Two distinct aetiologies of cardia cancer, evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status

Background: Non-cardia gastric adenocarcinoma is positively associated with Helicobacter pylori infection and atrophic gastritis. The role of H pylori infection and atrophic gastritis in cardia cancer is unclear. Aim: To compare cardia versus non-cardia cancer with respect to the premorbid state of the stomach. Methods: Nested case–control study. To each of 129 non-cardia and 44 cardia cancers, three controls were matched. Serum collected a median of 11.9 years before the diagnosis of cancer was tested for anti-H pylori antibodies, pepsinogen I:II and gastrin. Results: Non-cardia cancer was positively associated with H pylori (OR 4.75, 95% CI 2.56 to 8.81) and gastric atrophy (pepsinogen I:II ,2.5; OR 4.47, 95% CI 2.71 to 7.37). The diffuse and intestinal histological subtypes of non-cardia cancer were of similar proportions and both showed a positive association with H pylori and atrophy. Cardia cancer was negatively associated with H pylori (OR 0.27, 95% CI 0.12 to 0.59), but H pylori-positive cardia cancer showed an association with gastric atrophy (OR 3.33, 95% CI 1.06 to 10.5). The predominant histological subtype of cardia cancer was intestinal and was not associated with gastric atrophy compared with the diffuse subtype ((OR 0.72, 95% CI 0.19 to 2.79) vs (OR 3.46, 95% CI 0.32 to 37.5)). Cardia cancer in patients with atrophy had an intestinal: diffuse ratio (1:1) similar to non-cardia cancer (1.9:1), whereas cardia cancers in patients without atrophy were predominantly intestinal (7:1). Conclusion: These findings indicate two aetiologies of cardia cancer, one associated with H pylori atrophic gastritis, resembling non-cardia cancer, and the other associated with non-atrophic gastric mucosa, resembling oesophageal adenocarcinoma. Serological markers of gastric atrophy may provide the key to determining gastric versus oesophageal origin of cardia cancer

Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B

Background: HBV infection is a serious global heath problem. It is crucial to monitor this disease more closely with a non-invasive marker in clinical trials. We aimed to evaluate the predictive value of serum hyaluronate for the presence of extensive liver fibrosis and inflammation. Methods: 28 healthy volunteers and 65 patients with HBeAg negative chronic hepatitis B were enrolled. Liver biopsies scored according to Ishak system. Association of serum hyaloronate with liver fibrosis and inflammation were assessed, and cut off points for serum hyaluronate levels were identified by receiver operating characteristics (ROC) curves and their values for prediction of fibrosis and inflammation were assessed. Results: In patients with CHB serum hyaluronate had the most significant correlation and predictive values for the liver fibrosis and inflammation comparing to the other variables. At the cut off point of 126.4 ngm/ml it could discriminate extensive fibrosis from milder ones with sensitivity of 90.9% and specificity of 98.1%. With the same value it could discriminate extensive inflammation from their milder counterparts with sensitivity of 63.6% and specificity of 92.6%. Conclusion: Serum hyaluronate was the best predictor of extensive liver fibrosis and inflammation and it could discriminate subgroups of patients with chronic hepatitis B. It could be used as a non-invasive test to monitor these patients more closely with developing anti viral agents in clinical trials

Combination of gastric atrophy, reflux symptoms and histological subtype indicates two distinct aetiologies of gatric cardia cancer.

<b>INTRODUCTION</b> Atrophic gastritis is a risk factor for non-cardia gastric cancer, and gastro-oesophageal reflux disease (GORD) for oesophageal adenocarcinoma. The role of atrophic gastritis and GORD in the aetiology of adenocarcinoma of the cardia remains unclear. We have investigated the association between adenocarcinoma of the different regions of the upper gastrointestinal tract and atrophic gastritis and GORD symptoms. <b>METHODS</b> 138 patients with upper GI adenocarcinoma and age and sex matched controls were studied. Serum pepsinogen I/II was used as a marker of atrophic gastritis and categorised to five quintiles. History of GORD symptoms, smoking and H.pylori infection was incorporated in logistic regression analysis. Lauren classification of gastric cancer was used to subtype gastric and oesophageal adenocarcinoma. <b>RESULTS</b> Non-cardia cancer was associated with atrophic gastritis but not with GORD symptoms; 55% of these cancers were intestinal subtype. Oesophageal adenocarcinoma was associated with GORD symptoms, but not with atrophic gastritis; 84% were intestinal subtype. Cardia cancer was positively associated with both severe gastric atrophy [OR, 95% CI: 3.92 (1.77 – 8.67)] and with frequent GORD symptoms [OR, 95% CI: 10.08 (2.29 – 44.36)] though the latter was only apparent in the nonatrophic subgroup and in the intestinal subtype. The association of cardia cancer with atrophy was stronger for the diffuse versus intestinal subtype and this was the converse of the association observed with non-cardia cancer. <b>CONCLUSION</b> These findings indicate two distinct aetiologies of cardia cancer, one arising from severe atrophic gastritis and being of intestinal or diffuse subtype similar to non-cardia cancer, and one related to GORD and intestinal in subtype, similar to oesophageal adenocarcinoma. Gastric atrophy, GORD symptoms and histological subtype may distinguish between gastric versus oesophageal origin of cardia cancer

CXCL-10: a new candidate for melanoma therapy?

Background: Melanoma is a malignancy that stems from melanocytes and is defined as the most dangerous skin malignancy in terms of metastasis and mortality rates. CXC motif chemokine 10 (CXCL10), also known as interferon gamma-induced protein-10 (IP-10), is a small cytokine-like protein secreted by a wide variety of cell types. CXCL10 is a ligand of the CXC chemokine receptor-3 (CXCR3) and is predominantly expressed by T helper cells (Th cells), cytotoxic T lymphocytes (CTLs), dendritic cells, macrophages, natural killer cells (NKs), as well as some epithelial and cancer cells. Similar to other chemokines, CXCL10 plays a role in immunomodulation, inflammation, hematopoiesis, chemotaxis and leukocyte trafficking. Conclusions: Recent studies indicate that the CXCL10/CXCR3 axis may act as a double-edged sword in terms of pro- and anti-cancer activities in a variety of tissues and cells, especially in melanoma cells and their microenvironments. Most of these activities arise from the CXCR3 splice variants CXCR3-A, CXCR3-B and CXCR3-Alt. In this review, we discuss the pro- and anti-cancer properties of CXCL10 in various types of tissues and cells, particularly melanoma cells, including its potential as a therapeutic target. © 2020, International Society for Cellular Oncology

Fungal peritonitis in Iranian children on continuous ambulatory peritoneal dialysis: a national experience.

INTRODUCTION. Fungal peritonitis (FP), causing catheter obstruction, dialysis failure, and peritoneal dysfunction, is a rare but serious complication of peritoneal dialysis. In this study, the frequency and risk factors of FP are evaluated in children who underwent peritoneal dialysis. MATERIALS AND METHODS. A retrospective multicenter study was performed at the 5 pediatric peritoneal dialysis centers in Iran from 1971 to 2006, and FP episodes among 93 children were reviewed. Risk ratios were calculated for the clinical and demographic variables to determine the risk factors of FP. RESULTS. Ninety-three children aged 39 months on average were included in study. Sixteen out of 155 episodes of peritonitis were fungi infections, all by Candida albicans. The risk of FP was higher in those with relapsing bacterial peritonitis (P = .009). Also, all of the patients had received antibiotics within the 1 month prior to the development of FP. Catheters were removed in all patients after 1 to 7 days of developing FP. Six out of 12 patients had catheter obstruction and peritoneal loss after the treatment and 5 died due to infection. CONCLUSIONS. Fungal peritonitis, accompanied by high morbidity and mortality in children should be reduced by prevention of bacterial peritonitis. Early removal of catheter after recognition of FP should be considered

Fungal peritonitis in Iranian children on continuous ambulatory peritoneal dialysis: a national experience.

INTRODUCTION. Fungal peritonitis (FP), causing catheter obstruction, dialysis failure, and peritoneal dysfunction, is a rare but serious complication of peritoneal dialysis. In this study, the frequency and risk factors of FP are evaluated in children who underwent peritoneal dialysis. MATERIALS AND METHODS. A retrospective multicenter study was performed at the 5 pediatric peritoneal dialysis centers in Iran from 1971 to 2006, and FP episodes among 93 children were reviewed. Risk ratios were calculated for the clinical and demographic variables to determine the risk factors of FP. RESULTS. Ninety-three children aged 39 months on average were included in study. Sixteen out of 155 episodes of peritonitis were fungi infections, all by Candida albicans. The risk of FP was higher in those with relapsing bacterial peritonitis (P = .009). Also, all of the patients had received antibiotics within the 1 month prior to the development of FP. Catheters were removed in all patients after 1 to 7 days of developing FP. Six out of 12 patients had catheter obstruction and peritoneal loss after the treatment and 5 died due to infection. CONCLUSIONS. Fungal peritonitis, accompanied by high morbidity and mortality in children should be reduced by prevention of bacterial peritonitis. Early removal of catheter after recognition of FP should be considered

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts

Objective We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients. Design The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD. Results Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively. Conclusion Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD

Environmental and lifestyle risk factors of gastric cancer

Effective prevention and early diagnostic strategies are the most important public health interventions in gastric cancer, which remains a common malignancy worldwide. Preventive strategies require identification and understanding of environmental risk factors that lead to carcinogenesis. Helicobacter pylori (H. pylori) is the primary carcinogen as this ancient bacterium has a complex ability to interact with its human host. Smoking and salt are strong independent risk factors for gastric cancer whereas alcohol is only a risk when it is heavily consumed. Red meat and high fat increase the risk of gastric cancer however fresh fruits, vegetables (allium family) and certain micronutrients (selenium, vitamin C) reduce the risk, with evidence lacking for fish, coffee and tea. Foods that inhibit H. pylori viability, colonization and infection may reduce cancer risk. Obesity is increasingly recognized as a contributory factor in gastric cardia carcinogenesis. Therefore, modest daily physical activities can be protective against cancer. Foundry workers are at risk for developing gastric cancer with dust iron being an important cause. Other risk factors include Epstein-Barr virus (EBV), possibly JC virus and radiation but the effects of these are likely to remain small