoing esophageal cancer surgery: A retrospective observational study.
Sci Rep
2017
;
7
:
14020
19.
Enlund
M
,
Berglund
A
,
Andreasson
K
,
Cicek
C
,
Enlund
A
,
Bergkvist
L
:
The choice of anaesthetic–sevoflurane or propofol–and outcome from cancer surgery: A retrospective analysis.
Ups J Med Sci
2014
;
119
:
251
61
20.
Kim
MH
,
Kim
DW
,
Kim
JH
,
Lee
KY
,
Park
S
,
Yoo
YC
:
Does the type of anesthesia really affect the recurrence-free survival after breast cancer surgery?
Oncotarget
2017
;
8
:
90477
87
21.
Dai
X
,
Li
T
,
Bai
Z
,
Yang
Y
,
Liu
X
,
Zhan
J
,
Shi
B
:
Breast cancer intrinsic subtype classification, clinical use and future trends.
Am J Cancer Res
2015
;
5
:
2929
43
22.
Gradishar
WJ
,
Anderson
BO
,
Balassanian
R
,
Blair
SL
,
Burstein
HJ
,
Cyr
A
,
Elias
AD
,
Farrar
WB
,
Forero
A
,
Giordano
SH
,
Goetz
MP
,
Goldstein
LJ
,
Isakoff
SJ
,
Lyons
J
,
Marcom
PK
,
Mayer
IA
,
McCormick
B
,
Moran
MS
,
O’Regan
RM
,
Patel
SA
,
Pierce
LJ
,
Reed
EC
,
Salerno
KE
,
Schwartzberg
LS
,
Sitapati
A
,
Smith
KL
,
Smith
ML
,
Soliman
H
,
Somlo
G
,
Telli
M
,
Ward
JH
,
Shead
DA
,
Kumar
R
:
NCCN guidelines insights: Breast cancer, version 1.2017.
J Natl Compr Canc Netw
2017
;
15
:
433
51
23.
Govindarajulu
US
,
Spiegelman
D
,
Thurston
SW
,
Ganguli
B
,
Eisen
EA
:
Comparing smoothing techniques in Cox models for exposure-response relationships.
Stat Med
2007
;
26
:
3735
52
24.
Durrleman
S
,
Simon
R
:
Flexible regression models with cubic splines.
Stat Med
1989
;
8
:
551
61
25.
Cole
SR
,
Hernán
MA
:
Adjusted survival curves with inverse probability weights.
Comput Methods Programs Biomed
2004
;
75
:
45
9
26.
Pérez-González
O
,
Cuéllar-Guzmán
LF
,
Soliz
J
,
Cata
JP
:
Impact of regional anesthesia on recurrence, metastasis, and immune response in breast cancer surgery: A systematic review of the literature.
Reg Anesth Pain Med
2017
;
42
:
751
6
27.
Christopherson
R
,
James
KE
,
Tableman
M
,
Marshall
P
,
Johnson
FE
:
Long-term survival after colon cancer surgery: A variation associated with choice of anesthesia.
Anesth Analg
2008
;
107
:
325
32
28.
Biki
B
,
Mascha
E
,
Moriarty
DC
,
Fitzpatrick
JM
,
Sessler
DI
,
Buggy
DJ
:
Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: A retrospective analysis.
Anesthesiology
2008
;
109
:
180
7
29.
Gupta
A
,
Björnsson
A
,
Fredriksson
M
,
Hallböök
O
,
Eintrei
C
:
Reduction in mortality after epidural anaesthesia and analgesia in patients undergoing rectal but not colonic cancer surgery: A retrospective analysis of data from 655 patients in central Sweden.
Br J Anaesth
2011
;
107
:
164
70
30.
Wang
Y
,
Wang
L
,
Chen
H
,
Xu
Y
,
Zheng
X
,
Wang
G
:
The effects of intra- and post-operative anaesthesia and analgesia choice on outcome after gastric cancer resection: A retrospective study.
Oncotarget
2017
;
8
:
62658
65
31.
Exadaktylos
AK
,
Buggy
DJ
,
Moriarty
DC
,
Mascha
E
,
Sessler
DI
:
Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis?
Anesthesiology
2006
;
105
:
660
4
32.
Forget
P
,
Tombal
B
,
Scholtès
JL
,
Nzimbala
J
,
Meulders
C
,
Legrand
C
,
Van Cangh
P
,
Cosyns
JP
,
De Kock
M
:
Do intraoperative analgesics influence oncological outcomes after radical prostatectomy for prostate cancer?
Eur J Anaesthesiol
2011
;
28
:
830
5
33.
Capmas
P
,
Billard
V
,
Gouy
S
,
Lhommé
C
,
Pautier
P
,
Morice
P
,
Uzan
C
:
Impact of epidural analgesia on survival in patients undergoing complete cytoreductive surgery for ovarian cancer.
Anticancer Res
2012
;
32
:
1537
42
34.
Myles
PS
,
Peyton
P
,
Silbert
B
,
Hunt
J
,
Rigg
JR
,
Sessler
DI
;
ANZCA Trials Group Investigators
:
Perioperative epidural analgesia for major abdominal surgery for cancer and recurrence-free survival: Randomised trial.
BMJ
2011
;
342
:
d1491
35.
Liu
ZQ
,
Chen
XB
,
Li
HB
,
Qiu
MT
,
Duan
T
:
A comparison of remifentanil parturient-controlled intravenous analgesia with epidural analgesia: A meta-analysis of randomized controlled trials.
Anesth Analg
2014
;
118
:
598
603
36.
Kast
K
,
Link
T
,
Friedrich
K
,
Petzold
A
,
Niedostatek
A
,
Schoffer
O
,
Werner
C
,
Klug
SJ
,
Werner
A
,
Gatzweiler
A
,
Richter
B
,
Baretton
G
,
Wimberger
P
:
Impact of breast cancer subtypes and patterns of metastasis on outcome.
Breast Cancer Res Treat
2015
;
150
:
621
9
37.
Hortobagyi
GN
,
Connolly
JL
,
D’Orsi
CJ
,
Edge
SB
,
Mittendorf
EA
,
Rugo
HS
,
Solin
LJ
,
Weaver
DL
,
Winchester
DJ
,
Guiliano
A
:
Breast, AJCC Cancer Staging Manual
, 8th edition. Edited by
Amin
MB
,
Edge
S
,
Greene
F
,
Byrd
DR
,
Brookland
RK
,
Washington
MK
,
Gershenwald
JE
,
Compton
CC
,
Hess
KR
,
Sullivan
DC
,
Jessup
JM
,
Brierley
JD
,
Gaspar
LE
,
Schilsky
RL
,
Balch
CM
,
Winchester
DP
,
Asare
EA
,
Madera
M
,
Gress
DM
,
Meyer
LR
.
New York
,
Springer International Publishing
,
2016
38.
Gottschalk
A
,
Sharma
S
,
Ford
J
,
Durieux
ME
,
Tiouririne
M
:
The role of the perioperative period in recurrence after cancer surgery.
Anesth Analg
2010
;
110
:
1636
43
39.
Woo
JH
,
Baik
HJ
,
Kim
CH
,
Chung
RK
,
Kim
DY
,
Lee
GY
,
Chun
EH
:
Effect of propofol and desflurane on immune cell populations in breast cancer patients: A randomized trial.
J Korean Med Sci
2015
;
30
:
1503
8
40.
Miyata
T
,
Kodama
T
,
Honma
R
,
Nezu
Y
,
Harada
Y
,
Yogo
T
,
Hara
Y
,
Tagawa
M
:
Influence of general anesthesia with isoflurane following propofol-induction on natural killer cell cytotoxic activities of peripheral blood lymphocytes in dogs.
J Vet Med Sci
2013
;
75
:
917
21
41.
Benzonana
LL
,
Perry
NJ
,
Watts
HR
,
Yang
B
,
Perry
IA
,
Coombes
C
,
Takata
M
,
Ma
D
:
Isoflurane, a commonly used volatile anesthetic, enhances renal cancer growth and malignant potential via the hypoxia-inducible factor cellular signaling pathway in vitro.
Anesthesiology
2013
;
119
:
593
605
42.
Cakmakkaya
OS
,
Kolodzie
K
,
Apfel
CC
,
Pace
NL
:
Anaesthetic techniques for risk of malignant tumour recurrence.
Cochrane Database Syst Rev
2014
, pp
CD008877
43.
Owusu-Agyemang
P
,
Cata
JP
,
Fournier
KF
,
Zavala
AM
,
Soliz
J
,
Hernandez
M
,
Hayes-Jordan
A
,
Gottumukkala
V
:
Evaluating the impact of total intravenous anesthesia on the clinical outcomes and perioperative NLR and PLR profiles of patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.
Ann Surg Oncol
2016
;
23
:
2419
29
44.
Margarit
SC
,
Vasian
HN
,
Balla
E
,
Vesa
S
,
Ionescu
DC
:
The influence of total intravenous anaesthesia and isoflurane anaesthesia on plasma interleukin-6 and interleukin-10 concentrations after colorectal surgery for cancer: A randomised controlled trial.
Eur J Anaesthesiol
2014
;
31
:
678
84
45.
Gach
K
,
Wyrębska
A
,
Fichna
J
,
Janecka
A
:
The role of morphine in regulation of cancer cell growth.
Naunyn Schmiedebergs Arch Pharmacol
2011
;
384
:
221
30
46.
Singleton
PA
,
Moss
J
:
Effect of perioperative opioids on cancer recurrence: A hypothesis.
Future Oncol
2010
;
6
:
1237
42
47.
Cronin-Fenton
DP
,
Heide-Jørgensen
U
,
Ahern
TP
,
Lash
TL
,
Christiansen
PM
,
Ejlertsen
B
,
Sjøgren
P
,
Kehlet
H
,
Sørensen
HT
:
Opioids and breast cancer recurrence: A Danish population-based cohort study.
Cancer
2015
;
121
:
3507
14
48.
Aloia
TA
,
Zimmitti
G
,
Conrad
C
,
Gottumukalla
V
,
Kopetz
S
,
Vauthey
JN
:
Return to intended oncologic treatment (RIOT): A novel metric for evaluating the quality of oncosurgical therapy for malignancy.
J Surg Oncol
2014
;
110
:
107
14
49.
Cao
L
,
Chang
Y
,
Lin
W
,
Zhou
J
,
Tan
H
,
Yuan
Y
,
Zeng
W
:
Long-term survival after resection of hepatocellular carcinoma: A potential risk associated with the choice of postoperative analgesia.
Anesth Analg
2014
;
118
:
1309
16