Abstract
Background/Aim: SARS-CoV-2 with a dramatical worldwide spread, impacted greatly daily life and healthcare. In order to avoid delay in cancer treatment, many strategies and measures were implemented. The Awake breast surgery was a strategy implemented in our Unit during the pandemic, aimed to reduce operatory room occupancy and increase the number of procedures performed during the daily surgical session. The aim of the study was to evaluate how the use of this strategy has changed before and after the advent of the COVID-19 pandemic, and its relative benefits. Patients and Methods: This was a retrospective study analysing all patients subjected to breast conservative surgery for oncological disease from July 2018 to December 2021. Results: Out of 498 patients enrolled in the study, 253 (50.8%) cases were treated before the pandemic and were designated as “pre-COVID-19” group. The remaining 245 (49.1%) cases were considered the “COVID-19” group. Cases of awake surgery in COVID-19 group were 141 (54.7%) vs. 84 (33.2%), p<0.001. Length of hospitalization and surgical time were comparable between the groups: relative p=0.188 and 0.264, respectively. Differently, operation room occupation was significantly shorter in the COVID-19 group, p<0.001; and number of outpatient surgical procedures was higher, p=0.0304. Multivariate analysis identified the period of surgery (OR=1.47) as a statistically significant factor, p=0.011, predictive of prolonged operatory room occupancy. Conclusion: Awake surgery was one of the strategies which made more operating rooms available and allowed avoiding further delays.
The COVID-19 pandemic has brought change to in all aspects of daily life (1-3). This emergency forced the health care systems to reshape themselves (3). During each wave of the pandemic, health care systems shifted resources towards COVID-19 patients and subsequently, as infection rates decreased, redirected to non-COVID-19-related patients. We have somehow learned to live with this virus and its associated implications, as we have learned many other lessons from the pandemic (4).
Many strategies were adopted by the scientific community in order to avoid delay in cancer treatment, especially during the pandemic waves; these strategies can come in handy in our routine life (5, 6). Benefits of awake surgery, when possible, are well established in the literature (7-9). During the pandemic, this approach was preferred in our Breast Unit whenever possible; in order to reduce hospitalization and the risk of hospital SARS-CoV-2 infection, and to reduce hospital bed occupancy as much as possible (9).
In addition to the fundamental role of avoiding deterioration of the immune system, awake surgery also offers an advantage in reducing surgical times and saving resources (e.g., hospital beds, operating rooms) (9). Furthermore, it minimizes healthcare costs by maintaining standards of efficacy and safety (10). Our experience with awake surgery began before the COVID-19 pandemic, as we strongly believe in its favourable influence on the patient immune system. During the pandemic, we decided to implement the use of awake surgery (7). Moreover, since this is a valid strategy in our opinion, we have decided to further its use, as much as possible, outside emergency periods.
The aim of this retrospective study was to evaluate how employment of the awake breast surgery strategy has evolved, before and after the advent of the COVID-19 pandemic. Further, we assessed the potential benefits of implementing this strategy outside the pandemic frame.
Patients and Methods
In our retrospective monocentric study, we analyzed data from the Breast Unit of Policlinico Tor Vergata, Rome, Italy. All patients who undergone breast surgery for oncological disease from July 2018 to December 2021 were evaluated. The manuscript was approved by the local Ethical Committee of the Fondazione Policlinico Tor Vergata (Comitato Etico Indipendente PTV, reference 122/20).
According to the cut-off date of 10 March 2020, when the pandemic was declared in Italy, our population was divided into “Pre-COVID-19” and “COVID-19” groups. Age and BMI of each patient were collected from clinical notes.
Surgical and anesthesiologic procedure. Surgical procedures were distinguished between conservative and radical breast surgery. Breast-conservative surgeries included all procedures with partial gland removal while radical surgery comprised the complete removal of the glandular tissue with or without sparing the nipple areola complex. In our analysis we considered only patients undergoing a breast-conservative surgery. The axillary surgical procedure was evaluated in the study. Removal of sentinel lymph nodes, or complementary lymph node removal of ≤3 lymph nodes were classified as sentinel lymph node biopsy (SLNB), otherwise it was described as an axillary lymph node dissection (ALND).
Anesthesiologic strategies were reported as Awake breast surgery and Non-awake breast surgery. In the Non-awake group, patients were enlisted when supraglottic or subglottic devices were used. All procedures with administration of local anesthetics or regional anesthesia (peripheral nerve block, erector spinae block, central neuraxial blocks) without mechanical ventilation were defined as Awake. These patients were eligible to receive a mild sedation with Richmond agitation-sedation scale ≥−4 and spontaneous breathing. Awake surgery was proposed in selected patients (inclusion and exclusion criteria; Table I) and performed in those who adhere to such treatment after an exhaustive interview with surgeon. During the procedure, in case of sentinel lymph nodes positive at frozen section, and candidacy to ALND; anesthesia regimen was converted into Non-awake. According to our unit’s policy, we do not perform ALND in awake surgeries. Additionally, in cases of uncontrolled pain, anxiety, agitation, or according to patient’s request, anesthesia regimen was converted.
Awake surgery inclusion and exclusion criteria.
Surgical time was defined as skin-to-skin surgical time and reported in min. Moreover, operating room occupancy time was considered from entrance to, to exit from the operating room. Length of hospitalization was reported in days, considered from the date of admission to discharge home.
Clinical data. Tumor maximum diameter was collected from pathological examination and reported in cm. In addition, tumor staging was collected from phytological reports and reported according to TNM, NCCN Guidelines. Estrogen receptor (ER), progesterone receptor (PR) and Ki67 index were expressed as percentages of positive cells in specimen studied through immunohistochemistry (IHC). Overexpression of Her2 gene (HER2+) was identified by IHC or by FISH, as indicated by the recommendations of the 2018 ASCO/CAP and reported as a dichotomous variable (HER2+ yes/no).
Statistical analysis. All data were collected into the database (EXCEL software, Microsoft, Washington, DC, USA). For continuous variables, we calculated and used mean and standard deviation. t-test was performed to determine whether there were significant differences between the two different groups. Categorical data were reported in numbers and relative percentages. The Fisher’s exact test was applied to determinate significant differences between group in case of a dichotomous variable. Otherwise, Monte Carlo test was performed to determinate significant differences between groups in case of non-dichotomous variables. Variables with p-values <0.05 were considered statistically significant. Cox regression was performed for multivariate analysis. All the statistical analysis was performed in SPSS statistical package version 23.0 (SPSS Inc., Chicago, IL, USA).
Results
From July 2018 to December 2021, 627 patients underwent breast surgery for oncological disease. Out of these, 498 (79.5%) underwent breast conservative surgery and were retrospectively enrolled in the analysis. Mean age was 60.1±13.5 years and mean BMI 22±5.2.
Until 10 March 2020, 253 (50.8%) patients underwent surgery and were considered Pre-COVID-19 group, while the cases after the cut-off date included 245 (49.1%) patients who were designated as COVID-19 group. Following the beginning of the COVID-19 era, 141 (57.6%) patients underwent awake breast conservative surgery versus 84 (33.2%) cases in the preceding period. The increase in patients undergoing awake breast conservative surgery showed a statistically significant difference with a relative p-value <0.001. Surgical procedure and anesthesia regimen with relative p-values are reported in Table II.
Type of surgery and type of anesthesia performed between groups.
In 14 (5.7%) cases of the COVID-19 group, surgery began with an awake anesthesia regimen that was then converted to a non-awake surgery. Out of these, 5 (2%) cases were due to the need to perform ALND, while the remaining nine (3.6%) cases were according to patients request due to pain, severe anxiety or agitation. Differently, 26 (10.2%) cases were converted in the Pre-COVID-19 group: 4 (1.6%) cases due to the need to perform ALND, and 22 (8.7%) cases by virtue of patients request. Although we did not observe statistically significant differences in absolute numbers of anesthesia regimen conversion and in numbers of anesthesia regimen switch due to the need to perform ALND (p=0.091 and 0.748, respectively), we reported a higher anesthesia regimen conversion rate in the Pre-COVID-19 group following patients request due to pain, severe anxiety or agitation (p=0.025). Reasons of conversion and relative p-values are resumed in Table III.
Anesthesia regimen conversion in general surgery and relative reasons.
No statistically significant differences were reported in terms of age and BMI, and relative p-value were, respectively, 0.095 and 0.327: mean age was 60.7±14.1 years in the COVID-19 group and 59.5±13.1 years in the control group; BMI was 22.4±5.3 and 22.4±5.1. Mean lesion maximum diameter was 1.3±0.56 cm in the Covid-19 group and 1.3±0.59 cm in the preceding period, p=0.906. Tumor and lymph node involvement did not show any statistically significant differences between the two different periods and relative p-values were, respectively, 0.077 for T and 0.200 for N. Distribution and values are resumed in Table IV. No cases with metastasis were reported in either of the groups, p=1.000. Percentage of cancer cells expressing Estrogen Receptor was 75.2±33.3% in the pandemic period versus 76.2±34.8% in the Pre-COVID-19 group. Percentage of cells expressing progesterone receptor was 55.1±37.8% in the COVID-19 period versus 59.43±38.3% in the control. Cancer proliferation index Ki67 in the COVID-19 group showed a mean of 18.2±14.1% versus 17.5±13.4% in the control group. All these predictive factors did not show any statistically significant differences between the groups and p-values were 0.529, 0.910 and 0.483, respectively (Table IV).
Patient tumor characteristics between groups.
According to the primary aim of our analysis, time of occupation of operatory room and time of surgical procedures were evaluated. No statistically significant difference was reported regarding the surgical procedure duration: 70.0±8.4 min in the COVID-19 group versus 68.3±8.5 min in the group of the preceding period, p=0.264. Differently, we observed a significant reduction of operatory room occupancy in the COVID-19 group; mean time of patient stay in the operatory room was 134.1±27.6 min versus 146.3±24.7 min in the Pre-COVID-19 group, with a relative p-value <0.001.
Mean of hospital stay was comparable among the two periods with a p-value of 0.188, 1.31±0.6 days in the Pre-COVID-19 and 1.31±0.5 in the COVID-19 groups. Differently, we observed a significant increase in number of patients undergoing outpatient breast conservative surgery during the pandemic: 11 (4.5%) cases vs. 3 (1.2%) in the Pre-COVID-19 group, showing a statistically significant difference between the groups (relative p-value=0.0304). All variables and relative p-values are resumed in Table V.
Short-term surgical outcomes between groups.
At logistic binary regression, period of surgery was the variable associated with an increased risk for prolonged operatory room occupancy time (univariate p=0.001). Multivariate logistic regression analysis identified period of surgery (OR=1.47) as a statistically significant factor (p=0.011), predictive for prolonged operatory room occupancy time. Other factors analyzed by multivariate analysis are depicted in Table VI.
Predictive factors of operative room occupancy: Univariate and multivariate analyses.
Discussion
During the last years, since the first cases of SARS-CoV-2 infection were reported, COVID-19 rapidly spread worldwide and upset all aspects and daily routines (1-3).
The emergency forced health systems to shape themselves and redirecting resources (3). We experienced several pandemic waves during the last years. During each peak, the healthcare system shifted resources towards COVID-19 patients, and subsequently redirected to patients without COVID-19 as the rate of infections decreased, trying to limit inconvenience and delays for non-COVID-19-related diseases as much as possible (11-13). Despite all measures, at the end of each wave, the waiting lists for surgery have grown out of proportion, along with an increasing number of tumors at advanced stages (14-18). In our series, we did not report a reduction of absolute number of surgeries, nor a greater number of advanced-stage tumors. The longer follow-up of the current study could explain such results. With time, we somehow learned to live with the new virus and its related implications (4). All the measures and strategies used made it possible to limit delays. In fact, the awake surgery strategy was greatly implemented during the COVID-19 pandemic; and probably, despite a global reduction of hospital beds, healthcare personnel and operation room availability, absolute number of surgical procedures did not suffer a significant decline.
In a previous study, conducted immediately following the declaration of COVID-19 pandemic, we reported benefits and advantages of awake breast surgery in terms on operative room occupancy and length of hospital stay (9). According to these results and in accordance with the current analysis, we report a significant reduction in operation room occupancy. This reduction, evident at multivariate analyses, is strongly correlated with the COVID-19 period and the relative high percentage of awake breast conservative cancer surgeries performed. Awake breast surgery could reduce anesthesiology time, as often local anesthetics administration or regional anesthesia (peripheral nerve block, erector spinae block, central neuraxial blocks) are also performed for post-operative pain management in patients undergoing general anesthesia (19-20). Accordingly, surgical time was not impacted by this strategy, as reported in our previous study (9). We managed to minimize delays for cancer patients by prioritizing selected cases, while non-urgent surgical procedures were postponed and waiting lists for benign diseases grew longer (9). We strongly believe that strategies adopted during the pandemic in order to minimize delays in cancer treatments could be utilized in order to enhance efficiency and resolve the long waiting lists problem.
In addition to the advantage in terms of health resources, awake surgery was shown to bring economic benefits to the healthcare system (10, 21, 22). Importantly, in our opinion, awake surgery plays a fundamental role regarding on the immune system (7). General anesthesia, as reported in many studies, is correlated with an impairment of the immune system (7, 23-26). Surgical stress and general anesthesia may cause a temporary reduction of lymphocytes (27-28). Reduced cytotoxic activity due to lymphopenia can increase the probability of tumor progression (26, 27, 29). Furthermore, a compromised immune system may predispose to complications of infections, which should not be underestimated during a pandemic period (30). Conversely, a minimally invasive approach and local anesthesia seem to better preserve immune functions; despite the lack of high-level evidence (31-32).
No differences were reported in terms of length of hospitalization. Differently, in a previous paper we registered a significant decrease in hospitalization (9). This result is probably related to the different patients included in the analysis. In this study, we excluded mastectomy and reported only on patients undergoing breast conservative surgery, with short hospitalization, where the length of hospitalization is related to hospital policy rather than clinical discharge criteria. Nonetheless, we observed a higher percentage of cases undergoing outpatient breast conservative surgeries following the COVID-19 pandemic. Probably, patient anxiety of COVID-19 infection, together with not having to be subjected to general anesthesia, led to the increase in outpatient breast conservative surgery (33-34).
We observed a reduction of anesthesia regimen conversion to general anesthesia in the COVID-19 group. But when the reasons of anesthesia regimen conversion from awake to non-awake were analyzed; we reported higher conversion rates following patients request due to pain, severe anxiety, or agitation in the Pre-COVID-19 group. Perhaps, benefits of awake surgery explained during a comprehensive conversation with patients could have influenced this result. Many failure reasons for awake surgery were reported in literature (35-36). Patients assisted by noninvasive ventilation could have hypoxemic acute respiratory failure especially when associated with a position other than supine (36-37). Moreover, miss-diagnosed COVID-19 could be an associated risk factor for respiratory failure (37). Furthermore, the fear of such complications and the risk that patient’s agitation could influence surgical outcome is not widely accepted in the scientific community (35). In our study no cases of acute respiratory failure were reported probably due to supine position adopted and COVID-19 screening routinely performed.
Conclusion
Although COVID-19 has hindered cancer surgery considerably, hard work and different strategies allowed to minimize the impact of the pandemic on cancer patients. Awake surgery, by reducing the procedure time, was one of the strategies that enabled us to have more available operating rooms and avoid further delays. Awake surgery is safety, well tolerated and strategy chosen by the patients when proposed. Awake surgery can also be used for non-cancer patients, when possible, to shorten the long waiting lists caused by the pandemic and the prioritization of cancer cases. In our opinion, this strategy should be implemented also in non-emergency periods. Further randomized clinical trials are required to evaluate its actual and potential benefits.
Footnotes
Authors’ Contributions
GV and MP: conceptualization, methodology, formal analysis, design of the study, and equally contributed to the manuscript. MP: writing original draft. MM and JC: statistical analysis. FT, GN, CB and AN: data collection. IP: revision. GV: writing, review. MD and OCB: supervision. All the Authors reviewed and approved the final version to be published.
Conflicts of Interest
The Authors declare that they have no potential conflicts of interest.
- Received July 18, 2022.
- Revision received July 31, 2022.
- Accepted August 6, 2022.
- Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
