Long Term Implications in Surgical Re-assisting (L.I.S.A. study) During Covid-19 Outbreak: A Retrospective Observational Study on a Rural Population.

Abstract

Background

The spread of the COVID-19 is having a worldwide impact on surgical

treatment. Our aim was to investigate the impact of the pandemic in a rural hospital in a low

densely populated area.

Methods

We investigated the volume and type of surgical operations during the pandemic

(March 2020 - February 2021) versus pre-pandemic period (March 2019 - February 2020) as

well as during the first and second pandemic waves compared to the pre-pandemic period.

We compared the volume and timing of emergency appendectomy and cholecystectomy

during the pandemic versus pre-pandemic period, the volume, timing and stages of elective

gastric and colorectal resections for cancer during the pandemic versus the pre-pandemic

period.

Results

In the prepandemic versus pandemic period, 42 versus 24 appendectomies and 174

versus 126 cholecystectomies (urgent and elective) were performed. Patients operated on

before as opposed to during the pandemic were older (58 vs. 52 years old, p=0.006),

including for cholecystectomy (73 vs. 66 years old, p=0.01) and appendectomy (43 vs. 30

years old, p = 0.04).

The logistic regression analysis with regard to cholecystectomy and appendectomy performed

in emergency showed that male sex and age were both associated to gangrenous type

histology, both in pandemic and prepandemic period. Finally, we found a reduction in cancer

stage I and IIA in pandemic versus prepandemic period, with no increase in the more

advanced stages.

Conclusions

the reduction in services imposed by governments during the first months of

total lock down did not justify the whole decrease in surgical interventions in the year of the

pandemic. Data suggest that greater "non-operative management" for cases of appendicitis

and acute cholecystitis does not lead to an increase in cases operated over time, nor to an

increase in the "gangrenous" pattern, which seems to depend on age advanced and male

population.

Background

The rapid spread of the new Coronavirus causing the COVID-19 disease is having a worldwide

impact on the remodelling of surgical treatment (1,2). Before the pandemic declaration by the

WHO, it was already clear that postponing elective activities was a fundamental step in order

to preserve patients’ safety and to limit the viral spread. This measure increases the resources

for COVID-19 patients, clearing ward and intensive care unit (ICU) beds. Moreover, it avoids

unnecessary patient traffic in the hospital and reduces the risk of cross-infection between

elective patients, hospital visitors, and COVID-19 patients, preventing spread of infection from

the hospital to the community (3). To conserve resources and to limit the spread of the virus,

many hospitals were forced to delay elective surgical operations. Nearly 38% of cancer

surgeries are estimated to have been postponed worldwide during the 12-week peak of the

pandemic (4). Recent studies suggest that postponing elective colorectal cancer (CRC) surgery

by more than four weeks after diagnosis is associated with poorer outcomes (4,5). However,

the lack of evidence-based standards for what is considered a delay in cancer surgery has led

to inconsistent study designs and few attempts at meta-analysis (4). A 2007 meta-analysis

found delays in surgery for CRC did not worsen survival; however, the interpretation of these

results is limited since colon and rectal cancers were not evaluated separately (6). The state of

the art and most triage guidelines discourage delaying curative-intent surgery for colon cancer

(7,8). For resectable colon cancer, curative intent surgery should be carried out, while

preoperative chemotherapy could be considered for locally advanced colon cancer. For rectal

cancer, all preoperative treatment options should be considered (3). As for gastric cancer,

instead, priority should be given to surgical resection of tumour stage cT1b and patients with

ongoing perioperative treatment, while patients with cT2 cancer or higher should undergo

preoperative therapy (3).

Other aspects involve emergency surgery during COVID-19 pandemic. Based on recent

published literature, urgent surgery should be performed for: obstructive or nearly obstructive

CRC (prefer diversion in rectal cancer), acutely transfusion-dependent tumours, cancers with

pending evidence of local perforation and sepsis, and post-surgical and post-colonoscopy

complications (3). Non-operative or conservative management of acutely ill patients should be

considered when feasible and safe, and it is strongly encouraged with COVID-19 patients (3).

As the rate of new COVID-19 cases decrease, a progressive reopening of elective procedures

will be necessary. To date, the information on the long-term effects of the reorganization during

the COVID-19 pandemic of the surgical units serving rural population basins is scant.

However, such information may contribute to improve the management of health care

resources during new COVID-19 pandemic waves as well as other pandemics. Our research

group has already analysed the first effects of the COVID-19 pandemic on surgical activities

in a University Hospital serving mainly an urban area and in the emerging setting (1,9).

Our aim was now to investigate the impact of the Pandemic on general surgery operations,

including emergency and cancer surgeries, in a district hospital serving a wide, low densely

populated rural area.

Methods And Materials

This is an observational, retrospective cohort study conducted in a hospital serving a wide least

densely populated rural area in the Province of Ferrara, in North-eastern Italy.

To investigate the impact of the Pandemic on general surgery operations in such a hospital we

specifically evaluated:

1) The volume and type of surgical operations during the pandemic versus pre-pandemic

periods as well as during the first and second pandemic waves compared to the pre-pandemic

period;

2) The volume and timing of emergency appendectomy and cholecystectomy during the

pandemic versus pre-pandemic period;

3) The volume and timing of elective gastric and colorectal resections for cancer during the

pandemic versus the pre-pandemic period.

We considered prepandemic period from March 2019 to February 2020 and pandemic period

from March 2020 to February 2021, the two 12-month time intervals before and during the

COVID-19 pandemic, respectively.

We also focused on all surgical operations performed in the first quarter (January-April) of the

year 2019 (prepandemic), 2020 (first pandemic wave), and 2021 (second pandemic wave).

We collected data on all adult patients undergoing elective or emergency surgery for the

pandemic period (March 2020 - February 2021), from a prospective database, and prepandemic

period (March 2019 - February 2020), retrospectively.

To evaluate the impact of the COVID-19 pandemic on emergency surgery we elected

cholecystectomies and appendectomies for the possibility of "non-operative-management" of

cholecystitis and appendicitis as compared to other diseases. In particular, we evaluated

patients’ age, surgical approach (i.e., open or laparoscopic technique), and final pathology to

detect gangrenous cholecystitis and appendicitis.

As far as cancer surgery is concerned, we evaluated the patients’ age, the use of preoperative

chemotherapy, and TNM tumour stage (AJCC 8th edition) of both colorectal and gastric

cancers. We also evaluated the need of neoadjuvant and adjuvant therapies in the two periods

(prepandemic and pandemic).

Finally, in order to detect any delay attributable to the pandemic burden, we reviewed the data

of the multidisciplinary colorectal cancer team to detect the time elapsed between endoscopic

cancer diagnosis and the preoperative computerized tomography (CT) staging, surgery, and

final pathology reporting.

Results

Between March 2019 and February 2020 (prepandemic period), a total of 663 surgical

operations were performed at our institution as opposed to 493 between March 2020 and

February 2021 (pandemic period). Fig. 1 summarizes the number of surgical procedures

performed in the two periods, detailing the type of surgical operations. In the prepandemic

compared to pandemic period, 42 versus 24 appendectomies and 174 versus 126

cholecystectomies (urgent and elective) were performed.

In the first quarters of 2019, 2020, and 2021 the total number of elective surgical operations

was 137, 116, and 130, respectively (p=0.79, Fig. 2). There was no statistical difference in the

total number of procedures performed in the first quarters of 2019 versus 2020 (p=0.21) and

2020 versus 2021 (p=0.21), although a reduction in lower G.I. Surgery (13 vs 18) and

cholecystectomies (28 vs. 46) were observed in 2020 versus 2019, while inguinal hernia repair

and haemorrhoidectomies increased in 2021 versus 2020.

Regarding emergency appendectomies and cholecystectomies, 93 operations were performed

in the prepandemic period compared to 63 in the pandemic period (Tab. 1). Patients operated

on before as opposed to during the Pandemic were older (58 vs. 52 years old, p=0.006), both

for cholecystectomy (73 vs. 66 years old, p=0.01) (Tab. 2) and appendectomy (43 vs. 30 years

old, p = 0.04) (Tab. 3). In the prepandemic versus pandemic period, the rate of gangrenous

cholecystitis at final pathology report was 37.3% (19 out of 51) and 35.9% (14 out of 39)

(p=0.90), while for gangrenous appendicitis was 23.8% (10 out of 42) and 20.8%(5 out of 24)

(p=0.78) (Tab. 1-3).

There were no substantial differences in the number of laparotomic appendectomy operations

performed during the period 2019-2020 (3 out of 42; 7,1%) versus 2020-2021 (2 out of 24;

8,3%).

In prepandemic period, 6 out of 51 laparotomic cholecystectomies were performed (11,7%)

compared to 3 out of 39 (7,7 %) during the pandemic period.

The logistic regression analysis, performed to evaluate factors associated to gangrenous pattern

in emergency cholecystectomy and appendectomy, showed that the male sex (OR 3.14, 95%

CI 1.47-6.10; p = 0.008) and age (OR 1.02, 95% CI 1.01-1.04; p = 0.003) were associated to a

gangrenous type histology both in pandemic and prepandemic period (Tab. 4).

Similar results were obtained in a subgroup analysing considering cholecystectomies (Tab. 5)

and appendectomy (Tab. 6) separately. Fig. 3 reports the total volumes of urgent procedures

performed in the prepandemic (2019) and pandemic (2020), differentiated by type of surgery

(cholecystectomies and appendectomies).

Ten patients underwent gastric resection for cancer in the prepandemic period compared to 9

in the pandemic period, with no difference between groups in terms of age, comorbidities, and

tumour size (Tab. 7).

We also evaluated the need of neoadjuvant and adjuvant therapies in the two periods and from

the analysis of these subgroups, no significant differences emerged (Tab. 8).

Sixty-five patients underwent colorectal cancer surgery in the prepandemic period compared

to 46 in the pandemic period.

For patients who underwent to colorectal resection for colonic cancer, the time elapsed between

endoscopic diagnosis, preoperative staging (contrast enhanced CT of the thorax, abdomen, and

pelvis), surgery, and final pathology during the prepandemic and pandemic period did not show

a significant difference (Tab. 9). Finally, we considered any differences between the groups in

terms of the need for neoadjuvant therapy.

Discussion

This study shows that Covid-19 pandemic has change our activity in emergency surgery, while

elective surgery did not significantly change. As the COVID-19 pandemic has put the Italian

national health care system under pressure, we hypothesized three possible scenarios after the

reopening of surgical activities at the end of the total lockdown between March and May 2020

(first pandemic period):

1) A rapid increase in hospital admission of surgical patients compared to the same period

in2019;

2) A progressive increase in surgical patients’ admission distributed over a several months

period of time;

3) A non-recovery of unoperated surgical patients’ admission, compared to the same

period in 2019.

The data analysed shows a reduction in operating volumes in the first quarter of 2020 (first

pandemic wave), as a consequence of government restrictions (Fig. 1), which was not followed

by an increase in cases in the following months, until the interruption of the observation period

in April 2021 (Fig. 1-2).With the reopening of the main activities in Italy, starting from May

2020, separate diagnostic-therapeutic paths for positive Covid-19 patients and negative Covid-

19 patients were instituted. Comparing the first quarters of the three consecutive years (i.e.,

2019, 2020, and 2021), there was an overall recovery in terms of volumes of surgical

interventions during the second pandemic wave (2021) as compared to the prepandemic period

(2019) (Fig. 2).

Regarding emergency surgery, we focused on emergency appendectomy and cholecystectomy.

Data shows that patients operated on during the pandemic (March - May 2020) were younger

as compared to the prepandemic period (March - May 2019) (Tab. 1-3). In pandemic versus

prepandemic period, both urgent cholecystectomies (51 vs. 39, p) and appendectomies (42 vs.

24, p) decreased, but There were no significant changes in the age of colon and stomach cancer

patients (Tab. 7,8). we did not detect a greater number of histological exams with a

"gangrenous" pattern. We identified, however, an association between gangrenous pattern of

the gallbladder and older age and male sex (Tab. 5). This data has not been identified in the

appendices. The decline in emergency operated patients for appendectomy and

appendicectomy is in accordance with other district hospitals in the Province of Ferrara.

The number of cases of stomach cancer who had surgery remained constant in between periods.

Interestingly, the number of patients who underwent preoperative chemotherapy in the

prepandemic period compares well with the prepandemic period.

The curative treatment of colon cancer did not show a delay in the diagnostic-therapeutic path

during pandemic versus prepandemic period (Tab. 9). In particular, there were no statistically

significant differences in time intervals between endoscopic diagnosis, preoperative contrast

enhanced CT, surgery, and definitive histological report. In prepandemic period, 62 patients

had surgery, compared to 44 cases in pandemic. Four patients in pandemic underwent

neoadjuvant chemotherapy, while in prepandemic we did not register any cases. Of note,

looking at the stages of colonic tumours of patients undergoing surgery, there was a clear

reduction in stage I and IIA in the pandemic versus prepandemic period (Fig. 4).

The presence of a pre-established multidisciplinary team and a perioperative pathway for

colorectal cancer patients may have helped to preserve the diagnostic and treatment steps

during the Pandemic.

A possible explanation for the drop in surgical admissions in the pandemic period may rely on

the advanced age of Covid-19 patients, who is the population with highest incidence of colon

cancer and cholelithiasis. The increase in mortality and morbidity in the elderly during the

Pandemic, could explain the decline in surgical admission as well as the reduction in the age

of patients who underwent emergency surgery during the Pandemic.

Another possible explanation, however, could be the fear of the population, in particular the

elderly, to go to the hospital during the Pandemic due to the risk of contagion in crowded

environments. This could explain the decline in hospitalizations for acute appendicitis in

pandemic and the younger age, as younger people may have less fear of Covid-19 as compared

to the elderly as they were affected by a mild form of the disease.

Finally, as the decrease of surgical activity in the first quarter of 2020 was not recovered

subsequently, including urgent appendectomy and cholecystectomy, may suggest greater use

of medical treatment or non-operational management.

The limitations of the study are related to the retrospective nature which introduces bias.

Conclusion

The decrease in surgical interventions in the Pandemic due to the reduction in services imposed

by the health reorganization to face the Covid-19 spread was not recuperated in the following

months, although the subsequent reopening with Covid-free pathways.

Increased medical treatment and non-operative management for acute appendicitis and acute

cholecystitis may have occurred operated in the Pandemic, but no increase in the "gangrenous"

pattern could be detected.

The curative treatment of colon cancer was not delayed during the Pandemic, possibly for the

presence of a multidisciplinary team and a consolidated perioperative pathway for such

patients.

Finally, new pathogen affecting more the elderly may have influenced the reduction of surgical

interventions in pandemic compared to prepandemic.

Abbreviations

AJCC: American Joint Committee on Cancer 

ANOVA:  analysis of variance

COVID-19: CoronaVirus Disease-19

CRC:  colorectal cancer

CT:  computerized tomography

ICU:  intensive care unit

SD:  standard deviation

STROBE:  Strenghtening the Reporting of Observational Studies in Epidemiology

WMA:  World Medical Association

Declarations

Funding

This study did not receive any grant from funding agencies in the public, commercial, or not-for-profit sectors.

Acknowledgement

Authors would thank all the collaborators of this research:

Dr. M. Bertasi, Dr. L. Di Marco, Dr. G. Bisi, Dr. A. Cataldi, Dr. D. D’Antonio, Dr. M. Fazzin, Dr. S.

Gennari, Dr. F. Pindozzi, Dr. M. Poledrelli, Dr R. Salmi, Dr V. Sciascia, Dr. S. Severi, Dr. R. Soverini, Dr M. Torchiaro, Dr A. Campagnaro.

Ethics approval and consent to participate

This study was approved by Institutional Review Board, Azienda USL di Ferrara, Italy.

Consent for publication

Not applicable.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Author details

1) General Surgery Unit, Azienda USL di Ferrara, Lagosanto, Italy

2) Department of Medical Sciences, University of Ferrara, Ferrara, Italy

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