Gallbladder cancer: Progress in the Indian subcontinent

Table 1 Studies on etiopathogenesis of gall bladder cancer

Serial No.	Sample size	Findings	Ref.
1	GBC (214) controls (214)	Biomass burning was recognized as a significant risk factor for GBC	Shridhar et al[20]
2	GBC (200); Gall stone disease (200) controls (200)	Residence in the Gangetic belt, consumption of tea, tobacco, joint family structure, chemical exposure, fried food, and high levels of secondary bile salts are risk factors of GBC	Jain et al[21]
3	GBC (54)	Cholelithiasis is a predisposing factor for GBC	Bhattacharjee and Nanda[22]
4	GBC (1291)	Exposure to high soil arsenic levels and proximity to river ganga are risk factors for GBC	Madhawi et al[23]
5	GBC (333)	Smoking, cholelithiasis, alcohol consumption, typhoid in the past, post-menopausal women are risk factors for GBC	Tyagi et al[24]
6	GBC (63)	Poor hygiene and water supply, malnutrition, cholelithiasis, tobacco and alcohol consumption are modifiable risk factors for GBC	Khan et al[25]
7	GBC (122); controls (122)	Education, intake of vitamin C, parity, and type of fuel used were significant factors for GBC	Panda et al[26]
8	GBC (49)	About 75% of patients diagnosed with GSD showed detectable H. pylori DNA in their gallbladder tissue	Bansal et al[27]
9	GSD (330)	As the stone size increases, gallbladder mucosa changes progress from cholecystitis to carcinoma	Mathur et al[28]
10	GBC (n = 11), Chronic cholecystitis (n = 23), Xantho-granulomatous cholecystitis (n = 11)	The cholesterol content in gallstones of GBC was significantly lower compared to that in benign gallbladder diseases	Srivastava et al[29]
11	GBC (390)	Chronic bacterial infection of bile is considered an etiological factor in the development of gallbladder carcinoma	Sharma et al[30]
12	GSD (101)	H. pylori colonizes regions of gastric metaplasia within the gallbladder	Misra et al[31]
13	GBC (328); controls (328)	Females, consumption of mustard oil, Family history, low socioeconomic status and drinking water from hand pump were the risk factors for GBC	Kumar et al[32]
14	GBC (27), GSD (196)	High prevalence of salmonella typhi in gall bladder carcinoma	Vaishnavi et al[33]
15	GBC (38)	Higher levels of biliary nitrate associated with the gallbladder carcinogenesis	Shukla et al[34]
16	GBC (n = 30); controls (n = 30)	Decreased levels of selenium (Se), zinc (Zn), and vitamin E are associated with an increased risk of gallbladder carcinoma	Shukla et al[35]
17	GBC (n = 30); controls (n = 30)	Significantly high biliary benzene hexachloride and dichloro diphenyl trichloroethane associated with gallbladder carcinogenesis	Shukla et al[36]
18	150 GBC	Gall stones associated with development of metaplastic, dysplastic and neoplastic mucosal changes of gall bladder mucosa	Gupta et al[37]

GSD: Gallstone disease; GBC: Gallbladder cancer; H. pylori: Helicobacter pylori.

Table 2 Studies on genetics and polymorphism in gall bladder cancer

Serial No.	Sample size	Findings	Ref.
1	-	IGF-MAPK cascade, p38 MAPK pathway, p53 pathway, and FAS signaling pathway as highly enriched among dysregulated miRNAs in GBC	Saxena et al[51]
2	-	PARP1 rs1136410 (A/G) associated with early onset of GBC	Anjali et al[52]
3	GBC (29), controls (29)	VEGF-A expression can be used as potential prognostic biomarker in GBC	Singh et al[53]
4	-	Studied the prognostic significance of the oxidative stress marker 8-OH-dG and genes associated with the BER pathway	Singh et al[54]
5	GBC (25)	In gallbladder cancer patients, mutations were identified in both P53 and codon 12 of KRAS	Shukla et al[55]
6	-	Mutations in the sorcin gene associated with poor overall survival in GBC	Shabnam et al[56]
7	GBC (523), controls (274)	Studied the TERT-CLPTM1L and 8q24 Genetic Variants in GBC	Yadav et al[57]
8	GBC (50)	Individual and repetitive mutations of shh gene in GBC can be used as diagnostic marker	Dixit et al[58]
9	GBC (50)	Overexpression of Her2/neu and Ki67 in gallbladder cancer associated with lymph node metastasis	Pujani et al[59]
10	GBC (541), controls (307)	KRAS rs61764370 polymorphism is significantly associated with GBC	Kazmi et al[60]
11	-	Studied Epigenetic silencing of APC in advanced GBC.	Tekcham et al[61]
12	GBC (24)	Found 7 hypermethylated or down-regulated (e.g., FBN1, LPP, and SOD3) and 61 hypomethylated or up-regulated markers (e.g., HBE1, SNRPF, TPD52) for GBC	Sharma et al[62]
13	Cases (50)	The level of EGFR expression correlates with the aggressiveness of the disease	Kumar et al[63]
14	GBC (52)	Tγδ17 could serve as a potential predictive biomarker in GBC	Patil et al[64]
15	GBC (30)	The MTHFR A1298C polymorphism associated with development of GBC	Dixit et al[65]
16	GBC (37)	Telomere dysfunction and alterations are the earlier events in progression of GBC	Poojary et al[66]
17	GBC (148), controls (256)	CYP-17 gene polymorphism is associated with risk of gallbladder cancer	Dwivedi et al[67]
18	-	LXR-β polymorphisms associated with GBC	Sharma et al[68]
19	GBC (195), controls (300)	Vascular endothelial growth factor single nucleotide polymorphism associated with GBC	Mishra et al[69]
20	GBC (35)	mitochondrial D-loop mutation associated with GBC	Maurya et al[70]
21	GBC (410), controls (210)	Estrogen and progesterone receptor sequence associated with increased risk of GBC	Srivastava et al[71]
22	-	KRAS p.Q25H polymorphism associated with development of GBC	Parmanik et al[72]
23	GBC (230), controls (230)	Caspase-8 polymorphisms associated with GBC	Srivastava et al[73]
24	GBC (51)	p53 mutation are early events in the evolution of GBC	Agrawal et al[74]
25	GBC (185), controls (195)	CYP7A1 haplotype associated with GBC	Srivastava et al[75]
26	GBC (230), controls (230)	The role of pre-microRNA variants in GBC uncertain	Srivastava et al[76]
27	GBC (62)	Most common alteration in the p53 was frameshift mutation at codon 271	Nigam et al[77]
28	GBC (40)	High LOH in CDH1 associated with pathogenesis of GBC	Priya et al[78]
29	GBC (212), controls (219)	Studied the DNMT3B -579 G > T promoter polymorphism	Srivastava et al[79]
30	GBC (233), controls (260)	Angiotensin I-converting enzyme insertion/deletion polymorphism associated with GBC	Srivastava et al[80]
31	GBC (126), controls (190)	Role of DNA repair pathways GB carcinogenesis	Srivastava et al[81]
32	GBC (171), controls (221)	Patients with ABCG8 variant allele are at a higher risk of GBC	Srivastava et al[82]
33	GBC (185), controls (200)	Complement receptor polymorphism associated with pathogenesis of GBC	Srivastava and Mittal[83]
34	GBC (173), controls (204)	Single nucleotide polymorphisms of DNA repair genes OGG1 and XRCC1; associated with low risk for GBC	Srivastava et al[84]
35	GBC (144), controls (210)	Role of CCR5+/Delta32 polymorphism associated with risk of GBC	Srivastava et al[85]
36	GBC (124), controls (166)	IL-1 gene polymorphisms associated with GBC	Vishnoi et al[86]
37	GBC (142), controls (217)	CYP1A1 C allele frequency associated with GBC	Pandey et al[87]
38	-	CYP7A1 polymorphism associated with GBC	Srivastava et al[88]
39	-	The X (+), D haplotype of APOB is associated risk for development of GBC	Pandey et al[89]
40	-	NAT2 slow acetylator phenotype associated with risk of GBC	Pandey et al[90]
41	GBC (129), controls (208)	LRPAP1 polymorphism associated with GBC	Pandey et al[91]
42	GBC (39)	Mutation in codon 12 of the K-ras oncogene associated with GBC, which indicate role of chronic inflammation in gallbladder carcinogenesis.	Singh et al[92]
43	GBC (117), controls (137)	The apoB-XbaI gene polymorphism associated with GBC	Singh et al[93]

GBC: Gallbladder cancer; GB: Gallbladder.

Table 3 Clinico pathological studies

Serial No.	Sample size	Findings	Ref.
1	GBC (50)	Her2 neu, p53, p16, survivin, COX-2, and EZH-2 expression associated with GBC	Gupta et al[115]
2	GBC (200), Dysplasia (32), CC (100)	HER-2/neu overexpression seen in patients with GBC	Jain et al[116]
3	GBC (128)	HER 2 and Ki-67 can be used as a prognostic biomarker for gallbladder carcinoma	Halder et al[117]
4	-	Combination of ALU247 and cfDNA provides good sensitivity, specificity in diagnosis of GBC	Kumari et al[118]
5	-	Proposed a scoring system for XGC	Rajaguru et al[119]
6	GBC (34)	Quantitative analysis of cfDNA may aid in early diagnosis	Kumari et al[120]
7	GBC (39), cholelithiasis (30), and control (25)	Overexpression of survivin is associated with poor prognosis	Nigam et al[121]
8	(GSD, n =30; GBC, n = 39) healthy control (n = 25)	Expression of survivin in peripheral blood could be useful both in the diagnosis and prognosis of GBC	Nigam et al[122]
9	GBC (80)	P53 expression is positively correlated with increasing tumor grade, whereas beta-catenin nuclear expression is associated with tumor grade and depth of invasion	Ghosh et al[123]
10	9 case of Squamous cell carcinoma	Ultrasound-guided fine-needle aspiration is a useful minimally invasive investigation in the preoperative diagnosis of squamous cell carcinoma of the gallbladder	Gupta and Gupta[124]
11	GBC (55), vontrols (8)	Assay of CA242, CA19-9, CA15-3, and CA125 can be used as marker of carcinoma of the gallbladder	Shukla et al[125]
12	GBC (40)	Intraoperative bile cytology can be used for diagnosis of in situ and early invasive GBC	Arora et al[126]

GBC: Gallbladder cancer; CC: Chronic cholecystitis.

Table 4 Studies on diagnostic methods and imaging

Serial No.	Sample size	Findings	Ref.
1	-	PET-CT can be used to rule out metastatic disease and for post-therapy surveillance for recurrence in patients of GBC	Bisht et al[147]
2	GBC (38)	Potential utility of CT texture-based radiomics analysis in patients with GBC.	Gupta et al[148]
3	GBC (141)	Raised levels of serum CA19-9 beyond 20 units/mL should be used for prognostication purposes after EC	Agrawal et al[149]
4	GBC (141)	NMR-based methods can be used as a diagnostic modality for GBC	Sharma et al[150]
5	GBC (41)	CEA expression may help in diagnosis of GBC	Mondal et al[151]
6	GBC (203)	Discontinuous mucosal lining, diffuse wall thickening, intramural nodules, and cholelithiasis may indicate XGC rather than gallbladder carcinoma	Sureka et al[152]
7	GBC (74)	Duodenal involvement significantly decreases resectability but does not preclude resection	Kalayarasan et al[153]
8	XGC (31)	Mass-forming XGC mimics GBC	Agarwal et al[154]
9	GBC (117)	CA 242 is a promising tumor marker for GBC and performs better than CEA and CA19-9.	Rana et al[155]
10	GBC (15)	Dynamic MRI with MRCP is a reliable method of showing gall bladder carcinoma.	Kaza et al[156]
11	GBC (60)	Color Doppler USG together can improve pickup rate of GBC	Pradhan et al[157]

PET: Positron emission tomography; CT: Computed tomography; GBC: Gallbladder cancer; MRI: Magnetic resonance imaging; MRCP: Magnetic resonance cholangiopancreatography.

Table 5 Studies on surgical approaches and resection

Serial No.	Sample size	Findings	Ref.
1	GBC (521)	Surgical resection improves survival in GBC with jaundice	Goel et al[186]
2	GBC (97)	Radical cholecystectomy with wedge resection of the liver oncological equivalence compared to formal segment IVb/V excision	Patkar et al[187]
3	GBC (20)	The technique of LHBRL is safe and feasible for patients with GBC	Nag et al[188]
4	07 incidental GBC	Re-exploration and aggressive resection followed by adjuvant chemotherapy for incidental gallbladder carcinoma are safe and provide hope for long-term survival	Kaman et al[189]

GBC: Gallbladder cancer; LHBRL: Laparoscopic hepatic bisegmentectomy with regional lymphadenectomy.

Table 6 Studies on adjuvant therapy on gall bladder carcinoma

Serial No.	Sample size	Findings	Ref.
1	GBC (176)	CT followed by CTRT improves outcomes in patients with limited volume disease	Alam et al[205]
2	GBC (550)	CT followed by cCTRT appears to improve survival in responders with good PS	Alam et al[206]
3	GBC (38)	Her2neu directed therapy significantly improved survival	Das et al[207]
4	GBC (66)	FOLFOX-4 is an effective and well-tolerated regimen as a second-line treatment	Dodagoudar et al[208]
5	GBC (87)	CAP-IRI is a well-tolerated second-line chemotherapeutic regimen in advanced GBC	Ramaswamy et al[209]
6	GBC (121)	Reduced dose intensity of chemotherapy in GBC	Gangopadhyay et al[210]
7	GBC (210)	Use of gem-platinum in Indian patients associated with slightly worse outcomes	Sirohi et al[211]
8	-	Autologous immune enhancement therapy associated with, an improvement of the quality of life	Bhamare et al[212]
9	GBC (104)	Adjuvant chemoradiation improve survival	Mallick et al[213]
10	-	Chemoradiation improve survival in locally advanced GBC	Engineer et al[214]

GBC: Gallbladder cancer; CTRT: Chemo-radiotherapy; cCTRT: Consolidation chemoradiation.

Table 7 Studies on neo-adjuvant therapy on gall bladder carcinoma

Serial No.	Sample size	Findings	Ref.
1	GBC (510)	Surgery and peri-operative systemic therapy associated with improved survival	Patkar et al[218]
2	GBC (28)	Locally advanced GBC may benefit from neoadjuvant chemoradiation	Engineer et al[219]
3	GBC (37)	Neoadjuvant chemotherapy in patients with locally advanced gallbladder cancer	Sirohi et al[220]
4	GBC (21)	Resection after neoadjuvant chemotherapy improve survival	Selvakumar et al[221]

GBC: Gallbladder cancer.