Original Paper Received: October 20, 2013 Accepted: November 13, 2013 Published online: February 12, 2014

Dig Surg 2013;30:472–475 DOI: 10.1159/000357259

Is It Necessary to Send Gallbladder Specimens for Routine Histopathological Examination after Cholecystectomy? The Use of Macroscopic Examination Jaap L.P. van Vliet a Thomas M. van Gulik b Paul C.M. Verbeek a Flevoziekenhuis, Almere, and b Academic Medical Centre, Amsterdam, The Netherlands

Key Words Cholecystectomy · Gallbladder, pathology · Gallbladder, carcinoma

Abstract Background/Aims: Gallbladder specimens are routinely sent for histopathological examination after cholecystectomy in order to rule out the presence of gallbladder carcinoma (GBC). However, there is no evidence for the benefit of this costly practice. Our aim was to determine whether a selective strategy based on macroscopic appearance of gallbladder specimens is a reliable strategy to exclude them from histopathological examination. Methods: A retrospective study was conducted from January 2007 until November 2011 in a large community hospital in the Netherlands. All gallbladder specimen reports (n = 1,393) after cholecystectomy were included and searched for abnormal findings. Reports were excluded when a full histopathological report was not available (n = 18). Results: Out of the 1,375 patients, 185 had a macroscopically abnormal gallbladder specimen. Of these patients, 6 had GBC. All patients with GBC had macroscopic abnormalities, giving a negative predictive value of 100% to exclude gallbladder specimens from histopathological examination based on macroscopic abnormalities. Conclusions: Based on our study it seems justified to exclude gallbladder specimens from histopathological examination

© 2014 S. Karger AG, Basel 0253–4886/14/0306–0472$39.50/0 E-Mail [email protected] www.karger.com/dsu

based on the absence of macroscopic abnormalities. A more selective policy will reduce medical costs, saving EUR 1.3 million a year in the Netherlands alone, whilst maintaining patient safety. © 2014 S. Karger AG, Basel


Gallbladder carcinoma (GBC) is a rare disease, occurring in 3 per 100,000 people in the United States [1]. The prevalence is greater among women than men (3:1) [2]. The 5-year overall survival rate of GBC is low (5–15%) [3], which can be attributed to late presentation of symptoms and high age of affected patients. The median age at time of diagnosis of this carcinoma is 74 years (range 45– 93) [4]. Besides symptomatic presentation, GBC can be found incidentally during routine histopathological examination after cholecystectomy. Worldwide, the incidental finding of GBC during such routine histopathology varies from 0.17% [5] to 3.3% [6], with an average of 0.4–0.7% in Western countries. In the Netherlands all gallbladder specimens (n = 24,751 in 2009) [7] are routinely sent for histopathological examination after cholecystectomy. This is in accordance with the guideline ‘Cholecystolithiasis’ of the Dutch Japp L.P. van Vliet, MD Maasstraat 80-I NL–1078 HM Amsterdam (The Netherlands) E-Mail jlpvanvliet @ gmail.com

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Surgical Society (NVvH). Besides being common practice in the Netherlands, routine histopathological examination after cholecystectomy is standard practice worldwide. However, several retrospective studies have argued the need for routine examination of all gallbladder specimens in order to identify those patients with symptomless GBC [8–14]. Recently a prospective study suggested a more selective strategy based on macroscopic judgement by surgeons and patient characteristics [15]. The aim of this study was to investigate whether a selective strategy based on macroscopic appearance of gallbladder specimens is feasible in a large community hospital.

Table 1. Abnormal findings in histopathological reports of gallbladder specimens

Ulcer Cyst Irregularity Polyp Lesion Suspicious spot Hardening Gallbladder in several parts Purulent mucous Prominence Deviation Porcelain gallbladder

We conducted a retrospective study including all histopathology reports of consecutive cholecystectomy specimens between January 2007 and November 2011. The reports were obtained from the digital hospital database. All gallbladder specimens in our hospital are routinely sent for histopathological examination. In case of an incomplete histopathological report, the patient was excluded from the study. We focused on macroscopic examination as mentioned in the pathology report. See table 1 for findings that were stated as abnormal. The main outcome measure was the amount of patients with GBC that had no macroscopic abnormality. In case of a proven malignancy, preoperative imaging studies, intraoperative findings and subsequent patient management after diagnosis were reviewed. The expenses of routine histological examination were calculated for our hospital and estimated for the Netherlands. The costs of one histopathological examination are based on a fixed price in the Netherlands [16].

A total number of 1,393 cholecystectomies were performed in our hospital between January 2007 and November 2011. All of these gallbladder specimens were sent for histopathological examination; 18 out of 1,393 specimens lacked a full report and were therefore excluded from further analysis. Chronic inflammation was found in 1,067 specimens, whereas active inflammation was found in 102 specimens, of which 40 were classified as necrotic. Cholesterolosis was detected in 174 gallbladders, 16 had xanthogranulomatous inflammation and 4 were found to be normal. Dysplasia was reported in 3 specimens and metastasis of a mamma tumour in 1. Primary GBC was detected in 6 specimens (0.44%), of which 5 were adenocarcinoma and 1 a sarcoma. There were 3 stage T2, 2 T3 (1 was the

sarcoma) and 1 T4 tumour found. The median age of these patients was 81 years (range 65–89). At preoperative ultrasound the gallbladder of 1 of these patients was found suspicious for malignancy. GBC was suspected twice during intraoperative assessment, which included the patient with the suspicious ultrasound. At macroscopic examination of the specimens, 185 gallbladder specimens showed abnormalities. These specimens included the 6 specimens that, on microscopical examination, proved to contain GBC. (table 2) Thus, a total of 13.5% of all gallbladder specimens had macroscopic abnormalities, including all GBCs. Of these patients, 75 (41%) were under the age of 45. Further treatment was instituted in 2 patients with a T2 and T3 tumour, respectively. One patient underwent re-exploration with lymph node dissection of the hepatoduodenal ligament, the other excision of the gallbladder bed in the adjacent liver. No re-intervention was undertaken in the remaining 4 patients. This was based on medical grounds in case of 3 patients and on request of 1 patient. All patients were followed up until November 2011 or until death (n = 4). Histopathological examination of the gallbladder by a pathologist costs EUR 62.78 in the Netherlands. Hence, histopathological examination of all gallbladder specimens in this study had cost our hospital EUR 87,453 over the last 5 years. If only the gallbladder specimens that were abnormal on macroscopic examination were sent for histopathological examination, total costs would have been reduced to EUR 11,614. In the Netherlands, with a population of over 16 million, 24,751 cholecystectomies were performed in 2009, which all together cost EUR 1,553,868. When extrapolating our data to the Netherlands, these costs could be reduced to EUR 209,772.

Selective Histopathology after Cholecystectomy

Dig Surg 2013;30:472–475 DOI: 10.1159/000357259



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Table 2. Patients with GBC

Age Sex Preoperative ultrasound

Operative findings

Macroscopic aberrations

Further treatment (tumour)

Survival, months



Stones and biliary congestion

Enlarged gallbladder with thickened wall

Gallbladder wall 13 mm, cysts

None (T2NxMx)





Conversion due to adhesions

Yellow, sharp defined prominences

None (T2NxMx)




Cystic lesion, unknown origin, necrotic tumour?

Gallbladder tumour, widespread in liver

Irregular, yellow glassy aspect

None (T4N0Mx)




Stones and chronic cholecystitis

Hydrops gallbladder

Multiple cysts

Re-exploration and lymph node dissection (T2N0Mx)



Thickened gallbladder wall with perforation


Rigid gallbladder wall 7 mm, irregular

None (T3NxM1)



Hydrops and chronic cholecystitis

Porcelain gallbladder

Porcelain gallbladder pale mucosa

Gallbladder bed and liver 2 segment resection (T3N1M0) Alive

The need for routine histopathological gallbladder examination after cholecystectomy has been questioned for more than a decade [14]. Current practice entails sending all gallbladder specimens for histopathological examination, regardless of the clinical characteristics of the patient or macroscopic aspect of the gallbladder. This practice is not based on solid evidence (level of evidence D). Overall, the costs for this routine procedure are significant, amounting to more than EUR 1.5 million a year in the Netherlands alone. The results of our study suggest that clinical patient characteristics, as well as postoperative assessment of the gallbladder by the surgeon, potentially are reliable determinants to decide whether gallbladder specimens can be excluded from histopathological examination. Based on macroscopic appearance, not one unsuspected GBC was found in 1,375 gallbladder specimens. A total of 185 specimens, i.e. 13.5% of all gallbladder specimens, showed macroscopic abnormalities for which they would require further histopathological examination in case of a selective policy. Malignancy was found in 6 of these specimens. Pre- or intraoperative findings showed not to be reliable in ruling out GBC, as 4 out of 6 gallbladder specimens were not suspicious. Based on these findings it may be justified to exclude gallbladder specimens from histopathological examination by means of macroscopical examination. It would result in a negative predictive value 474

Dig Surg 2013;30:472–475 DOI: 10.1159/000357259


of 100%. Hence, the surgeon would be advised to cut open the gallbladder after cholecystectomy and to look and feel for abnormalities of the gallbladder wall before deciding to send the specimen to the pathology department. Furthermore, GBC is very rare under the age of 50 years and the incidence rises rapidly above 60 years [4]. Indeed in our study, none of the patients under the age of 65 were found to have a GBC. This suggests less need for histopathological examination in younger patients when a macroscopic normal-looking gallbladder is found. When a gallbladder specimen is excluded from histopathological examination after cholecystectomy, there should be some certainty that no GBC is missed. For a guideline to be adapted, a negative predictive value of 100% must be assured, as patient safety is obviously first priority. Based on our findings this seems possible when guidelines are based on macroscopic appearance of the gallbladder and patient characteristics. There are some limitations to our study. Firstly, our study is retrospective. Prospective studies are needed to further assess and test our finding. Secondly, the number of included patients is limited. In view of the low incidence of GBC, a high number of patients is required to provide sufficient power. Hence, in order to safely modify the current guideline, a prospective, multicentre study is needed. Increasingly more studies are conducted in current medical practice that discuss the need for various routine procedures. Most of these studies are driven by economic objectives as medical costs in most Western countries are rising exponentially. van Vliet /van Gulik /Verbeek  



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22 Alive

Next to revealing possible economic advantages, these studies provide us with information to improve our evidence-based practice. Our study has shown that there seems to be no need for routine histopathological examination of gallbladder specimens. This finding is supported by several other studies. Abolishing the need for routine histopathological gallbladder examination will not only decrease medical costs, but will also improve our evidence-based medical practice.

In conclusion, it seems justified to exclude gallbladder specimens from histopathological examination based on macroscopic examination.

Disclosure Statement The authors have no conflicts of interest to disclose.


Selective Histopathology after Cholecystectomy

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Is it necessary to send gallbladder specimens for routine histopathological examination after cholecystectomy? The use of macroscopic examination.

Gallbladder specimens are routinely sent for histopathological examination after cholecystectomy in order to rule out the presence of gallbladder carc...
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