Incidental gallbladder cancer: what is the prevalence and how do we perform cholecystectomy for presumably benign biliary disease?

ABSTRACT Objective: to determine the prevalence of incidental gallbladder cancer (IGBC) in cholecystectomies performed in a tertiary public hospital and to describe technical and epidemiological aspects of performing cholecystectomies for presumably benign disease. Method: descriptive, retrospective observational study, based on analysis of medical records of patients undergoing cholecystectomy with preoperative hypothesis of benign disease between January 2018 and January 2022. Results: prevalence of gallbladder adenocarcinoma in our sample was 0.16%, similar to data in the literature. Technical aspects during cholecystectomy were also described with a frequency similar to that found in the literature. Conclusion: despite a rare disease, IGBC is relevant in the routine of the General Surgeon. Its diagnosis, staging and treatment directly affect the prognosis. Technical aspects during cholecystectomy are not always remembered by surgeons and can interfere with the prognosis and subsequent treatment of the patient.


INTRODUCTION
C holelithiasis is the most prevalent disease of the biliary tree, responsible for most elective surgeries performed annually 1,2 .It is mainly characterized by abdominal complaints and its leading treatment is laparoscopic cholecystectomy 3,4 , currently recommended early in the absence of contraindications, to prevent disease-related complications and symptoms' recurrence 5 .
Gallbladder carcinoma is a rare malignant neoplasm, with high lethality and rapid progression of symptoms, variable incidence and prevalence, corresponding to the biliary tract tumor with the lowest survival rate at diagnosis 3,[6][7][8] and whose most prevalent risk factor is cholelithiasis 9 .
More recently, it has been incidentally diagnosed as a finding after laparoscopic cholecystectomies 6 .The management of incidental gallbladder cancer was recently established in the Brazilian Consensus of the disease 10 .
The disease's prognosis is variable, according to the stage at the time of diagnosis, and its surgical treatment (re-resection) is indicated when there is no distant disease, which may include liver resections, retroperitoneal lymphadenectomy, and resection of extrahepatic bile duct or other organs, based on histopathological findings and staging imaging tests 11 .
Some technical aspects in cholecystectomies must be considered in view of the incidental diagnosis of the neoplasm.Injuries to the gallbladder wall and bile leakage can interfere with staging and change the prognosis, and should be avoided 12 .

RESULTS
We analyzed 642 medical records of patients who underwent cholecystectomies at the HULW between 2018 and 2021.After applying the inclusion and exclusion criteria, we selected 618 patients, 139 (22.5%) male and 479 (77.5%) female.We excluded 24 records in which cholecystectomy was performed as part of procedures in patients with a preoperative clinical and/or histopathological diagnosis of gastric, duodenal, pancreatic, or main bile duct cancer.
Of the 618 surgeries performed for presumably benign biliary disease, 596 (96.4%) were scheduled electively and 22 (3.6%) were operated on an urgent basis.The histological diagnosis was made available on average 14.9 days (±8.66) after the surgical procedure.There were no cases of conversion from laparoscopy to laparotomy in the sample.
Resident physicians in the 2 nd (73.3%) and 3 rd (15.6%) years of the institutional program of Medical Residency in General Surgery, affiliated with the hospital unit, were the main surgeons, under the supervision and participation of the assistant surgeon responsible for the procedure.From the surgical operative reports present in the medical records, we verified that there was gallbladder perforation in 13 cases (28.9%), while there was no violation of the gallbladder in 30 (66.7%), and such information was absent in 2 records (4.4%).
Table 2 describes the technical aspects of the 42 laparoscopic cholecystectomies performed at the HULW between August 2021 and January 2022.An intracavitary drain was not used in the evaluated cholecystectomies.
All 45 patients in the sample were discharged from the hospital, with three complications recorded, without the need for surgical reintervention, according to the Clavien-Dindo scale (Table 3).

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Incidental gallbladder cancer: what is the prevalence and how do we perform cholecystectomy for presumably benign biliary disease?

DISCUSSION
The present research found a prevalence of 0.16% of incidental gallbladder adenocarcinoma in cholecystectomies performed for a presumably benign disease, data corroborated by other similar studies, which show a prevalence ranging from 0.14% to 1.07% (Table 4).Two Japanese studies in patients undergoing surgical resection with curative intent identified that the cystic (12c), pericholedocian (12b), and posterosuperior peripancreatic (13a) lymph nodes were the initial and, therefore, more prevalent sites of lymphatic metastasis, suggesting that the risk of pN1 pathological staging is 0% when sampling from lymph nodes 12c and 12b is negative for malignancy 20,21 .
The mean length of stay of patients undergoing cholecystectomy in our sample was high, probably due to the inclusion of records of patients with long hospitalizations for other clinical diseases and who manifested biliary pathology during hospitalization, motivating surgery on an urgent basis or scheduled within the same hospital stay.An analysis of 985 patients who underwent laparoscopic cholecystectomy between May 2006 and February 2015 in a tertiary hospital in Italy suggested that prolonged hospital stay (defined as greater than 2 days) is not related to the surgical procedure, but to the patient's comorbidities 22 .
Regarding inflation of the pneumoperitoneum, in our study there was a predominance of the open technique (Hasson or its modifications) compared with the closed one, with a Veress needle.There were no complications related to either technique.There are several studies comparing both techniques regarding the incidence of major and minor complications, the time required to establish pneumoperitoneum, and the technique's safety, with divergent results favoring one or the other [23][24][25] .
Iatrogenic perforation of the gallbladder with intracavitary bile leakage was present in 28.9% of cases in our sample, at a rate similar to that described in the literature, between 10 and 37% 26,27 .This finding is related to the increase in operative time, use of drains 26 , and length of hospital stay, but with no impact on the risk of surgical site infection or postoperative collections 27 .
As for incidental gallbladder cancer, bile extravasation may be associated with incomplete resections and systemic recurrences, as malignant cells may implant from the extravasated content 16 , with a worse prognosis 28 , and a greater probability of peritoneal carcinomatosis, less chance of radical resection, and new surgery with R0 margins, in addition to a shorter disease-free survival time 29 .

Silva Incidental gallbladder cancer: what is the prevalence and how do we perform cholecystectomy for presumably benign biliary disease?
There was resection of the laparoscopic portsites in the patient identified with incidental gallbladder adenocarcinoma, with subsequent reoperation due to incisional hernia and recurrence at the port-sites.Most (58.5%) of the laparoscopic cholecystectomies in our sample used a plastic or latex bag to remove the surgical specimen through the portals.The Brazilian Consensus recommends the routine use of plastic bags for gallbladder removal 10 .In cases where perforation has already occurred intraoperatively, there is no benefit in removing the gallbladder in collection bags 28 .
The guidelines of the European Society of Medical Oncology (ESMO) recommend that the laparoscopic port-sites should be resected in the IGBC when a plastic bag was not used in the removal of the gallbladder or there was bile leakage in the first surgery 17 , while the Brazilian Consensus does not routinely recommend the use of this procedure due to the high incidence of incisional hernia and the reduced oncological benefit 10 .
Opening and inspection of the specimen by the main surgeon did not routinely occur in the surgeries evaluated in our study.According to Tian, Ji 16 , all surgical specimens of the gallbladder must be opened and carefully examined during laparoscopic cholecystectomy, with indication of immediate frozen section biopsy in case of identification of any suspicious lesions, recommendation corroborated by the Brazilian Consensus on IGBC 10 .
The emptying of the pneumoperitoneum at the end of the surgical procedure was performed with at least one trocar positioned in the peritoneal cavity in most of the surgeries described in our study.Animal experimental models from the end of the 20 th century suggest the existence of a "Chimney Effect", in which the circumferential leakage of gas around a trocar could accelerate the infiltration of peritoneal fluid containing aerosolized tumor at the portal site, relating to the activity of that surgical site 30 .
The Brazilian Consensus on IGBC considers that the implantation of tumor cells in the portals' sites can occur by direct (mechanical factors) and indirect mechanisms (leakage of the pneumoperitoneum), and does not formally recommend the emptying of the pneumoperitoneum with the trocars still in the operative site 10 , a routine practice advocated by Cavallaro, Piccolo 31 .

CONCLUSION
The prevalence of incidental gallbladder cancer in cholecystectomies performed between 2018 and 2021 at the Lauro Wanderley University Hospital was 0.16%.
Incidental gallbladder cancer is a rare pathology, but not negligible in the routine of the General Surgeon.Its diagnosis, staging, and treatment directly affect patients' prognosis.Some technical aspects may not always be remembered by surgeons and may interfere with the patient's subsequent treatment and prognosis.

R E S U M O R E S U M O
The objectives of this research are to determine the prevalence of incidental gallbladder cancer (IGBC) in cholecystectomies performed between 2018 and 2021 at the Lauro Wanderley University Hospital (HULW), at the Federal University of Paraíba, in João Pessoa, State of Paraíba, Brazil, and to describe its epidemiological Diego Arley gomes DA silvA 1,2 ; olgA lAnusA leite veloso 1 ; mAtheus souto PerAzzo vAlADAres 1 ; roDrigo soAres DA CostA 1 ; mAriAnA gAlinDo silveirA 1 ; FernAnDA CostA De CArvAlho 1 ; mArCelo gonçAlves sousA, tCBC-PB1 .METHODSThis is a descriptive, retrospective, observational study, using a non-probabilistic, convenience sample, which included all medical records of patients undergoing cholecystectomy with indication for gallstones and/or their complications in a highly complex public hospital in João Pessoa, Paraíba, between January 2018 and January 2022.We excluded all patients who underwent cholecystectomy for other pathologies or who had an established or presumed diagnosis of gallbladder neoplasia or periampullary tumors.In the epidemiological and surgical evaluation, we included patients who underwent laparoscopic or conventional cholecystectomy in the HULW with a preoperative diagnosis of benign biliary disease, admitted to the institution between August 2021 and January 2022.To calculate the annual prevalence of gallbladder incidental malignancy, we evaluated pathological anatomy reports performed at the HULW in cholecystectomies (open or laparoscopic) between January 2018 and December 2021.The data collected in the standardized record from the established flowchart (Figure 1) were tabulated using the descriptive statistics tool of the Microsoft Excel software, for the calculation of frequencies, percentages, means, and standard deviations (SD), and subsequently arranged in tables.

Figure 1 .
Figure 1.Flowchart for data collection and systematization.

Table 1 -
Anatomopathological diagnosis of patients undergoing cholecystectomy at the Lauro Wanderley University Hospital between 2018 and 2021 (n=618).

Table 2 -
Technical aspects in laparoscopic cholecystectomies at the Lauro Wanderley University Hospital between August 2021 and January 2022 (n=42).

Table 3 -
Postoperative complications in cholecystectomies performed at the HULW between August 2021 and January 2022 (n=45).
SilvaIncidental gallbladder cancer: what is the prevalence and how do we perform cholecystectomy for presumably benign biliary disease?

Table 4 -
Prevalence of incidental gallbladder cancer in other studies.
out that, in patients whose neoplasm diagnosis is performed only in the histopathological analysis of the surgical specimen, the management of incidental cancer would take place from the T stage, since generally there is no information about lymph node involvement.