Clinical approaches to non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)ranges from simple steatosis to nonalcoholic steatohepatitis(NASH),leading to fibrosis and potentially cirrhosis,and it is one of the most common causes of liver disease worldwide.NAFLD is associated with other medical conditions such as metabolic syndrome,obesity,cardiovascular disease and diabetes.NASH can only be diagnosed through liver biopsy,but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis,reducing the need for liver biopsy and risk to patients.Disease progression varies between individuals and is linked to a number of risk factors.Mechanisms involved in the pathogenesis are associated with diet and lifestyle,influx of free fatty acids to the liver from adipose tissue due to insulin resistance,hepatic oxidative stress,cytokines production,reduced very low-density lipoprotein secretion and intestinal microbiome.Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD.Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial.Omega 3 polyunsaturated fatty acids and statins may offer additional benefits.Bariatric surgery should be considered in morbidly obese patients.More research is needed to assess the impact of these treatments on a long-term basis.The objective of this article is to briefly review the diagnosis,management and treatment of this disease in order to aid clinicians in managing these patients.     

Comparing human and mouse salivary glands: A practice guide for salivary researchers

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes.     

Laparoscopic Colorectal Surgery for Obese Patients: Decreased Conversions with the Hand-Assisted Technique

Background

Laparoscopic surgery benefits obese patients but technical difficulties associated with suboptimal exposure and access in these subjects may prompt conversion to open surgery. Hand-assisted laparoscopic surgery (HALS) confers advantages over standard laparoscopy (LAP) by facilitating tactile feedback, assisted dissection, and retraction. These benefits could be particularly valuable in obese patients, allowing completion of difficult laparoscopic procedures in this subgroup. Our aim was to compare intra-operative and post-operative outcomes of HALS and LAP approaches in obese patients undergoing colorectal resection at our institution.

Methods

A retrospective study of a prospectively maintained laparoscopic colorectal surgery database was performed. HALS and LAP cases performed in obese patients (body mass index (BMI)?>30) were identified and compared for the following outcomes: operative time, intra-operative complications, rate of conversion to open, blood loss, length of stay, post-operative morbidity, and mortality. Outcomes for the converted patients were included on an intention-to-treat basis for all primary analyses. A secondary analysis of nonconverted and converted cases was also performed.

Results

Over a 5-year period, 496 obese patients underwent laparoscopic colorectal resection; 86 HALS and 410 LAP cases. The two groups were comparable in terms of age, gender, BMI, and indications for surgery. Conversion to open surgery was less often necessary in HALS compared to LAP cases (3.5 % vs. 12.7 %, p?=?0.014). The LAP group had a significantly smaller incision length for specimen extraction (HALS (7.0?±?1.3 cm) vs. LAP (5.7?±?2.1 cm), p?<?0.001). Length of stay, operative time, morbidity, and mortality rates were comparable between the two groups.

Conclusion

In obese patients who require colectomy, the HALS approach increases the likelihood of a successful minimally invasive operation. At the cost of a clinically negligible increase in incision length, HALS may save a high-risk group conversion to formal laparotomy and the adverse outcomes related to this.     

Bouveret's syndrome--a rare presentation of gallstone ileus

We present the case of an elderly Irish male with Bouveret's syndrome--a very unusual cause of gallstone ileus, where a large gallstone occludes the gastric outlet or duodenum causing obstruction. Management of this condition is often controversial. We discuss the various medical, radiological and surgical therapies available for treatment of this rare entity. Bouveret's Syndrome--A Rare Presentation of Gallstone Ileus     

Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome

The hyperimmunoglobulinemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent febrile attacks with abdominal distress, joint involvement (arthralgias/arthritis), headache, skin lesions, and an elevated serum IgD level (> 100 U/mL). This familial disorder has been diagnosed in 59 patients, mainly from Europe. The pathogenesis of this febrile disorder is unknown, but attacks are joined by an acute-phase response. Because this response is considered to be mediated by cytokines, we measured the acute-phase proteins C-reactive protein (CRP) and soluble type-II phospholipase A2 (PLA2) together with circulating concentrations and ex vivo production of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) and the inhibitory compounds IL-1 receptor antagonist (IL-1ra), IL-10, and the soluble TNF receptors p55 (sTNFr p55) and p75 (sTNFr p75) in 22 patients with the hyper-IgD syndrome during attacks and remission. Serum CRP and PLA2 concentrations were elevated during attacks (mean, 213 mg/L and 1,452 ng/mL, respectively) and decreased between attacks. Plasma concentrations of IL-1 alpha, IL-1 beta, or IL-10 were not increased during attacks. TNF alpha concentrations were slightly, but significantly, higher with attacks (104 v 117 pg/mL). Circulating IL-6 values increased with attacks (19.7 v 147.9 pg/mL) and correlated with CRP and PLA2 values during the febrile attacks. The values of the antiinflammatory compounds IL-1ra, sTNFr p55, and sTNFr p75 were significantly higher with attacks than between attacks, and there was a significant positive correlation between each. The ex-vivo production of TNF alpha, IL-1 beta, and IL-1ra was significantly higher with attacks, suggesting that the monocytes/macrophages were already primed in vivo to produce increased amounts of these cytokines. These findings point to an activation of the cytokine network, and this suggests that these inflammatory mediators may contribute to the symptoms of the hyper-IgD syndrome.     

T cells from patients with Hodgkin's disease have a defective T-cell receptor zeta chain expression that is reversible by T-cell stimulation with CD3 and CD28

To investigate the mechanisms underlying the deficiency of T lymphocytes from patients with Hodgkin's disease, we investigated the expression of the T-cell receptor (TCR) zeta chain in patients with Hodgkin's disease. By flow cytometry using an anti-zeta chain monoclonal antibody, peripheral blood T lymphocytes from patients with untreated Hodgkin's disease were shown to express decreased levels of the TCR zeta chain. After stimulation by combined CD3 and CD28 cross- linking, T cells from Hodgkin's disease patients upregulated zeta chain protein expression to normal values within 48 hours and achieved a cytolytic potential and levels of interleukin (IL)-2 secretion that were not different from T cells obtained from healthy controls. These results show that downregulation of the TCR zeta chain in Hodgkin's T lymphocytes is a reversible event. Costimulation of CD3 and CD28 is a novel approach for overcoming the T-cell deficiency in Hodgkin's disease and might be exploited clinically. As upregulation of the zeta chain can also be achieved using bispecific monoclonal antibodies (BI- MoAbs) with specificity for tumor antigens and CD3 and CD28, respectively, an immunotherapy with CD3/CD30 and CD28/CD30 Bi-MoAbs may overcome and should therefore, not be jeopardized by the inherent T- cell deficiency in patients with Hodgkin's disease.