Management of Symptomatic Gallstone Disease during COVID-19 Lockdown in a High-Resource Setting: Is There a Need for Treatment Alterations?

Abstract

Introduction

Cholecystectomy (CCE) is the treatment of choice of symptomatic gallstones. Due to the SARS-CoV-2 pandemic, operating room (OR) capacities have been reduced. The goal of this study was to evaluate the duration of symptoms of patients presenting with gallstone disease during a lockdown, the surgical management, and the severity grade of their disease.

Materials and Methods

A cohort study of 353 CCEs performed at a university hospital over two 10-week periods during 2 pandemic lockdowns in Germany compared to corresponding periods in 2018 and 2019.

Results

During the lockdowns, 101 CCEs were performed compared to 252 in the prior years. The number of elective CCEs was reduced to save OR capacities (p < 0.001), and the most common indication for CCE was acute cholecystitis. The median time to CCE after symptom onset was 3 days in both groups for acute cholecystitis. The severity of cholecystitis was comparable (p = 0.760). The time to CCE after choledocholithiasis was shorter during the lockdowns (median of 4 days vs. 9 days; p = 0.006).

Conclusions

The incidence and severity of acute cholecystitis during the lockdowns were comparable to the prior years. Acute care surgery was provided at the expense of elective procedures, and there was no need for treatment alterations.

Introduction

Symptomatic gallstones (SGs) and cholecystitis are among the most common diseases treated by general surgery departments around the globe. In Germany alone, around 200,000 cholecystectomies (CCEs) are performed per year [1], most of them laparoscopically. Due to the global SARS-CoV-2 pandemic that hit central Europe in the spring of 2020, management of gastrointestinal disease and acute care surgery had to be adapted.

According to several study groups, pandemic lockdowns appeared to decrease the admission rate of general surgery emergencies [2, 3, 4], while others saw an increase in case load [5]. Recently, several groups (including one from our department) published data on a higher incidence of complicated appendicitis during the first SARS-CoV-19 lockdown that lasted from March 15 to May 31. This is believed to be caused by both delayed doctor consultation and delays in diagnosis and treatment due to in-house precautions and limited operating room (OR) capacity [4, 6]. The CovidSurg Collaborative study group published data on the increased morbidity and mortality in SARS-CoV-2-positive individuals [7]. Therefore, elective and nonurgent procedures are recommended to be postponed to after recovery from COVID-19 [8]. Cholecystitis and SGs usually are easy to manage, yet potentially life-threatening diseases. The 2018 Tokyo Guidelines provide clear treatment algorithms based on the severity of disease [9, 10].

In light of reduced OR capacities and potentially increased perioperative morbidity, physicians and surgeons have advocated for nonsurgical treatment of acute biliary disease, given the often favorable outcomes. Many studies were published on the “reinvention” of percutaneous gallbladder drainage as a replacement for early CCE [11, 12, 13, 14]. The ACDC trial [15] and subsequent meta-analyses have shown that early CCE is beneficiary for the patient compared to delayed procedures [16, 17]; thus, the true role of treatment alternatives is still under discussion.

The purpose of this study was to compare the frequency and indications for CCEs during the lockdown periods to the same time periods in 2018 and 2019. Our goal was to see if the behavior of patients or the surgeon's treatment was altered by the fact that we were in a pandemic.

Materials and Methods

The University Hospitals of Tuebingen are a tertiary teaching facility. It is the sole provider of bile duct intervention and gallbladder surgery for the district of Tuebingen, which has around 230,000 inhabitants. The department of general, visceral, and transplantation surgery performed an average of ∼330 individual CCEs per annum prior to the pandemic [18]. In Germany, the first SARS-CoV-2 wave leads to a lockdown from around March 15 to the end of May 2020. Hospitals were restricted to provide surgical care only to patients from their districts, while patients were instructed to present to their local care facilities in order to contain the viral spread. Due to a shift in resources and OR capacities, available OR slots were lowered by 25–33% in our department, and thus, the focus was put on emergency and oncologic surgery. With a low incidence of the virus over the summer months, OR capacities normalized and were decreased again when the COVID-19 incidence increased again in fall of 2020. A second lockdown was introduced in November, which was tightened in December and lasted until mid-January 2021. We retrospectively analyzed all individual CCEs that were performed during 2, each lasting 10 weeks, lockdowns (1st from March 15, 2020 to May 31, 2020 and November 1, 2020 to January 15, 2021) prior to the commencement of vaccination in Germany and compared them to the same time periods in 2018 and 2019.

The treatment algorithm at our center follows the current guidelines. Patients who are diagnosed with acute cholecystitis are supposed to undergo CCE no later than 72 h of symptom onset, if possible within 24 h after presentation. Patients who present with choledocholithiasis (CDL) usually have CDL resolved first by endoscopic retrograde cholangiography (ERC) and undergo CCE within the same inpatient stay after ruling out post-ERC pancreatitis. Intraoperative cholangiography is used on indication, mainly if ERC was unsuccessful in clearing the bile duct. Patients who presented with documented ongoing symptoms for >72 h are supposed to complete anti-inflammatory and antibiotic treatment and are scheduled to undergo CCE approximately 6 weeks later.

Laparoscopic CCE is performed in the standard 4-port technique. Open CCE is performed via midline or subcostal incision at the surgeon's discretion.

Indication for CCE

We divided the indications that led to CCE into 3 different groups. In group A, CCE was performed for acute cholecystitis (as defined by the 2018 Tokyo Guidelines); in group B, CCE was performed after an episode of CDL as secondary prophylaxis of recurrent CDL/pancreatitis; and group C was symptomatic cholecystolithiasis, chronic cholecystitis, or suspected gallbladder neoplasia. During the lockdown period, staff was instructed not to perform CCE in the absence of acute inflammation, CDL, or when no good argument for CCE could be made (e.g., recurrent presentations due to intolerable pain).

Timing of Procedures and Clinical Course

Our goal was to identify differences regarding the timing of presentation to the hospital, date, and time of the intervention. We screened the patient charts for treatment alterations made to reduce the inpatient stay (e.g., omission of intraoperative drain placement or prescription of oral perioperative antibiotics, instead of intravenous).

In order to maximize OR turnover after hours and weekend, CCE was possible but had to be coordinated with other surgical specialties and anesthesia for proper prioritization. Thus, we analyzed the weekdays and starting hours of surgical interventions to investigate whether the limited OR capacity had an influence on the timing of CCE. During normal working times, the ORs were scheduled with predominantly oncologic patients starting at 8 a.m. in the morning to 5 p.m. in the afternoon from Monday to Friday. There are no scheduled procedures past 5 p.m., on weekends and holidays.

Severity of Cholecystitis

The severity of cholecystitis was classified according to the 2018 Tokyo Guidelines. Since the duration of symptoms is part of the severity grading of cholecystitis, the date of symptom onset was confirmed retrospectively from the patient history. When patients claimed to be symptomatic for months or weeks and were unable to specify the date, we chose to use the date of physician consultation/presentation to the emergency room as the onset of acute symptoms.

Statistics

A comparison between groups was carried out by a χ² test or Fisher's exact test for nominal variables and a Mann-Whitney U test or a Kruskal-Wallis test for continuous variables, as appropriate. A probability of <0.05 was considered statistically significant. All p values reported are results of 2-sided testing. Where needed, Bonferroni correction was applied. Statistical analysis was carried out using IBM SPSS Statistics for Windows, version 27.0 (IBM Corp., Armonk, NY, USA).

Results

CCEs during hepatectomy or other abdominal procedures were excluded from the analysis. In total, 353 individual CCEs were performed in the study periods. During the 2 lockdowns, a total of 101 CCEs were performed (47 in Spring 2020 and 54 in Winter 2020/2021) compared to 119 in 2019 (55 in Spring and 64 in Winter) and 133 in 2018 (69 in Spring and 64 in Winter). Regarding baseline characteristics, both groups had similar gender distribution, median age, and body mass index. During 2018 and 2019, CCE was most commonly performed as an elective procedure for symptomatic cholecystolithiasis (46%), followed by emergent CCE for acute cholecystitis (35%) or bile duct stones (19%). During the lockdowns, acute cholecystitis was the most common indication (52%), followed by symptomatic cholecystolithiasis (31%) and bile duct stones (17%). While the absolute numbers for acute cholecystitis and bile duct stones were nearly equal during the corresponding time periods, the number of CCEs performed for symptomatic cholecystolithiasis was significantly lower during the lockdowns (p = 0.006). The number of elective CCEs made up 62% of the pre-lockdown period compared to 39% during the lockdowns (p < 0.001). Overall, around 90% of these CCEs were finished laparoscopically. Of the 252 CCEs pre-lockdown, 25 were completed as open procedures (including 9 conversions to open and 16 primarily open cases). During the lockdown, 2 conversions to open alongside 7 primarily open CCEs made up 9 open CCEs. (For details, see Table 1.)

Table 1.

Patient characteristics

	Pre-lockdown era	COVID-19-lockdown era	p value
Patient characteristics	N = 252	N = 101
Gender (f), n (%)	147 (58)	49 (49)	0.093
Median age, years (range)	72 (24–96)	68 (29–90)	0.835
BMI, kg/m2 (±SD)	26 (±5.0)	27 (±5.6)	0.870
Elective cases, n (%)	147 (62)	39 (39)	<0.001
Indication for CCE, n (%)
Acute cholecystitis	87 (35)	53 (52)
CDL/pancreatitis	49 (19)	17 (17)	0.006
Symptomatic cholecystolithiasis	116 (46)	31 (31)
ERC prior to CCE, n (%)	50 (20)	27 (27)	0.156
Median time between ERC and CCE, days (±SD)	9 (±96)	4 (±18)	0.006
Laparoscopic CCE, n (%)	225 (90)	92 (91)	0.771
Open CCE, n (%)	25 (10)	9 (9)
Cholangiography, n (%)	7 (3)	1 (1)	0.448

CDL, choledocholithiasis; ERC, endoscopic retrograde cholangiography; CCE, cholecystectomy; BMI, body mass index. Table 1 displays the patient characteristics of the study populations both before the lockdown (2018 & 2019) and during the COVID-19 lockdowns (2020).

Timing of CCE as a Secondary Prophylaxis

In our patient cohort, 77 patients underwent ERC for (suspected) CDL and/or pancreatitis. In the pre-lockdown cohort, 50/252 patients underwent ERC prior to CCE (20%) compared to 27/101 patients during the COVID-19 lockdowns (27%) (p = 0.156). During the ERC, 21/50 (42%) patients were admitted to the surgical department pre-lockdown and 29/50 (58%) to the medical department. During the lockdowns, the numbers were similar (12/27 (44%) in surgery and 15/27 (56%) patients in medicine (p = 0.836)). We compared the time that passed between ERC and CCE during the 2 periods. The median time to CCE pre-lockdown was 9 days (SD ±96; range 1–646). During the lockdown, the median time to CCE after ERC was 4 days (SD ±18; range 1–91) and thus significantly shorter (Mann-Whitney U test: p = 0.006, r = 0.314; median effect size).

Acute Cholecystitis

For all cases of acute cholecystitis, the median time between symptom onset and CCE was 3 days both during and before the lockdown (p = 0.606). The number of procedures that were performed after 5 p.m., on weekends or holidays, was also comparable. Of the 87 CCEs in the pre-lockdown group, 19 (22%) were performed after hours compared to 12 out of 53 (23%) CCEs during the lockdown (p = 0.912). Procedure length for these cases was similar around a median of 100 min. The severity of acute cholecystitis according to the 2018 Tokyo Guidelines did not differ between the 2 study populations. Pre-lockdown 39% was classified as mild cholecystitis, 48% as moderate, and 13% as severe. During the lockdown, 34% of cholecystitis cases were classified as mild, 55% as moderate, and 11% as severe (p = 0.760). There was no difference in the rate of intraoperative diagnosis of gangrenous cholecystitis (p = 0.389) or perforated cholecystitis (p = 0.695). The number of patients who had a drain placed during the procedure was similar (62% vs. 66%) as was the median duration of these drains (in days: 2 vs. 2; SD ±2.49 vs. ±2.07; p = 0.583). The rate and duration of perioperative antibiotics were comparable in both groups. In the pre-lockdown group, 72 out of 87 patients received more than a perioperative single shot (83%) than 44 of 53 (83%) in then lockdown group. In both groups, the median length of perioperative antibiotic treatment was 5 days (SD ±2.60 vs. SD ±3.90; p = 0.903). There was no need for endoscopic or percutaneous gallbladder drainage in our study cohort. (For details, see Table 2.)

Table 2.

Perioperative outcome of the acute cholangitis and cholecystitis patients

	Pre-lockdown era	COVID-19 lockdown era	p value
Acute cholecystitis	n = 87	n = 53	0.087
Median duration of symptoms, days	3	3	0.606
Severity according to TG 2018, n (%)
Mild	34 (39)	18 (34)
Moderate	42 (48)	29 (55)	0.760
Severe	11 (13)	6 (11)
Duration of procedure, min (±SD)	103 (±38)	102 (±33)	0.258
Drains placed in total, n (%)	54 (62)	35 (66)	0.636
Median duration of drains, days	2	2	0.583
Median postoperative stay, days	4	4	0.467
After hours procedure, n (%)	19 (22)	12 (23)	0.912
Open CCE, n (%)	14 (16)	6 (11)	0.434

CCE, cholecystectomy.

Referrals

Even though patients were instructed to present to a hospital within their district, our center − being a tertiary facility − continued to accept referrals from other hospitals when they were unable to treat a patient. The percentage of patients who were residents of a different (mainly neighboring) district who underwent CCE at our center was 33% pre-lockdown and 25% during the lockdown. There was no statistical difference (p = 0.132).

Lockdown Interval and Overall Caseload

For the purpose of an analysis of the overall caseload, we defined the start of the year as March 15 for the 3 years included. From March 15, 2018 to March 14, 2019 (year 1), 327 CCEs were performed compared to 331 between March 15, 2019 and March 14, 2020 (year 2) and 261 between March 15, 2020 and March 14, 2021. This was an overall reduction of ∼18%, which is close to the overall reduction in OR capacities. The overall case load and distribution were different in year 3 (p = 0.023). When we performed a subgroup analysis of the composition of these cases for the lockdown and interval periods, the difference in diagnosis that leads to CCE was only significant during for lockdown (lockdown p = 0.008 vs. interval p = 0.425). The severity of acute cholecystitis was comparable during both the lockdown and interval periods during year 3 (p = 0.581).

Outpatient Treatment

In order to understand how gall stones were treated in our outpatient/emergency department after COVID-19 hit our district, we evaluated patients who were diagnosed with (symptomatic) gall stones in the ED. Aside from the patients who underwent CCE, 47 patients were treated at our outpatient clinic for suspected or confirmed SGs throughout year 3 (March 15, 2020 to March 14, 2021). Of these 47 patients, 3 patients were treated medically for acute cholecystitis. One was offered CCE but declined due to nondisclosed reasons, one was symptomatic for over a week and was scheduled for CCE after 6 weeks later but did not present to his appointment, and one was diagnosed with SARS-CoV-2 on the date the cholecystitis was diagnosed. That patient underwent uneventful CCE 10 weeks after recurrence from both illnesses.

Of the remaining 44 patients, 11 had symptoms that could be attributed to gall stones or gastritis and were scheduled to undergo upper endoscopy (3 during the lockdown, 8 during the interval). None of them scheduled an appointment for a CCE later. Twenty-six patients were managed with analgesics in the presence of pain but the absence of inflammation (9 during the lockdown and 15 during the interval). All of these patients were offered to schedule an appointment for preparation of a CCE; however, none did. In 6 patients, the reason for not scheduling an appointment is known. None of these patients named the fear of COVID-19. Four patients were scheduled for CCE but did not show up on the date of operation (2 during the lockdown and 2 during the interval). In 2 patients, there was no clearance for surgery by cardiology, and in a single case, we were unable to offer the procedure OR timely enough for the patient to be willing to be treated at our center.

Discussion

Cholecystitis and SGs are among the most common reasons for clinical presentations to gastroenterology and general surgery departments [1]. Urgent (early) CCE is the treatment of choice in acute cholecystitis to prevent secondary complications and repeated inflammation [15, 19]. Similarly, all patients with CDL, cholangitis, and/or biliary pancreatitis should undergo CCE after resolution of the primary episode as a secondary prophylaxis [20, 21]. Aside from these 2 main indications, biliary colic caused by symptomatic cholecystolithiasis frequently leads to CCE to control pain and prevent development of cholecystitis or CDL.

When CCE is not available, cholecystitis can be treated with anti-inflammatory and antimicrobial medication. However, the recurrence rate is high, and thus, patients should be referred for CCE after recovery from the acute episode [19]. In CDL, sphincterotomy combined with biliary stents or drains usually prevents complications and repeated biliary obstruction. Recent studies showed long-lasting effect of transpapillary internal endoscopic gallbladder drainage [22, 23]. In patients who are too unfit for ERC or CCE, a percutaneous (transhepatic) drainage (PD) of the gallbladder can alleviate symptoms [13, 24]. PD however is not without risk and frequently associated with dislocation and therefore commonly requires interval CCE as well [14].

When the SARS-CoV-2 pandemic reached Europe in early 2020, many hospitals had to allocate resources and OR personnel away from elective surgery toward intensive care units (ICUs)/respiratory therapy of COVID-19 patients. With limited OR capacity and potentially infectious patients, strategies were developed on how to treat biliary disease nonsurgically [25]. Subsequently, a multicentric German study has published trends of admission during the first pandemic lockdown. They reported a decrease in admission for cholelithiasis during the early lockdown with an increase in admission for cholelithiasis between late May and the end of June 2020 [26]. Others have also reported reduced rates of cholecystitis during the lockdown [4, 27], which is interesting in light of increased weight gain [28, 29] and substance use during these time periods [30]. The south of Germany was hit hard and early by the pandemic. The state of Baden-Wuerttemberg went into a lockdown on March 15 that lasted till May 31. While there was a low incidence during the summer, a second lockdown started on November 1 that lasted till January 15. While most authors reported a reduction in general surgery caseload [2, 26, 27], some also saw an increase [5]. This was attributed to the reluctancy of the general population to present to an emergency room with nonsevere symptoms and poses the risk of delayed proper care [26].

While our medical department and ICU treated a fair share of severe COVID-19 patients, there was never the need to instruct the population to stay away from the hospital or to introduce a triage system. Nonacute and less urgent CCEs were postponed during the lockdown; thus, we saw a decrease in elective CCEs for SG disease, similar to what has been reported by a multicentric Spanish study group [31]. Most nonacute CCEs were performed in patients who were previously treated for CDL and had nonbearable pain spells or suspicion for malignancy. While Vallès et al. [27] reported a decrease in Grad I (mild) cholecystitis, we did not see a difference regarding overall caseload, timing of presentation, and severity of disease of our cholecystitis patients during the lockdown. The perception of the local hospital's situation may have a hard-to-calculate influence on primary care physicians in their decision to admit a patient for surgery or treat medically. During the low-incidence interval between the first and the second lockdown, as well as after the second lockdown, there was no surge in more severe acute or chronic cases of cholecystitis at our center. While the overall number of CCEs performed at our center dropped by 18% during year 3, the indication for CCE was only different during the lockdowns but not during the interval.

What surprised us the most is the fact that the time that passed between ERC and CCE was significantly shorter during the pandemic. Initially, we hypothesized that it may be due to a higher admission rate in the surgical department during the pandemic and thus a more streamlined scheduling of the procedure. However, both departments admitted the same proportions of patients. There is some truth to it though. In a subgroup analysis (not shown), we compared the time to CCE in patients admitted to the medical ward and the surgical ward. Both before COVID-19 and during the lockdowns, the time to CCE was shorter when patients were admitted to the surgical ward. Also the severity of CDL/cholangitis and pancreatitis was comparable between the patients admitted to medicine and surgery, and thus, there was likely no confounder. Performing CCE as early as possible after ERC is according to the recommendations of the PONCHO trial and international guidelines that recommend same stay early CCE to avoid complications and lower conversion rates [21, 32].

Given the 2 effective lockdown strategies, there fortunately was never the need to introduce alternative treatment measures for biliary disease in our hospital. By reducing elective surgical procedures, there was no need to offer − what is considered − suboptimal treatment to the patients and also there was no need to perform CCE during after-hours more than it was already done prior to the lockdowns. In hindsight, none of the patients who underwent CCE for acute cholecystitis had presented to our ED with symptomatic stones before the acute episode. The successful reduction of elective CCEs leaves the question whether these interval CCEs are truly necessary; however, in accordance to most guidelines, we still recommend elective CCE for all symptomatic patients to avoid complications [33].

The pandemic has put several alternative treatment strategies (back) on the map. The fact that mild cholecystitis can successfully be managed with antibiotic treatment is no news [19]. Since the recommendation not to use fluoroquinolones for nonsevere infections any more, orally available antibiotics with good biliary penetration are scarce [34, 35]. Ciprofloxacin was a very effective antimicrobial substance for biliary infections and must not be forgotten as the most potent orally available substance. While a quarter of medically treated patients will suffer recurrence, nonsurgical treatment appears to preserve OR capacities in the short term [36]. However, putting these procedures on the back burner may backfire when OR capacities do not turn out as prior anticipated.

While percutaneous cholecystostomy is considered to be an alternative for severely ill patients, both the CHOCOLATE Trial and a recent US multicenter study have shown a disadvantage of PC compared to CCE [37]. In our department, it is not considered an alternative to CCE. Rather we accept PC as a treatment option in critically ill patients (e.g., for patients in the ICU with extracorporeal membrane oxygenation and elevated intracranial pressure), who cannot undergo CCE and fail to improve under medical treatment. Surgeons and anesthesiologists will have to carefully weigh the perioperative (pulmonary) risk of patients with acute cholecystitis and active SARS-CoV-19 infection against the risk of suboptimal interventional treatment. While we agree that PC may be a good alternative to reduce respiratory complications in COVID-19 patients, we advise against the use of PC in non-COVID-19 cholecystitis patients.

Strengths and Limitations

We present a single-center experience of the management of symptomatic gall stones during 2 pandemic lockdowns in 2019 and 2020. The district of Tuebingen is one of a few districts in Germany whose entire inpatient treatment is covered by a single tertiary care facility that serves as both a community hospital and an academic center. Thus, we believe our study is less at risk for bias caused by city- or district-wide patient referral policies. Due to a reduction of elective cases, we were able to offer guideline-driven first-line treatment to all our patients and emergent referrals. Given that the district itself is inhabited by just over 200,000 people, our results will need to be compared to nation-wide registry data in the future.

Conclusion

While it is crucial to have alternative strategies in the management of disease during a pandemic, it is crucial to constantly evaluate one's own resources and chances in order to offer the patient the best possible treatment. We strongly advocate to adhere to guidelines and local treatment algorithms for as long as possible. Especially hospitals in a high-resource setting should provide the best possible care to avoid preventable short- and long-term complications. Treatment alterations should remain reserved for those that are by no means candidates for the standard care.

Statement of Ethics

This study protocol was reviewed and approved by the Ethics Committee of the University Hospital of Tuebingen, approval number 715/2020/B02. Informed consent was waived by said committee due to the retrospective analysis of pseudonymized data.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study or article did not receive any funding.

Author Contributions

Jens Strohaeker was involved in study conception and design, performed the analysis of data and interpretation, and drafted the manuscript. Julia-Maria Sabrow assisted with data acquisition and performed the analysis of data and interpretation. Can Yurttas drafted the manuscript and performed the analysis of data and interpretation. Alfred Königsrainer was involved in the drafting of the manuscript and critical revision of the manuscript. Ruth Lad­urner was involved in study conception and design and critical revision of the manuscript. Felix Hoenes assisted with data acquisition, drafting of the manuscript, analysis and interpretation of data, and critical revision of manuscript.

Data Availability Statement

All data and material can be provided upon further request.