Paediatric pancreaticobiliary endoscopy: a 21-year experience from a tertiary hepatobiliary centre and systematic literature review.

BACKGROUND: In adults ERCP and endoscopic ultrasound (EUS) are standard methods of evaluating and treating many hepatopancreaticobiliary (HPB) conditions. HPB disease is being diagnosed with increasing frequency in children but information about role of ERCP and EUS and their outcomes in this population remain limited. Therefore the aims of this study were to describe the paediatric ERCP and EUS experience from a large tertiary referral HPB centre, and to systematically compare outcomes with those of other published series. METHODS: All patients <18 years undergoing an ERCP or EUS between January 1992-December 2014 were included. Indications for the procedure, rates of technical success, procedural adverse events and reinterventions were recorded in all cases. RESULTS: Ninety children underwent 111 procedures (87 ERCPs and 24 EUS). 53% (48) were female with a median age of 14 years (range: 3 months - 17 years). Procedures were performed under general anaesthesia (n = 48) or conscious sedation (n = 63). Common indications for ERCP included chronic or recurrent pancreatitis and biliary obstruction. Patients frequently had multiple comorbidities, with a median ASA grade of 2 (range 1-4). Therapeutic procedures performed included biliary or pancreatic sphincterotomy, common bile duct or pancreatic duct stone removal, biliary or pancreatic stent insertion, EUS-guided fine needle aspiration and endoscopic transmural drainage of pancreatic fluid collections. No adverse events were reported following ERCP but there was one complication requiring surgery following EUS guided cystenterostomy. CONCLUSION: ERCP and EUS in children and adolescents have high technical success rates and low rates of adverse events when performed in high volume HPB centres.

Eosinophilic oesophagitis: investigations and management.

Eosinophilic oesophagitis (EO) is an immune/antigen mediated, chronic, relapsing disease characterised by dysphagia, food bolus impaction and a dense oesophageal eosinophilic infiltrate. Characteristic endoscopic features include corrugated rings, linear furrows and white exudates, but none are diagnostic. Despite its increasing prevalence, EO remains underdiagnosed. There is a strong association with other atopic conditions. Symptoms, histology and endoscopic findings can overlap with gastro-oesophageal reflux disease. Currently endoscopy and oesophageal biopsies are the investigation of choice. Oesophageal physiology studies, endoscopic ultrasound, impedance planimetry and serology may have a role in the diagnosis and monitoring of response to therapy. Acid reducing medication is advocated as first line or adjuvant therapy. Dietary therapy is comprised of elimination diets or can be guided by allergen assessment. In adults, topical corticosteroids are the mainstay of therapy. Endoscopic dilatation is safe and effective for the treatment of non-responsive strictures. Other therapeutic options (immunomodulators, biological agents, leukotriene receptor antagonists) are under investigation.

Suppression of tumour-specific CD4⁺ T cells by regulatory T cells is associated with progression of human colorectal cancer.

BACKGROUND: There is indirect evidence that T cell responses can control the metastatic spread of colorectal cancer (CRC). However, an enrichment of CD4(+)Foxp3(+) regulatory T cells (Tregs) has also been documented. OBJECTIVE: To evaluate whether CRC promotes Treg activity and how this influences anti-tumour immune responses and disease progression. METHODS: A longitudinal study of Treg activity on a cohort of patients was performed before and after tumour resection. Specific CD4(+) T cell responses were also measured to the tumour associated antigens carcinoembryonic antigen (CEA) and 5T4. RESULTS: Tregs from 62 preoperative CRC patients expressed a highly significant increase in levels of Foxp3 compared to healthy age-matched controls (p=0.007), which returned to normal after surgery (p=0.0075). CD4(+) T cell responses to one or both of the tumour associated antigens, CEA and 5T4, were observed in approximately two-thirds of patients and one third of these responses were suppressed by Tregs. Strikingly, in all patients with tumour recurrence at 12 months, significant preoperative suppression was observed of tumour-specific (p=0.003) but not control CD4(+) T cell responses. CONCLUSION: These findings demonstrate that the presence of CRC drives the activity of Tregs and accompanying suppression of CD4(+) T cell responses to tumour-associated antigens. Suppression is associated with recurrence of tumour at 12 months, implying that Tregs contribute to disease progression. These findings offer a rationale for the manipulation of Tregs for therapeutic intervention.

Identification of foods that affect the anti-cancer activity of pitavastatin in cells.

Statins inhibit the synthesis of mevalonate, a precursor isoprenoid molecule to geranylgeraniol that is necessary for the post-translational modification of several small GTPase oncogenes. Despite numerous preclinical studies suggesting that statins can be effective anticancer agents, prospective clinical trials have failed to demonstrate any clinical benefit in patients with cancer. We previously demonstrated that geranylgeraniol suppresses the activity of statins in cell culture studies, and that pitavastatin can cause regression of ovarian cancer xenografts in mice if the animals' diet is modified to avoid the inclusion of geranylgeraniol. Dietary sources of geranylgeraniol may consequently limit the activity of statins in cancer clinical trials. The present study tested several foods to identify those that affected the cytotoxic activity of pitavastatin towards ovarian cancer cells. Solvent extracts of several foods were tested for their ability to suppress the effects of pitavastatin in cell growth assays. The results revealed that pitavastatin induced cell death in ovarian cancer cells (IC50=5.2 µM) and this was blocked by geranylgeraniol whereas other products of the mevalonate pathway (coenzyme Q, dolichol or cholesterol) had no effect on the activity of pitavastatin in cell growth assays. Solvent extracts from several foods, especially oils (apart from rapeseed), also blocked the cytotoxic activity of pitavastatin. Several extracts from a range of fruit, vegetables and carbohydrate-rich foods also did not block the activity of pitavastatin. However, extracts from beans, lettuce, oats, eggs and various nuts reduced the activity of pitavastatin. These data identified foods that patients could eat to potentially improve the outcome of clinical trials of pitavastatin in cancer.

Acute Immune Signatures and Their Legacies in Severe Acute Respiratory Syndrome Coronavirus-2 Infected Cancer Patients.

Given the immune system's importance for cancer surveillance and treatment, we have investigated how it may be affected by SARS-CoV-2 infection of cancer patients. Across some heterogeneity in tumor type, stage, and treatment, virus-exposed solid cancer patients display a dominant impact of SARS-CoV-2, apparent from the resemblance of their immune signatures to those for COVID-19+ non-cancer patients. This is not the case for hematological malignancies, with virus-exposed patients collectively displaying heterogeneous humoral responses, an exhausted T cell phenotype and a high prevalence of prolonged virus shedding. Furthermore, while recovered solid cancer patients' immunophenotypes resemble those of non-virus-exposed cancer patients, recovered hematological cancer patients display distinct, lingering immunological legacies. Thus, while solid cancer patients, including those with advanced disease, seem no more at risk of SARS-CoV-2-associated immune dysregulation than the general population, hematological cancer patients show complex immunological consequences of SARS-CoV-2 exposure that might usefully inform their care.

Ocular radiation exposure during endoscopic retrograde cholangiopancreatography: a meta-analysis of studies.

BACKGROUND: The increasing complexity involved in procedures requiring fluoroscopy such as endoscopic retrograde cholangiopancreatography (ERCP) results in heightened screening times with attendant radiation exposure during these procedures. There is increasing awareness of tissue-reactions to the lens of the eye due to radiation exposure, with evidence suggesting that threshold doses may be lower than previously considered. MATERIALS AND METHODS: A literature search was performed to identify studies involving ERCP in which radiation exposure was reported. Demographic data and data on fluoroscopy time and ocular exposure were extracted. Fixed and random-effects meta-analyses were conducted. RESULTS: Twenty-six studies (8016 procedures) were identified, of which 10 studies (818 procedures) contained data on ocular exposure. The mean screening time per procedure was 3.9 min with a mean of three images captured per procedure. On fixed effects meta-analysis, the point estimate for the effective ocular exposure dose per procedure was 0.018 (95% confidence interval: 0.017-0.019) mSv. On random-effects meta-analysis, the effective ocular exposure dose was 0.139 (0.118-0.160) mSv (Q=2590.78, I=99.5, P<0.001). On comparing these point estimates to the ocular dose limit of 20 mSv/year, 1111 ERCPs (using fixed effects data) and 144 ERCPs (using random-effects data), with a mean of 627 ERCPs/individual/year, could deliver an ocular radiation dose equivalent to this dose limit. CONCLUSION: Ocular radiation exposures in high-volume ERCP operators (>200 procedures/year) and operators performing complex ERCPs involving prolonged fluoroscopy, need to exercise caution in relation to ocular exposure. Shielding using lead-lined glasses may be reasonable in this group.

Intrahepatic and intra-abdominal splenosis: A case report and review of literature.

BACKGROUND: Splenosis is defined as the process by which tissue from the spleen disseminates through the body and grows in an ectopic location following trauma or a splenectomy. Visceral sites of splenosis are rare. CASE SUMMARY: We report a case of intrahepatic splenosis in a 57-year-old man with a history of trauma over 40 years ago who initially presented with chest pain. Findings initially mimicked malignancy but a diagnosis of intrahepatic splenosis was confirmed using computed tomography and scintigraphy with technetium-99m heat-denatured red blood cells (Tc-99 DRBC). CONCLUSION: Scintigraphy with Tc-99 DRBC is a reliable technique to diagnose splenosis and should be performed before using more invasive procedures are carried out. Splenosis should be considered as a possible differential diagnosis for a hepatic nodule in any patient with a history of abdominal trauma, previous splenectomy or atypical radiological features on imaging.

Application of Nanoparticle Technologies in the Combat against Anti-Microbial Resistance.

Anti-microbial resistance is a growing problem that has impacted the world and brought about the beginning of the end for the old generation of antibiotics. Increasingly, more antibiotics are being prescribed unnecessarily and this reckless practice has resulted in increased resistance towards these drugs, rendering them useless against infection. Nanotechnology presents a potential answer to anti-microbial resistance, which could stimulate innovation and create a new generation of antibiotic treatments for future medicines. Preserving existing antibiotic activity through novel formulation into or onto nanotechnologies can increase clinical longevity of action against infection. Additionally, the unique physiochemical properties of nanoparticles can provide new anti-bacterial modes of action which can also be explored. Simply concentrating on antibiotic prescribing habits will not resolve the issue but rather mitigate it. Thus, new scientific approaches through the development of novel antibiotics and formulations is required in order to employ a new generation of therapies to combat anti-microbial resistance.

Prevalence of Microalbuminuria among Rural North Indian Population with Diabetes Mellitus and its Correlation with Glycosylated Haemoglobin and Smoking.

INTRODUCTION: Macrovascular and microvascular complications of diabetes mellitus are a consequence of metabolic derangement mainly hyperglycemia. Diabetic nephropathy being one of them causes end stage renal disease. Hence, to detect renal involvement, microalbuminuria can be considered as an early marker. AIM: To study mean albumin creatinine ratio (ACR) in type 1 and type 2 diabetes mellitus with respect to HbA1c, duration of diabetes and smoking. MATERIALS AND METHODS: Two hundred cases of type 1 and type 2 diabetes mellitus and 100 controls, age and sex matched were included in this study and measured for spot urinary albumin, spot urinary creatinine, fasting plasma glucose and HbA1c. RESULTS: It was observed that mean ACR was significantly elevated in type 1 and type 2 diabetes mellitus as compared to the controls. Mean ACR increases in diabetics with poor glycemic control, duration of diabetes and smoking. CONCLUSION: The early detection of microalbumin in diabetics can significantly reduce the progression of renal complications and before the development of proteinuria.

Probiotics and their Effects on Metabolic Diseases: An Update.

Probiotics are lactic acid bacteria which are used extensively in therapeutic preparations and added to foods. There are many studies which have demonstrated the effects of probiotics on metabolic diseases. One study has shown the effect of fermented dairy products on the serum cholesterol, especially with selected strains of lactic acid bacteria. It has been found that a minute quantity of the dry culture of Lactobacillus fermentum KC4b, for example, can remove 14.8 mg of cholesterol from the culture medium. Lactobacilli also play an important role in deconjugating the bile salts in the intestine to form bile acids and thereby inhibiting the micelle formation. Probiotics reduce the lipid peroxidation and improve the lipid metabolism in vivo. The addition of probiotics to the diet for weeks improved the immune response without the release of inflammatory cytokines, thereby reducing the onset of systemic inflammatory induced diabetes. There are evidences that the differences in the composition of the gut microbiota may precede the development of obesity in children. This review has illustrated the potential of probiotics in mediating metabolic diseases via the positive modulation of several different physiological systems, apart from its conventional benefits for the gastrointestinal health.