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ORIGINAL ARTICLE
Year : 2020  |  Volume : 57  |  Issue : 1  |  Page : 89-92
 

Chronic calculus cholecystitis: Is histopathology essential post-cholecystectomy?


1 Department of Pathology, North Delhi Municipal Corporation Medical College and Hindu Rao Hospital, New Delhi, India
2 Department of Surgery, North Delhi Municipal Corporation Medical College and Hindu Rao Hospital, New Delhi, India

Date of Submission26-Jul-2018
Date of Decision01-Jul-2019
Date of Acceptance20-Jul-2019
Date of Web Publication26-Feb-2020

Correspondence Address:
Namrata Sarin
Department of Pathology, North Delhi Municipal Corporation Medical College and Hindu Rao Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_487_18

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 » Abstract 


Background: Carcinoma of the gall bladder (GB) is the most common malignancy of the gastrointestinal tract. One percent of cholecystectomy specimens show incidental gall bladder cancers (GBCs).
Aim: Our aim of the study to was evaluate the utility of routine histopathology of cholecystectomy specimens removed with a diagnosis of gall bladder diseases (GBD).
Materials and Methods: A retrospective study was done reviewing the histopathological records of 906 patients who underwent cholecystectomy. Demographic details, gross findings, and microscopic findings noted. All the cases were categorized into two groups, A and B. Group A included the cases with any gross abnormality including wall thickness ≥4 mm and group B included rest of the cases.
Results: Majority of the patients were in the age group of 31–40 years of age. Out of 906 patients studied, majority of them were females with F:M ratio of 6.14:1. Of the 47 cases which were included in group A (with macroscopic abnormality), six cases had gall bladder carcinoma on microscopy. One case from group B with macroscopically normal-appearing GB had invasive carcinoma on microscopy. In our study, we found a sensitivity of 85.71% and specificity of 95.44%, while positive predictive value (PPV) was 91.11% and negative predictive value (NPV) was 99.65% of macroscopic abnormality in the diagnosis of invasive carcinoma.
Conclusion: All cholecystectomy specimens must be examined by histopathologists who must decide whether processing for microscopy is needed. Microscopic examination may be reserved for the specimen with a macroscopic lesion. This will result in a reduction of costs and pathology workload without compromising patient management.


Keywords: Cholecystectomy, gall bladder cancer, gall stone disease, health economics


How to cite this article:
Butti AK, Yadav SK, Verma A, Das A, Naeem R, Chopra R, Singh S, Sarin N. Chronic calculus cholecystitis: Is histopathology essential post-cholecystectomy?. Indian J Cancer 2020;57:89-92

How to cite this URL:
Butti AK, Yadav SK, Verma A, Das A, Naeem R, Chopra R, Singh S, Sarin N. Chronic calculus cholecystitis: Is histopathology essential post-cholecystectomy?. Indian J Cancer [serial online] 2020 [cited 2020 Apr 10];57:89-92. Available from: http://www.indianjcancer.com/text.asp?2020/57/1/89/279175





 » Introduction Top


In India, carcinoma of the gall bladder (GB) is the most common malignancy of the gastrointestinal tract.[1] Its incidence is more along the Gangetic plains of northern India.[2] Several risk factors have been implicated of which gall stone disease (GSD) is one of the important risk factors.[3] GSD affects 10–15% of the western population.[4],[5] However, studies in India have revealed a prevalence rate of 6.12% and this disease is more common in women (9.6%) than men (3.1%).[6] Cholecystectomy is the surgical procedure commonly done for symptomatic GSD. Gall bladder cancer (GBC) is found in approximately 1% of all elective cholecystectomy specimens done for GSD.[7]

It is a standard practice that all the cholecystectomy specimens operated for symptomatic GSD are sent for histopathology to rule out incidental GBC. It is been argued that in all patients with incidental GBC, suspicious features have been found in radiology or intraoperatively.[8],[9],[10],[11]

Our aim of the study was to evaluate the utility of routine histopathology of cholecystectomy specimens removed with a diagnosis of GSD. A selective approach, rather than a routine histopathology of cholecystectomy specimens, operated for GSD to rule out malignancies may help in reducing pathology work and thus saving hospital resources.


 » Materials and Methods Top


A retrospective study was done, reviewing the histopathological records of 906 patients who underwent cholecystectomy. Demographic details, gross findings, and microscopic findings were noted. All the cases were categorized into two groups A and B. Group A included the cases with any gross abnormality including wall thickness ≥4 mm and group B included rest of the cases. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated in group A cases, taking histopathologically proven malignancy as the gold standard.


 » Results and Observation Top


The majority of the patients were in the age group of 31–40 years of age with an age range of 11–81 years. The mean age of males was 40.41 ± 13.25 and of females was 39.10 ± 13.11. Out of 906 patients studied, majority were females (n = 778) with F:M ratio of 6.13:1.

All the cases were categorized into group A and group B. Group A included all the cases with an increased wall thickness ≥4 mm, nodular/polypoidal lesions, papillary excrescences or any other gross abnormality of the mucosal surface. Group B included the rest of the cases. Group A included a total of 47 cases whereas group B included 859 cases. Distribution of cases according to the histopathological diagnosis is given in [Table 1].
Table 1: Distribution of cases according to the histopathological diagnosis

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Ultrasonographic findings were available in only 452 cases, out of which 26 cases were labeled as increased GB wall thickness. Out of these 26 cases, 10 were labeled as suspicious for malignancy and five of these were found to have adenocarcinoma GB on histopathology. The ultrasonographic findings were only available in five out of seven cases of histologically confirmed adenocarcinoma, and all were found suspicious for malignancy on ultrasonography. The rest of the two cases showed increased wall thickness (>3.5 mm).

Considering the significance of group A, assuming that it requires an adequate histopathological examination (HPE) to rule out malignancy; sensitivity, specificity, positive predictive value, and negative predictive value were calculated. We found the sensitivity of 85.71% and specificity was 95.44%, while positive predictive value (PPV) was 91.11% and negative predictive value (NPV) was 99.65%.

Receiver operating characteristic (ROC) curve was plotted for the GB wall thickness and a cut-off value of 3.5 mm was found to have a sensitivity of 85.7% and specificity of 98.9% [Figure 1].
Figure 1: Area under the receiver operating characteristic curve for gall bladder (GB) wall thickness for diagnosing gall bladder cancer (GBC)

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 » Discussion Top


GBC is the most common malignancy of gastrointestinal tract[1] and GSD is a well-established risk factor associated with it.[3] In India, the prevalence rate of GBC is more common in females than males with an F:M ratio of 3:1.[6] GB malignancies reported from India showed regional differences and majority of the cases reported are from the Gangetic plains of North India.[2]

Clinically, early GBC presents with nonspecific symptoms similar to acute or chronic cholecystitis. Radiodiagnosis is helpful in detecting early lesions having gross abnormality including increased wall thickness but not all early GBCs show obvious lesions on ultrasonography.[12] Hence all cholecystectomy specimens are routinely sent for HPE to rule out early GBC.

In our study, out of the 906 cases studied, seven cases had invasive malignancy. The present study showed the frequency of primary incidental GB carcinoma to be 0.77%. Tantia et al.[13] and Mittal et al.[14] also found a similar frequency of incidental GBC of 0.6% and 0.9%, respectively in India which is closer to our study. Meanwhile the study by Daphna et al.[15] in Israel, also noted a lesser frequency of 0.3%.

In our study, six carcinoma cases showed an abnormality on macroscopic examination including nodular growth, polypoidal growth, and increased wall thickness while one case did not show any obvious gross abnormality [Table 2]. Thus we found a PPV and NPV of 99.11% and 99.65%, respectively.
Table 2: Utility of gross abnormality as an indicator of histopathological examination (HPE)

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In a study by Bazoua et al.[9] found five (0.17%) cases positive for malignancy in 2890 consecutive cases and all those showed obvious gross abnormality. Dix et al.[10] also found that five (0.38%) out of 1308 cases were malignant and all those showed gross abnormality. Similar findings were also noted in studies by Darmas et al.[8] in which four (0.27%) out of 1452 cases were positive malignancy with the obvious macroscopic abnormality.

In a previous study from our institute,[16] we emphasized the importance of HPE of all cholecystectomy specimens because of the high incidence of GB carcinoma in our geographical region. A different set of cases were included in the previous study. However, in that study also all 18 cases of incidental GB carcinomas showed macroscopic abnormality. Hence our previous publication and present publication are not in contradiction to each other.

The Royal College of Pathologists recommended that all cholecystectomy specimens should be routinely examined as significant pathology which may be present even in a normal-appearing gallbladder.[17] However, in the present scenario, the role of routine HPE in all cholecystectomy specimens is debatable. The rate of occurrence of incidental GBCs in grossly normal GB specimen is extremely low as evident by NPV of 99.65%. Thus, routine HPE of all GB specimens in an already overburdened pathology could be done best only for selected specimens with obvious gross pathology. Similar studies by some authors have also proposed a selective HPE as incidental carcinomas, if found during HPE it would be at an early stage and simple cholecystectomy is sufficient to give clinical outcome.[9],[18] This can be a cost-effective method to reduce the burden in pathology.

In the present study, we did not find any case of incidental high-grade dysplasia of the cystic duct. However, in a retrospective study by Bickenbach et al.[19] involving 7,50,000 specimens of cholecystectomy, concluded that the incidence of high-grade dysplasia at the cystic duct margin in the absence of associated GBC is extremely rare. They found only seven cases of incidental cystic duct dysplasia without GB adenocarcinoma, out of which five underwent MRI scan with cholangiography. All these patients were above 50 years of age. Only one patient, on imaging, had dilated cystic duct and enlarged portal lymph nodes reported as cholangiocarcinoma while others were found negative for malignancy.

Shukla HS et al.,[20] in ICMR consensus document on management of GBC, have recommended that all cholecystectomy specimens must be sent for HPE. Although they stated that early, GBC/incidental GBC will show increased wall thickness or gross lesion on imaging pre or perioperatively.

Recent studies have shown up 25–40% of all lab tests may not be necessary and routine HPEs of certain specimens can be omitted if there is no significant macroscopic abnormality.[21]

Limitations

The present study, being a retrospective study, a follow-up was not planned in all cases and only patients diagnosed as GBC were kept on follow-up. However, to date, none of our patient who underwent cholecystectomy have presented to us with related complications. However, a larger prospective study with proper follow-up may be undertaken for the validation of our results.


 » Conclusion Top


In conclusion, GBC is associated with a macroscopic lesion in almost all the cholecystectomy specimens. However, all cholecystectomy specimens must be examined by the histopathologist who must decide whether processing for microscopy is needed. The findings of the present study suggest that microscopic examination of all cholecystectomies done for GSD is not necessary. Microscopy is recommended only for the specimens with macroscopic lesion i.e., increased wall thickness (>3.5 mm), polyp and growth. However, age, radiological findings, and comorbid conditions must be considered while deciding for the need for microscopic examination. This will help in the reduction of cost and workload without compromising patient management.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Dhir V, Mohandas KM. Epidemiology of digestive tract cancers in India IV. Gall bladder and pancreas. Indian J Gastroenterol 1999;18:24-8.  Back to cited text no. 1
[PUBMED]    
2.
Indian Council of Medical Research (ICMR). Annual Report of Population Based Cancer Registries of the National Cancer Registry Programme (1993), Vol. 18. New Delhi: ICMR Publication; 1996.  Back to cited text no. 2
    
3.
Diehl AK. Gallstone size and the risk of gallbladder cancer. JAMA 1983;250:2323-6.  Back to cited text no. 3
    
4.
Gallstones and Laparoscopic Cholecystectomy, NIH Consens Statement Online 1992 Sep 14-16;10:1-20. [Last cited on 2019 Feb 18].  Back to cited text no. 4
    
5.
Halldestam I, Enell EL, Kullman E, Borch K. Development of symptoms and complications in individuals with asymptomatic gallstones. Br J Surg 2004;91:734-8.  Back to cited text no. 5
    
6.
Khuroo MS, Mahajan R, Zargar SA, Javid G, Sapru S. Prevalence of biliary tract disease in India: A sonographic study in adult population in Kashmir. Gut 1989;30:201-5.  Back to cited text no. 6
    
7.
Ahrendt SA, Pitt HA. Malignant disease of the biliary tract. In: Morris PJ, Wood WC, editors. Oxford Textbook of Surgery. 2nd ed, vol 2. Oxford: Oxford University Press; 2000. p. 1699-703.  Back to cited text no. 7
    
8.
Darmas B, Mahmud S, Abbas A, Baker AL. Is there any justification for the routine histological examination of straight forward cholecystectomy specimens? Ann R Coll Surg Engl 2007;89:238-41.  Back to cited text no. 8
    
9.
Bazoua G, Hamza N, Lazim T. Do we need histology for a normal-looking gallbladder? J Hepatobiliary Pancreat Surg 2007;14:564-8.  Back to cited text no. 9
    
10.
Dix FP, Bruce IA, Krypcyzk A, Ravi S. A selective approach to histopathology of the gallbladder is justifiable. Surgeon 2003;1:233-5.  Back to cited text no. 10
    
11.
Taylor HW, Huang JK. 'Routine' pathological examination of the gallbladder is a futile exercise. Br J Surg 1998;85:208.  Back to cited text no. 11
    
12.
Kapoor VK, Pradeep R, Haribhakti SP, Sikora SS, Kaushik SP. Early carcinoma of the gallbladder: An elusive disease. J Surg Oncol 1996;62:284-7.  Back to cited text no. 12
    
13.
Tantia O, Jain M, Khanna S, Sen B. Incidental carcinoma gallbladder during laparoscopic chlecystectomy for symptomatic gallstone disease. Surg Endosc 2008; [Epub ahead of print].  Back to cited text no. 13
    
14.
Mittal R, Jesudason MR, Nayak S. Selective histopathology in cholecystectomy for gallstone disease. Indian J Gastroenterol 2010;29:26-30.  Back to cited text no. 14
    
15.
Daphna W, Mehrdad H, Noa BJ, Sandbanand AH. Incidental finding of gallbladder carcinoma. Israel Med Assoc J 2002;4:334-6.  Back to cited text no. 15
    
16.
Kalita D, Pant L, Singh S, Jain G, Kudesia M, Gupta K, Kaur C. Impact of routine histopathological examination of gall bladder specimens on early detection of malignancy-a study of 4,115 cholecystectomy specimens. Asian Pac J Cancer Prev 2013;14:3315-8.  Back to cited text no. 16
    
17.
Royal College of Pathologists. Histopathology and cytopathology of limited or no clinical value. Report of working group of The Royal College of Pathologists. 2nd ed. London: Royal College of Pathologists; 2005.  Back to cited text no. 17
    
18.
Bisgaard T, Hansen BF, Lassen AH, Rosenberg J. Histological examination of the gallbladder after cholecystectomy. Ugeskr Laeger 2001;163:5025-8.  Back to cited text no. 18
    
19.
Bickenbach KA, Shia J, Klimstra DS, DeMatteo RP, Fong Y, Kingham TP, et al. High-grade dysplasia of the cystic duct margin in the absence of malignancy after cholecystectomy. HPB 2011;13:865-8.  Back to cited text no. 19
    
20.
Shukla HS, Sirohi B, Behari A, Sharma A, Majumdar J, Ganguly M, et al. Indian Council of Medical Research consensus document for the management of gall bladder cancer. Indian J Med Paediatric Oncol 2015;36:79-84.  Back to cited text no. 20
    
21.
Matthyssens LE, Ziol M, Barrat C, Champault GG. Routine surgical pathology in general surgery. Br J Surg 2006;93:362-8.  Back to cited text no. 21
    


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