Open Access

Influence of anesthetic technique on survival after tumor debulking surgery of elderly patients with ovarian cancer:
Results of a retrospective cohort study

  • Authors:
    • Katharina Anic
    • Mona Wanda Schmidt
    • Annika Droste
    • Roxana Schwab
    • Marcus Schmidt
    • Slavomir Krajnak
    • Miriam Renz
    • Erik Kristoffer Hartmann
    • Roland Hardt
    • Annette Hasenburg
    • Marco Johannes Battista
  • View Affiliations

  • Published online on: August 26, 2022     https://doi.org/10.3892/ol.2022.13481
  • Article Number: 361
  • Copyright: © Anic et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Epidural analgesia could influence the postoperative oncologic outcomes in patients with specific types of non‑metastatic solid neoplasms. The present study aimed to investigate the impact of anesthetic technique on survival in elderly patients with ovarian cancer (OC). The records of all women with OC older than 60 years of age undergoing tumor debulking surgery at the University Medical Center of the Johannes Gutenberg University Mainz (Mainz, Germany) between January 2008 and December 2019 were obtained. The study cohort was divided into two groups based on the use of perioperative epidural anesthesia or not. First, Kaplan‑Meier analysis was performed to analyze the prognostic influence of anesthetic technique on survival. Second, multivariate Cox proportional hazards model was adjusted for multiple conventional prognostic factors concerning three main categories: i) Current clinical‑pathological tumor characteristics; ii) anesthesiologic parameters, including mean age, American Society of Anesthesiologists Performance Status and preexisting comorbidities summarized in the Charlson Comorbidity Index; and iii) oncological and surgical parameters such as oncological radicality and Surgical complexity Score. A total of 110 patients were included in the study and 71 (64.5%) of them received epidural analgesia. The median survival time was 26.0 months from primary debulking surgery and no significant differences in progression‑free (PFS) and overall survival (OS) were noted between the ‘Epidural’ and ‘non‑Epidural’ cohorts. After adjustment for the selected risk factors from the three categories, the effects of epidural analgesia on PFS and OS remained non‑significant [PFS: hazard ratio (HR), 1.26; 95% CI, 0.66‑2.39; and OS: HR, 0.79; 95% CI, 0.45‑1.40]. The present results did not support the independent association between epidural‑supplemented anesthesia and improved PFS or OS in elderly patients with standardized ovarian cancer debulking surgery.

Introduction

Ovarian carcinoma (OC) is one of the most common neoplasms of the female reproductive tract (1). With over 240,000 new diagnoses and 152,000 annual deaths worldwide in 2020 according to the Global Cancer Statistics (2), OC exhibits the worst prognosis among gynecological malignancies (3). With a median age of 68 years at diagnosis, OC is a typical cancer of the older generation (4). However, increasing biological age is independently associated with more aggressive and advanced diseases (5,6).

At present, radical primary or interval surgical debulking remains as the preferred first-line treatment option, possibly with extensive multivisceral cytoreduction to achieve complete macroscopic tumor reduction with no residual tumor burden (79). Although, excessive surgical resections have been shown to initiate metastasis via circulating tumor cells to blood and lymph or activate dormant pre-existing micrometastases (1012). Whether the minimal residual tumor burden results in clinical metastases depends primarily on the balance between the body's immunity and natural killer (NK) cell activity and the tumor's ability to proliferate or colonize a new site (13). The most popular hypothesis about the immunomodulation effect of surgical stress explains the adverse impact of the inhibition of the body's innate tumor defense mechanism (14). Otherwise, an effective immune response is affected by the integrated network of different cytokines, including interleukins and interferons. Certain cytokines are antitumorigenic and permit cancer growth (e.g. IL-2 and IFN-γ), whereas others are pro-tumorigenic and promote the immune system's anti-tumor capability (e.g. IL-6 and IL-8) (15).

Interestingly, the technique of anesthesia may influence the long-term outcome of solid cancer patients by modulating the neuroendocrine and cytokine imparted immune competence and stress response during excessive surgery (16,17). Compared with general anesthesia using intravenous opioids or inhaled anesthetics, regional anesthesia can effectively increase the level of activated NK cells to preserve host immunity, as a primary immunological defense against cancer cells (18,19). This possible survival advantage for epidural-supplemented anesthesia with decreased levels of opioids depends on a reduction of cancer recurrences and postoperative mortality without metastasis, mainly in elderly cancer patients (20,21). Besides, exposure to volatile anesthetics leads to resistance of cancer cells against apoptosis in a dose-dependent pattern (22). Moreover, opioids may suppress the NK cell cytotoxicity, as one component of the human cellular immune system, as well as promote tumor growth by activating the µ-opioid receptor (23,24). As an unavoidable adverse effect of general anesthesia during partial cell vagotomy, an endocrine stress response followed (25).

Thereof, this study aimed to evaluate the prognostic influence of epidural-supplemented anesthesia on cancer survival in a highly specified cohort of older ovarian cancer patients after major oncological surgery.

Materials and methods

Inclusion and exclusion criteria

Patients with all stages of OC [based on the 2010 FIGO staging system (26)] older than 60 years of age, who underwent standardized surgical treatment at the University Medical Center of the Johannes Gutenberg University Mainz between January 2008 and December 2019, were included in the retrospective cohort study. Standardized oncological surgery required primary or interval tumor debulking operations to decrease the postoperative residual tumor burden as much as possible (aim R0 resection) and was defined as a further inclusion criterion. Exclusion criteria were: 1) surgically treatment not in the University Medical Center Mainz, 2) Non-malignant or borderline ovarian tumors, 3) No information about epidural analgesia available and 4) No complete follow-up information. Long-term follow-up was performed by evaluation of patient's clinical records, written inquiries to the patients or their physicians, and by telephone calls up to February 2021. The follow-up ended at death, and the longest follow-up period lasted nearly 11.5 years (June 2008-December 2019 according to 138 months).

Baseline characteristics

We screened the archives and the electronically patients' records to gather all using general patient information. Clinical-pathological tumor characteristics were collected according to the current national guidelines, which may influence the postoperative prognosis in OC patients. These factors are summarized within three categories: 1) clinical-pathological tumor parameters, including the tumor stage [TNM and International Fédération of Gynecology and Obstetrics (FIGO) (26)], histological subtype and grading, 2) anesthesiologic parameters such as comorbidities [summarized in the Charlson Comorbidity Index (CCI) (27,28)] and American Society of Anesthesiologists Performance Status (ASA PS) (29) and 3) oncological and surgical parameters (e.g. postoperative residual tumor burden, surgical radicality retrospectively evaluated through Surgical Complexity Score (SCS) (30), as well as timing and completeness of chemotherapy).

Anesthetic techniques

Epidural catheter anesthesia was placed during the anesthesiologic induction before the surgical intervention. Epidural analgesia was administrated in OC patients expect those with contraindications like local infections or malformations, as well as spinal surgery or trauma, bacteremia, that may cause epidural infection and urinary tract infections, for example. Furthermore, low coagulation status or insufficient stopping time anticoagulant and patients who refused the technique were absolute contraindications for epidural anesthesia. Relative contraindications arise from preexisting neurological deficits and failures such as signs of paralysis subsequently slipped disc. Intraoperative epidural anesthesia was provided by bupivacaine 0,25% or ropivacaine 0,375% with or without addition of epidural sufentanil according to the attending anesthetist. All patients that received epidural catheter placement were treated by postoperative patient-controlled epidural anesthesia consisting of bupivacaine 0.125%. Epidural fentanyl was added as long as the patients were in intensive or intermediate care units, whereas bupivacaine 0,125% alone was applied in the normal ward. Patients that did not receive epidural catheter placement or showed signs of insufficient epidural anesthesia received a patient-controlled intravenous anesthesia-device with piritramide. All patients were cared for by a physician-based acute pain service affiliated to the Department of Anesthesiology as long as they received a patient-controlled anesthesia.

General anesthesia was conducted as balanced or total intravenous anesthesia according to the standard operating procedures of the Department of Anesthesiology as amended (31,32).

Statistical analysis

The data were recorded in Microsoft Excel and SPSS statistical software program, version 23.0 V5 R (SPSS Inc, Chicago, IL, U.S.A.), as well as StataBE 17 V5 were performed for the data analyses. Patients' characteristics were expressed as a mean +/- standard deviation [SD], or as median with their interquartile range [IQR]. We divided the study cohort into two groups, according to the epidural supplementing. Normal distribution was explored by Shapiro-Wilk test. Categorical variables were compared using the chi-square or Fisher's exact test. Kaplan-Meier estimates were used to determine the progression-free survival (PFS) and overall survival (OS) rates after five years for univariate analyses. The Log-Rank-Test was used to compare the curves. Timepoints in months were the date of diagnosis which resulted in the date of tumor debulking surgery up to death (or recurrence) or last follow-up. PFS included loco-regional lower abdomen recurrences and/or distant metastasis and death as an event. The Cox proportional hazards regression model was determined for multivariate analyses of the survival time after debulking surgery. At first, univariate Cox regression analyses for all factors that affect oncological survival after cancer surgery were performed. Secondly, each hypothesis with a significance level of <0.05 was included in the multivariate Cox regression analysis. The variable selection was examined via backward elimination. All tests were two-sided and a P-value of <0.05 was considered statistically significant. Because no correction was made for multiple testing due to the exploratory nature of the study, these are descriptive measures that should be interpreted with caution.

Results

Clinical features of OC patients

A total of 152 patients, with OC were screened and recruited from the achieves of the University Medical center Mainz (Fig. 1). Our final cohort was composed of 110 women aged 60 years and older (mean 70.9+/-5.9 years). Missing data arise from the inclusion and exclusion criteria (Fig. 1). All baseline factors, including various clinical-pathological tumor characteristics, as well as anesthesiologic, oncological and surgical parameters, were compared between the ‘Epidural’ and ‘non-Epidural’ group. Demographic and clinical characteristics are summarized in Table I.

Table I.

Patient characteristics for the two types of anesthesia techniques.

Table I.

Patient characteristics for the two types of anesthesia techniques.

ParameterTotal (n=110)Epidural (n=71)Non-epidural (n=39)P-value
Clinical-pathological tumor characteristics
  Tumor stage (TNM), n (%) (n=107) 0.272
    I17 (15.9)10 (9.3)7 (6.5)
    II8 (7.5)7 (6.5)1 (0.9)
    III81 (75.7)52 (48.6)29 (27.1)
    IV0 (0.0)0 (0.0)0 (0.0)
    Tx1 (0.9)0 (0.0)1 (0.9)
  Tumor stage (FIGO), n (%) (n=106) 0.106
    Early ovarian cancer < FIGO IIa15 (14.2)7 (6.6)8 (7.5)
    Late ovarian cancer ≥ FIGO IIa91 (85.8)62 (58.5)29 (27.4)
  Histological subtype, n (%) (n=110) 0.240
    Low grade serous + others33 (30.0)24 (21.8)9 (8.2)
    High grade serous77 (70.0)47 (42.7)30 (27.3)
  Histological grading, n (%) (n=108) 0.854
    G16 (5.6)4 (3.7)2 (1.9)
    G220 (18.5)14 (13.0)6 (5.6)
    G382 (75.9)52 (48.1)30 (27.8)
Anesthesiologic characteristics
  Mean age, years (+/-SD)71.08 (+/-5.95)72.18 (+/-6.17)70.55 (+/-5.75)
  CCI, n (%) (n=110) 0.020
    CCI 122 (20.0)18 (16.4)4 (3.6)
    CCI 261 (55.5)41 (37.3)20 (18.2)
    CCI 327 (24.5)12 (10.9)15 (13.6)
American Society of Anesthesiologists
  Performance Status, n (%) (n=109) 0.020
    1+40 (0.0)0 (0.0)0 (0.0)
    248 (44.0)37 (33.9)11 (10.1)
    361 (56.0)34 (31.2)27 (24.8)
Oncological and surgical characteristics
  Postoperative residual tumor burden, n (%) (n=109) 0.533
    None63 (57.8)42 (38.5)21 (19.3)
    Present46 (42.2)28 (25.7)18 (16.5)
  SCS, n (%) (n=110) 0.837
    SCS 137 (33.6)23 (20.9)14 (12.7)
    SCS 253 (48.2)34 (30.9)19 (17.3)
    SCS 320 (18.2)14 (12.7)6 (5.5)
  Completeness of chemotherapy, n (%)75 (68.2)62 (82.7)13 (17.3)0.008
  Timing of chemotherapy, n (%) (n=99) 0.911
    Neoadjuvant chemotherapy22 (22.2)14 (14.1)8 (8.1)
    Adjuvant chemotherapy77 (77.8)50 (50.5)27 (27.3)
  Clinical events, n (%)
    Relapse46 (41.8)33 (30.0)13 (11.8)0.181
    Death due to OC44 (44.9)29 (29.6)15 (15.3)0.937
    Death52 (53.1)34 (34.7)18 (18.3)0.834

[i] Comparison of baseline clinical data between the two groups. To compare the categorical variables, a χ2 test was used. OC, ovarian cancer; FIGO, International Federation of Gynecology and Obstetrics; CCI, Charlson Comorbitidy Index; SCS, Surgical Complexity Score.

Comparison of baseline clinical data between the two groups

Most patients were diagnosed with high-grade serous histology (n=77, 70.0%) and had a higher histological grading (G3: n=82, 75.9%). Approximately fifty-eight percent of the patients (n=63) underwent optimal tumor debulking. We reported no differences between the ‘Epidural’ and the ‘non-Epidural’ group concerning the clinical prognostic parameters (all P values >0.05) with the expectation of the ASA PS and CCI evaluation (P=0.020) (Table I). Furthermore, a lower number of relevant comorbidities was associated with more epidural-supplemented anesthesia. The median survival time for all OC patients was 26.0 months (11.8–38.0). The ‘Non-Epidural’ cohort survived with 27.0 months (15.0–39.0) longer than the ‘Epidural’-supplemented group with 19.0 months (8.0–36.5), respectively. No significant differences were found between the groups (P=0.355).

Comparison of survival data between the two groups

The Kaplan-Meier analyses indicated no association between epidural-supplemented anesthesia and prolonged progression-free or overall survival (PFS: 32.8% vs. 27.8%; P=0.478 and OS: 29.5% vs. 15.0%; P=0.409; respectively) (Fig. 2). In contrast, the preoperative ASA classification showed statistically significant differences in terms of 5-years OS (ASA 2 49.9% vs. ASA 3 12.9%; P=0.023) as also shown in Fig. 3. In the subgroup of ASA 2 patients, significantly more patients received combined anesthesia with epidural anesthesia as solely general anesthesia (77.1% vs. 22.9%; P=0.020) whereby no differences were found in the ASA 3 group (‘Epidural’: 55.7% vs. ‘non-Epidural’: 44.3%).

The Cox regression model indicated no significant association between epidural use and prolonged survival after cancer debulking surgery (PFS: HR: 1.26; 95%-CI [0.66–2.39] and OS: HR: 0.79; 95%-CI [0.45-1.40]; respectively) (Table II). In the multivariate Cox model, only the conventional clinical-pathological tumor parameter TNM-tumor stage retained its independent significance for PFS and OS (PFS: HR: 3.09; 95%-CI: [1.72–5.55] and OS: HR: 3.11; 95%-CI: [1.73–5.58]; respectively).

Table II.

Cox univariate and multivariate regression analyses.

Table II.

Cox univariate and multivariate regression analyses.

Univariate analysisMultivariate analysis


PFSOSPFSOS




ParameterHR95% CIP-valueHR95% CIP-valueHR95% CIP-valueHR95% CIP-value
Clinical-pathological tumor parameters
  Tumor stage-TNM2.811.59–4.95<0.0013.702.05–6.68<0.0013.091.72–5.55<0.0013.111.73–5.58<0.001
  Tumor stage-FIGO6.782.07–22.260.00211.472.73–47.910.0012.140.38–12.210.3922.130.37–12.170.394
  Histological subtype1.480.77–2.870.2411.730.90–3.290.098a- -
  Histological grading1.680.94–3.020.082a1.781.01–3.140.048- 1.140.63–2.080.667
Anaesthesiologic parameters
  Mean age0.790.44–1.420.4281.190.69–2.060.533- -
  CCI0.950.63–1.430.7911.430.95–2.150.091a- -
  ASA PS1.490.81–2.730.2021.971.08–3.570.026- 1.240.67–2.290.494
  Epidural analgesia1.260.66–2.390.4870.790.45–1.400.413- -
Oncological and surgical parameters
  Postoperative residual tumor burden2.261.25–4.070.0072.631.49–4.620.0011.140.61–2.120.6801.130.60–2.120.715
  SCS1.390.91–2.130.1291.440.96–2.160.079a- -
  Completeness of CTX1.760.69–4.480.2340.650.30–1.400.267- -
  Timing of CTX0.920.42–1.980.8250.930.43–2.020.863 -

a Survival data were analyzed using univariate and multivariate Cox regression analyses for all relevant baseline characteristics according to the technique of analgesia. PFS, Progression-free survival; OS, Overall survival; HR, hazard ratio; FIGO, International Federation of Gynecology and Obstetrics; CCI, Charlson Comorbidity Index; ASA PS, American Society of Anesthesiologists Performance Status; SCS, Surgical Complexity Score; CTX, chemotherapy.

Discussion

The results of this retrospective study did not confirm a definite association between epidural-supplemented anesthesia and cancer progression and OS in elderly patients following tumor debulking surgery for all stages of ovarian cancer.

Possible benefits of regional anesthesia techniques on the postoperative analgetic effect in gynecological malignancies, especially in OC patients have been examined (33,34). With regard to survival data of OC related to the presence of an epidural, controversial data have been published (3539). Overall, the positive impact of neuraxial analgesia seems to be solely detectable in more advanced disease, the prolonged relapse-free survival seems to depend on the timing of catheter insertion. In the study by Tseng et al (35), 435 women with advanced stages of OC receiving epidural anesthesia during primary debulking surgery were compared to 213 patients did not. The median PFS and OS was significantly improved in those who received epidurals (PFS: 20.8 months vs. 13.9 months; P=0.021 and OS: 62.4 months vs. 41.9 months, P<0.001; respectively). Oliveira and colleagues demonstrated the epidural-related preservation of the immune system function resulting in an increased time to tumor recurrence after surgery in 182 patients executively for intraoperative used epidural catheters (HR: 0.37; 95%-CI [0.19–0.73]) (37).

Other published reports showed similar findings to those of the current study. In Lacassies's prospective clinical registry, there were no benefits in survival in patients with advanced stages of OC after the use of epidural reported (38). They obtained propensity score matching, adjusting for chemotherapy, besides the multivariate Cox regression model, without any differences in cancer prognosis. In 2012, Capmas et al (39) examined 104 advanced-stage OC patients and declared no clear impact of regional analgesia on cancer recurrence. A systematic Cochrane Review addressing this topic showed no association between epidural use with lengthened survival in solid cancer patients (40).

Physiologic negative stress was highest at the time of surgery and affected the adaptive immune surveillance (41). Immune disturbance due to surgical distress may facilitate cancer cell migration (16). Various types of anesthesia showed different effects on human cancer immunity and carcinogenesis. Epidural analgesia could attenuate intraoperative suppression of NK cell function and help preserve effective defense against tumor progression, by limiting the use of opioids (42). Additionally, regional anesthesia was linked to earlier recovery times by reducing postoperative complications such as thromboembolic, cardiac and pulmonary, as well as gastrointestinal complications and inflammation (43). The role of cytokines in cancer immunity was either directly influenced by proliferative effects or indirectly by enhancing proinflammatory and proangiogenic pathways in host cells.

The results of our trial suggested that survival prognosis in OC disease might not be primarily determined by immunomodulatory effects caused by the epidural analgesia, especially not in elderly cancer patients. Although, increasing age resulted in changes in body's homeostasis and vulnerability to external stressors increased the relevant prognostic factors remain. In advanced cancer diseases the best option of controlling progression and lengthening survival was optimal surgical tumor debulking as well as completeness of platinum-based chemotherapy (44). Anesthesia and analgesia techniques were important, but they did not appear to have an independent and significant impact on cancer prognosis in this population.

Study limitations arise from the biases associated with the retrospective single-institution nature of the study. The single institution design allowed the patients in both groups, ‘Epidural’ and ‘non-Epidural’ to receive the same perioperative care. Our follow-up period of almost 14 years was robust and we also performed a through multivariate analysis, controlling for conventional-established prognostic factors in OC. Even though, the intraoperative epidural technique was approximately homogenous (bupivacaine 0.25% or ropivacaine 0.375% and postoperative with bupivacaine 0.125% in combination with fentanyl concentration varied between 0.75% and 1.0% and was administered with or without an opioid).

Because of the fact that elderly patients were underrepresented in the vast majority of existing comparative reports, prospective studies to investigate the effects of perioperative epidural anesthesia use in the special cohort of elderly ovarian cancer women on survival are warranted. Given the limited number of modifiable prognostic parameters for elderly OC patients, studies investigating the impact of different anesthetic techniques potentially influencing the immune function after debulking surgery will be desirable.

In conclusion, we could not find a survival benefit in patients with ovarian cancer after the perioperative use of epidural anesthesia after debulking surgery. Primary tumor stage in combination with optimal cytoreduction and completeness of chemotherapy are still the strongest prognostic factors.

Acknowledgements

Not applicable.

Funding

Funding: No funding was received.

Availability of data and materials

The dataset used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors' contributions

KA and MJB contributed to the study design. KA, MJB, MWS, RS, AD, MS, SK, MR, RH, EKH and AH contributed to the data acquisition. KA and MJB analyzed the data. KA and MJB wrote the paper. KA and MJB confirm the authenticity of all the raw data. KA and MJB revised the manuscript for important intellectual content. All authors critically and substantively revised the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The retrospective cohort study was conducted in accordance with the ‘Ethical principles for medical research involving human subjects’ of the current version of the Declaration of Helsinki. Data collected for the present study were obtained as part of routine medical care. Ethical approval for use of these samples for research purposes was not required for the present study in accordance with local/national guidelines. Written informed consent from participants was obtained in accordance with local/national guidelines.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

Wimberger P, Lehmann N, Kimmig R, Burges A, Meier W, Hoppenau B and du Bois A: AGO-OVAR: Impact of age on outcome in patients with advanced ovarian cancer treated within a prospectively randomized phase III study of the arbeitsgemeinschaft gynaekologische onkologie ovarian cancer study group (AGO-OVAR). Gynecol Oncol. 100:300–307. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI

3 

Martins FC, Couturier DL, Paterson A, Karnezis AN, Chow C, Nazeran TM, Odunsi A, Gentry-Maharaj A, Vrvilo A, Hein A, et al: Clinical and pathological associations of PTEN expression in ovarian cancer: A multicentre study from the ovarian tumour tissue analysis consortium. Br J Cancer. 123:793–802. 2020. View Article : Google Scholar : PubMed/NCBI

4 

Courtney-Brooks M, Tellawi AR, Scalici J, Duska LR, Jazaeri AA, Modesitt SC and Cantrell LA: Frailty: An outcome predictor for elderly gynecologic oncology patients. Gynecol Oncol. 126:20–24. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Anic K, Birkert S, Schmidt MW, Linz VC, Heimes AS, Krajnak S, Schwab R, Schmidt M, Westphalen C, Hartmann EK, et al: G-8 geriatric screening tool independently predicts progression-free survival in older ovarian cancer patients irrespective of maximal surgical effort: Results of a retrospective cohort study. Gerontology. 1–10. 2021.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

6 

Gibson SJ, Fleming GF, Temkin SM and Chase DM: The application and outcome of standard of care treatment in elderly women with ovarian cancer: A literature review over the last 10 years. Front Oncol. 6:632016. View Article : Google Scholar : PubMed/NCBI

7 

Cannistra SA: Cancer of the ovary. N Engl J Med. 351:2519–2529. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Fotopoulou C, Planchamp F, Aytulu T, Chiva L, Cina A, Ergönül Ö, Fagotti A, Haidopoulos D, Hasenburg A, Hughes C, et al: European society of gynaecological oncology guidelines for the peri-operative management of advanced ovarian cancer patients undergoing debulking surgery. Int J Gynecol Cancer. 31:1199–1206. 2021. View Article : Google Scholar : PubMed/NCBI

9 

Landrum LM, Java J, Mathews CA, Lanneau GS Jr, Copeland LJ, Armstrong DK and Walker JL: Prognostic factors for stage III epithelial ovarian cancer treated with intraperitoneal chemotherapy: A gynecologic oncology group study. Gynecol Oncol. 130:12–18. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Tsuchiya Y, Sawada S, Yoshioka I, Ohashi Y, Matsuo M, Harimaya Y, Tsukada K and Saiki I: Increased surgical stress promotes tumor metastasis. Surgery. 133:547–555. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Eschwège P, Dumas F, Blanchet P, Le Maire V, Benoit G, Jardin A, Lacour B and Loric S: Haematogenous dissemination of prostatic epithelial cells during radical prostatectomy. Lancet. 346:1528–1530. 1995. View Article : Google Scholar : PubMed/NCBI

12 

Hiller JG, Perry NJ, Poulogiannis G, Riedel B and Sloan EK: Perioperative events influence cancer recurrence risk after surgery. Nat Rev Clin Oncol. 15:205–218. 2018. View Article : Google Scholar : PubMed/NCBI

13 

Bar-Yosef S, Melamed R, Page GG, Shakhar G, Shakhar K and Ben-Eliyahu S: Attenuation of the tumor-promoting effect of surgery by spinal blockade in rats. Anesthesiology. 94:1066–1073. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Chen XB, Zhang HL and Fang XD: Surgery-induced immunomodulation in breast cancer. J Surg Oncol. 103:197author reply 196. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Rao VS, Dyer CE, Jameel JK, Drew PJ and Greenman J: Potential prognostic and therapeutic roles for cytokines in breast cancer (Review). Oncol Rep. 15:179–185. 2006.PubMed/NCBI

16 

Pei L, Tan G, Wang L, Guo W, Xiao B, Gao X, Wang L, Li H, Xu Z, Zhang X, et al: Comparison of combined general-epidural anesthesia with general anesthesia effects on survival and cancer recurrence: A meta-analysis of retrospective and prospective studies. PLoS One. 9:e1146672014. View Article : Google Scholar : PubMed/NCBI

17 

Reed N, Balega J, Barwick T, Buckley L, Burton K, Eminowicz G, Forrest J, Ganesan R, Harrand R, Holland C, et al: British Gynaecological cancer society (BGCS) cervical cancer guidelines: Recommendations for practice. Eur J Obstet Gynecol Reprod Biol. 256:433–465. 2021. View Article : Google Scholar : PubMed/NCBI

18 

Brittenden J, Heys SD, Ross J and Eremin O: Natural killer cells and cancer. Cancer. 77:1226–1243. 1996. View Article : Google Scholar : PubMed/NCBI

19 

Snyder GL and Greenberg S: Effect of anaesthetic technique and other perioperative factors on cancer recurrence. Br J Anaesth. 105:106–115. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Cummings KC III, Xu F, Cummings LC and Cooper GS: A comparison of epidural analgesia and traditional pain management effects on survival and cancer recurrence after colectomy: A population-based study. Anesthesiology. 116:797–806. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Gottschalk A, Ford JG, Regelin CC, You J, Mascha EJ, Sessler DI, Durieux ME and Nemergut EC: Association between epidural analgesia and cancer recurrence after colorectal cancer surgery. Anesthesiology. 113:27–34. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Kawaraguchi Y, Horikawa YT, Murphy AN, Murray F, Miyanohara A, Ali SS, Head BP, Patel PM, Roth DM and Patel HH: Volatile anesthetics protect cancer cells against tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via caveolins. Anesthesiology. 115:499–508. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Yeager MP, Colacchio TA, Yu CT, Hildebrandt L, Howell AL, Weiss J and Guyre PM: Morphine inhibits spontaneous and cytokine-enhanced natural killer cell cytotoxicity in volunteers. Anesthesiology. 83:500–508. 1995. View Article : Google Scholar : PubMed/NCBI

24 

Singleton PA, Moss J, Karp DD, Atkins JT and Janku F: The mu opioid receptor: A new target for cancer therapy? Cancer. 121:2681–2688. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Wang J, Guo W, Wu Q, Zhang R and Fang J: Impact of combination epidural and general anesthesia on the long-term survival of gastric cancer patients: A retrospective study. Med Sci Monit. 22:2379–2385. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Colombo N, Peiretti M, Parma G, Lapresa M, Mancari R, Carinelli S, Sessa C and Castiglione M; ESMO Guidelines Working Group, : Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 21 (Suppl 5):v23–v30. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H and Ghali WA: New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol. 57:1288–1294. 2004. View Article : Google Scholar : PubMed/NCBI

28 

D'Hoore W, Bouckaert A and Tilquin C: Practical considerations on the use of the Charlson comorbidity index with administrative data bases. J Clin Epidemiol. 49:1429–1433. 1996. View Article : Google Scholar : PubMed/NCBI

29 

Davenport DL, Bowe EA, Henderson WG, Khuri SF and Mentzer RM Jr: National surgical quality improvement program (NSQIP) risk factors can be used to validate American Society of anesthesiologists physical status classification (ASA PS) levels. Ann Surg. 243:636–41; discussion 641-4. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Aletti GD, Dowdy SC, Podratz KC and Cliby WA: Relationship among surgical complexity, short-term morbidity, and overall survival in primary surgery for advanced ovarian cancer. Am J Obstet Gynecol. 197:676e1–e7. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Eger EI II, Saidman LJ and Brandstater B: Minimum alveolar anesthetic concentration: A standard of anesthetic potency. Anesthesiology. 26:756–763. 1965. View Article : Google Scholar : PubMed/NCBI

32 

Campagna JA, Miller KW and Forman SA: Mechanisms of actions of inhaled anesthetics. N Engl J Med. 348:2110–2124. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Kuniyoshi H, Yamamoto Y, Kimura S, Hiroe T, Terui T and Kase Y: Comparison of the analgesic effects continuous epidural anesthesia and continuous rectus sheath block in patients undergoing gynecological cancer surgery: A non-inferiority randomized control trial. J Anesth. 35:663–670. 2021. View Article : Google Scholar : PubMed/NCBI

34 

Zhong S, Zhong X, Zhong X and Liu Y: Comparison between the effect of epidural anesthesia combined with epidural analgesia and general anesthesia combined with intravenous analgesia on prognosis of ovarian cancer patients. Oncol Lett. 17:5662–5668. 2019.PubMed/NCBI

35 

Tseng JH, Cowan RA, Afonso AM, Zhou Q, Iasonos A, Ali N, Thompson E, Sonoda Y, O'Cearbhaill RE, Chi DS, et al: Perioperative epidural use and survival outcomes in patients undergoing primary debulking surgery for advanced ovarian cancer. Gynecol Oncol. 151:287–293. 2018. View Article : Google Scholar : PubMed/NCBI

36 

Lin L, Liu C, Tan H, Ouyang H, Zhang Y and Zeng W: Anaesthetic technique may affect prognosis for ovarian serous adenocarcinoma: A retrospective analysis. Br J Anaesth. 106:814–822. 2011. View Article : Google Scholar : PubMed/NCBI

37 

de Oliveira GS Jr, Ahmad S, Schink JC, Singh DK, Fitzgerald PC and McCarthy RJ: Intraoperative neuraxial anesthesia but not postoperative neuraxial analgesia is associated with increased relapse-free survival in ovarian cancer patients after primary cytoreductive surgery. Reg Anesth Pain Med. 36:271–277. 2011. View Article : Google Scholar : PubMed/NCBI

38 

Lacassie HJ, Cartagena J, Brañes J, Assel M and Echevarría GC: The relationship between neuraxial anesthesia and advanced ovarian cancer-related outcomes in the Chilean population. Anesth Analg. 117:653–660. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Capmas P, Billard V, Gouy S, Lhommé C, Pautier P, Morice P and Uzan C: Impact of epidural analgesia on survival in patients undergoing complete cytoreductive surgery for ovarian cancer. Anticancer Res. 32:1537–1542. 2012.PubMed/NCBI

40 

Cakmakkaya OS, Kolodzie K, Apfel CC and Pace NL: Anaesthetic techniques for risk of malignant tumour recurrence. Cochrane Database Syst Rev. ((11)): CD0088772014.PubMed/NCBI

41 

Bartal I, Melamed R, Greenfeld K, Atzil S, Glasner A, Domankevich V, Naor R, Beilin B, Yardeni IZ and Ben-Eliyahu S: Immune perturbations in patients along the perioperative period: Alterations in cell surface markers and leukocyte subtypes before and after surgery. Brain Behav Immun. 24:376–386. 2010. View Article : Google Scholar : PubMed/NCBI

42 

Li JM, Shao JL, Zeng WJ and Liang RB: General/epidural anesthesia in combination preserves NK cell activity and affects cytokine response in cervical carcinoma patients undergoing radical resection: A cohort prospective study. Eur J Gynaecol Oncol. 36:703–707. 2015.PubMed/NCBI

43 

Shavit Y, Ben-Eliyahu S, Zeidel A and Beilin B: Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats. Neuroimmunomodulation. 11:255–260. 2004. View Article : Google Scholar : PubMed/NCBI

44 

Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, et al: Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 363:943–953. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October-2022
Volume 24 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Anic K, Schmidt MW, Droste A, Schwab R, Schmidt M, Krajnak S, Renz M, Hartmann EK, Hardt R, Hasenburg A, Hasenburg A, et al: Influence of anesthetic technique on survival after tumor debulking surgery of elderly patients with ovarian cancer: <br />Results of a retrospective cohort study. Oncol Lett 24: 361, 2022
APA
Anic, K., Schmidt, M.W., Droste, A., Schwab, R., Schmidt, M., Krajnak, S. ... Battista, M.J. (2022). Influence of anesthetic technique on survival after tumor debulking surgery of elderly patients with ovarian cancer: <br />Results of a retrospective cohort study. Oncology Letters, 24, 361. https://doi.org/10.3892/ol.2022.13481
MLA
Anic, K., Schmidt, M. W., Droste, A., Schwab, R., Schmidt, M., Krajnak, S., Renz, M., Hartmann, E. K., Hardt, R., Hasenburg, A., Battista, M. J."Influence of anesthetic technique on survival after tumor debulking surgery of elderly patients with ovarian cancer: <br />Results of a retrospective cohort study". Oncology Letters 24.4 (2022): 361.
Chicago
Anic, K., Schmidt, M. W., Droste, A., Schwab, R., Schmidt, M., Krajnak, S., Renz, M., Hartmann, E. K., Hardt, R., Hasenburg, A., Battista, M. J."Influence of anesthetic technique on survival after tumor debulking surgery of elderly patients with ovarian cancer: <br />Results of a retrospective cohort study". Oncology Letters 24, no. 4 (2022): 361. https://doi.org/10.3892/ol.2022.13481