Confusion and prospects for carcinogenesis of gastric adenoma and dysplasia: What is the correct answer currently?

There are differences in the diagnoses of superficial gastric lesions between Japan and other countries. In Japan, superficial gastric lesions are classified as adenoma or cancer. Conversely, outside Japan, the same lesion is classified as low-grade dysplasia (LGD), high-grade dysplasia, or invasive neoplasia. Gastric carcinogenesis occurs mostly de novo, and the adenoma-carcinoma sequence does not appear to be the main pathway of carcinogenesis. Superficial gastric tumors can be roughly divided into the APC mutation type and the TP53 mutation type, which are mutually exclusive. APC-type tumors have low malignancy and develop into LGD, whereas TP53-type tumors have high malignancy and are considered cancerous even if small. For lesions diagnosed as category 3 or 4 in the Vienna classification, it is desirable to perform complete en bloc resection by endoscopic submucosal dissection followed by staging. If there is lymphovascular or submucosal invasion after mucosal resection, additional surgical treatment of gastrectomy with lymph node dissection is required. In such cases, function-preserving curative gastrectomy guided by sentinel lymph node biopsy may be a good alternative.     

Primary Pulmonary Low-Grade Angiosarcoma Characterized by Mismatch between 18F-FDG PET and Dynamic Contrast-Enhanced CT

We report a rare case of primary pulmonary low-grade angiosarcoma on dynamic contrast-enhanced CT and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging. A 38-year-old, asymptomatic woman was hospitalized because of an abnormality on chest radiography. A dynamic contrast-enhanced chest CT showed a 1.2 cm-sized irregular-margined nodule with strong and persistent enhancement in the right lower lobe. The lesion had low metabolic activity on an ¹⁸F-FDG PET/CT scan. The patient underwent a wedge resection for the lesion, and pathology revealed a primary pulmonary low-grade angiosarcoma.     

Early cognitive impairment in a subset of patients with presumed low-grade glioma

We investigated the presence of cognitive impairment, in adults with presumed low-grade glioma at early stage of disease prior to major treatments, in relation to neurological symptoms and radiological characteristics of the tumour. Sixteen patients were evaluated. A subset of patients was identified with clearly impaired cognition. Patients with cognitive impairment often had large tumours in the left frontal lobe, were relatively young, and most of them were males. We conclude that cognitive dysfunction may be present already at early stage of disease, and that early identification of patients at risk is warranted.     

Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats

AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS: Rats with CCl₄-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy.     

Deep sequencing detects very-low-grade somatic mosaicism in the unaffected mother of siblings with nemaline myopathy

When an expected mutation in a particular disease-causing gene is not identified in a suspected carrier, it is usually assumed to be due to germline mosaicism. We report here very-low-grade somatic mosaicism in ACTA1 in an unaffected mother of two siblings affected with a neonatal form of nemaline myopathy. The mosaicism was detected by deep resequencing using a next-generation sequencer. We identified a novel heterozygous mutation in ACTA1, c.448A>G (p.Thr150Ala), in the affected siblings. Three-dimensional structural modeling suggested that this mutation may affect polymerization and/or actin’s interactions with other proteins. In this family, we expected autosomal dominant inheritance with either parent demonstrating germline or somatic mosaicism. Sanger sequencing identified no mutation. However, further deep resequencing of this mutation on a next-generation sequencer identified very-low-grade somatic mosaicism in the mother: 0.4%, 1.1%, and 8.3% in the saliva, blood leukocytes, and nails, respectively. Our study demonstrates the possibility of very-low-grade somatic mosaicism in suspected carriers, rather than germline mosaicism.     

Links between ectopic and abdominal fat and systemic inflammation: New insights from the SHIP-Trend study

BackgroundExcessive fat accumulation in adipose tissue depots and organs such as the pancreas and the liver is associated with systemic low-grade chronic inflammation.AimsTo investigate the association between abdominal, hepatic, and pancreatic fat and the circulating level of inflammatory biomarkers.MethodsWe used data from a subsample of the Study of Health in Pomerania (SHIP-Trend, n = 469). The plasma concentration of 37 inflammatory biomarkers was measured using the Bio-Plex-Pro?-Human-Inflammation-Panel-1. Subcutaneous and visceral adipose tissue (SAT and VAT), as well as hepatic and pancreatic fat, were determined by magnetic resonance imaging. We assessed the associations between fat content and inflammatory biomarkers using multiple linear regression.ResultsHepatic fat was associated with MMP-2 (β -0.11), PTX3 (β -0.14), and TNFSF12 (β -0.06). Pancreatic fat was associated with sTNFR1 (β 0.15), sTNFR2 (β 0.11), and sCD163 (β 0.13). VAT and SAT were associated with sCD163 (β^VAT 0.20, β^SAT 0.16), MMP-2 (β^VAT -0.12, β^SAT -0.10), OSTCN (β^VAT -0.16, β^SAT -0.10), sTNFR1 (β^VAT 0.13, β^SAT 0.13), sTNFR2 (β^VAT 0.13, β^SA 0.12), TNFSF12 (β^VAT -0.11, β^SAT -0.08), and TNFSF14 (β^VAT 0.21, β^SAT 0.20). VAT was additionally associated with TNFSF13B (β 0.08) and CHI3L1 (β 0.07).ConclusionsOur findings provide new insights into the involvement of hepatic and pancreatic fat on systemic inflammation.     

Clinical Outcomes of Endoscopic Resection for Low-Grade Dysplasia and High-Grade Dysplasia on Gastric Pretreatment Biopsy: Korea ESD Study Group

Background/AimsSome cases of gastric low-grade dysplasia (LGD) and high-grade dysplasia (HGD) on forceps biopsy (FB) are diagnosed as gastric cancer (GC) after endoscopic resection (ER). This study aims to evaluate the clinical outcomes of ER for gastric LGD and HGD on pretreatment FB and to identify the factors that predict pathologic upstaging to GC.MethodsPatients who underwent ER for LGD and HGD on pretreatment FB from March 2005 to February 2018 in 14 hospitals in South Korea were enrolled, and the patients’ medical records were reviewed retrospectively.ResultsThis study included 2,150 cases of LGD and 1,534 cases of HGD diagnosed by pretreatment FB. In total, 589 of 2,150 LGDs (27.4%) were diagnosed as GC after ER. Helicobacter pylori infection, smoking history, tumor location in the lower third of the stomach, tumor size >10 mm, depressed lesion, and ulceration significantly predicted GC. A total of 1,115 out of 1,534 HGDs (72.7%) were diagnosed with GC after ER. Previous history of GC, H. pylori infection, smoking history, tumor location in the lower third of the stomach, tumor size >10 mm, depressed lesion, and ulceration were significantly associated with GC. As the number of risk factors predicting GC increased in both LGD and HGD on pretreatment FB, the rate of upstaging to GC after ER increased.ConclusionsA substantial proportion of LGDs and HGDs on pretreatment FB were diagnosed as GC after ER. Accurate ER procedures such as endoscopic submucosal dissection should be recommended in cases of LGD and HGD with factors predicting pathologic upstaging to GC.     

Microbiota,infecciones gastrointestinales,inflamación de bajo grado y antibioticoterapia en el síndrome de intestino irritable. Una revisión basada en evidencias

BackgroundPost-infectious irritable bowel syndrome (PI-IBS) prevalence, small intestinal bacterial overgrowth (SIBO), altered microbiota, low-grade inflammation, and antibiotic therapy in IBS are all controversial issues.AimsTo conduct an evidence-based review of these factors.MethodsA review of the literature was carried out up to July 2012, with the inclusion of additional articles as far as August 2013, all of which were analyzed through the Oxford Centre for Evidence-Based Medicine (OCEBM) system.Results1. There is greater SIBO probability in IBS when breath tests are performed, but prevalence varies widely (2-84%). 2. The gut microbiota in individuals with IBS is different from that in healthy subjects, but a common characteristic present in all the patients has not been established. 3. The incidence and prevalence of PI-IBS varies from 9-10% and 3-17%, respectively, and the latter decreases over time. Bacterial etiology is the most frequent but post-viral and parasitic cases have been reported. 4. A sub-group of patients has increased enterochromaffin cells, intraepithelial lymphocytes, and mast cells in the intestinal mucosa, but no differences between PI-IBS and non-PI-IBS have been determined. 5. Methanogenic microbiota has been associated with IBS with constipation. 6. Rifaximin at doses of 400 mg TID/10 days or 550 mg TID/14 days is effective treatment for the majority of overall symptoms and abdominal bloating in IBS. Retreatment effectiveness appears to be similar to that of the first cycle.ConclusionsFurther studies are required to determine the nature of the gut microbiota in IBS and the differences in low-grade inflammation between PI-IBS and non-PI-IBS. Rifaximin has shown itself to be effective treatment for IBS, regardless of prior factors.     

Low-grade albuminuria is associated with peripheral artery disease in Chinese diabetic patients

Background

Increasing studies have suggested that albuminuria might be an important risk factor for peripheral artery disease (PAD). However, studies focusing on the association between low-grade albuminuria and PAD are limited. It would be of great interest to elucidate the association between low-grade albuminuria and PAD in diabetic subjects.

Methods

A cross-sectional study was conducted in 1386 diabetic subjects (age ≥ 40 years) with normal urinary albumin levels from Shanghai, China. A first voided early morning spot urine sample was obtained for urinary albumin and creatinine measurements. Subjects were divided into three groups according to sex-specific cutoff points of urinary albumin–creatinine ratio (UACR) tertiles. Subjects in the upper tertile of UACR were classified as having low-grade albuminuria. PAD was defined by ankle–brachial index (ABI) <0.9 or >1.4.

Results

Overall, 106 (7.7%) of the study population had PAD. The prevalence of PAD in tertile 3 of UACR was higher than the prevalence in tertile 2 and tertile 1 (10.2%, 6.4% and 6.4%, respectively; P < 0.05). A fully adjusted logistic regression analysis revealed that compared with subjects in tertile 1 of normal UACR, those in tertile 3 had 1.7-fold increased risk for the presence of PAD.

Conclusions

In diabetic patients, high normal UACR level, which is below the current cutoff point of microalbuminuria, was associated with the increased prevalence of PAD. It suggested that low-grade albuminuria might be an early marker for the detection of PAD in diabetic patients.