GBC accounts for 1.2% of all global cancer diagnoses, but 1.7% of all cancer deaths. According to GLOBOCAN 2018 data, GBC is the 22nd most incident but 17th most deadly cancer worldwide.6 Women are 2 to 6 times more frequently affected as men. The incidence rate for GBC in women of North India (11.8/100,000) and North-East India (17.1/100,000) is very high compared to South and Western India (< 1/100,000 population) which is similar to the high incidence areas such as Bolivia (14/100,000), Chile (9.3/100,000) and South American (27/100,000).2, Among the risk factors in the development of GBC, gall stones are present in 85% of patients. The relative risk (RR) of GBC with gallstone diameters of 2.0 to 2.9 cm (vs. stone size less than 1 cm) is 2.4 and for stones larger than 3 cm the risk drastically increases to 10.1. The RR of GBC increases with the duration of gall stones, with RR being 4.9 with duration of 5–19 years and RR of 6.2 for duration > 20 years. The other risk factors for GB include: porcelain gall bladder, primary sclerosing cholangitis, anomalous pancreatico biliary duct junction, polyps more than 10 mm in size, solitary polyps, sessile polyps, polyps with associated gall stones, and polyps in those aged more than 65 years of age.
In the US, the average survival rates for Stage II, III and IV are 49, 24 and 8 months respectively, however we do not have sufficient data in India. The clinical presentation of GBC is often vague or delayed relative to pathologic progression, contributing to advanced staging and dismal prognosis at the time of diagnosis. Most of the patients present with vague upper abdominal pain or with an incidental finding radiologically or on histology. Incidental GBCs are detected histologically in 0.5%−1.5% of laparoscopic cholecystectomies performed for cholelithiasis. The presence of jaundice, abdominal lump, anorexia and weight loss are usually indicative of advanced stages. A mucocele of GB in absence of any stone may be early marker for malignancy arising in cystic duct or at neck. GBC are rarely diagnosed before it has advanced or metastasized. GBC may arise as a nidus in pre-existing background of chronic cholecystitis, which delays the diagnosis of cancer. This is evident in our case, a 65 year old female presented with non-specific symptom of abdominal pain due to gallstones for 12 years (RR-4.9) and the largest stone of size 3.5 cm (RR-10.1) with a T2a N0 M0 (Stage II) giant carcinoma gall bladder of size 24 × 9 cms.
It is important to differentiate at an early stage which eventually is likely to have better prognosis. Ultrasound (USG), computed tomography (CT), and magnetic resonance imaging (MRI) have improved the possibility of differentiating and choosing the correct treatment. Mass occupying lesion may be present in 40–65% of patients with GBC at initial detection. GBC may present as focal or diffuse asymmetric wall thickening, which can be detected by imaging techniques like contrast-enhanced CT and MRI.11 The features suggestive of a GBC on CT are a discrete focal gallbladder mass, irregular focal wall thickening, and a ‘2-layer pattern’ of enhancement in a thickened gallbladder wall, infiltration of the surrounding structures, locoregional lymphadenopathy and metastatic deposits in the liver, peritoneum and omentum. Diffuse symmetric wall thickening may imply a benign pathology, whereas asymmetric, irregular, or extensive thickening, with marked enhancement should heighten suspicion of GBC.11
Although there are no clear-cut definitions, gallbladders of size > 14 cm and volume ≥ 1.5 L have been regarded as Giant gall bladders (GGB).5 There have been few articles on GGB published in literature by Panaro et al (43 × 21 × 20 cm), Zong et al (30 × 31 × 18 cm) and Yadav et al (30 cm).,, Among the various GGBs only 3 such cases (including our case) were malignant (Table 1). 5,17,18.19,20,21,22,23,24,25 Chapman et al reported a 10 × 6.5 × 0.5 cm papillary, circumferential tumor located primarily in the body and neck of the 18 cm large gallbladder and Hsu et al reported a 16.4 × 13.6 × 7.8 cm GB with poorly differentiated adenocarcinoma.22,24 Junior et al reported a case of giant squamous cell carcinoma of gall bladder infiltrating the transverse colon, however the size was not mentioned. Based on the sizes mentioned in indexed literature, it appears that our case is the largest resectable GBC reported till date.
Table 1
Giant gall bladders (according to size) in recent literature
|
Article
|
Age (years)
|
Sex
|
GB size (cm)
|
GB volume
|
Diagnosis
|
1
|
Panaro et al., 201217
|
17
|
NR
|
43 × 21 × 20
|
2.7L
|
Byler’s disease
|
2
|
Zong et al., 201318
|
55
|
F
|
30 × 31 × 18
|
4.0L
|
NA
|
3
|
Yadav et al., (2017)19
|
46
|
F
|
30
|
NR
|
Chronic cholecystitis with mucocele
|
4
|
Bains, Maranna et al, 2020
(current case)
|
65
|
F
|
24 × 9
|
-
|
Adenocarcinoma of gall bladder
|
5
|
Jahantab et al, 202025
|
|
|
22 × 6 × 1
|
|
Gangrenous cholecystitis
|
6
|
Borodach et al., 200520
|
67
|
F
|
20 × 12
|
1.5L
|
NA
|
7
|
Fultang et al., 20195
|
63
|
F
|
19.5 × 5.4 × 5.6
|
NR
|
Chronic cholecystitis with cholelithiasis
|
8
|
Maeda et al., 197921
|
36
|
F
|
18 × 4
|
NR
|
Chronic cholecystitis
|
9
|
Chapman et al., 201422
|
59
|
F
|
18
|
NR
|
Gall bladder adenocarcinoma with liver metastasis
|
10
|
Kuznetsov et al., 201423
|
77
|
F
|
17.2 × 16.1 × 24.0
|
3.35L
|
Chronic cholecystitis
|
11
|
Hsu et al., 201124
|
87
|
F
|
16.4 × 13.6 ×
7.8
|
NR
|
Gall bladder adenocarcinoma with empyema
|
NA = not available NR = not reported
|
Surgery is the mainstay of treatment of GBC which essentially is radical cholecystectomy with resection of 3 cm of liver parenchymal segments IVb and V along with regional lymphadenectomy. A minimum of 6 retrieved lymph nodes are necessary for adequate staging, indicating a thorough lymphadenectomy. Regional lymphadenectomy improves survival in T1b to T3 GBC. Patient underwent radical cholecystectomy with albeit surprisingly no infiltration and preserved planes. Laparoscopic cholecystectomy for a benign GGB can be performed with adequate surgical expertise.5,19 Laparoscopic radical cholecystectomy for early T1 and T2 GBC has been performed in experienced centers with satisfactory results.,, However open surgery is the current standard of care for malignant cases especially in giant GB.