Pre-endoscopic intravenous proton pump inhibitors therapy for upper gastrointestinal bleeding: A prospective,multicentre study

Background/AimThe indiscriminate use of high-dose, proton pump inhibitor (PPI) infusion in non-variceal upper gastrointestinal bleeding (UGIB) patients to reduce the rate of peptic ulcers with high-risk stigmata (HRS) has been questioned. We evaluated the prevalence of HRS on peptic ulcer and non-ulcer lesions in patients receiving or not receiving pre-endoscopic PPI therapy.MethodsData of consecutive UGIB patients observed in 50 Italian centres were analysed. The prevalence of both HRS on peptic ulcers and active bleeding on non-ulcer lesions between patients treated or not treated with PPI were compared. Multivariate analysis was performed.ResultsA total of 1,792 (69.8%) out of 2,566 patients received PPI therapy. Prevalence of HRS on ulcers was 51.8% and 53.4% (P = 0.58) in treated and not treated patients, respectively, and the rate of endoscopic therapy did not differ between groups. Prevalence of non-ulcer bleeding lesions was higher in patients treated than in those not treated with PPI (18.7% vs 10.6%; P = 0.023). At multivariate analysis, PPI therapy (OR: 1.16, 95% CI = 0.82–1.64; P = 0.4) was not an independent factor affecting HRS prevalence, which was inversely correlated with timing to endoscopy (OR: 0.85, 95% CI = 0.76–0.95; P = 0.005).ConclusionsOur data failed to detect a significant role of pre-endoscopic PPI therapy in decreasing prevalence of HRS and need for endoscopic treatment in bleeding patients with either peptic ulcer or non-ulcer lesions.     

Combined effects of major depression, pain and somatic disorders on general functioning in the general adult population

This study was carried out to assess the prevalence of major depressive disorder (MDD) in persons suffering from pain symptoms in various locations, both with and without comorbid somatic disorders and to analyze the single and combined effects of MDD, pain symptoms and somatic disorders on general functioning in the community. The 12-month prevalence of MDD, somatic disorders and pain symptoms, grouped according to location, were determined among 4181 participants from a community sample. Depression was assessed utilising the Composite International Diagnostic Interview. Pain symptoms were self-reported by participants whereas medical diagnoses were validated by medical examinations. General functioning was evaluated utilising the established MOS-SF-36 scale. The prevalence of MDD was significantly increased for persons with pain in any location. In the absence of a somatic disorder, MDD prevalence was highest in persons with abdominal/chest pain (9.3%) and arm or leg pain (7.9%) and lowest in persons with back pain (6.2%). Mental and physical well-being were lowest for persons with both MDD and a somatic disorder, irrespective of pain locations. Increasing numbers of pain locations impaired mental and physical well-being across all groups, but the effect on mental well-being was most marked in participants with MDD and comorbid somatic disorders. The presence of pain increases risk of associated MDD. The number of pain locations experienced, rather than the specific location of pain, has the greatest impact on general functioning. Not only chronic pain, but pain of any type may be an indicator of MDD and decreased general functioning.     

Carbohydrate-antigen-125 levels predict hospital stay duration and adverse events at long-term follow-up in Takotsubo cardiomyopathy

The aim of this study is to evaluate the possible role of carbohydrate-antigen(CA)-125 as prognostic marker at short- and long-term follow-up, in subjects with Takotsubo cardiomyopathy (TTC). Sixty-three consecutive subjects with TTC were enrolled in the study and followed for a median 139 days. Circulating levels of CA-125, NT-proBNP, and left ventricular ejection fraction (LVEF) were evaluated at admission. Duration of hospital stay, incidence of death, re-hospitalization and recurrence of TTC during follow-up were recorded. The mean hospital stay was 8.3 days, adverse events occurred during follow up in 17 % of cases. CA-125 levels at admission are inversely related to LVEF (r ?0.30, p < 0.05) and directly related to hospital stay (r 0.29, p < 0.05). CA-125 levels at admission are higher in subjects with adverse events at follow-up (88.9 ± 200.0 vs 20.9 ± 30.0 U/mL, p < 0.05). Rates of incidence of adverse events are proportionally increased with CA-125 tertiles (0, 6, 11 % respectively, p for trend <0.01), at survival analysis (Log Rank p < 0.05) and after correction for age, gender, LVEF and NT-proBNP levels in multivariable Cox analysis (p < 0.05). CA-125 levels <10 U/ml are predictors of adverse events at follow up with 91 % sensitivity, 52 % specificity, 29 % positive predictive power, and 96 % negative predictive power. Increased CA-125 admission levels are associated with a longer hospital stay, a lower LVEF, and a higher risk of adverse events during follow up. CA-125 might be useful for early risk stratification of subjects with TTC.     

Primary lymphoma of the liver showing immunohistochemical evidence of T-cell origin

Summary Primary malignant lymphomas of the liver are extremely rare. Thus far, 28 cases (1–13) of this entity have been described, but after careful clinical and histological staging, no other sites of extrahepatic involvement were demonstrated in 17 of these cases (2, 3, 5–13). We recently had the opportunity to investigate and manage a case of true primary malignant peripheral T-cell lymphoma of the liver in a 22-year-old man. To our knowledge this is the first reported case of a primary T-cell lymphoma of the liver. The patient was successfully treated with a right trisegmentectomy and no tumor recurrence has appeared after five years.     

Telomerase activity,telomere length and hTERT DNA methylation in peripheral blood mononuclear cells from monozygotic twins with discordant smoking habits

Increased telomerase expression has been implicated in the pathogenesis of lung cancer and, since the primary cause of lung cancer is smoking, an association between telomerase reactivation and tobacco smoke has been proposed. In this work an investigation has been performed to assess the relationship between tobacco smoke exposure and telomerase activity (TA) in peripheral blood mononuclear cells of healthy smokers. The methylation status of the catalytic subunit of telomerase hTERT was concurrently investigated to assess the possible association between epigenetic modifications of hTERT and TA. Besides, the association between smoke and telomere length (TL) has been evaluated. Healthy monozygotic twins with discordant smoking habits were selected as study population to minimize inter‐individual differences because of demographic characteristics and genetic heterogeneity. Statistically significant higher values of TA and TL were observed in smokers compared to nonsmoker co‐twins. The multivariate analysis of data showed, besides smoking habits (P = 0.02), an influence of gender (P = 0.006) and BMI (P = 0.001) on TA and a borderline effect of gender (P = 0.05) on TL. DNA methylation analysis, focused on 100 CpG sites mapping in hTERT, highlighted nine CpG sites differentially methylated in smokers. When co‐twins were contrasted, selecting as variables the intra‐twin difference in TA and hTERT DNA methylation, a statistically significant inverse correlation (P = 0.003) was observed between TA and DNA methylation at the cg05521538 site. In conclusion, these results indicate an association of tobacco smoke with TA and TL and suggest a possible association between smoke‐induced epigenetic effects and TA in healthy smokers. Environ. Mol. Mutagen. 58:551–559, 2017. © 2017 Wiley Periodicals, Inc.     

Enzyme- and immunohistochemical study of a case of histiocytic necrotizing lymphadenitis

Summary A combined morphological, immunohistological, and enzyme histochemical analysis was performed on frozen and fixed lymph node tissue in a case of histiocytic necrotizing lymphadenitis (HNL) using conventional histology, a panel of monoclonal and polyclonal antibodies, and a series of common haematological enzyme reactions. Histology showed multiple paracortical necrotizing foci which, in a prominently necrobiotic background devoid of granulocytes, contained large numbers of foamy histiocytes and macrophages intermingled with cells resembling degenerating plasmacytoid T-cells. Most of the histiocytes were alpha₁-antichymotrypsin positive and foamy cells were also distinctly Leu-M1 positive. Strong granular acid phosphatase (AP) positivity was present in the cytoplasm of the macrophages and histiocytes. The cells with plasmacytoid features showed weaker and homogeneously diffuse AP staining. Alpha-naphthyl acetate esterase (ANAE) activity was much less striking than AP in the necrotizing foci and most of the ANAE negative cells corresponded to those with plasmacytoid features. No cells with B-cell lineage markers were present within the necrotizing foci; most of the occasional T-cells (Leu-1⁺, Leu-4⁺) present in the foci were Leu-2a⁺ (OKT8⁺) whereas OKT10⁺ lymphoid cells were abundant and appeared to correspond with the cells with plasmacytoid features. Our combined data confirm that the special type of necrosis found in HNL develops within foci of plasmacytoid T-cells undergoing regressive changes and apparently exhibiting distinct immunohistological and enzyme histochemical features.This study was supported in part by Grant n. 84.00525.44 from Consiglio Nazionale delle Ricerche Progetto Finalizzato Oncologia, Roma and by the Associazione Italiana per la Ricerca sul Cancro, Milano     

A pilot study of capsule endoscopy after a standard meal for the detection and grading of oesophageal varices in cirrhotic patients

Background

Capsule endoscopy has been proposed as an alternative to fibreoptic endoscopy for oesophageal varices evaluation in cirrhotics. However, it shows only moderate sensitivity compared to fibreoptic endoscopy.

Aim

To compare post-meal capsule endoscopy to fibreoptic endoscopy, based on the hypothesis that meal-induced increase of portal pressure can enhance its sensitivity.

Methods

Twenty-five patients were submitted to fibreoptic endoscopy and, after a standard meal, capsule endoscopy.

Results

Post-meal capsule endoscopy detected varices in the 18 patients in whom fibreoptic endoscopy detected varices plus 3 more subjects (sensitivity 100%, specificity 70%); large varices in the 4 patients in whom fibreoptic endoscopy graded varices as large, plus 5 more subjects; red markers in the 5 patients in whom fibreoptic endoscopy detected red markers, plus 3 more subjects. High-risk varices were identified in 11 patients by post-meal capsule endoscopy and in 10 by fibreoptic endoscopy (sensitivity 100%, specificity 93.8%).

Conclusions

Post-meal capsule endoscopy identified more varices, large varices and red markers than fibreoptic endoscopy. The two methods detected similar proportions of high-risk varices. These data suggest that a standard meal can enhance the sensitivity of capsule endoscopy in the detection and grading of oesophageal varices in cirrhotics.     

Behavior of Circulating CD4+CD25+Foxp3+ Regulatory T Cells in Colon Cancer Patients Undergoing Surgery

CD4+CD25+Foxp3+ regulatory T cells (Treg) specialize in suppressing immune responses. In this study, 47 consecutive colon cancer patients were subjected to circulating Treg frequency assessment by flow cytometry before and after cancer resection. Thirty-two healthy subjects served as controls. Circulating Treg frequencies were significantly higher in colon cancer patients with respect to healthy controls. When patients were subgrouped according to Dukes stages, a linear relationship was observed between Dukes stages and Treg frequencies. In radically resected patients, Treg frequencies were shown to have significantly dropped down. Patients with advanced colon cancer were more likely to have significantly higher proportions of circulating Treg frequencies than Dukes A and B patients when compared to healthy subjects. Of note, nonradically resected patients were found to display reductions in—but not normalization of—Treg frequencies. These results suggest that cancer itself may be able to drive Treg recruitment as a strategy of immunoevasion.