Abstract
Background/Aim: The coronavirus disease 2019 (COVID-19) pandemic has reduced hospital visits due to concerns regarding infection and also resulted in cancer screening delays. These changes may have had an impact on the progression of colorectal cancer (CRC). Therefore, the present study investigated the effects of the COVID-19 pandemic on minimally invasive surgery (MIS) for CRC using a correlation analysis of clinical outcomes before and during the COVID-19 pandemic. Patients and Methods: The present study targeted CRC patients who underwent MIS between January 2018 and December 2019 (pre-COVID-19) and between April 2020 and March 2021 (COVID-19). A comparison analysis of clinical, surgical, and pathological findings between the pre-COVID-19 and COVID-19 groups was performed. Results: Ninety-one patients underwent MIS for CRC pre-COVID-19 and 67 during COVID-19. The number of CRC cases detected by fecal occult blood tests was slightly higher in the pre-COVID-19 group than that in the COVID-19 group. Re-evaluations of laparoscopic videos revealed that the number of cases of surgical T4 CRC resected with the combined resection of the adjacent organs was significantly higher in the COVID-19 group than that in the pre-COVID-19 group (16.4 vs. 4.4%, p=0.010). Furthermore, surgical times were significantly longer in the COVID-19 group than those in the pre-COVID-19 group (p<0.001). Pathological findings showed that the number of pT4 cases was significantly higher in the COVID-19 group than that in the pre-COVID-19 group (p=0.026). Conclusion: The number of T4 CRC cases was higher during than before the COVID-19 pandemic, with increases in the surgical difficulty of MIS.
The novel coronavirus disease 2019 (COVID-19) was initially reported in Wuhan, China and then rapidly spread worldwide. The World Health Organization declared the outbreak an official pandemic on March 11, 2020 (1). Although the target organs in COVID-19 is considered to be the respiratory organs, infected patients often develop life-threatening multiorgan dysfunctions (2-4). Furthermore, COVID-19 infection has been shown to increase the risk of thrombotic complications (5, 6). Organ dysfunctions and thrombotic complications significantly contribute to mortality and morbidity. Many risk factors for the progression of COVID-19 into a life-threatening severe stage have been identified and include an older age, ethnicity, diet, smoking, comorbidities, and cancer (7-10).
The first confirmed case of COVID-19 infection in Japan was recorded on January 16, 2020 (11). The number of cases then rapidly increased, mainly in urban areas. Since the beginning of the pandemic and with a more detailed understanding of the pathology of COVID-19, the diversion of medical resources towards COVID-19 and the cautiousness of medical institutions to accept COVID-19-infected patients have had a major impact on planned public healthcare, including cancer screening (12, 13). A previous study reported that screening delays significantly increased the number of advanced colorectal cancer (CRC) cases as well as mortality among patients surviving more than 12 months (12). The number of T4 CRC cases has significantly increased during the COVID-19 pandemic (14). Furthermore, surgical aggressiveness, as shown by the proportion of patients undergoing minimally invasive surgery (MIS) and adjacent organ resection, has been significantly influenced by the pandemic (15).
A recent advance in the treatment of CRC is MIS, such as laparoscopic or robotic surgery. The rate of laparoscopic or robotic surgery for CRC has continuously increased because of its surgical safety and requests by CRC patients (16). Therefore, MIS for CRC needs to be performed as soon as possible during the COVID-19 pandemic. However, the influence of the COVID-19 pandemic on MIS for CRC has not yet been investigated in Japan. Therefore, the present study examined the impact of the COVID-19 pandemic on MIS for CRC using a correlation analysis of clinical outcomes before and during the pandemic.
Patients and Methods
Study design and patients. This was a retrospective study that investigated differences in clinical, surgical, and pathological findings in MIS for CRC before and during the COVID-19 pandemic. The present study was approved by the Research Ethics Committee of Kyoto Okamoto Memorial Hospital (2020-45) and included patients with CRC who underwent laparoscopic colectomy at the Department of Digestive Surgery, Kyoto Okamoto Memorial Hospital between January 2018, and March 2021. CRC patients between January 2020 and March 2020 were excluded from the present study because it was the transitional period to the COVID-19 pandemic. Patients who underwent open or emergency surgery were also excluded. Enrolled patients were divided into a pre-COVID-19 group, which included those who underwent MIS between January 2018 and December 2019, and a COVID-19 group, which included those treated between April 2020 and March 2021 (Figure 1A).
COVID-19 pandemic in Japan. A) COVID-19 cases reported monthly in Japan between December 2019 and March 2021; B) The number of fecal blood tests and colonoscopies for screening of colorectal cancer in the pre-COVID-19 and COVID-19 periods in our hospital.
The screening for colorectal cancer in our hospital. Medical screening for digestive disease, fecal blood test, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), computed tomography, and upper endoscopy, were performed in the medical examination center of our hospital. The medical staff recommend colonoscopy to the patients with positive fecal bold test according to the results of the screening.
Surgical procedures. All surgeries were performed or supervised by surgeons with sufficient experience and certificated by the Japan Society of Endoscopic Surgery or the Japanese Society of Gastrointestinal Surgery. The surgical procedure and treatment strategy were decided in an expert meeting based on the Japanese CRC guidelines (17). Extended surgery for colorectal cancer, such as pelvic exenteration, para-aortic lymph node dissection, combined resection of genitourinary system, duodenum, or simultaneous resection of primary tumor and liver metastasis, were excluded from surgical indication of laparoscopic surgery. Colectomy with radical lymph node dissection was performed on all patients with CRC.
Clinical, surgical, and pathological findings. Clinical and surgical findings were extracted from surgical and medical records. The surgical T stage was re-evaluated using surgical videos by the first author, M.K. Pathological diagnoses were reached by two expert pathologists according to the 9th edition of the Japanese Classification of Colorectal, Appendiceal and Anal Carcinoma (18).
Statistical analysis. A univariate analysis was performed using the variables of CRC patients grouped by the COVID-19 pandemic. The Student’s t-test was used for parametric continuous variables and the Mann-Whitney test for non-parametric variables. The chi-squared test or Fisher’s exact test was used for categorical variables. All statistical tests were two-sided. p-Values <0.05 were considered to be significant. All statistical analyses were performed using JMP 10 (SAS Institute, Cary, NC, USA).
Results
The number of examinations for screening of colorectal cancer in the period of pre-COVID-19 and COVID-19 pandemic. Figure 1B shows the number of fecal blood tests and colonoscopies in the pre-COVID-19 and COVID19 periods. The number of the screening tests tended to decrease during COVID-19 pandemic compared to the period of pre-COVID-19.
Comparison of clinicopathological characteristics between pre-COVID-19 and COVID-19 groups. One-hundred seven patients underwent radical surgery for colorectal cancer in the pre-COVID-19 and 74 during the COVID-19 periods. Laparotomy was performed for 16 cases (14%) in pre-COVID-19 and 7 cases (9%) during COVID-19 because of intestinal perforation or extended surgery. As a result, ninety-one patients underwent MIS for CRC in pre-COVID-19 and 67 during COVID-19. Table I shows a comparison of clinicopathological characteristics between the pre-COVID-19 and COVID-19 groups. No significant differences were observed in sex, age, symptoms, or the bridge to surgery. The number of CRC cases detected by the fecal occult blood test was slightly higher in the pre-COVID-19 group than that in the COVID-19 group. The number of right-side colon cancer cases was significantly higher in the COVID-19 group than that in the pre-COVID-19 group (p=0.036). Furthermore, tumor sizes were significantly larger in the COVID-19 group than those in the pre-COVID-19 group.
Relationships between the COVID-19 pandemic and clinical factors in enrolled colorectal cancer patients.
Relationships between the COVID-19 pandemic and surgical factors in MIS for CRC. Re-evaluations of laparoscopic videos revealed that the number of cases of surgical T4 CRC, which was resected with the combined resection of adjacent organs, such as the intestinal tract, urogenital organs, and retroperitoneal tissue, was significantly higher in the COVID-19 group than that in the pre-COVID-19 group (16.4 vs. 4.4%, p=0.010) (Table II). Furthermore, the level of lymph node dissection was slightly higher in the COVID-19 group than that in the pre-COVID-19 group (p=0.052). The surgical time for MIS was also significantly longer in the COVID-19 group than that in the pre-COVID-19 group (332 vs. 232 min, p<0.001). No significant differences were observed in simultaneous surgery, conversion rates, blood loss, or postoperative hospital days between the groups.
Relationships between the COVID-19 pandemic and surgical factors in colorectal cancer patients.
Relationships between the COVID-19 pandemic and pathological factors. The relationships between pathological factors and the COVID-19 pandemic were examined (Table III). Although no significant differences were observed in the pathological N or M stage between the COVID-19 and pre-COVID-19 groups, the number of pT3 and pT4 cases was significantly higher in the COVID-19 group than that in the pre-COVID-19 group (p=0.026). Differences in surgical and pathological T stages are summarized in Figure 2.
Relationships between the COVID-19 pandemic and pathological factors in colorectal cancer patients.
T stage during the COVID-10 pandemic. A) The number of surgical T4b CRC cases significantly increased during the COVID-19 pandemic. B) The number of pathological T4b CRC cases significantly increased during the COVID-19 pandemic.
Discussion
The present study investigated whether the COVID-19 pandemic affected laparoscopic colectomy for CRC patients. The results obtained revealed that the tumor size of CRC was significantly larger in the first year of the COVID-19 pandemic in Japan than in the previous period before the pandemic. Furthermore, the number of surgeries with the combined resection of adjacent organs as well as pathological T4 tumors increased during the COVID-19 pandemic, resulting in longer surgical times for laparoscopic colectomy because of high surgical difficulty. To the best of our knowledge, this is the first study to investigate whether the COVID-19 pandemic has had an impact on laparoscopic colectomy for CRC patients in Japan.
The number of patients diagnosed with CRC was lower during than before the COVID-19 pandemic. Nevertheless, the number of cases showing progression of CRC increased during the COVID-19 pandemic. Cui et al. reported that elective surgery for CRC decreased during the COVID-19 pandemic; the number of cases of T3 and T4 CRC significantly increased, while the tumor stage was not markedly affected (14). Kuzuu et al. found that the number of cases of stage III CRC diagnosed each month was significantly higher during than before the COVID-19 pandemic (19). Choi et al. showed that MIS for CRC significantly decreased during the COVID-19 pandemic, whereas palliative surgery, such as stoma creation or bypass surgery, significantly increased, and the number of CRC patients receiving pre-operative treatments also significantly increased (15). Thus, the aspects of CRC under the COVID 19 pandemic differ regionally. However, since the COVID-19 pandemic resulted in the progression of the T stage in CRC, as indicated by the present results and the findings by Cui et al., increases in high-risk Stage II CRC, such as T4N0M0 CRC, may be predicted without significant differences in the total stage (20-22). High-risk Stage II CRC is clearly associated with a poor prognosis; therefore, indications for perioperative treatments need to be more carefully considered during the COVID-19 pandemic than before. Furthermore, the oncological feasibility of the safety of MIS for T4 CRC cases, particularly T4b, remains controversial (23-25).
Pre-operative evaluations based on detail examinations of imaging modalities or pre-operative biomarkers are essential for performing MIS on T4 cases with oncological safety. Improvements in the pre-operative evaluation of T4 cases may be required for the treatment of CRC during the COVID-19 pandemic.
Concerns regarding COVID-19-related risks to medical staff with the re-introduction of major MIS have been raised. The safety of MIS during the COVID-19 pandemic has been investigated, and the findings obtained showed that precautions, such as pre-operative laboratory testing for COVID-19, minimized the risk of infection, which has enabled the safe re-introduction of MIS and open surgery for both patients and medical staff (26-29). In our institution, MIS for CRC is performed with such preventive measures within one month of the definitive diagnosis of CRC. Therefore, treatment delays from the diagnosis of CRC due to the COVID-19 pandemic did not affect our results, suggesting that the progression of the T stage during the COVID-19 pandemic is attributed to screening delays or medical avoidance.
The present study revealed that the COVID-19 pandemic affected the T stage in CRC patients. However, the results obtained showed a change in the treatment of CRC within only one year of the emergence of COVID-19. Further studies on long-term oncological outcomes from the start of the COVID-19 pandemic are needed to continue providing appropriate treatment for CRC patients during the pandemic. Collectively, the present results and previous findings suggest the deterioration of long-term outcomes in CRC patients during the COVID-19 pandemic. Further studies are warranted to assess long-term oncological changes due to the COVID-10 pandemic.
There are some limitations that need to be addressed. This was a retrospective study with a small sample size in only one region, which may have limited the statistical power and generated a statistical bias. Furthermore, the present study only targeted laparoscopic surgery; therefore, other aspects of CRC under laparotomy have not been evaluated. Furthermore, the real-time evaluation of intraoperative findings was not performed due to the retrospective analysis of laparoscopic videos. Nevertheless, the present results revealed a change in MIS during the COVID-19 pandemic and will contribute to the treatment of CRC with oncological safety in the future.
Conclusion
The present study on MIS for CRC during the COVID-19 pandemic revealed that the number of T4 CRC cases was higher during than before the COVID-19 pandemic, which increases the surgical difficulty of MIS. During the COVID-19 pandemic, treatment strategies for advanced CRC need to be carefully decided based on a detail pre-operative examination.
Footnotes
Authors’ Contributions
MK contributed to the study conception and design. HI acquired data. MY, YY, TN, and YY, YS contributed to the analysis and interpretation of data. HI and KF wrote the manuscript. EO made the critical revision. All Authors have read and approved the manuscript.
Conflicts of Interest
The Authors have no conflicts of interest to declare in relation to this study.
- Received July 22, 2022.
- Revision received August 18, 2022.
- Accepted August 22, 2022.
- Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
