Search

Background: Recent data suggest that in children, the proportion of gastroduodenal ulcers/erosions associated with Helicobacter pylori infection is currently lower than expected. In this study, we trace this proportion over two decades., Methods: We reviewed the reports of all upper gastrointestinal endoscopies with biopsies for histology and culture over the past 23 years. H pylori status was assessed using several invasive methods. The infection rate during different time periods was compared between children with lesions and controls., Results: A total of 7849 endoscopies were performed in 5983 children (2874 F/3109 M, median age 7.6 years, range 0.1-17.9 years). The endoscopy report was missing in 316 patients. At the first upper gastrointestinal endoscopy, 12.1% of the children presented with gastric and/or duodenal ulcers or erosions with an H pylori infection rate of 35.4%, whereas no such lesions were observed in 87.9% of children in whom the H pylori infection rate was 21.3%. The risk factors associated with such lesions were older age (P < 0.001), male sex (P = 0.002), and H pylori infection (P < 0.0001). Gastric ulcers were not significantly associated with H pylori (24% infected), whereas 52% of duodenal ulcers, 33% of gastric erosions, and 38% of duodenal erosions were associated with H pylori. The proportion of gastroduodenal lesions associated with H pylori remained stable over time. Children with H pylori infection and ulcers were older than those with H pylori infection without ulcers (P < 0.001)., Conclusions: Our study indicates that in our pediatric population, the proportion of ulcers without H pylori infection is higher than previously suggested, and this prevalence has not changed over the past two decades., (© 2019 John Wiley & Sons Ltd.)

International guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-EGFR agents for metastatic colorectal cancer (CRC) patients. Daily, new data emerges on the theranostic and prognostic role of molecular biomarkers; this is a strong incentive for a validated, sensitive, and broadly available molecular screening test. Next-generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. We report here our 2 years of clinical practice using NGS results to guide therapeutic decisions. The Ion Torrent AmpliSeq colon/lung cancer panel, which allows mutation detection in 22 cancer-related genes, was prospectively used in clinical practice (BELAC ISO 15189 accredited method). The DNA of 741 formalin-fixed paraffin-embedded CRC tissues, including primary tumors and metastasis, was obtained from 14 different Belgian institutions and subjected to targeted NGS. Of the tumors tested, 98% (727) were successfully sequenced and 89% (650) harbored at least one mutation. KRAS, BRAF and NRAS mutations were found in 335 (46%), 78 (11%) and 32 (4%) samples, respectively. These mutation frequencies were consistent with those reported in public databases. Moreover, mutations and amplifications in potentially actionable genes were identified in 464 samples (64%), including mutations in PIK3CA (14%), ERBB2 (0.4%), AKT1 (0.6%), and MAP2K1 (0.1%), as well as amplifications of ERBB2 (0.3%) and EGFR (0.3%). The median turnaround time between reception of the sample in the laboratory and report release was 8 calendar days. Overall, the AmpliSeq colon/lung cancer panel was successfully applied in daily practice and provided reliable clinically relevant information for CRC patients., Competing Interests: CONFLICTS OF INTEREST The authors have declared no conflicts of interest.

Dysfunction in vital brainstem centers, including those controlling cardiorespiratory- and sleep/arousal pathophysiology, is reported in sudden infant death syndrome (SIDS). Biological mechanisms underlying SIDS, however, remain unclear. Cytokines are inter-cellular signaling chemicals. They can interact with neurotransmitters and might thus modify neural and neuroimmune functions. Cytokines could therefore act as neuromodulators. Interleukin (IL)-2 is a major immune-related cytokine. It has not been previously depicted in vital brainstem centers. We detected intense neuronal IL-2 immune-reactivity in the SIDS brainstem, namely in vital neural centers. This IL-2 overexpression might interfere with neurotransmitters in those critical brainstem centers, causing disturbed homeostatic control of cardiorespiratory and arousal responses, possibly leading to SIDS., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

The major neuropathological substrate associated with cerebral palsy (CP) is a form of white matter (WM) injury known as periventricular leukomalacia (PVL). Proinflammatory cytokines were recently shown to be implicated in PVL pathogenesis. Many PVL patients develop cortical and deep gray neuronal dysfunctions such as epilepsy, cognitive deficits and extrapyramidal disorders. The precise nature of the relationship between the WM lesion and the subsequent neuronal disorders is unclear. Cytokines were shown to exert neurotoxicity in experimental models. This raises the need to investigate a possible noxious effect by cytokines on neuronal cortical development. In situ immunohistochemical methods were applied on 22 brains from infants both with PVL (study group) and without PVL (control group) to detect any immunoreactivity for cytokines (TNF-alpha, IL-1beta, IL-6) in cortical and gray matter neurons. While cortical and other neuronal structures in PVL brains did not display noticeable pathological anomalies, strong cytokine immunoreactivity was detected in many neurons in the neocortex, hippocampus, basal ganglia and thalamus. There were, however, regional differences in cytokine labeling. In addition, there was more TNF-alpha staining than IL-1beta; IL-6 was negative. In contrast, neuronal cytokine labeling in the "control" brains was negligible. In conclusion, we report and characterize, for the first time, the in situ immunoreactivity for proinflammatory cytokines in cortical and deep gray neurons in PVL. These findings might provide insights into the neuro-anatomical correlate for the intellectual deficits and the other cortical and deep gray neuronal dysfunctions associated with PVL.

Acute disseminated encephalomyelitis (ADEM) is thought to be an autoimmune disorder of the central nervous system in which myelin is targeted. Pathological studies on closely related human diseases (eg, multiple sclerosis) and on animal models for these demyelinating disorders have suggested the involvement of cytokines. Studies on peripheral immunocytes and on cerebrospinal fluid revealed the presence of cytokine-mediated responses in ADEM. We carried out this neuroimmunopathologic exploration and report for the first time the in situ expression of "inflammatory" cytokines in ADEM. Moreover, we note a particular spatial and molecular pattern whereby tumor necrosis factor-alpha and interleukin (IL)-1beta are intensely expressed, whereas IL-6 is absent. Differential expression at different levels of the neuraxis was also noticed. Our findings suggest that these cytokines, reported to be toxic to myelin, are implicated in the molecular cascade, resulting in the neural damage. These observations might provide insights into molecular pathways involved in the immunopathogenesis of ADEM and might open new horizons in neuroimmunomodulation and anticytokine treatment., (Copyright 2003, Elsevier Inc.)

"HP testing must be regarded as ONE of the important elements of the proper diagnostic work-up of a DISEASE, managed in close cooperation between GP's and specialists": that's the key message of the national consensus meeting held in CHU Brugmann on February 6th and 7th 1998. HP testing (usually by 2 direct methods: RUT-histology) and eradication treatment (ER), in infected patients, are strongly recommended in: 1. Past or current GDU (absolute indication), regardless of activity, complication(s), NSAID intake; 2. Low-grade MALT Lymphomas (Stage IE1) unequivocally diagnosed, managed and followed-up in specialised centers; 3. Post endoscopic resection of EGC. ER is advisable in HP carriers with a family history of gastric cancer. Chronic atrophic-, lymphocytic-, giant folds gastritis and hyperplastic polyps are acceptable indications for ER as well as scheduled long-term NSAID treatment in individuals with known HP status. Systematic ER in HP+ patients with fully investigated NUD is not indicated but could be considered in individual patients. Extra alimentary disorders and auto immune gastritis are no indication and there was no consensus for a "test and treat" policy in patients under 45 yrs old without alarm symptoms. Systematic screening of asymptomatic individuals is not recommended. A correct monitoring of eradication after treatment is recommended, mainly by UBT. In severe or refractory PUD, symptom recurrence and follow-up of EGC and Maltomas, endoscopic follow-up with HP testing is mandatory. The recommended first line treatment course (except known allergy or intolerance) is PPI full dose bid, Clarithromycin 500 mg bid Amoxycillin 1000 mg bid (7 days minimal 10 days maximal). RBC-based schemes must be locally validated and quadruple therapy is proposed when retreatment is needed. Culture, optional after the first treatment failure, is strongly recommended after a second failure. Overall, ER therapies are safe and neither the decreased efficacy of acid-lowering drugs, nor the possible increased risk of peptic oesophagitis are considered as contra-indications to eradicate. ER is cost-effective and cost-beneficial in PUD and adjusted number of pills delivered would cut costs. No clear economic data are currently available for a potential benefit of ER in GC prevention or NUD management. A national monitoring of HP resistance (Macrolides and Imidazoles) must be organized by specialised centers.

In a series of 92 patients with gastric cancer who had biopsies of the antrum and fundus, we compared the 65 patients with Helicobacter pylori (71%) with the 27 negative patients. No difference was observed for age, gender or histology (intestinal or diffuse). Significant differences concerned location (11% of H. pylori positive patients had a cancer at the cardia or fundus vs 44%), the presence of a normal mucosa (3% vs 30%) and atrophy in the antrum (53% vs 17%). Seven of the ten patients with a normal mucosa had a cancer located at the cardia (p < 0.05) and in nine of the eleven patients younger than fifty, the cancer was of the diffuse type (p < 0.005). Thus, patients with H. pylori and gastric cancer differ from those uninfected. Of future concern is the large increase in cancers of the cardia, a cancer unassociated with H. pylori.

Objectives: The aim of the study was to determine in a large group of patients with a gastric ulcer the differences between patients, ulcers and gastric mucosa as related to the presence or absence of Helicobacter pylori (H. pylori)., Methods: This prospective study evaluated 150 patients with a benign gastric ulcer. A patient was considered as H. pylori positive on the basis of a positive culture or the presence of gastritis and another positive diagnostic test for H. pylori (urease test, cytology, histology, serology)., Results: One hundred and five patients were positive for H. pylori (70%) whereas 45 patients were not infected (30%). There were significant differences regarding the clinical characteristics of patients, the ulcer and the mucosa. H. pylori positive patients differed in terms of past history of ulcer (63 vs 12%), age (57 vs 50 years), sex (48% males vs 24%) and consumption of non steroidal antiinflammatory drugs (39 vs 75%). H. pylori positive ulcers were more often single (79 vs 53%) and located on the small curvature (76 vs 33%). Chronic gastritis was always present in positive patients, with associated intestinal metaplasia (35 vs 2%) and atrophy (45 vs 9%). Negative patients often had a normal gastric mucosa (53%) or reactive gastritis (27%)., Conclusion: Seventy percent of gastric ulcer are associated with H. pylori infection, corresponding to the classical ulcer. The majority of H. pylori negative ulcers appears to be associated to non steroidal antiinflammatory drugs.

Azole-derived antifungal medications are particularly involved in drug-induced hepatic injury encountered in patients with AIDS. Fluconazole may induce multiple hepatic abnormalities usually characterized by asymptomatic and reversible mild hepatic necrosis. We here describe severe subacute liver damage occurring in a patient with AIDS who was receiving fluconazole maintenance therapy for a cryptococcosis. Hepatotoxicity was essentially characterized by mixed cytolytic and cholestatic liver tests abnormalities which improved after fluconazole discontinuation and worsened on fluconazole rechallenge. Optical microscopy demonstrated nonspecific abnormalities including granular aspect of the cytoplasm of the hepatocytes. In contrast, analysis of electron microscopy revealed unusual unreported features characterized by giant mitochondria with paracrystalline inclusions and enlarged smooth endoplasmic reticulum. All microscopic abnormalities were reversed after discontinuation of fluconazole. We suggest that persistent increased hepatic enzymes in HIV-infected patient taking fluconazole should prompt suspension of the treatment. Prospective studies are needed to determine whether careful monitoring of hepatic tests should be recommended in AIDS patients on prolonged fluconazole maintenance therapy.

This study characterises morphonuclear parameters from normal, cirrhotic, tumoral benign and malignant liver specimens obtained by computerized morphonuclear images analyses. The material is obtained by cytological aspirations or by imprint smears from liver biopsy. The monoparametric analysis differentiates a benign and a malignant cellular populations. In the malignant populations, two types are individualised: the well differentiated and the pleiomorphic hepatocarcinoma. The treatment of the data by canonical projections onto the factorial plan and by discriminant analysis allowed the selection of homogeneous cell populations belonging to each of the pathological groups described above.

We studied 55 renal tissue samples from 16 patients corresponding to normal (19 samples, group 1), low-grade (18 samples, group 2), and high-grade (18 samples, group 3) tumoral tissues. For this purpose, we used digital cell image analysis (the SAMBA 200 processor) to describe the morphonuclear patterns of Feulgen-stained nuclei from the 3 above-mentioned groups. Our results show that nuclear DNA ploidy is positively correlated with histopathological differentiation, which is also positively correlated with an increase in nuclear DNA heterogeneity. Morphometric and textural parameters computed on such Feulgen-stained nuclei make it possible to describe the typical morphonuclear patterns of normal, low-grade, and high-grade neoplastic renal tissues. Using multiparametric, i.e. principal-component and canonical analyses, we set up preliminary morphonuclear data banks that we used to assess the diagnosis of 6 ungraded samples. We expect that this kind of morphonuclear data banks might be helpful, on one hand, to select specific morphonuclear parameters related to patient survival, and on the other hand to establish the cytological diagnosis of deep fine-needle aspiration material, sonographically assisted, on suspicious kidneys. Such hypotheses are now under further study.

In our early experience, orthotopic liver transplantation was found to be successful in fulminant and subacute hepatic failure due to viral hepatitis in adults, with 66% 1-year survival rate. In the future, more accurate prognostic criteria would probably improve overall survival rate in acute hepatic failure, by allowing better and earlier selection of patients requiring liver transplantation.

We analyzed the relationship between several morphonuclear parameters related to nuclear size, densitometry (deoxyribonucleic acid content and ploidy) and the chromatin pattern versus the histopathological grading of 46 bladder cancer samples graded according to the World Health Organization classification. We used a SAMBA 200 cell image processor with software allowing for the discrimination of 15 different parameters on Feulgen-stained imprint smears. In addition, we set up preliminary data banks that enable objective and reproducible grading of unknown cases. This approach must be validated in a large series of cases to create an expert system for bladder malignancy diagnosis.

The efficacy of various antimicrobial and anti-ulcer agents on the eradication of Campylobacter pylori in patients with antral gastritis or duodenal ulcers was investigated by several open studies or double-blind, placebo-controlled protocols. Among the anti-ulcer agents, ranitidine, cimetidine or sucraflate had no effect on C. pylori. Colloidal bismuth subcitrate achieved clearance of C. pylori in 40% of treated patients at the end of therapy but a high relapse rate (14/16 patients) was observed after a 6-month follow-up period. The antibacterial agents doxycycline, minocycline, ofloxacin, clindamycin, paromomycin and nifuroxazide failed to eradicate C. pylori in most patients. By contrast, short term elimination of C. pylori could be achieved in more than 90% of patients treated with amoxycillin. However, relapse occurred as a rule in all amoxycillin-treated patients within one month after therapy. Overall, we observed no correlation between the in-vitro activity of the different antibacterial agents and their in vivo efficacy. Development of resistance during therapy does not seem to account for this discrepancy since it occurred only with ofloxacin. On the basis of these results, we conclude that long term eradication of C. pylori from the gastric antrum cannot be achieved after monotherapy either with antibiotics or with bismuth salts.

Gallbladder volvulus, a rare disease generally affecting older aged women, is generally due to an abnormal anatomical fixation of the gallbladder. As clinical and radiological signs are poor the diagnosis is generally made at laparotomy. The prognosis is excellent when early surgical treatment is performed.

In this paper the clinical and pathological aspects of a case of sarcomatoid carcinoma (spindle cell squamous carcinoma) of the larynx are reported. The diagnosis is confirmed by immunohistochemical analysis.

The authors report a case of generalised Kaposi sarcoma complicated by pulmonary cryptococcosis and cerebral toxoplasmosis. Clinical features were dominated by the cerebral condition. The infectious pathogenesis could be related to disturbances in immune defences. Ultrastructural study revealed the presence of several types of tumour cells. Endothelial cells formed vascular lumens and contained Weibel-Palade granules and reticulo-tubular inclusions.