Case Report Open Access
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Feb 6, 2022; 10(4): 1296-1310
Published online Feb 6, 2022. doi: 10.12998/wjcc.v10.i4.1296
Surgical treatment of acute cholecystitis in patients with confirmed COVID-19: Ten case reports and review of literature
Katya Bozada-Gutiérrez, Mario Trejo-Avila, Fátima Chávez-Hernández, Carlos Valenzuela-Salazar, Jesús Herrera-Esquivel, Mucio Moreno-Portillo, Department of General and Endoscopic Surgery, Hospital General Dr. Manuel Gea Gonzalez, Mexico City 14090, Mexico
Sara Parraguirre-Martínez, Department of Pathology, Hospital General Dr. Manuel Gea Gonzalez, Mexico City 14090, Mexico
ORCID number: Katya Bozada-Gutierrez (0000-0003-3148-2295); Mario Trejo-Avila (0000-0001-9249-3321); Fátima Chávez-Hernández (0000-0001-6336-5048); Sara Parraguirre-Martinez (0000-0002-8573-9212); Carlos Valenzuela-Salazar (0000-0002-4999-5489); Jesús Herrera-Esquivel (0000-0001-6287-8386); Mucio Moreno-Portillo (0000-0001-8453-9385).
Author contributions: Bozada-Gutiérrez K designed and performed the research, contributed to the analysis and wrote the paper; Trejo-Avila M designed the research, contributed to the analysis, wrote the paper, provided clinical advice and supervised the report; Chávez-Hernández F designed and performed the research, contributed to the analysis; Parraguirre-Martínez S performed the research, provided histopathological images and interpretation, contributed to the analysis; Valenzuela-Salazar C, Herrera-Esquivel J and Moreno-Portillo M designed the research, contributed to the analysis, provided clinical advice and supervised the report.
Informed consent statement: Informed consent was waived by competent authorities due to the use of anonymous data and due to its retrospective nature.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016) Statement and the manuscript was prepared and revised according to the CARE Checklist (2016) Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mario Trejo-Avila, MD, Surgeon, Department of General and Endoscopic Surgery, Hospital General Dr. Manuel Gea Gonzalez, Calzada de Tlalpan 4800, Mexico City 14090, Mexico. mario.trejo.avila@gmail.com
Received: July 27, 2021
Peer-review started: July 27, 2021
First decision: October 3, 2021
Revised: October 16, 2021
Accepted: December 25, 2021
Article in press: December 25, 2021
Published online: February 6, 2022
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Abstract
BACKGROUND

Research concerning postoperative outcomes of confirmed coronavirus disease 2019 (COVID-19) patients revealed unfavorable postoperative results with increased morbidity, pulmonary complications and mortality. Case reports have suggested that COVID-19 is associated with more aggressive presentation of acute cholecystitis. The aim of the present study is to describe the perioperative assessment and postoperative outcomes of ten patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with concomitant acute cholecystitis who underwent cholecystectomy.

CASE SUMMARY

We report a total of 10 SARS-CoV-2 positive patients with concomitant acute cholecystitis that underwent cholecystectomy. Six patients were males, the mean age was 47.1 years. Nine patients had moderate acute cholecystitis, and one patient had severe acute cholecystitis. All patients were treated with urgent/early laparoscopic cholecystectomy. Regarding the Parkland grading scale, two patients received a Parkland grade of 3, two patients received a Parkland grade of 4, and six patients received a Parkland grade of 5. Eight patients required a bail-out procedure. Four patients developed biliary leakage and required endoscopic retrograde cholangiopancreatography with biliary sphincterotomy. After surgery, five patients developed acute respiratory distress syndrome (ARDS) and required intensive care unit (ICU) admission. One patient died after cholecystectomy due to ARDS complications. The mean total length of stay (LOS) was 18.2 d. The histopathology demonstrated transmural necrosis (n = 5), vessel obliteration with ischemia (n = 3), perforation (n = 3), and acute peritonitis (n = 10).

CONCLUSION

COVID-19 patients with acute cholecystitis had difficult cholecystectomies, high rates of ICU admission, and a prolonged LOS.

Key Words: COVID-19; SARS-CoV-2; Cholecystectomy in COVID-19; Acute cholecysti- tis in COVID-19; Case report

Core Tip: Several studies have described multiple gastrointestinal complications in patients with coronavirus disease 2019, including advanced stages of cholecystitis. we found in the present study that patients with confirmed severe acute respiratory syndrome coronavirus 2 infections who presented with acute cholecystitis, tended to have a higher grade on the Parkland grading scale (including gallbladder perforation, empyema and total wall necrosis), had difficult laparoscopic cholecystectomies with an increased need for a bail-out procedure, had high rates of intensive care unit admission, and had a prolonged length of hospital stay.



INTRODUCTION

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China, in December 2019, causing a new disease named coronavirus disease 2019 (COVID-19)[1].

Research concerning postoperative outcomes of confirmed COVID-19 patients revealed unfavorable postoperative results with increased morbidity, pulmonary complications and mortality[2-5].

Several studies have described gastrointestinal symptoms in patients with COVID-19, with nearly 25% of patients referring abdominal pain[6]. Association with other gastrointestinal complications for example, liver injury and late cholestasis, have been reported[7]. Concerning the gallbladder, some studies have described the presence of acute ischemic gangrenous cholecystitis, with or without perforation, and with or without associated cholelithiasis[8-30]. Studies have suggested that COVID-19 is associated with more aggressive presentation of acute cholecystitis[15,19,24,27,28].

The guidelines for the treatment of acute cholecystitis before the pandemic recommended early laparoscopic cholecystectomy (Lap-C) for patients with mild acute cholecystitis as the treatment of choice[31-33]. For patients with moderate acute cholecystitis the treatment of choice is urgent/early Lap-C when advanced laparoscopic techniques are available. The indications for urgent Lap-C in confirmed COVID-19 patients should not differ from those without COVID-19[19].

Since the beginning of the pandemic in 2020, several surgical societies have published their recommendations to treat acute cholecystitis[2,34]. The firsts recommendations were to avoid surgeries and to adopt a non-operative management when possible[28,35]. The finding of virus particles in the peritoneal fluid and the idea that pneumoperitoneum could allow the transmission of virus led many surgical societies to publish recommendations for gastrointestinal laparoscopic surgery[34,36-38]. More recent recommendations sustain that laparoscopy is not more likely to spread the COVID-19 infection than open surgery, and minimally invasive surgery provides better outcomes that laparotomy[2].

Since acute cholecystitis represents a very frequent cause of hospital admission worldwide[39], it is important to know the perioperative outcomes of patients with confirmed COVID-19 and cholecystitis, also it is important to know what to expect during surgeries.

The aim of the present study was to describe the perioperative assessment and postoperative outcomes of patients with confirmed SARS-CoV-2 infection with concomitant acute cholecystitis who underwent urgent cholecystectomy.

CASE PRESENTATION
Chief complaints

We included symptomatic and asymptomatic SARS-CoV-2 positive patients (asymptomatic carriers) who required urgent/early cholecystectomy. During the pandemic all the patients that were admitted to our hospital were screened for SARS-CoV-2 infection.

Regarding the chief complaints, patients presented with the characteristic right upper quadrant pain related to acute cholecystitis.

History of present illness

All patients had concomitant acute cholecystitis with SARS-CoV-2 infection. We included patients with the SARS-CoV-2 infection confirmed either by reverse-transcriptase polymerase chain reaction (RT-PCR) assay of a nasopharyngeal swab or a rapid antigenic test. Several variables were recorded including demographic parameters and preoperative quick Sequential Organ Failure Assessment (qSOFA) score[40]. Data is shown in Table 1.

Table 1 Demographic information of confirmed coronavirus disease 2019 patients with acute cholecystitis (n = 10) (mean ± SD).
Classification
n = 10
Sex, n (%)
Female4
Male6
Age (yr), mean (range)47.1 (20-74)
BMI (kg/m2), mean (range)28.4 (20-43)
Current Smokers, n (%)3
ASA classification, n (%)
I2
II4
III4
Comorbidities, n (%)
Diabetes2
Hypertension4
CRD2
Lupus1
No6
Preoperative qSOFA score, n (%)
Not high risk (0-1)4
High risk (> 2)6
COVID-19 symtoms
Yes6
No 4
Preoperative studies
Hemoglobin (g/dL)12.8 (2.8)
Platelets (n × 103/μL)284 (128.7)
Leucocytes (n/μL)11.95 (5.6)
CRP (mg/dL)20.1 (12.5)
Total Bilirubin (mg/dL)1.29 (1.7)
Gamma-glutamyl transferase (IU/L)163.1 (198.1)
Alanine aminotransferase (IU/L)86.1 (102.8)
Aspartate aminotransferase (IU/L)59.9 (46.7)
Alkaline fosfatase (IU/L)199 (189.7)
LDH (IU/L)215.1 (63.3)
Albumin (g/dL)4.17 (0.4)
Ferritin (ng/mL)565 (304.5)
Creatinine (md/dL)1.02 (0.5)
History of past illness

Of the ten patients, four had history of past illness. The most frequent comorbidity was hypertension (n = 4). The complete list of comorbidities is presented in Table 1.

Personal and family history

The personal and family history was noncontributory.

Physical examination

On physical examinations patients had right upper quadrant pain (n = 10), right upper quadrant mass (n = 6), and positive Murphy´s sign (n = 10).

Demographic data included age (years), gender, body mass index in kg/m2, comorbidities, smoking status, American Society of Anesthesiology classification. The preoperative qSOFA score was calculated and we divided the patients in high risk (> 2 point) or not high risk patients (0-1 points).

Laboratory examinations

Preoperative laboratory examinations are shown in Table 1. Of relevance, the mean preoperative C-reactive protein level was 20.1 mg/dL, the mean total bilirubin was 1.29 mg/dL, and the mean ferritin level was 565 ng/mL.

Imaging examinations

All patients underwent chest computed tomography (CT) scans prior to surgery. Also, all patients underwent gallbladder ultrasound. We diagnosed acute cholecystitis according to Tokyo Guidelines (TG18) ultrasound criteria (thickened gallbladder wall, enlarged gallbladder, pericholecystic fluid collection)[32,41].

FINAL DIAGNOSIS

Regarding the timing of COVID-19 diagnosis, nine patients were diagnosed preoperatively and one was diagnosed postoperatively. Of the 10 patients, four were asymptomatic SARS-CoV-2 carriers. The rest of patients (n = 6) presented with symptomatic disease and preoperative CT scans with COVID-19 pneumonia (bilateral ground-glass opacities with consolidation).

We diagnosed and graded the severity of acute cholecystitis according to the 2018 TG18[32,41]. All patients were diagnosed with definite acute cholecystitis according to the TG18. Regarding the severity assessment, nine patients had grade II (moderate) acute cholecystitis and one patient had grade III (severe) acute cholecystitis. Additionally, one patient was diagnosed with grade II acute cholangitis, and the other patient had concomitant mild acute pancreatitis. Both patients were operated after resolution of cholangitis and pancreatitis, respectively.

TREATMENT

All surgeries were performed at a COVID-19 dedicated operating theater and all the medical staff were equipped with personal protective equipment. Laparoscopic cholecystectomies were performed with a 3 or 4 trocar technique depending the case, using a 12-mm umbilical trocar (optical), a 12-mm trocar in the sub-xiphoid area, and a 5-mm in the right flank. We performed diagnostic laparoscopy and we graded the intraoperative findings according with the Parkland scale. After that, bile and purulent collections were drained and intraabdominal adhesions were taken down. The decision to perform a bail-out procedure was done when the critical view of safety was difficult to achieve. In our hospital, we employ the reconstituting subtotal cholecystectomy or the open conversion as bailout procedures. The reconstituting subtotal cholecystectomy consisted in making an incision in the gallbladder, aspirating the contents including the stones, removing the peritonealized portion of the gallbladder, except the lowest portion (infundibulum and Hartmann´s pouch), and partially excising the posterior wall adherent to the liver. After that, the lowest part of the gallbladder is closed with sutures obliterating the cystic duct, leaving a closed gallbladder remnant[15,41].

During laparoscopy we filtered the pneumoperitoneum through filters able to remove most viral particles as suggested by several authors[2,42,43].

Two patients required preoperative endoscopic retrograde cholangiopancreatography (ERCP). One patient had cholestasis and a type I Mirizzi syndrome was found at ERCP. The other patient had grade II acute cholangitis and required early endoscopic treatment (ERCP biliary drainage).

All patients were treated with urgent/early Lap-C. Eight surgeries were completed via laparoscopy and two patients required conversion to open cholecystectomy due to operative difficulty.

Regarding the Parkland grading scale, all patients were found to have severe inflammation (grades 3-5): Two patients had pericholecystic fluid, adhesions to the gallbladder body, hyperemia and distended gallbladder (Parkland 3); One patient had adhesions obscuring the majority of the gallbladder and one patient had Mirizzi syndrome (Parkland 4); And six patients had Parkland 5 (six patients with complete necrosis of the gallbladder body infundibulum and cystic duct, three of them with gallbladder perforation) see Figure 1. Six cases were treated with subtotal reconstituting cholecystectomy, because a critical view of safety could not be achieved.

Figure 1
Figure 1 Intraoperative findings of confirmed coronavirus disease 2019 patients with acute cholecystitis. A: Gangrenous and perforated; B: Fundus and body wall necrosis; C: Wall necrosis; D: Gangrene extended to the infundibulum and cystic duct.

The mean estimated blood loss (EBL) was 258 mL, the mean operative time was 133.5 min, and eight patients required intraabdominal closed drainage.

OUTCOME AND FOLLOW-UP

Operative outcomes included modality of cholecystectomy (laparoscopic, open or converted), EBL in mL, operative time in minutes, and requirement of intraabdominal drainage. We graded the intraoperative findings according with the Parkland grading scale for cholecystitis[42]. Preoperative or postoperative need for ERCP and findings were registered.

Postoperative complications were classified and presented according with the Clavien-Dindo classification. The need for intensive care unit (ICU), vasopressors and invasive mechanical ventilation were recorded. The hospital length of stay (LOS) in days was registered.

Five patients developed biliary leak after subtotal cholecystectomy. Of these patients, two had low-output leak, while three patients had high-output biliary leak. Patients with low-output leaks were treated with closed suction drainage alone, while patients with high-output leaks needed ERCP with biliary sphincterotomy and biliary stent placement. The complete list of postoperative complications classified according to Clavien-Dindo is shown in Table 2.

Table 2 Description of postoperative complications according with the Clavien-Dindo classification (n = 10).
Grade
Grade I
Hydroelectrolytic imbalance8
Antiemetics3
Antipyretic (for fever ≥ 38.3)4
Grade II
Blood transfusions3
Total parenteral nutrition3
Postoperative Ileus1
Pneumonia6
Delirium4
Biliar leak5
Wound infection3
Grade IIIb
Evisceration1
Bleeding1
ERCP3
Grade IVa
Respiratory5
Renal3
Hepatic2
Cardiovascular5
Dialysis2
Grade IVb5
Multiorganic failure
Grade V1
Death of a patient

After surgery five patients required ICU admission, and one patient was admitted preoperatively and remained in the ICU after surgery. The five patients were on invasive mechanical ventilation and vasopressor therapy. These patients developed acute respiratory distress syndrome (ARDS) related to SARS-CoV-2. One patient died after cholecystectomy and due to ARDS complications.

Considering the complete cohort of patients, the mean total LOS was 18.2 d.

The histopathological diagnosis was performed using hematoxylin-eosin (H&E) stained slides (Table 3). As demonstrated in Figure 2, H&E slides displayed the inflammatory infiltration (n = 10), with transmural necrosis (n = 5), hemorrhagic infarction (n = 2), mucosal ulcerations (n = 1), vessel obliteration with ischemia (n = 3), gallbladder wall perforation (n = 3), and acute peritonitis (n = 10).

Table 3 Perioperative outcomes of coronavirus disease 2019 patients with acute cholecystitis.
Perioperative outcomes

ERCP result
Preop Mirizzi syndrome 11
Preop Cholangitis + CBD stones1
Postoperative Biliary leak3
ERCP Biliary stent 3
Modality of cholecystectomy, n (%)
Laparoscopic8
Lap converted to open2
Type of cholecystectomy
Total4
Sub-total6
Parkland grading scale, n (%)
32
42
56
Estimated blood loss (mL), mean (range)258 (30-500)
Operative time (min), mean (range)133.5 (70-190)
Intraabdominal drainage, n (%)8
ICU admission, n (%)
Yes, Preoperative1
Yes, Postoperative4
ICU treatment, n (%)
Invasive ventilation5
Vasopressors5
Hospital LOS (days), mean (range)18. 2 (3-50)
Histopathology results, n (%)
Ischemic/segmental necrosis3
Transmural necrosis5
Perforated3
Mucosal ulcerations1
Acute peritonitis10
GB empyema4
Hemorrhagic2
Figure 2
Figure 2 Histopathological findings (hematoxylin and eosin staining). A: Total transmural necrosis; B: Gallbladder wall hemorrhage; C: Arterial thrombosis; D: Inflammatory infiltrate.
DISCUSSION

We found in the present study that patients with confirmed SARS-CoV-2 infections with concomitant acute cholecystitis tended to have high grades on the Parkland grading scale (including gallbladder perforation, empyema and total wall necrosis), difficult Lap-C with an increased need for a bail-out procedure (open conversion or subtotal cholecystectomy), high ICU admission rates, high rates of postoperative biliary leaks that required ERCP (with biliary stent placement), and prolonged length of hospital stay.

Several studies have described the presentation of acute cholecystitis concomitant with a SARS-CoV-2 infection. A literature review of the research concerning COVID-19 and acute cholecystitis is summarized in Table 4. We have noticed that the majority of studies that have been published during the pandemic are case reports and letters to the editor (see Table 4). The first case report of histopathological findings of an acute ischemic gangrenous cholecystitis as a late complication in a COVID-19 patient was published by Bruni et al[21]. Since then, the description of gangrenous cholecystitis in patients with COVID-19 has been found in at least six other studies[15,18,19,24,27,28]. In our series, 3 patients had wall ischemia and segmental necrosis, and 5 patients had complete transmural necrosis. Of note, some of these case reports outlined the presence of gangrenous cholecystitis but without cholelithiasis (acalculous)[18,19,27]. In our series, only one patient presented with acalculous cholecystitis, and the rest of the patients had cholelithiasis. This could represent a different physiopathological pathway that should be further investigated. Nevertheless, patients with both etiologies required cholecystectomy.

Table 4 Review of previous studies reporting coronavirus disease 2019 and acute cholecystitis treatment approach.
Ref.
Study design
Country
Sample size, n (%)
Age/sex (F:M)
COVID-19 diagnosis
Tokyo class
Treatment
Morbidity/PO complications
ICU, n (%)
LOS (d)
Mortality
Findings/histopathology
Çakır and Kabuli[8], 2021Retrospective studyTurkey18M: 14 (78%); F: 4 (22%); Age: 73.3 (67-81)RT-PCRGI: 3 (16.7%); GII: 9 (50%); GIII: 6 (33.3%)THGDNo complications3 (16.6%)16 (3-32)3 (16.6%)NR
Barabino et al[9], 2021Retrospective studyItaly 37: 36 non-COVID; 1 COVID64 (38-94); Male: 21 (56.7%); Female 16 (43.3%)RT-PCRGI: 13 (35.1%); GII: 15 (40.5%); GIII: 8 (21.6%); COVID: GII Antibiotic only 11 (29.7%); THGD 8 (21.6%); L 18 (48.7%); COVID: THGD 1Emergency LC 1; Bleeding 1; Cholangitis 229 (2-12)--
Martínez Caballero et al[10], 2021 Multicentre-combined (retrospective–prospective) cohort studySpain42 Age: COVID: 83 (65-87); COVID: 28 M/14 F Clinics 10.9%; Imaging test 11.3%; RT-PCR 12.5% GI: 112 (43.6%); GII: 121 (47.1%); GIII: 24 (9.3%) Antibiotic therapy 47.9%; Surgical treatment 31.5%; THGD 20.6%. COVID: 93.3% non surgical treatmentGallblader perforation 8.4%; Biliar setic shock 8.4%23%Non-COVID: 5 d (3–8). COVID: 11.0 d (7.5–27.5)Non-COVID: 3.25%; COVID: 11.9%-
Çiyiltepe et al[11], 2021Retrospective studyTurkey65 non-COVID; 7 COVIDAge: 57.3; F: 40 (55.6)/M: 32 (44.4) GI: 35 (48.6%); GII: 37 (51.3%)11 THGD--9.2 (6-20)--
Somuncu et al[12], 2021Retrospective studyTurkey4 COVID; 32 non-COVIDAge: 53 (26-78); M: 17/F: 19Thorax CT-Antibiotic therapy 14; THGD 14 (39%); LC 8 --7 (2-20)1: Cardiac arrest -
Puig et al[13], 2021Case reportSpain2M: 65/57 RT-PCRGIII: 2Percutaneous cholecystostomy 2Pulmonary tromboemboly 22340-
Abaleka et al[14], 2021Case reportUnited States1Age: 76; F RT-PCRGrade IIAntibiotics-----
Lovece et al[15], 2020Case reportItaly1Age: 42/MRT-PCRGrade IIILCGallblader perforation----
Famularo and Spada[16], 2021Letter/case reportItaly190/MRT-PCR +NRTHGDNoNo26NoNR
Vaishnav and Patel[17], 2021Observational/prospectiveIndia1650/F: 7 (29%); M: 17 (70%)RT-PCR + CT +GIIILCNoNR4.9NRNR
Alhassan et al[18], 2020Case reportQatar140/FConfirmed 14 d priorAACAntibioticsNoYes (1, 100%)NRNo-
Asti et al[19], 2020Letter/case reportItaly340-86/F: 1 (33%); M: 2 (66%)ConfirmedAACLCNRNRNRNRAcalculous, gangrene
Balaphas et al[20], 2020Letter/case reportSwitzerland283-84/F: 1 (50%); M: 1 (50%)RT-PCR +AACLC/AntibioticsNRYes (1, 50%)NRYes (1, 50%)qRT-PCR revealed the presence of SARS-CoV-2 in the gallbladder wall
Bruni et al[21], 2020Case reportItaly159/MRT-PCR +AC/GIIIOCNRYes (1, 100%)44NoGangrenous, Hemorrhagic, vasculitis
Cirillo et al[22], 2020Letter/case reportItaly179/MConfirmedAACCholecystectomyNoNRNRNoPerforated acalculous cholecystitis
Giulio et al[23], 2020Letter/case reportItaly145/FRT-PCR +AC/GILCNoNR30NoNR
Gupta et al[24], 2020Retrospective original articleIndia553.2/NRConfirmedACOCBile leakNR4-9NoAcute on chronic calculous cholecystitis, gangrenous acalculous cholecystitis
Kabir et al[25], 2020Letter/case reportSingapore1Middle-aged/MRT-PCR +Gangrenous cholecystitisSubtotal reconstituting OCNRNRNRNRNR
Lisotti et al[26], 2020Case reportItaly180/FCT suspiciousAC/GIIEUS-GBDNoNo1NRNR
Mattone et al[27], 2020Case reportItaly166/MRT-PCR +AACInitially THGDLCNoYesNRNoGangrenous gallbladder
F Narvaez et al[28], 2020Brief report/reviewUnited States1NR/FConfirmedACLCNoNoNRNoNear-gangrenous gallbladder
Safari et al[29], 2020Case reportIran175/FRT-PCR +CT +AC/GIILCNRYes (1, 100%)9YesNR
Ying et al[30], 2020Case reportChina 168/FRT-PCR +AC/GIITHGDNoNo25NoNR

An editorial by Cirillo et al[22], reported the finding of acalculous hemorrhagic cholecystitis in a patient with a SARS-CoV-2 infection who needed emergent cholecystectomy. In our histopathological analysis we found that 2 patients had hemorrhagic changes in the gallbladder wall after surgery. Our report differs from the report of Cirillo et al[22], in the fact that they preoperatively diagnosed the hemorrhage by CT scan with active contrast extravasation around and inside a perforated gallbladder. The presence of hemorrhage from an inflamed gallbladder is rare and larger studies are needed to confirm an association with SARS-CoV-2 infection.

Considering the potential association of SARS-CoV-2 with gallbladder disease, several hypothesis have been formulated. One hypothesis is that the systemic inflammation, the immune system changes induced by SARS-CoV-2, and the immunotherapy employed to treat it, may contribute to the late onset of cholecystitis by pro-inflammatory pathways[15]. Also, the findings of small-vessel thrombosis and gallbladder wall ischemia suggested a correlation with the coagulopathy and pro-thrombotic state induced by this coronavirus[21,44]. Furthermore, it has been suggested that due to the expression of angiotensin-converting enzyme 2 receptor in gallbladder epithelial cells, SARS-CoV-2 could target that cells[45]. Taking into account these inflammatory changes, we found on the histopathological examination of our patients, acute peritonitis, acute inflammatory infiltrates, as well as ischemic and necrosis associated with small vessel thrombi, and hemorrhagic changes in the gallbladder wall of our patients.

Regarding the treatment of acute cholecystitis, some authors reported the treatment with antibiotics[46], others reported percutaneous cholecystostomy[16,26], and others published their outcomes after laparoscopic or open cholecystectomy[46,47] (Table 4). The relevance of our study is that we described the outcomes of 10 patients with positive COVID-19 tests who required urgent cholecystectomy. Urgent/early cholecystectomies were performed due to gallbladder perforation (n = 3) and gangrenous cholecystitis (n = 8), where medical treatment with antibiotics only or cholecystostomy were considered insufficient treatments[19,32,41].

Concerning the intraoperative findings, we found that patients were operated on at a very advanced stage of acute cholecystitis with severe inflammation (a Parkland score > 3); thus, the critical view of safety was very difficult to achieve. The majority of our patients required a bail-out procedure for a safe cholecystectomy. As mentioned in the results section, 2 underwent conversion to laparotomy and 6 required sub-total reconstituting cholecystectomy. Of note, 3 of the 6 patients who needed sub-total cholecystectomy required ERCP due to biliary leak. Leaks developed in patients with complete gangrenous cholecystitis that extended to the infundibulum and to the cystic duct. Therefore, it is important to consider that in patients with suspected gallbladder necrosis, ischemia could extend to the cystic duct, thereby increasing the risk of postoperative biliary leakage or fistula. In our series, patients who develop postoperative bile leakage where treated with ERCP. Endoscopic management of biliary leaks (sphincterotomy with or without biliary stent) is associated with more than 90% of biliary leak healing or closure[48]. ERCP is currently considered the first-line treatment option for biliary leaks, specially cystic stump leaks[48]. Surgeons should be aware that when treating patients with difficult cholecystectomies, the goals are to resolve the septic process and to prevent secondary damage. As reported in previous COVID-19 cases[19,21,24], as well as in our series, operated patients during this pandemic tended to have severe inflammation of the gallbladder thus increasing the risks of postoperative complications including bile duct injury. As suggested by international guidelines[41], choosing a bail-out procedure (subtotal cholecystectomy or open conversion) based on intraoperative findings is recommended to avoid a secondary damage. Both bail-out procedures have been reported to reduce bile duct injury and overall postoperative complications, although it has been recognized that laparoscopic subtotal cholecystectomy is associated with increased rates of postoperative bile leakage in comparison with open conversion[41,49].

There are some limitations to our study that need to be mentioned. The most important limitation is that this was a single-center study with a small sample, which predisposes the study to all the biases inherent to the design (selection, information and confusion biases). Further prospective and multi-center studies should be performed and published, in order to better understand the effects of COVID-19 on acute cholecystitis. However, despite these limitations we consider that the results of this study could help us to describe some of the implications of SARS-CoV-2 infections in patients who require urgent/early Lap-C.

CONCLUSION

In conclusion, we found in the present study that patients with confirmed SARS-CoV-2 infections who presented with acute cholecystitis, tended to have a higher grade on the Parkland grading scale (including gallbladder perforation, empyema and total wall necrosis), had difficult laparoscopic cholecystectomies with an increased need for a bail-out procedure, had high rates of ICU admission, and had a prolonged length of hospital stay. As suggested by our case series and previously published literature, we advise to surgeons performing cholecystectomy in confirmed SARS-CoV-2 patients to be prepared for a difficult surgery and to consider a bail-out procedure to prevent secondary damage.

ACKNOWLEDGEMENTS

We would like to thank all medical and nurse staff dedicated to COVID-19 surgical care at our Hospital. Special thanks to Dr. Karina Flores, for sharing her surgical images.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Medicine, research and experimental

Country/Territory of origin: Mexico

Peer-review report’s scientific quality classification

Grade A (Excellent): A

Grade B (Very good): B, B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Abdolusefi MS, Osorno JF, Tazegul G S-Editor: Fan JR L-Editor: A P-Editor: Fan JR

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