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.

Formation of a seroma most frequently occurs after mastectomy and axillary surgery. Prolonged drainage is troublesome as it increases the risk for infection and can significantly delay adjuvant therapy. Seroma has been defined as serous fluid collection under the skin flaps or in the axillary dead space following mastectomy and/or axillary dissection. Because the true etiology of a seroma is unknown, a multifactorial-causation hypothesis has been accepted. Surgical factors include technique, extent of dissection and the surgical devices used for dissection. Obliteration of dead space with various flap fixation techniques, use of sclerosants, fibrin glue and sealants, octreotide, and pressure garments have been attempted with conflicting results and none have been consistent. Early movement of the shoulder during the postoperative period may increase the formation of seroma, although delayed physiotherapy decreases the formation of seroma. A detailed analysis of the use of drains showed that use of single or multiple drains, early or late removal, and drains with or without suction are not significantly different for the incidence of seroma. Although there is evidence for reduced seroma formation after early drain removal, very early removal within 24 hours seems to increase formation of seroma. No patient or tumor factors seem to affect seroma formation except body mass index and body weight. Consensus is lacking among studies/trials with different groups producing conflicting evidence. Besides a few established factors such as body mass index, the use of electrocautery for dissection, early drain removal, low vacuum drains, obliteration of dead space, and delayed shoulder physiotherapy, most of the hypothesized causes have not been demonstrated consistently. Thus, seroma remains a threat to both the patient and surgeon. Recurrent transcutaneous aspiration remains the only successful management.

Apoptosis, or programmed cell death, is a complex network of biochemical pathways for controlling such events in a cell. Apoptosis is essential, as its failure can lead to disease. Because apoptosis concerns the regulation of sequential events, including the removal of inflammatory cells and the evolution of granulation tissue into scar tissue, it has an essential role in wound repair. This article examines the literature and proposes that apoptosis features in the development of diabetic foot wounds. Hyperglycemia deregulates the sequential apoptotic events by multiple mechanisms, leading to delayed wound healing. Deregulated apoptosis is emerging as a prominent cause of delayed wound healing, especially in diabetic wounds, along with the well-known triad of peripheral vascular disease, neuropathy, and infection.