Pouch-vaginal fistulas are a difficult problem in females following restorative proctocolectomy. However, local repair can be successful with good functional outcomes. Redo restorative proctocolectomy may also achieve healing if local repairs are not possible or have failed. A delayed diagnosis of Crohn's disease results in worse treatment outcome and higher pouch failure rates.
Emerging evidence reveals that adipose tissue-associated inflammation is a main mechanism whereby obesity promotes colorectal cancer risk and progression. Increased inflammasome activity in adipose tissue has been proposed as an important mediator of obesity-induced inflammation and insulin resistance development. Chronic inflammation in tumor microenvironments has a great impact on tumor development and immunity, representing a key factor in the response to therapy. In this context, the inflammasomes, main components of the innate immune system, play an important role in cancer development showing tumor promoting or tumor suppressive actions depending on the type of tumor, the specific inflammasome involved, and the downstream effector molecules. The inflammasomes are large multiprotein complexes with the capacity to regulate the activation of caspase-1. In turn, caspase-1 enhances the proteolytic cleavage and the secretion of the inflammatory cytokines interleukin (IL)-1β and IL-18, leading to infiltration of more immune cells and resulting in the generation and maintenance of an inflammatory microenvironment surrounding cancer cells. The inflammasomes also regulate pyroptosis, a rapid and inflammation-associated form of cell death. Recent studies indicate that the inflammasomes can be activated by fatty acids and high glucose levels linking metabolic danger signals to the activation of inflammation and cancer development. These data suggest that activation of the inflammasomes may represent a crucial step in the obesity-associated cancer development. This review will also focus on the potential of inflammasome-activated pathways to develop new therapeutic strategies for the prevention and treatment of obesity-associated colorectal cancer development.
The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose‐derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single‐blind clinical trial, recruiting 57 patients. Forty‐four patients were categorized as belonging to the intent‐to‐treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re‐epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long‐term and sustained fistula healing.
Preoperative chemotherapy in LACC patients is safe and able to induce major tumor regression. Survival times are encouraging, and further research seems warranted.
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