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  Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 54  |  Issue : 4  |  Page : 681-684
 

Radiological diagnosis alone risks overtreatment of benign disease in suspected gallbladder cancer: A word of caution in an era of radical surgery


1 Department of Surgical Oncology, Tata Memorial Hospital Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Interventional Radiology, Tata Memorial Hospital Tata Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Pathology, Tata Memorial Hospital Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Web Publication30-Jul-2018

Correspondence Address:
Dr. Mahesh Goel
Department of Surgical Oncology, Tata Memorial Hospital Tata Memorial Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_516_17

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 » Abstract 


BACKGROUND: Incidental gallbladder cancer (iGBC) is on the rise world over. This may be a good scenario as we get to treat GBC in early stages. However, there is a practice of diagnosing patients based on clinicoradiological findings alone and subjecting them to a radical surgical procedure. This approach over-treats patient and has important implications for resource utilization. METHODS: We performed a retrospective analysis of 284 consecutive patients undergoing upfront surgery for suspected GBC from January 2010 to December 2016. The study cohort was divided into two groups, group A – benign (n = 138, 48.6%) and group B – malignant (n = 146, 51.4%). Both groups were compared with respect to demographic characteristics, tumor marker levels, clinicoradiological features, and perioperative outcomes. RESULTS: Approximately 48.6% patients with clinicoradiological suspicion of GBC turned out to be benign on final histology as confirmed on frozen section evaluation (FS). Only 2 patients who were reported benign on FS required revision surgery for malignancy in the final histopathology report. Demographic and clinicoradiological characteristics in both groups were comparable. However, there was a significant difference in blood loss, postoperative hospital stay, and complications between the two groups (P < 0.005). CONCLUSION: Every other patient who presented to a tertiary cancer center with high index suspicion for malignancy, based on clinicoradiological findings, turned out to be benign on final histology. This emphasizes the fact that, as a norm, for radiologically suspected gallbladder malignancy, we need to have a confirmed histological diagnosis at least during surgery before proceeding to radical resection.


Keywords: Benign gallbladder disease, gallbladder cancer, radical surgery


How to cite this article:
Patkar S, Shinde RS, Kurunkar SR, Niyogi D, Shetty NS, Ramadwar M, Goel M. Radiological diagnosis alone risks overtreatment of benign disease in suspected gallbladder cancer: A word of caution in an era of radical surgery. Indian J Cancer 2017;54:681-4

How to cite this URL:
Patkar S, Shinde RS, Kurunkar SR, Niyogi D, Shetty NS, Ramadwar M, Goel M. Radiological diagnosis alone risks overtreatment of benign disease in suspected gallbladder cancer: A word of caution in an era of radical surgery. Indian J Cancer [serial online] 2017 [cited 2020 Sep 27];54:681-4. Available from: http://www.indianjcancer.com/text.asp?2017/54/4/681/237904





 » Introduction Top


For varied indications, cholecystectomies–laparoscopic/open have resulted in a large number of patients being diagnosed at a relatively early stage of gallbladder cancer (GBC) and getting treated subsequently as incidental GBC (iGBC). iGBC is on the rise across the world, which may potentially be a good scenario as we get to treat GBC in an early stage where surgical resection can be offered to achieve a meaningful survival.[1],[2] However, we need to be cautious in our approach. There is a widespread practice, especially in endemic regions of India, of diagnosing patients with GBC based purely on clinicoradiological findings and subjecting them to radical surgery without a proven diagnosis. This not only over-treats a lot of patients but also has important implications in terms of resource utilization. At a tertiary care referral center for cancer in India, we analyzed our data to see how many patients referred with presumed diagnosis of GBC were actually benign and did not merit radical surgery.


 » Methods Top


A retrospective analysis of patients who presented to our institution with a suspicion of GBC based on clinicoradiological findings between January 2010 and December 2016 from a prospectively maintained surgical database was performed. All patients of iGBC, with locally advanced, metastatic GBC, and patients with a confirmed histological diagnosis of GBC were excluded.

Contrast-enhanced computed tomography scan (CECT) of the abdomen and pelvis was the initial investigation performed for all patients with suspected GBC. Patients presenting with obstructive jaundice underwent magnetic resonance imaging with cholangiopancreatography in addition to ascertaining the cause of obstruction and planning further intervention for drainage to alleviate jaundice.

All patients underwent an upfront surgery, namely, simple cholecystectomy with frozen section (FS) for confirmation of malignancy. A radical surgery was performed only if FS report was positive for malignancy. Radical cholecystectomy entailed interaortocaval nodal sampling followed by complete periportal lymphadenectomy along with a wedge excision of the liver with an aim to achieve negative margins (R0 resection). Extrahepatic bile duct excision (EHBDE) or additional organ resection was performed in a selected group of patients. A signed informed consent was obtained from each patient for surgery.

The study cohort was divided into two groups based on final histology as group A (benign) and group B (malignant). Both groups were compared with respect to demographic characteristics, carbohydrate antigen 19-9 (CA 19-9) levels, and clinicoradiological features. Data analysis was done using IBM SPSS Statistics for Windows, Version 20.0. IBM Corp., Armonk, NY, USA. Data collection was as per the ethical guidelines of the declaration of Helsinki.[3]


 » Results Top


A total of 284 patients presented to us with a suspicion of GBC during the study period. Group A included 138 (48.6%) patients whereas group B included 146 (51.4%) patients. [Figure 1] illustrates the study cohort.
Figure 1: Study design

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Demographic and clinicoradiological characteristics in both groups, as elaborated in [Table 1], were comparable barring an exception of gender distribution with malignancy being more common in females. Ultrasonography (USG) of the abdomen was the first investigation in most patients before referral to our center followed by a CECT scan.
Table 1: Demographic/clinico-radiological characteristics of the study cohort

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The surgeries performed in the two groups are shown in [Figure 2]. In group A, simple cholecystectomy alone was the most commonly performed procedure in 95% patients (n = 131) after confirmation of a benign pathology on FS. Six patients required additional choledochotomy for extraction of impacted stones in the bile duct not amenable for retrieval by endoscopic methods. Only one patient (0.7%) in this group underwent EHBDE (for suspected Mirrizi's syndrome). Radical cholecystectomy was the standard and most commonly performed procedure after FS confirmation of malignancy in group B (n = 146). A total of 17 patients (11.6%) underwent EHBDE, and 3 patients (2%) required additional organ excision (namely duodenum or colon) to achieve R0 resection. As all patients in this study cohort underwent upfront surgery without tissue diagnosis, extent of the surgery was based on intraoperative findings and FS report on histology. There was a significant difference in intraoperative blood loss, postoperative hospital stay, and complications in both groups (P < 0.005) [Table 1].
Figure 2: Type of surgeries performed in both groups (a) Benign; (b) Malignant (SC: Simple cholecystectomy, RC: Radical cholecystectomy, EHBTE: Extrahepatic bile tract excision)

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The histological spectrum in the benign group is shown in [Figure 3]. Thirty-four percent of our patients (47 out of 138) in the benign group were diagnosed with xanthogranulomatous cholecystitis (XGC) on final histopathology. Thirty-two percent of the patients with XGC in group A were diabetic (15 out of 47).
Figure 3: Histological spectrum in benign group

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 » Discussion Top


GBC is a disease with poor outcomes with almost 80% of the cases presenting in advanced stage.[4],[5],[6],[7],[8] Surgery is curable only in early-stage GBC, therefore, it becomes imperative to accurately diagnose and treat this disease in early stages to improve the treatment outcomes. Unfortunately, accurate diagnosis in early stages is hindered by socioeconomic factors coupled with lack of specific diagnostic modalities and variety of benign conditions mimicking this malignancy. We attempted to differentiate benign pathologies from malignant ones based on clinicoradiological features.

There is no difference in the symptomatology of benign gallbladder disease and GBC, especially in early stages due to common predisposing factors. Clinical presentation [Table 1] was similar for both groups in our study. Symptomatic presentation in gallbladder malignancy usually indicates advanced disease with abdominal pain being the most common symptom.[9],[10]

Tumor markers also have limited value in distinguishing the pathological groups. The sensitivity and specificity of CA 19-9 for diagnosis of GBC is 66% and 90%, respectively,[11] however, falsely elevated CA 19-9 levels are frequently seen in jaundice and inflammatory conditions of biliary tract, which makes distinction between benign and malignancy difficult in the absence of a tissue diagnosis. We also did not find any statistically significant difference in CA 19-9 level in both groups, emphasizing that a diagnosis of malignancy cannot be reliably made on the basis of elevated tumor markers alone.

Similarly, radiological features cannot reliably distinguish gallbladder malignancy from other benign conditions in early stages. [Table 1] enlists various radiological findings in our study cohort. USG of the abdomen is usually the first radiological tool to evaluate these patients, with further imaging based on its findings. Ultrasound findings are nonspecific for a conclusive diagnosis of gallbladder malignancy in early stages with both high false-positive and false-negative findings.[12],[13]

Recent advances in the form of elastography and endoscopic USG have increased the diagnostic yield of this modality, however, their incorporation in routine clinical practice is not feasible in the Indian setting because of lack of widespread availability and expertise.[14],[15] CECT scan of the abdomen and pelvis is the mainstay of imaging for the diagnosis and staging of gallbladder malignancy. However, similar to USG, CECT scan findings in early stages of gallbladder malignancy are often nonspecific, limiting the diagnostic accuracy of this modality.[16],[17] Various findings in favor of malignancy include definite mass with liver infiltration, mucosal irregularity, and persistent enhancement in venous phase. We observed a similar spectrum of radiological findings in both benign and malignant cases in our study cohort, underlining the fact that imaging alone is not sufficient for diagnosis.

Patients with XGC are extremely difficult to distinguish from malignancy, as they have very similar imaging characteristics.[17] [Figure 4] elaborates the radiological and histological appearance of XGC. Preoperative diagnosis of this entity is often not possible due to a close resemblance with malignancy in clinical presentation, imaging, and intraoperative findings. A differential diagnosis of XGC must be considered, especially in diabetic patients. It can also coexist with malignancy.[18],[19]
Figure 4: Radiological pathological appearance of Xanthogranulomatous cholecystitis (a and b) Contrast-enhanced computed tomography scan showing diffuse thickening of gallbladder with liver infiltration. (c) A section from gall bladder showing features of xanthogranulomatous cholecystitis consisting of sheets of foamy macrophages admixed with several acute and chronic inflammatory cells. H and E staining

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In our study, the use of FS was a reliable method to confirm the diagnosis and decide the extent of surgical resection. Only two patients who were reported to be benign on FS required revision surgery for malignancy in the final histopathology report.

An increase in intraoperative blood loss, duration of postoperative hospital stay, and morbidity was seen in patients of group B undergoing radical surgery (P < 0.005). If facilities for FS are not available, it may be prudent to conclude surgery after simple cholecystectomy and wait for final histology before proceeding to radical surgery.


 » Conclusion Top


One in two patients who presented to a tertiary cancer center with a high index of suspicion for malignancy based on clinicoradiological findings turned out to be benign on final histology. This emphasizes the fact that, as a norm, for radiologically suspected gallbladder malignancy, we need to have a confirmed histological diagnosis at least during surgery before proceeding to radical resection. An intraoperative FS can be reliably used to confirm the same. In today's era of medicolegal jurisprudence, a cautious approach is advocated in not over-treating patients with unwarranted extensive surgery with associated increased morbidity and hospital stay, which ultimately translates into increased resource utilization both for patient and health-care sector.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Kumari N, Agrawal V, Behari A, Singh MK, Kapoor VK. Etio-pathogenesis of Gallbladder Cancer; ECAB, Clinical Update: Surgical Gastroenterology and Liver Transplantation: 2014; 1-10. Elsevier Publications-ISBN 978-81-312-3640-6.  Back to cited text no. 1
    
2.
Kapoor VK, McMichael AJ. Gallbladder cancer: An 'Indian' disease. Natl Med J India 2003;16:209-13.  Back to cited text no. 2
    
3.
World Medical Association. Declaration of Helsinki; 1964. JAMA 2013; 310:2191-94.  Back to cited text no. 3
    
4.
Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB, editors. Cancer Incidence in Five Continents No 155. Vol. 8. Lyon, France: International Agency for Research on Cancer, IARC Scientific Publication; 2002.  Back to cited text no. 4
    
5.
Population Based Cancer Registry, Biennial Report, 2000 and 2001. Department of Epidemiology and Bio-Statistics. Bangalore, India: Kidwai Memorial Institute of Oncology; 2004.  Back to cited text no. 5
    
6.
National Cancer Registry Programme. Two-Year Report of Population Based Cancer Registries 2004–2005: Incidence and Distribution of Cancer. Mumbai, India: Indian Council of Medical Research; 2008.  Back to cited text no. 6
    
7.
Population Based Cancer Registry, Biennial Report, 2002. Department of Epidemiology and Bio-Statistics. Bangalore, India: Kidwai Memorial Institute of Oncology; 2005.  Back to cited text no. 7
    
8.
Cancer Incidence and Patterns in Urban Maharashtra – 2001. Report to the State of Maharashtra on Status on Cancer. Mumbai, India: Cancer Registry Division, Indian Cancer Society; 2007.  Back to cited text no. 8
    
9.
Miller G, Jarnagin WR. Gallbladder carcinoma. Eur J Surg Oncol 2008;34:306-12.  Back to cited text no. 9
    
10.
Lai CH, Lau WY. Gallbladder cancer – A comprehensive review. Surgeon 2008;6:101-10.  Back to cited text no. 10
    
11.
Kankonkar SR, Joshi SV, Deshpande R. Significance of tumour markers in cancer of gall bladder. Open J Immunol 2013;3:33-6.  Back to cited text no. 11
    
12.
Onoyama H, Yamamoto M, Takada M, Urakawa T, Ajiki T, Yamada I, et al. Diagnostic imaging of early gallbladder cancer: Retrospective study of 53 cases. World J Surg 1999;23:708-12.  Back to cited text no. 12
    
13.
Wibbenmeyer LA, Sharafuddin MJ, Wolverson MK, Heiberg EV, Wade TP, Shields JB, et al. Sonographic diagnosis of unsuspected gallbladder cancer: Imaging findings in comparison with benign gallbladder conditions. AJR Am J Roentgenol 1995;165:1169-74.  Back to cited text no. 13
    
14.
Kapoor A, Kapoor A, Mahajan G. Differentiating malignant from benign thickening of the gallbladder wall by the use of acoustic radiation force impulse elastography. J Ultrasound Med 2011;30:1499-507.  Back to cited text no. 14
    
15.
Sadamoto Y, Kubo H, Harada N, Tanaka M, Eguchi T, Nawata H, et al. Preoperative diagnosis and staging of gallbladder carcinoma by EUS. Gastrointest Endosc 2003;58:536-41.  Back to cited text no. 15
    
16.
Yoshimitsu K, Honda H, Shinozaki K, Aibe H, Kuroiwa T, Irie H, et al. Helical CT of the local spread of carcinoma of the gallbladder: Evaluation according to the TNM system in patients who underwent surgical resection. AJR Am J Roentgenol 2002;179:423-8.  Back to cited text no. 16
    
17.
Ohtani T, Shirai Y, Tsukada K, Muto T, Hatakeyama K. Spread of gallbladder carcinoma: CT evaluation with pathologic correlation. Abdom Imaging 1996;21:195-201.  Back to cited text no. 17
    
18.
Rao RV, Kumar A, Sikora SS, Saxena R, Kapoor VK. Xanthogranulomatous cholecystitis: Differentiation from associated gall bladder carcinoma. Trop Gastroenterol 2005;26:31-3.  Back to cited text no. 18
    
19.
Ghosh M, Sakhuja P, Agarwal AK. Xanthogranulomatous cholecystitis: A premalignant condition? Hepatobiliary Pancreat Dis Int 2011;10:179-84.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1]



 

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