ABSTRACT
The co-occurrence of the three disease entities, inflammatory bowel disease (IBD), colorectal cancer (CRC), type 2diabetes mellitus (T2DM) along with inflammation and dismicrobism has been frequently reported. Some authors have even suggested that dysbiosis could be the link through a molecular crosstalk of multiple inflammatory loops including TGFß, NFKB, TNFα and ROS among others. This review focuses on the inflammatory process along with the role of microbiota in the pathophysiology of the three diseases. The etiology of IBD is multifactorial, and like CRC and T2DM, it is associated with a widespread and sustained GI inflammation and dismicrobism, whereby an array of pro-inflammatory mediators and other related biomolecules are up-regulated, both locally and systematically. Such a persistent or an inadequately resolved chronic inflammation may be a causative agent, in the presence other factors, leading to several pathologies such as IBD, CRC and T2DM. TGFß plays a crucial role in pancreatic ß cell malfunctioning as glucotoxicity stimulates its signaling cascade through smad 3, IL-6 and epithelial to mesenchymal transition. Such a cascade could lead to macrophages and other cells recruitment, inflammation, then IBD and CRC. NFkB is also another key regulator in the crosstalk among the pathways leading to the three disease entities. It plays a major role in linking inflammation to cancer development through its ability to up regulate several inflammatory and tumor promoting cytokines like: IL-6, IL-1 α and TNF α, as well as genes like BCL2 and BCLXL. It activates JAK/STAT signaling network via STAT3 transcription factors and promotes epithelial to mesenchymal transition. It also increases the risk for T2DM in obese people. In brief, NFKB is a matchmaker between inflammation, IBD, cancer and diabetes. In addition, TNFα plays a pivotal role in systemic inflammation. It is increased in the mucosa of IBD patients and has a central role in its pathogenesis. It also activates other signaling pathways like NFKB and MAPK leading to CRC. It is also overexpressed in the adipose tissues of obese patients thus linking it to T2DM, chronic inflammation and consequently CRC. On the other hand, increasing evidence suggests that dysbiosis plays a role in initiating, maintaining and determining the severity of IBD. Actually, among its functions, it modulates genotoxic metabolites which are able to induce CRC, a fact proven to be sustained by stool transfer from patients with CRC. Probiotics, however, may actively prevent CRC as well as IBD and results in a significant decrease in fasting glycemia in T2DM patients. In conclusion, IBD, CRC and T2DM are commonly occurring interrelated clinical problems. They share a common basis influenced by an inflammatory process, an imbalance in intestinal microbiota, and a crosstalk between various signaling pathways. Would probiotics interrupt the crosstalk or orient it in the physiological direction?
ABSTRACT
INTRODUCTION: Pruritus ani is a common medical condition that is difficult to treat in the absence of obvious predisposing factors. Hereby, we report more than a ten-year experience in the management of pruritus ani stressing the importance of early detection, identification of the etiology, and management. METHODOLOGY: A total of 124 patients were managed in the surgical clinic. The follow-up was between 11 to 17 months. All patients had the symptoms for a period of time ranging between 6 and 40 months. Patients were treated according to their respective etiology. Medical cases like contact dermatitis and psoriasis were treated by applying proper topical ointments, while other cases like anal fissure and fistula were treated surgically. Idiopathic patients were treated by tattooing (injection to perianal skin with methylene blue). RESULTS & DISCUSSION: The majority of patients with known medical etiology responded favorably to conservative treatment (≈ 92%). In addition, surgical management for anorectal disorders like hemorrhoids and fistula showed a consistent improvement (94%). However, patients who had their symptoms neglected for longtime or had used over the counter medication without a proper medical follow-up, experienced a lower success rate of cure (76%). CONCLUSION: Patients who were diagnosed and treated at first hand, showed better results than those who sought late medical advice and management (i.e. > 18 months). In light of the above, a multidisciplinary team approach consisting of a proctologist, a gastroenterologist and a dermatologist is recommended.
