Yingzhou Tu, Sen Wang, Haoran Wang, Peiyao Zhang, Mengyu Wang, Cunming Liu, Chun Yang, Riyue Jiang. The role of perioperative factors in the prognosis of cancer patients: A coin has two sides[J]. The Journal of Biomedical Research. DOI: 10.7555/JBR.38.20240164
Citation:
Yingzhou Tu, Sen Wang, Haoran Wang, Peiyao Zhang, Mengyu Wang, Cunming Liu, Chun Yang, Riyue Jiang. The role of perioperative factors in the prognosis of cancer patients: A coin has two sides[J]. The Journal of Biomedical Research. DOI: 10.7555/JBR.38.20240164
Yingzhou Tu, Sen Wang, Haoran Wang, Peiyao Zhang, Mengyu Wang, Cunming Liu, Chun Yang, Riyue Jiang. The role of perioperative factors in the prognosis of cancer patients: A coin has two sides[J]. The Journal of Biomedical Research. DOI: 10.7555/JBR.38.20240164
Citation:
Yingzhou Tu, Sen Wang, Haoran Wang, Peiyao Zhang, Mengyu Wang, Cunming Liu, Chun Yang, Riyue Jiang. The role of perioperative factors in the prognosis of cancer patients: A coin has two sides[J]. The Journal of Biomedical Research. DOI: 10.7555/JBR.38.20240164
Unproofed Manuscript: The manuscript has been professionally copyedited and typeset to confirm the JBR’s formatting, but still needs proofreading by the corresponding author to ensure accuracy and correct any potential errors introduced during the editing process. It will be replaced by the online publication version.
The role of perioperative factors in the prognosis of cancer patients: A coin has two sides
Chun Yang, Department of Anesthesiology and Perioperative Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. E-mail: chunyang@njmu.edu.cn
Riyue Jiang, Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. E-mail: riyuejiang@jsph.org.cn
Cancer, the second leading cause of mortality globally, poses a significant health challenge. The conventional treatment for solid tumors involves surgical intervention, followed by chemo- and radio-therapies as well as target therapies, but the recurrence and metastasis of cancers remain a major issue. Anesthesia is essential for ensuring patient comfort and safety during surgical procedures. Despite its crucial role during the surgery, the precise effect of anesthesia on cancer patient outcomes is not clearly understood. This comprehensive review aims to elucidate the various anesthesia strategies used in the perioperative care of cancer patients and their potential effects on patients' prognosis, but understanding the complex relationship between anesthesia and cancer outcomes is crucial, given the complexity in cancer treaments. Examining potential implications of anesthesia strategies on cancer patient prognosis may help better understand treatment efficacy and risk factors of cancer recurrence and metastasis. Through a detailed analysis of anesthesia practices in cancer surgery, this review aims to provide insights that may lead to improving the existing anesthesia protocols and ultimately reduce risk factors for patient outcomes in the field of oncology.
The cancer morbidity and mortality have rapidly escalated globally, with 19.3 million new cancer cases and nearly 10 million cancer-related deaths in 2020, and an estimated 28.4 million new cases by 2040[1]. While surgery remains the primary treatment for patients with solid tumors, many patients still succumb to the disease postoperatively due to cancer recurrence and metastasis, even after chemo- and radio-thrapies.[2] Surgical injury and perioperative stress may impair immune function, which may contribute to the recurrence and metastasis.[3] Several studies suggest that certain anesthetic agents, such as volatile anesthetics and opioids, may promote cancer cell survival, angiogenesis, and metastasis.[4] In contrast, other research indicates that regional anesthesia techniques, like epidurals, may reduce the risk of cancer recurrence.[5] This reduction is attributed to the preservation of immune function and decreased need for systemic opioids. However, the lack of large-scale, randomized controlled trials in this area complicates the issue. Consequently, the effect of perioperative anesthesia-related factors on the prognosis of cancer patients remains inconclusive. Therefore, we summarized the effects of perioperative anesthesia, including analgesics, anesthesia methods, and other perioperative anesthesia factors, on the prognosis of cancer patients.
Perioperative anesthesia and analgesic medications
Intravenous anesthetics
Propofol
Propofol, a commonly used intravenous anesthetic in clinical practice, is often used for anesthesia induction and maintenance. In recent years, propofol has been found to possess not only sedative-hypnotic effects but also non-anesthetic effects, such as antitumor properties.[6] Numerous studies have reported that propofol inhibits the proliferation and metastasis of various cancer cell types, including cancers of the colon, breast, lung, liver, cervix, and esophagus.[7–12] Propofol's inhibitory effects on cancer cells growth, migration, invasion, and glycolysis are mediated through diverse signaling pathways Studies have highlighted its efficacy in suppressing cervical cancer cell viability, colony formation, invasion, and migration, while promoting apoptosis through the HOTAIR/miR129-5p/RPL14 axis.[9] Sun et al. reported that propofol inhibits lung cancer A549 cells by downregulating miR-372 and thereby inhibiting the Wnt/β-catenin and mTOR pathways.[13]
In addition to its direct effect on the biological processes of cancer cells, propofol may also affect immune function of cancer patients after surgery. It has been shown that propofol may enhance the activity of cytotoxic T cells and decrease the production of pro-inflammatory cytokines.[14,15] Furthermore, propofol has been shown to enhance the function of peripheral blood natural killer (NK) cells in patients with esophageal squamous cell carcinoma, suggesting its potential to ameliorate postoperative immunosuppression.[16]
Propofol has also been found to have some significant effects on the sensitivity of cancer cells to chemotherapy drugs, thereby affecting the prognosis of cancer patients. For example, propofol enhanced the efficacy of paclitaxel by inhibiting the expression of microtubule labile instable proteins and the transcription factor Slug.[16–18] Han et al[17] demonstrated that propofol reduced cisplatin resistance in non-small cell lung cancer by inducing ferroptosis, thereby increasing the activity of chemotherapeutic agents.
These findings suggest that propofol plays a multifaceted role in modulating the sensitivity of cancer cells to chemotherapy, with potential implications for improving cancer treatment outcomes.
Ketamine
Ketamine, a racemic mixture consisting of (S)- and (R)-ketamine, is a non-competitive N-methyl-D-aspartate receptor antagonist. In addition to propofol, ketamine has been shown to affect cancer migration and invasion. Ketamine may inhibit the expression of vascular endothelial growth factor and cell migration, and reduce aerobic glycolysis in colorectal cancer cells, thereby inhibit cancer progression.[18,19] In lung cancer cells, ketamine-induced apoptosis by activating CD69 gene transcription.[20] However, in pancreatic cancer cells, ketamine directly inhibits cancer cell proliferation while also inhibiting apoptosis.[21] Similarly, ketamine exacerbates cancer by upregulating levels of the anti-apoptotic protein Bcl-2, which promotes the invasion and proliferation of breast cancer cells.[22] Ketamine has also been shown to induce lymphocyte apoptosis through the mitochondrial pathway and inhibit the functional maturation of dendritic cells.[23] At present, the effect of ketamine on cancer cells is still controversial, and its effect on different cancer cells may be tissue specific.
Inhalational anesthetics
Inhalation anesthetics such as sevoflurane, isoflurane, and desflurane play an important role in clinical anesthesia. Several in vitro studies have demonstrated the effects of inhaled anesthetics on the immune system.[24] A variety of immune cells play antitumor effects in the perioperative period, such as neutrophils, NK cells, B lymphocytes, and T lymphocytes. Among them, NK cells and T lymphocytes are prominent in the antitumor effects after the surgery.[25–27] For innate immunity, several studies have observed that inhaled anesthetics impairs neutrophil function.[28]As early as 1997, sevoflurane was found to reduce the number of neutrophils.[29] At the same time, isoflurane, sevoflurane, and halothane have all been shown to reduce the cytotoxicity of NK cells.[24] A combination of in vivo and in vitro studies showed that interferon-α and interferon-β stimulation of NK cell cytotoxicity were inhibited after exposure to halothane and isoflurane.[30] For adaptive immunity, sevoflurane, isoflurane, and desflurane induce T lymphocyte apoptosis both in vitro and in vivo, and upregulate HIF-1α expression to promote angiogenesis, cell proliferation, and metastasis.[31–34] In addition, inhalational anesthetics may also affect neuroendocrine response of the HPA axis and the sympathetic nervous system, and increase the secretion of immunosuppressive-related cytokines, such as vascular endothelial growth factor and transforming growth factor β (TGF-β), through immunomodulatory hormones, such as catecholamines and prostaglandins, thereby indirectly affecting the immune response.[35]
Analgesics
Opioid analgesics
Opioids play a crucial role in providing postoperative analgesia for cancer patients. Their potential effect on cancer recurrence and metastasis, however, remains largely unknown issue. Studies have revealed that opioids disrupt the functions of immune cells. For instance, fentanyl has been shown to inhibit macrophages and NK cells, while morphine is known to reversibly inhibit the cytotoxic effects of NK cells and the activation of cytotoxic T lymphocytes, particularly CD4+CD8+ cells.[36–38] Additionally, both in vitro and in vivo studies have shown that morphine at clinically relevant doses promotes angiogenesis, thereby facilitating the nutrient supply and growth of tumors, and aiding in evading host defenses.[39] Morphine has also been associated with the promotion of lymphangiogenesis, mast cell activation, and degranulation, leading to increased levels of inflammatory cytokines.[40]
In addition to numerous cell and animal studies, the effects of opioids on the prognosis of cancer patients have also been investigated in several clinical studies. Higher intraoperative opioid doses have been associated with a decreased risk of cancer recurrence in patients undergoing surgery for stage Ⅰ–Ⅲ adenocarcinoma of the colon.[41] However, Sessler et al reported that perioperative opioid use was not associated with an increased risk of breast cancer recurrence.[42] Notably, a recent study reported that intraoperative opioids were even protective against the recurrence of triple-negative breast cancer.[43] Furthermore, a randomized prospective clinical trial found no significant change in biochemical recurrence rates and biochemical recurrence-free survival in post-prostatectomy patients at moderate or high risk of biochemical recurrence due to opioid use.[44] Therefore, the effects of perioperative opioid use on the prognosis of cancer patients remain inconclusive, which requires future studies to validate.
Non-opioid analgesics
Non-opioid analgesics commonly used perioperatively include non-selective cyclooxygenase (COX) inhibitors and selective COX-2 inhibitors. Numerous studies have shown that non-selective COX inhibitors, such as non-steroidal anti-inflammatory drugs (NSAIDs), reduce the risk and mortality rate in patients with cancer. [45] COX-2 is widely expressed in various types of cancers, playing a versatile and multifaceted role in carcinogenesis, cancer progression, and resistance to chemotherapy and radiotherapy.[46] NSAIDs inhibit the COX activity, thereby blocking the conversion of arachidonic acid to prostaglandins, or indirectly affect cancer progression and metastasis through their analgesic effects, thereby benefiting patients. Similarly, selective COX-2 inhibitors affect the long-term prognosis of cancer patients. Interestingly, research indicates that selective COX-2 inhibitors help control chronic postoperative pain in esophageal cancer patients and may prolong patient survival.[47] Celecoxib has been shown to reduce the incidence of colorectal adenomas and colorectal cancer.[48] However, in a recent randomized clinical trial involving 2526 patients with stage Ⅲ colon cancer, the addition of celecoxib to standard adjuvant chemotherapy did not significantly improve disease-free survival (DFS), compared with placebo.[49] In conclusion, further large patient cohort studies are needed to investigate the effect of non-opioid analgesics on the prognosis of cancer patients.
Local anesthetics
Lidocaine, a widely used amide local anesthetic, is used for both systemic intravenous infusion and nerve blocks. It acts on cancer cells and the tumor microenvironment both in vivo and in vitro in ways similar to other anesthetics. Lidocaine may reinforce the function of NK cells by modulating the release of lytic granules, essential components of the antitumor immune response.[50] Moreover, perioperative lidocaine has been found to impede immune cell infiltration into the premetastatic microenvironment and prevent the release of pro-metastatic inflammatory cytokines, thereby reducing the risk of future metastases.[51] Furthermore, lidocaine has been shown to enhance the tumor-killing effect of traditional chemotherapy drugs. For example, Xing et al[52] demonstrated that lidocaine inhibited tumor growth and increased tumor sensitivity to cisplatin treatment in a xenograft model. Lidocaine not only inhibits cancer progression, but also alleviates pain, reduces surgical irritation, and mitigates stress responses in various cancers, effectively reducing postoperative pain and the inflammatory response in cancer.[53] These findings indicate the potential of lidocaine as an adjuvant drug for cancer treatment.
Recent clinical studies have investigated potential benefits of intraoperative lidocaine use in long-term survival of cancer patients. A study on clinical efficacy of lidocaine in the treatment of pancreatic cancer recurrence found that patients treated with intravenous lidocaine had better survival rates in one and three years, although there was no difference in DFS.[54] Another multicenter randomized controlled trial found that intraoperative lidocaine infusion did not improve OS or DFS in patients undergoing pancreatectomy for pancreatic cancer; however, it did reduce the formation of circulating neutrophil extracellular traps, which are associated with poor a prognosis, in pancreatic cancer tissue.[55] Similarly, intraoperative intravenous lidocaine infusion was correlated with an improved OS or DFS in patients undergoing primary cytoreductive surgery of ovarian cancer, as well as a reduction in intraoperative opioid use.[56] Furthermore, a prospective randomized controlled trial of patients undergoing ovarian tumor resection found that intraoperative and 72-hour intraperitoneal injection of ropivacaine shortened the time to chemotherapy administration.[57] Despite these positive effects, the use of lidocaine as an adjuvant drug still requires large-scale and scientifically rigorous prospective randomized controlled trials to thoroughly investigate its safety and efficacy.
Anesthetic techniques
General anesthesia
General anesthesia plays a critical role in the process of cancer surgery, with the two main methods of the inhalation anesthesia based on volatile anesthetics and total intravenous anesthesia using propofol. Emerging evidence indicates a potential association between volatile anesthetic-based inhalation anesthesia and a worse long-term cancer prognosis, compared with propofol-based intravenous anesthesia. Preclinical studies have also revealed that anesthetics affected cellular immunity and influence cancer cell proliferation, migration, and invasion.[58] Notably, inhalation anesthetics may exert direct inhibitory effects on innate and adaptive immunity, leading to reduced neutrophil recruitment, adhesion, and macrophage phagocytosis, as well as impaired cytotoxicity of NK cells and polarization of T lymphocytes to tumorigenic Th2 cell populations.[59] In contrast, intravenous anesthetics such as propofol have been shown to positively modulate immune function in cancer patients, thereby exhibiting some antitumor effects.[60]
Current clinical studies mainly focus on comparing the effects and outcomes of inhalation anesthesia versus intravenous anesthesia in cancer patients undergoing surgery. Findings from Kwon Hui Seo et al[61] indicated that patients undergoing surgery for non-small cell lung cancer exhibited over 20% higher recurrence risk in the inhalation anesthesia group, compared with the intravenous anesthesia group. Similarly, large study including colon cancer patients demonstrated better survival outcomes with intravenous anesthesia alone across different tumor-node-metastasis stages.[62] However, conflicting results have been also reported in patients undergoing breast cancer surgery, with some studies suggesting a lower risk of cancer recurrence with the propofol-based intravenous anesthesia, and others showing no significant difference in postoperative survival outcomes.[14][63] A long-term follow-up of a multicenter randomized trial, which enrolled 1,228 patients aged 65-90 years scheduled for major cancer surgery, found no difference in recurrence-free survival and event-free survival.[64] Similarly, a retrospective cohort study investigating the effects of anesthesia type on survival outcomes in patients who underwent elective surgical resection for papillary thyroid carcinoma found that propofol anesthesia was not associated with better survival compared to desflurane anesthesia.[65] Anonther systematic review and meta-analysis highlighted the potentially better OS during cancer surgery with the propofol-based intravenous anesthesia, compared with inhaled anesthesia.[66] Nevertheless, those conflicting findings call for more prospective multicenter studies with larger sample sizes to comprehensively investigate the effects of these two main anesthesia modalities on cancer recurrence related to surgical procedures.
Regional anesthesia
Regional anesthesia techniques, such as epidural anesthesia, spinal anesthesia, and nerve blocks, temporarily block the conduction function of the spinal cord or peripheral nerves to achieve anesthesia and analgesia. It has been suggested that regional anesthesia may reduce surgical stress response and immunosuppression, decrease the need for volatile anesthesia, and reduce pain and opioid requirements, potentially mitigating perioperative tumor pathways and improving long-term oncological outcomes.[67] A randomized controlled trial found a significant reduction in NK cell and T cell activities in those who received regional anesthesia compared with those who received general anesthesia.[68]
However, due to the heterogeneity of surgical scope, cancer type, patient characteristics, and limitations of study types, clinical studies on the long-term prognosis of cancer patients yield inconsistent results. Many studies compared regional anesthesia with general anesthesia alone instead of their combined effects. For example, Xu et al[69] investigated the outcomes of adult patients undergoing thoracoscopic lung cancer resection, finding that epidural analgesia combined with thoracic epidural block did not improve recurrence-free survival or other survival outcomes, nor did it benefit patients diagnosed with lung cancer. Likewise, in a randomized controlled trial of elderly patients undergoing major thoracic and abdominal surgery, general anesthesia combined with thoracic epidural block and epidural analgesia did not enhance OS and tumor-specific survival, although it did reduce inhaled anesthetics and long-acting opioids.[70]
Conversely, previous studies examining the effect of regional analgesia on breast cancer recurrence suggest that regional block combined with general anesthesia may be an appropriate anesthetic strategy for patients with breast cancer. One case-control study revealed that paravertebral block-regional anesthesia with the propofol-based sedation reduced locoregional recurrence in breast cancer patients undergoing breast-conserving surgery.[71] Additionally, a retrospective study found that patients with non-muscle-invasive bladder cancer who underwent transurethral resection of bladder cancers under neuraxial anesthesia had significantly longer recurrence-free survival than those who received general anesthesia.[72]
In conclusion, current clinical trials do not offer any unequivocal evidence that regional anesthesia may improve the long-term prognosis of cancer patients. Therefore, the decision to use regional anesthesia in the perioperative period should be based on patient characteristics and specific surgical needs, rather than specifically for preventing cancer recurrence.
Other anesthesia-related perioperative factors
Blood pressure
Hypotension during the perioperative period may lead to inadequate perfusion of vital organs, potentially causing acute or chronic irreversible damage, thus significantly affecting the postoperative outcome of patients. Notably, perioperative blood pressure not only correlates with adverse cardiovascular events and organ damage but also affects short- and long-term mortality. Moreover, there is an emerging evidence suggesting that perioperative blood pressure may have a potential effect on cancer outcomes. Perioperative hypotension may activate the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, subsequently diminishing tissue perfusion and leading to cell hypoxia, hypoxemia, metabolic acidosis, and increased lactate in severe cases, which, in turn, may impair immune cell function and promote cancer cell proliferation and metastasis. For example, Younes et al[73] observed that the frequency of hypotensive episodes played a pivotal role in influencing cancer recurrence rates in patients who had undergone complete resection of colorectal liver metastases. Consequently, they recommended avoiding hypotensive episodes during surgery to maximize the chance of cure and extend DSF in these patients. Similarly, Park et al[74] conducted a retrospective study involving renal cell carcinoma patients and found that perioperative blood pressure in the stage 2 hypertension range (≥ 160/100 mm Hg) emerged as an independent predictor of overall mortality. Despite these findings, the potential effect of perioperative blood pressure fluctuations on cancer prognosis warrants further investigation.
Blood transfusion
The phenomenon of transfusion-related immunomodulation refers to the immunosuppressive effects of allogeneic transfusions in the perioperative period that may negatively influence cancer recurrence and metastasis. Allogeneic transfusions lead to alterations in several facets of the recipient's immune function, including a decrease in the ratio of helper T lymphocytes to suppressor T lymphocytes, diminished NK cell function, defective antigen presentation, and reduced cell-mediated immunity.[75] Furthermore, studies in various experimental animal models have indicated the potential pro-tumor growth effects of allogeneic transfusion, which may be attributed to the presence of allogeneic donor leukocytes in transfused blood products.[76]
Although there is limited evidence from randomized trials concerning the relationship between blood transfusion and cancer recurrence and prognosis, most current relevant clinical studies are retrospective. A propensity-matched analysis of patients with hepatocellular carcinoma undergoing hepatectomy revealed that red blood cell transfusion (RBCT) promoted cancer recurrence and decreased long-term survival after radical resection, while other types of transfusions, including platelets, 5% albumin, and 25% albumin, did not affect long-term survival.[77] Similar associations have also been observed in gastric cancer, non-small cell lung cancer, and head and neck cancers.[78–80] However, a retrospective, single-center cohort study of patients with stage Ⅰ–Ⅲ colorectal cancer who underwent radical surgery between 2005 and 2017 found that perioperative RBCT was significantly associated with a poorer OS.[81] The survival outcomes in the group receiving perioperative RBCT were significantly worse than those without RBCT, and perioperative RBCT was significantly associated with a poorer OS in multivariable analysis.[81] Notably, when propensity scores were used to match transfused and non-transfused cases, no difference in OS and cancer-specific survival was observed.[81] The need for intraoperative blood transfusion is influenced by factors such as surgical complexity and the patient's physical condition. Similarly, cancer recurrence and prognosis are influenced by variables such as tumor stage and postoperative adjuvant therapy. Therefore, the effect of blood transfusion on cancer prognosis remains uncertain, and there is a need for more well-designed randomized controlled trials to provide conclusive evidence.
Hypothermia
In the perioperative period, hypothermia is a frequent complication that may lead to various adverse outcomes including postoperative infection, cardiovascular events, and an increased risk of blood transfusion.[82] Elevated temperatures generally promote the activation, function, and delivery of immune cells, while decreased temperatures inhibit these processes.[83] Zeba et al[84] conducted a single-center randomized controlled trial in 2020 to investigate the effect of intraoperative hypothermia on the cytokine profile. The study found that patients in the non-warming group had the lowest mean perioperative core body temperature and showed a sustained increase in the pro-inflammatory response. In addition, intraoperative warming to maintain normal body temperature was found to attenuate the harmful pro-inflammatory response. Furthermore, Nduka et al[85] used an animal model to investigate the effect of hypothermia on tumor growth during laparoscopic surgery. Their results showed that the tumor mass was significantly increased in the cold CO2 pneumoperitoneum group, compared with the warmed CO2 pneumoperitoneum group. However, there are still few clinical studies on the relationship between intraoperative hypothermia and cancer prognosis, and there are many factors that affect cancer prognosis, so it is difficult to explain the differences in long-term outcomes of cancer patients with intraoperative hypothermia alone. A retrospective clinical study of 124 patients with myoinvasive bladder cancer who underwent radical cystectomy from 2003 to 2016 showed no significant differences in OS and DFS between the hypothermic and normothermic groups.[86] However, in subgroup analysis based on pathologic stage, OS and DFS were significantly shorter in the hypothermic group than those in the normothermic group for stage Ⅱ patients.[86] Expanding on this, Lyon et al[87] increased the sample size to 852 patients undergoing radical cystectomy and found no significant difference in the 2-year survival rate between the hypothermic and the normothermic groups, and no significant correlation between intraoperative hypothermia and recurrence-free survival (RFS), tumor-specific survival (CSS), and OS. However, they found that a median body temperature of < 35 ℃ was an independent factor influencing OS.
Given the influence of hypothermia on tumor growth, hyperthermia has emerged as a potential cancer treatment to reduce cancer recurrence. Current evidence suggests that physiological responses to hyperthermia may enhance the ability of the microenvironment to resist tumors by regulating temperature-sensitive checkpoints in tumor vascular perfusion and metabolism.[88] However, an in vitro study reported that cancer cells were more resistant to higher temperatures than normal cells, signifying a need for further understanding of the effects of thermal stimulation on the tumor environment and antitumor immune responses.[89]
Limitation
This review examines the effects of anesthetics on tumor proliferation, apoptosis, and invasion, primarily utilizing in vitro studies. Several limitations must be acknowledged. First, some epidemiological results are inconsistent with findings from in vitro animal and cell studies. This discrepancy may be attributed to the fact that in vitro studies assess the direct effects of anesthetics on tumor cells, whereas in clinical practice, tumor tissue is typically excised, and anesthetics exert only transient effects on systemic tissues rather than directly affecting the tumor tissue itself. As a result, these in vitro findings may not accurately reflect the impact of anesthetics on tumor recurrence or metastasis in clinical settings.[42,90] Furthermore, the proficiency of the surgeon plays a critical role in influencing both the duration of the surgery and the thoroughness of tumor tissue removal. Incomplete resection of tumor tissue, often due to less meticulous surgical techniques, is a well-documented cause of cancer recurrence. Additional factors such as intraoperative blood loss, the duration of anesthesia, and the presence of tumor stem cells also significantly affect surgical outcomes and warrant further investigation. Given these considerations, we plan to undertake a more rigorous systematic review in the future, drawing on a broader range of clinical research data.
Conclusions and perspectives
In summary, the immunosuppression caused by anesthetics, surgical techniques, and other perioperative factors has been suggested to potentially facilitate metastasis and cancer recurrence (Fig. 1). However, there are conflicting findings regarding the effect of anesthesia on immune response and tumor growth (Table 1). As a result, the current evidence regarding different anesthetic strategies for perioperative cancer recurrence remains inconclusive. Therefore, to fill this knowledge gap, there is an urgent need for large, randomized multicenter prospective clinical trials to investigate the influence of different anesthetics, surgical techniques, and other relevant factors on the long-term prognosis of cancer surgery.
Figure
1.
Perioperative factors influence the prognosis of cancer patients.
The authors would like to express the deepest gratitude to all those who have supported us throughout the process of this paper.
The authors are grateful to our colleagues and peers for their constructive criticism and encouragement.
The authors would like to thank the anonymous reviewers for their helpful remarks.
Fundings
This study was supported by the Innovative and Entrepreneurial Team of Jiangsu Province (JSSCTD202144), the Nanjing Postdoctoral Program (BSHNJ2023006), and the National Natural Science Foundation of China (82201380).
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209–249. doi: 10.3322/caac.21660
[2]
Dillekås H, Rogers MS, Straume O. Are 90% of deaths from cancer caused by metastases?[J]. Cancer Med, 2019, 8(12): 5574–5576. doi: 10.1002/cam4.2474
[3]
Yap A, Lopez-Olivo MA, Dubowitz J, et al. Anesthetic technique and cancer outcomes: a meta-analysis of total intravenous versus volatile anesthesia[J]. Can J Anaesth, 2019, 66(5): 546–561. doi: 10.1007/s12630-019-01330-x
[4]
Smith L, Cata JP, Forget P. Immunological insights into opioid-free anaesthesia in oncological surgery: a scoping review[J]. Curr Oncol Rep, 2022, 24(10): 1327–1336. doi: 10.1007/s11912-022-01300-5
[5]
Illias AM, Yu K, Wu S, et al. Association of regional anesthesia with oncological outcomes in patients receiving surgery for bladder cancer: a meta-analysis of observational studies[J]. Front Oncol, 2023, 13: 1097637. doi: 10.3389/fonc.2023.1097637
[6]
Xu Y, Pan S, Jiang W, et al. Effects of propofol on the development of cancer in humans[J]. Cell Prolif, 2020, 53(8): e12867. doi: 10.1111/cpr.12867
[7]
Hu C, Iwasaki M, Liu Z, et al. Lung but not brain cancer cell malignancy inhibited by commonly used anesthetic propofol during surgery: implication of reducing cancer recurrence risk[J]. J Adv Res, 2021, 31: 1–12. doi: 10.1016/j.jare.2020.12.007
[8]
Sun C, Liu P, Pei L, et al. Propofol inhibits proliferation and augments the anti-tumor effect of doxorubicin and paclitaxel partly through promoting ferroptosis in triple-negative breast cancer cells[J]. Front Oncol, 2022, 12: 837974. doi: 10.3389/fonc.2022.837974
[9]
Sun N, Zhang W, Liu J, et al. Propofol inhibits the progression of cervical cancer by regulating HOTAIR/miR-129–5p/RPL14 axis[J]. Onco Targets Ther, 2021, 14: 551–564. doi: 10.2147/OTT.S279942
[10]
Wu Z, Wang H, Shi Z, et al. Propofol prevents the growth, migration, invasion, and glycolysis of colorectal cancer cells by downregulating lactate dehydrogenase both in vitro and in vivo[J]. J Oncol, 2022, 2022: 8317466. doi: 10.1155/2022/8317466
[11]
Hu C, Wang B, Liu Z, et al. Sevoflurane but not propofol enhances ovarian cancer cell biology through regulating cellular metabolic and signaling mechanisms[J]. Cell Biol Toxicol, 2023, 39(4): 1395–1411. doi: 10.1007/s10565-022-09766-6
[12]
Xu Y, Du Q, Zhang M, et al. Propofol suppresses proliferation, invasion and angiogenesis by down-regulating ERK-VEGF/MMP-9 signaling in Eca-109 esophageal squamous cell carcinoma cells[J]. Eur Rev Med Pharmacol Sci, 2013, 17(18): 2486–2494. doi: 10.1358/dof.2013.38.9.2040082
[13]
Sun H, Gao D. RETRACTED ARTICLE: propofol suppresses growth, migration and invasion of A549 cells by down-regulation of miR-372[J]. BMC Cancer, 2018, 18(1): 1252. doi: 10.1186/s12885-018-5175-y
[14]
Fang P, Zhou J, Xia Z, et al. Effects of propofol versus sevoflurane on postoperative breast cancer prognosis: a narrative review[J]. Front Oncol, 2021, 11: 793093. https://pubmed.ncbi.nlm.nih.gov/35127500/
[15]
Gu L, Pan X, Wang C, et al. The benefits of propofol on cancer treatment: Decipher its modulation code to immunocytes[J]. Front Pharmacol, 2022, 13: 919636. doi: 10.3389/fphar.2022.919636
[16]
Zhou M, Dai J, Zhou Y, et al. Propofol improves the function of natural killer cells from the peripheral blood of patients with esophageal squamous cell carcinoma[J]. Exp Ther Med, 2018, 16(1): 83–92. doi: 10.3892/etm.2018.6140
[17]
Han B, Liu Y, Zhang Q, et al. Propofol decreases cisplatin resistance of non-small cell lung cancer by inducing GPX4-mediated ferroptosis through the miR-744–5p/miR-615–3p axis[J]. J Proteomics, 2023, 274: 104777. doi: 10.1016/j.jprot.2022.104777
[18]
Duan W, Hu J, Liu Y. Ketamine inhibits colorectal cancer cells malignant potential via blockage of NMDA receptor[J]. Exp Mol Pathol, 2019, 107: 171–178. doi: 10.1016/j.yexmp.2019.02.004
[19]
Hu J, Duan W, Liu Y. Ketamine inhibits aerobic glycolysis in colorectal cancer cells by blocking the NMDA receptor-CaMK II-c-Myc pathway[J]. Clin Exp Pharmacol Physiol, 2020, 47(5): 848–856. doi: 10.1111/1440-1681.13248
[20]
Zhou X, Zhang P, Luo W, et al. Ketamine induces apoptosis in lung adenocarcinoma cells by regulating the expression of CD69[J]. Cancer Med, 2018, 7(3): 788–795. doi: 10.1002/cam4.1288
[21]
Malsy M, Gebhardt K, Gruber M, et al. Effects of ketamine, s-ketamine, and MK 801 on proliferation, apoptosis, and necrosis in pancreatic cancer cells[J]. BMC Anesthesiol, 2015, 15: 111. doi: 10.1186/s12871-015-0076-y
[22]
He H, Chen J, Xie W, et al. Ketamine used as an acesodyne in human breast cancer therapy causes an undesirable side effect, upregulating anti-apoptosis protein Bcl-2 expression[J]. Genet Mol Res, 2013, 12(2): 1907–1915. doi: 10.4238/2013.January.4.7
[23]
Ponferrada AR, Orriach JLG, Manso AM, et al. Anaesthesia and cancer: can anaesthetic drugs modify gene expression?[J]. Ecancermedicalscience, 2020, 14: 1080. doi: 10.3332/ecancer.2020.1080
[24]
Ackerman RS, Luddy KA, Icard BE, et al. The effects of anesthetics and perioperative medications on immune function: a narrative review[J]. Anesth Analg, 2021, 133(3): 676–689. doi: 10.1213/ANE.0000000000005607
[25]
Wang F, Lau JKC, Yu J. The role of natural killer cell in gastrointestinal cancer: killer or helper[J]. Oncogene, 2021, 40(4): 717–730. doi: 10.1038/s41388-020-01561-z
[26]
Dang Y, Shi X, Xu W, et al. The effect of anesthesia on the immune system in colorectal cancer patients[J]. Can J Gastroenterol Hepatol, 2018, 2018: 7940603. https://pubmed.ncbi.nlm.nih.gov/29805965/
[27]
Angka L, Khan ST, Kilgour MK, et al. Dysfunctional natural killer cells in the aftermath of cancer surgery[J]. Int J Mol Sci, 2017, 18(8): 1787. doi: 10.3390/ijms18081787
[28]
Stollings LM, Jia L, Tang P, et al. Immune modulation by volatile anesthetics[J]. Anesthesiology, 2016, 125(2): 399–411. doi: 10.1097/ALN.0000000000001195
[29]
Fröhlich D, Rothe G, Schwall B, et al. Effects of volatile anaesthetics on human neutrophil oxidative response to the bacterial peptide FMLP[J]. Br J Anaesth, 1997, 78(6): 718–723. doi: 10.1093/bja/78.6.718
[30]
Markovic SN, Knight PR, Murasko DM. Inhibition of interferon stimulation of natural killer cell activity in mice anesthetized with halothane or isoflurane[J]. Anesthesiology, 1993, 78(4): 700–706. doi: 10.1097/00000542-199304000-00013
[31]
Tavare AN, Perry NJS, Benzonana LL, et al. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents[J]. Int J Cancer, 2012, 130(6): 1237–1250. doi: 10.1002/ijc.26448
[32]
Shi Q, Zhang S, Liu L, et al. Sevoflurane promotes the expansion of glioma stem cells through activation of hypoxia-inducible factors in vitro[J]. Br J Anaesth, 2015, 114(5): 825–830. doi: 10.1093/bja/aeu402
[33]
Benzonana LL, Perry NJS, Watts HR, et al. Isoflurane, a commonly used volatile anesthetic, enhances renal cancer growth and malignant potential via the hypoxia-inducible factor cellular signaling pathway in vitro[J]. Anesthesiology, 2013, 119(3): 593–605. doi: 10.1097/ALN.0b013e31829e47fd
[34]
Zhu M, Li M, Zhou Y, et al. Isoflurane enhances the malignant potential of glioblastoma stem cells by promoting their viability, mobility in vitro and migratory capacity in vivo[J]. Br J Anaesth, 2016, 116(6): 870–877. doi: 10.1093/bja/aew124
[35]
Alsina E, Matute E, Ruiz-Huerta AD, et al. The effects of sevoflurane or remifentanil on the stress response to surgical stimulus[J]. Curr Pharm Des, 2014, 20(34): 5449–5468. doi: 10.2174/1381612820666140325105723
[36]
Wigmore T, Farquhar-Smith P. Opioids and cancer: friend or foe?[J]. Curr Opin Support Palliat Care, 2016, 10(2): 109–118. doi: 10.1097/SPC.0000000000000208
[37]
Shavit Y, Ben-Eliyahu S, Zeidel A, et al. Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats: dose and timing study[J]. Neuroimmunomodulation, 2004, 11(4): 255–260. doi: 10.1159/000078444
[38]
Shavit Y, Lewis JW, Terman GW, et al. Opioid peptides mediate the suppressive effect of stress on natural killer cell cytotoxicity[J]. Science, 1984, 223(4632): 188–190. doi: 10.1126/science.6691146
[39]
Lucia M, Luca T, Federica DP, et al. Opioids and breast cancer recurrence: a systematic review[J]. Cancers (Basel), 2021, 13(21): 5499. doi: 10.3390/cancers13215499
[40]
Nguyen J, Luk K, Vang D, et al. Morphine stimulates cancer progression and mast cell activation and impairs survival in transgenic mice with breast cancer[J]. Br J Anaesth, 2014, 113 Suppl 1(Suppl 1): i4–i13.
[41]
Yuval JB, Lee J, Wu F, et al. Intraoperative opioids are associated with decreased recurrence rates in colon adenocarcinoma: a retrospective observational cohort study[J]. Br J Anaesth, 2022, 129(2): 172–181. doi: 10.1016/j.bja.2022.04.024
[42]
Sessler DI, Pei L, Huang Y, et al. Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial[J]. Lancet, 2019, 394(10211): 1807–1815. doi: 10.1016/S0140-6736(19)32313-X
[43]
Montagna G, Gupta HV, Hannum M, et al. Intraoperative opioids are associated with improved recurrence-free survival in triple-negative breast cancer[J]. Br J Anaesth, 2021, 126(2): 367–376. doi: 10.1016/j.bja.2020.10.021
[44]
Rangel FP, Auler JOC, Carmona MJC, et al. Opioids and premature biochemical recurrence of prostate cancer: a randomised prospective clinical trial[J]. Br J Anaesth, 2021, 126(5): 931–939. doi: 10.1016/j.bja.2021.01.031
[45]
Kolawole OR, Kashfi K. NSAIDs and cancer resolution: new paradigms beyond cyclooxygenase[J]. Int J Mol Sci, 2022, 23(3): 1432. doi: 10.3390/ijms23031432
[46]
Hashemi Goradel N, Najafi M, Salehi E, et al. Cyclooxygenase-2 in cancer: a review[J]. J Cell Physiol, 2019, 234(5): 5683–5699. doi: 10.1002/jcp.27411
[47]
Fan X, Wang S, Pan K, et al. Selective COX-2 inhibitor is beneficial in suppressing chronic postsurgical pain in esophageal cancer patients and may prolong patient survival[J]. Oncol Res Treat, 2023, 46(12): 503–510. doi: 10.1159/000535183
[48]
Zhang Z, Ghosh A, Connolly PJ, et al. Gut-restricted selective cyclooxygenase-2 (COX-2) inhibitors for chemoprevention of colorectal cancer[J]. J Med Chem, 2021, 64(15): 11570–11596. doi: 10.1021/acs.jmedchem.1c00890
[49]
Meyerhardt JA, Shi Q, Fuchs CS, et al. Effect of celecoxib vs placebo added to standard adjuvant therapy on disease-free survival among patients with stage Ⅲ colon cancer: the CALGB/SWOG 80702 (Alliance) randomized clinical trial[J]. JAMA, 2021, 325(13): 1277–1286. doi: 10.1001/jama.2021.2454
[50]
Ramirez MF, Tran P, Cata JP. The effect of clinically therapeutic plasma concentrations of lidocaine on natural killer cell cytotoxicity[J]. Reg Anesth Pain Med, 2015, 40(1): 43–48. doi: 10.1097/AAP.0000000000000191
[51]
Wall TP, Buggy DJ. Perioperative intravenous lidocaine and metastatic cancer recurrence - a narrative review[J]. Front Oncol, 2021, 11: 688896. doi: 10.3389/fonc.2021.688896
[52]
Xing W, Chen D, Pan J, et al. Lidocaine induces apoptosis and suppresses tumor growth in human hepatocellular carcinoma cells in vitro and in a xenograft model in vivo[J]. Anesthesiology, 2017, 126(5): 868–881. doi: 10.1097/ALN.0000000000001528
[53]
Zhang C, Xie C, Lu Y. Local anesthetic lidocaine and cancer: insight into tumor progression and recurrence[J]. Front Oncol, 2021, 11: 669746. doi: 10.3389/fonc.2021.669746
[54]
Zhang H, Yang L, Zhu X, et al. Association between intraoperative intravenous lidocaine infusion and survival in patients undergoing pancreatectomy for pancreatic cancer: a retrospective study[J]. Br J Anaesth, 2020, 125(2): 141–148. doi: 10.1016/j.bja.2020.03.034
[55]
Zhang H, Qu M, Guo K, et al. Intraoperative lidocaine infusion in patients undergoing pancreatectomy for pancreatic cancer: a mechanistic, multicentre randomised clinical trial[J]. Br J Anaesth, 2022, 129(2): 244–253. doi: 10.1016/j.bja.2022.03.031
[56]
Zhang H, Gu J, Qu M, et al. Effects of intravenous infusion of lidocaine on short-term outcomes and survival in patients undergoing surgery for ovarian cancer: a retrospective propensity score matching study[J]. Front Oncol, 2021, 11: 689832. https://pubmed.ncbi.nlm.nih.gov/35070949/
[57]
Hayden JM, Oras J, Block L, et al. Intraperitoneal ropivacaine reduces time interval to initiation of chemotherapy after surgery for advanced ovarian cancer: randomised controlled double-blind pilot study[J]. Br J Anaesth, 2020, 124(5): 562–570. doi: 10.1016/j.bja.2020.01.026
[58]
Dubowitz JA, Sloan EK, Riedel BJ. Implicating anaesthesia and the perioperative period in cancer recurrence and metastasis[J]. Clin Exp Metastasis, 2018, 35(4): 347–358. doi: 10.1007/s10585-017-9862-x
[59]
Stollings LM, Jia L, Tang P, et al. Immune modulation by volatile anesthetics[J]. Anesthesiology, 2016, 125(2): 399–411.
[60]
Kim R, Kawai A, Wakisaka M, et al. Current status and prospects of anesthesia and breast cancer: does anesthetic technique affect recurrence and survival rates in breast cancer surgery?[J]. Front Oncol, 2022, 12: 795864. doi: 10.3389/fonc.2022.795864
[61]
Seo KH, Hong JH, Moon MH, et al. Effect of total intravenous versus inhalation anesthesia on long-term oncological outcomes in patients undergoing curative resection for early-stage non-small cell lung cancer: a retrospective cohort study[J]. Korean J Anesthesiol, 2023, 76(4): 336–347. doi: 10.4097/kja.22584
[62]
Wu Z, Lee MS, Wong CS, et al. Propofol-based total intravenous anesthesia is associated with better survival than desflurane anesthesia in colon cancer surgery[J]. Anesthesiology, 2018, 129(5): 932–941. doi: 10.1097/ALN.0000000000002357
[63]
Kim MH, Kim DW, Kim JH, et al. Does the type of anesthesia really affect the recurrence-free survival after breast cancer surgery?[J]. Oncotarget, 2017, 8(52): 90477–90487. doi: 10.18632/oncotarget.21014
[64]
Cao S, Zhang Y, Zhang Y, et al. Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial[J]. Br J Anaesth, 2023, 131(2): 266–275. doi: 10.1016/j.bja.2023.01.023
[65]
Chiu WC, Wu Z, Lee MS, et al. Propofol-based total intravenous anesthesia is associated with less postoperative recurrence than desflurane anesthesia in thyroid cancer surgery[J]. PLoS One, 2024, 19(1): e0296169. doi: 10.1371/journal.pone.0296169
[66]
Chang C, Wu M, Chien YJ, et al. Anesthesia and long-term oncological outcomes: a systematic review and meta-analysis[J]. Anesth Analg, 2021, 132(3): 623–634. doi: 10.1213/ANE.0000000000005237
[67]
Dockrell L, Buggy DJ. The role of regional anaesthesia in the emerging subspecialty of onco-anaesthesia: a state-of-the-art review[J]. Anaesthesia, 2021, 76 Suppl 1: 148–159.
[68]
Wang L, Liang S, Chen H, et al. The effects of epidural anaesthesia and analgesia on T lymphocytes differentiation markers and cytokines in patients after gastric cancer resection[J]. BMC Anesthesiol, 2019, 19(1): 102. doi: 10.1186/s12871-019-0778-7
[69]
Xu Z, Li H, Li M, et al. Epidural anesthesia-analgesia and recurrence-free survival after lung cancer surgery: a randomized trial[J]. Anesthesiology, 2021, 135(3): 419–432. doi: 10.1097/ALN.0000000000003873
[70]
Du Y, Li Y, Zhao B, et al. Long-term survival after combined epidural-general anesthesia or general anesthesia alone: follow-up of a randomized trial[J]. Anesthesiology, 2021, 135(2): 233–245. doi: 10.1097/ALN.0000000000003835
[71]
Zhang J, Chang CL, Lu C, et al. Paravertebral block in regional anesthesia with propofol sedation reduces locoregional recurrence in patients with breast cancer receiving breast conservative surgery compared with volatile inhalational without propofol in general anesthesia[J]. Biomed Pharmacother, 2021, 142: 111991. doi: 10.1016/j.biopha.2021.111991
[72]
Baba Y, Kikuchi E, Shigeta K, et al. Effects of transurethral resection under general anesthesia on tumor recurrence in non-muscle invasive bladder cancer[J]. Int J Clin Oncol, 2021, 26(11): 2094–2103. doi: 10.1007/s10147-021-02000-z
[73]
Younes RN, Rogatko A, Brennan MF. The influence of intraoperative hypotension and perioperative blood transfusion on disease-free survival in patients with complete resection of colorectal liver metastases[J]. Ann Surg, 1991, 214(2): 107–113. doi: 10.1097/00000658-199108000-00003
[74]
Park B, Jeong BC, Seo SI, et al. Influence of body mass index, smoking, and blood pressure on survival of patients with surgically-treated, low stage renal cell carcinoma: a 14-year retrospective cohort study[J]. J Korean Med Sci, 2013, 28(2): 227–236. doi: 10.3346/jkms.2013.28.2.227
[75]
Blajchman MA. Transfusion immunomodulation or TRIM: what does it mean clinically?[J]. Hematology, 2005, 10 Suppl 1: 208–214.
[76]
Blajchman MA, Bardossy L, Carmen R, et al. Allogeneic blood transfusion-induced enhancement of tumor growth: two animal models showing amelioration by leukodepletion and passive transfer using spleen cells[J]. Blood, 1993, 81(7): 1880–1882. doi: 10.1182/blood.V81.7.1880.1880
[77]
Nakayama H, Okamura Y, Higaki T, et al. Effect of blood product transfusion on the prognosis of patients undergoing hepatectomy for hepatocellular carcinoma: a propensity score matching analysis[J]. J Gastroenterol, 2023, 58(2): 171–181. doi: 10.1007/s00535-022-01946-9
[78]
Hsu FK, Chang WK, Lin K, et al. The associations between perioperative blood transfusion and long-term outcomes after stomach cancer surgery[J]. Cancers (Basel), 2021, 13(21): 5438. doi: 10.3390/cancers13215438
[79]
Hee HZ, Chang K, Huang CY, et al. Perioperative blood transfusion is dose-dependently associated with cancer recurrence and mortality after head and neck cancer surgery[J]. Cancers (Basel), 2022, 15(1): 99. doi: 10.3390/cancers15010099
[80]
Tai YH, Wu HL, Mandell MS, et al. The association of non-small cell lung cancer recurrence with allogenic blood transfusion after surgical resection: a propensity score analysis of 1, 803 patients[J]. Eur J Cancer, 2020, 140: 45–54. doi: 10.1016/j.ejca.2020.09.004
[81]
Turri G, Pedrazzani C, Malerba G, et al. Effect of peri-operative blood transfusions on long-term prognosis of patients with colorectal cancer[J]. Blood Transfus, 2022, 20(2): 103–111. https://pubmed.ncbi.nlm.nih.gov/33370231/
[82]
Xia S, Zhou D, Ge F, et al. Influence of perioperative anesthesia on cancer recurrence: from basic science to clinical practice[J]. Curr Oncol Rep, 2023, 25(2): 63–81. doi: 10.1007/s11912-022-01342-9
Zeba S, Surbatovic M, Stanojevic I, et al. The effects of intraoperative hypothermia on cytokine profile: a randomized pilot study[J]. J Clin Anesth, 2020, 63: 109779. doi: 10.1016/j.jclinane.2020.109779
[85]
Nduka CC, Puttick M, Coates P, et al. Intraperitoneal hypothermia during surgery enhances postoperative tumor growth[J]. Surg Endosc, 2002, 16(4): 611–615. doi: 10.1007/s00464-001-9055-0
[86]
Morozumi K, Mitsuzuka K, Takai Y, et al. Intraoperative hypothermia is a significant prognostic predictor of radical cystectomy especially for stage II muscle-invasive bladder cancer[J]. Medicine (Baltimore), 2019, 98(2): e13962. doi: 10.1097/MD.0000000000013962
[87]
Lyon TD, Frank I, Tollefson MK, et al. Association of intraoperative hypothermia with oncologic outcomes following radical cystectomy[J]. Urol Oncol, 2021, 39(6): 370. e1–370. e8.
[88]
Repasky EA, Evans SS, Dewhirst MW. Temperature matters! And why it should matter to tumor immunologists[J]. Cancer Immunol Res, 2013, 1(4): 210–216. doi: 10.1158/2326-6066.CIR-13-0118
[89]
Tang X, Cao F, Ma W, et al. Cancer cells resist hyperthermia due to its obstructed activation of caspase 3[J]. Rep Pract Oncol Radiother, 2020, 25(3): 323–326. doi: 10.1016/j.rpor.2020.02.008
[90]
Cao S, Zhang Y, Zhang Y, et al. Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial[J]. Br J Anaesth, 2023, 131(2): 266–275.
Authors and Reviewers
DownLoad:
