Cancer is fueled by deregulation of signaling pathways in control of cellular growth and proliferation. These pathways are also targeted by infectious pathogens en route to establishing infection. Gallbladder carcinoma (GBC) is frequent in the Indian subcontinent, with chronic Salmonella enterica serovar Typhi infection reported as a significant risk factor. However, direct association and causal mechanisms between Salmonella Typhi infection and GBC have not been established. Deconstructing the epidemiological association between GBC and Salmonella Typhi infection, we show that Salmonella enterica induces malignant transformation in predisposed mice, murine gallbladder organoids, and fibroblasts, with TP53 mutations and c-MYC amplification. Mechanistically, activation of MAPK and AKT pathways, mediated by Salmonella enterica effectors secreted during infection, is critical to both ignite and sustain transformation, consistent with observations in GBC patients from India. Collectively, our findings indicate that Salmonella enterica can promote transformation of genetically predisposed cells and is a causative agent of GBC.

AimTo evaluate the role of ultrasonography for differentiating cervical lymphadenopathy due to tuberculosis, metastasis and lymphoma.MethodsUltrasonography of the neck nodes was carried out prior to FNAC in 192 patients using a 10 mHz linear transducer. The sonographic findings were then correlated with the definitive tissue diagnosis obtained by FNAC or lymph node biopsy.ResultsThe most significant distinguishing feature was strong internal echoes seen in 84% of tubercular lymph nodes. This finding was found in only 11% of metastatic nodes and absent in lymphomatous nodes. The other findings such as L/S ratio, irregular margins, hypoechoic center, fusion tendency, peripheral halo and absent hilus were helpful in differentiating reactive from diseased nodes but showed considerable overlap in the 3 groups of tubercular, metastatic and lymphoma lymph nodes.ConclusionUltrasonography is noninvasive and can give useful clues in the diagnosis of cervical lymphadenopathy. It should be interpreted in conjunction with FNAC result. Ideally ultra-sonographic guided FNAC should be obtained from the sonographically most representative node. In FNAC indeterminate cases, sonographic features may obviate the need for an invasive lymph node biopsy.

Background: Although well studied the association between chronic typhoid carrier state and carcinoma of the gallbladder (CaGB) remains unproven. Methodology: The study was performed at a tertiary care medical center in North India and involved 52 patients with CaGB, 223 patients with benign gallbladder diseases, 508 healthy individuals and, 424 corpses. For the detection of Salmonella enterica serovar Typhi, hepatobiliary specimens were subjected to DNA extraction for specific nested-PCR amplification of the S. Typhi flagellin gene. Anti-Vi S. Typhi antibodies were detected in serum samples from patients by indirect haemagglutination. Results: Thirty five of the 52 (67.3%) CaGB patients were PCR-positive for the S. Typhi flagellin gene; significantly higher than for patients with benign gallbladder diseases (95/223, 42.6%; p<0.01) and corpses (35/424, 8.2%; p<0.001). The numbers of individuals that had significant anti-Vi antibody titres (≥160) in their serum were 20/52 (38.5%) for CaGB patients, 31/223 (13.9%) for patients with benign gallbladder diseases, and 47/508 (9.2%) for healthy individuals. Conclusions: Specific nested-PCR amplification of the S. Typhi flagellin gene in hepato-biliary specimens was more sensitive for detection of S. Typhi carriage than anti-Vi antibody titres in serum. The results demonstrate an association between typhoid carriage and gallbladder diseases, both CaGB and benign. S. Typhi specific immunosuppression is also suggested in patients with gallbladder diseases.