Considering an increase in the life expectancy leading to a rise in the elderly population, it is important to recognize the changes that occur along the process of aging. Gastrointestinal (GI) changes in the elderly are common, and despite some GI disorders being more prevalent in the elderly, there is no GI disease that is limited to this age group. While some changes associated with aging GI system are physiologic, others are pathological and particularly more prevalent among those above age 65 years. This article reviews the most important GI disorders in the elderly that clinicians encounter on a daily basis. We highlight age-related changes of the oral cavity, esophagus, stomach, small and large bowels, and the clinical implications of these changes. We review epidemiology and pathophysiology of common diseases, especially as they relate to clinical manifestation in elderly. Details regarding management of specific disease are discussed in detail if they significantly differ from the management for younger groups or if they are associated with significant challenges due to side effects or polypharmacy. Cancers of GI tract are not included in the scope of this article.

SummaryIn obesity and the early stages of type 2 diabetes (T2D), pro-inflammatory cytokines are mildly elevated in the systemic circulation. This low-grade systemic inflammation exposes pancreatic islets to these circulating cytokines, but at levels ~100-1000x lower than seen within the islet during insulitis, which have not been well described. We examined mouse islets treated overnight with a low-dose cytokine combination commonly associated with inflammation (TNF-alpha, IL-1 beta, and IFN-gamma). We then examined islet function primarily using intracellular calcium 2+ ] i dynamics as cytokine-treated islets. Additional studies of control islets showed that the cytokine-induced elevation in basal [Ca 2+ ] i was due to both greater calcium influx through L-typecalcium-channels and reduced endoplasmic reticulum (ER) calcium storage. Many of these cytokine-induced disruptions could be reproduced by SERCA blockade. Our data suggest that chronic low-grade inflammation produces circulating cytokine levels that are sufficient to induce beta-cell dysfunction and may play a contributing role in beta-cell failure in early T2D.

Suppurative portal vein thrombosis (pylephlebitis) is an uncommon condition usually associated with an intra-abdominal infection or inflammatory process. In this study, we aimed to synthesize data on previously published cases according to the PRISMA guidelines. A total of 103 patients were included. Patients were more commonly male (71.8%) and had a mean age of 49 years. The most common infection associated with pylephlebitis was diverticulitis (n = 29, 28.2%), and Escherichia coli was the most isolated pathogen (n = 21, 20.4%). Blood cultures were positive in 64 cases (62.1%). The most common site of thrombosis was the main portal vein (PV) in 59 patients (57.3%), followed by the superior mesenteric vein (SMV) in 40 patients (38.8%) and the right branch of the PV in 30 patients (29.1%). Sepsis developed in 60 patients (58.3%). The mortality rate in our review was 8.7%, and independent risk factors for mortality were the presence of pertinent comorbidities (OR 5.5, p = 0.02), positive blood cultures (OR 2.2, p = 0.02), and sepsis (OR 17.2, p = 0.049).

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life threatening severe cutaneous drug reaction. Most patients develop eosinophilia, a rash, a fever, lymphadenopathy and variable visceral organ involvement 2–6 weeks following exposure to the inciting medication. Unlike other severe cutaneous drug reactions, internal organ involvement that leads to high mortality is a unique feature of DRESS syndrome. While the liver is the most common internal organ involved, literally every other visceral organ can be affected in this syndrome. The lesser-known gastrointestinal manifestations of this syndrome include esophagitis, gastritis, enteritis, colitis, pancreatitis and a late autoimmune sequela due to pancreatic injury such as fulminant type 1 diabetes mellitus, autoimmune type 1 diabetes mellitus and type 2 diabetes mellitus. While these entities are less common, they are associated with equally severe complications and adverse patient outcomes. In this review, we synthetize data on these rare manifestations using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The liver, the most common visceral organ involved, has been described as part of DRESS elsewhere and is not included in the scope of this article.

Activation of adenosine A(2A) receptors inhibits inflammation in ischemia/reperfusion injury, and protects against cell damage at the injury site. Following transplantation 50% of islets die due to inflammation and apoptosis. This study investigated the effects of adenosine A(2A) receptor agonists (ATL146e and ATL313) on glucose-stimulated insulin secretion (GSIS) in vitro and transplanted murine syngeneic islet function in vivo. Compared to vehicle controls, ATL146e (100 nM) decreased insulin stimulation index [SI, (insulin)(high glucose)/(insulin)(low glucose)] (2.36 +/- 0.22 vs. 3.75 +/- 0.45; n = 9; p < 0.05). Coculture of islets with syngeneic leukocytes reduced SI (1.41 +/- 0.17; p < 0.05), and this was restored by ATL treatment (2.57 +/- 0.18; NS). Addition of a selective A(2A)AR antagonist abrogated ATL's protective effect, reducing SI (1.11 +/- 0.42). ATL treatment of A(2A)AR(+/+) islet/A(2A)AR(-/-) leukocyte cocultures failed to protect islet function (SI), implicating leukocytes as likely targets of A(2A)AR agonists. Diabetic recipient C57BL/6 mice (streptozotocin; 250 mg/kg, IP) received islet transplants to either the renal subcapsular or hepatic-intraportal site. Recipient mice receiving ATL therapy (ATL 146e or ATL313, 60 ng/kg/min, IP) achieved normoglycemia more rapidly than untreated recipients. Histological examination of grafts suggested reduced cellular necrosis, fibrosis, and lymphocyte infiltration in agonist-treated animals. Administration of adenosine A(2A) receptor agonists (ATL146e or ATL313) improves in vitro GSIS by an effect on leukocytes, and improves survival and functional engraftment of transplanted islets by inhibiting inflammatory islet damage in the peritransplant period, suggesting a potentially significant new strategy for reducing inflammatory islet loss in clinical transplantation.