Nearly all studies of gastric adenocarcinoma in the United States have relied on national cancer databases, which do not include data on Helicobacter pylori infection, the most well-known risk factor ...for gastric cancer. We collected data from a large cohort of patients in the United States to calculate the incidence of and risk factors for nonproximal gastric adenocarcinomas after detection of H pylori. Secondary aims included identifying how treatment and eradication affect cancer risk.
We performed a retrospective cohort study, collecting data from the Veterans Health Administration on 371,813 patients (median age 62 years; 92.3% male) who received a diagnosis of H pylori infection from January 1, 1994, through December 31, 2018. The primary outcome was a diagnosis of distal gastric adenocarcinoma 30 days or more after detection of H pylori infection. We performed a time to event with competing risk analysis (with death before cancer as a competing risk).
The cumulative incidence of cancer at 5, 10, and 20 years after detection of H pylori infection was 0.37%, 0.5%, and 0.65%, respectively. Factors associated with cancer included older age at time of detection of H pylori infection (subhazard ratio SHR, 1.13; 95% confidence interval CI, 1.11–1.15; P < .001), black/African American race (SHR, 2.00; 95% CI, 1.80–2.22), Asian race (SHR, 2.52; 95% CI, 1.64–3.89) (P < .001 for race), Hispanic or Latino ethnicity (SHR, 1.59; 95% CI, 1.34–1.87; P < .001), and history of smoking (SHR, 1.38; 95% CI, 1.25–1.52; P < .001). Women had decreased risk of gastric adenocarcinoma compared with men (SHR, 0.52; 95% CI, 0.40–0.68; P < .001); patients whose H pylori infection was detected based on serum antibody positivity also had a reduced risk of cancer (SHR 0.74; 95% CI, 0.54–1.04; P = .04). Patients who received treatment for their H pylori infection still had an increased risk of gastric cancer (SHR, 1.16; 95% CI, 0.74–1.83; P = .51) but confirmed H pylori eradication after treatment reduced risk of gastric cancer (SHR, 0.24; 95% CI, 0.15–0.41; P < .001).
In a study of 371,813 veterans with a diagnosis of H pylori infection, we found significantly higher risks of gastric cancer in racial and ethnic minorities and smokers. Treatment of H pylori infection decreased risk only if eradication was successful. Studies are needed on the effects of screening high-risk persons and to identify quality measures for diagnosis, resistance patterns, and treatment efficacy.
LINKED CONTENT
This article is linked to Hwang et al papers. To view these articles, visit https://doi.org/10.1111/apt.17406 and https://doi.org/10.1111/apt.17444
Summary
Background
Potassium‐competitive acid blockers (P‐CABs) are a novel group of acid‐suppressing medicines for the management of acid‐related disorders.
Aims
To review published clinical ...pharmacology studies and clinical trials of P‐CABs.
Methods
We conducted a comprehensive literature search including Medline (PubMed), EMBASE, Web of Science and the Cochrane Library from inception until November 2020, for studies of the clinical pharmacology of P‐CABs and relevant clinical trials of those that are currently licensed or in development.
Results
Most publications concerned vonoprazan, which forms the bulk of this review. It is currently licensed in some Asian and South American countries and is being developed for North America. In clinically relevant doses, P‐CABs have produced more rapid and profound suppression of intragastric acidity than proton pump inhibitors (PPIs). Vonoprazan was non‐inferior to lansoprazole in healing erosive oesophagitis (2 randomised controlled trials RCTs in 1137 subjects) and superior in maintaining remission (1 RCT; 607 subjects). In 2 RCTs (1120 total subjects), both vonoprazan and tegoprazan were non‐inferior to lansoprazole for healing peptic ulcers. Three RCTs and numerous non‐randomised studies have compared vonoprazan‐based and PPI‐based regimens for Helicobacter pylori infection; vonoprazan‐based triple or dual regimens have been highly effective.
Conclusions
P‐CABs have some potential advantages over PPIs. To date, most research has been conducted in Asia; results of clinical trials that are underway in the United States and Europe are anticipated in 2021.
We present the first copper iridium binary metal oxide with the chemical formula Cu2IrO3. The material is synthesized from the parent compound Na2IrO3 by a topotactic reaction where sodium is ...exchanged with copper under mild conditions. Cu2IrO3 has the same monoclinic space group (C2/c) as Na2IrO3 with a layered honeycomb structure. The parent compound Na2IrO3 is proposed to be relevant to the Kitaev spin liquid on the basis of having Ir4+ with an effective spin of 1/2 on a honeycomb lattice. Remarkably, whereas Na2IrO3 shows a long-range magnetic order at 15 K and fails to become a true spin liquid, Cu2IrO3 remains disordered until 2.7 K, at which point a short-range order develops. Rietveld analysis shows less distortions in the honeycomb structure of Cu2IrO3 with bond angles closer to 120° compared to Na2IrO3. Thus, the weak short-range magnetism combined with the nearly ideal honeycomb structure places Cu2IrO3 closer to a Kitaev spin liquid than its predecessors.
Summary Background The interest in neonatal screening for lysosomal storage disorders has increased substantially because of newly developed enzyme replacement therapies, the need for early ...diagnosis, and technical advances. We tested for Gaucher's disease, Pompe's disease, Fabry's disease, and Niemann-Pick disease types A and B in an anonymous prospective nationwide screening study that included genetic mutation analysis to assess the practicality and appropriateness of including these disorders in neonatal screening panels. Methods Specimens from dried blood spots of 34 736 newborn babies were collected consecutively from January, 2010 to July, 2010, as part of the national routine Austrian newborn screening programme. Anonymised samples were analysed for enzyme activities of acid β-glucocerebrosidase, α-galactosidase, α-glucosidase, and acid sphingomyelinase by electrospray ionisation tandem mass spectrometry. Genetic mutation analyses were done in samples with suspected enzyme deficiency. Findings All 34 736 samples were analysed successfully by the multiplex screening assay. Low enzyme activities were detected in 38 babies. Mutation analysis confirmed lysosomal storage disorders in 15 of them. The most frequent mutations were found for Fabry's disease (1 per 3859 births), followed by Pompe's disease (1 per 8684), and Gaucher's disease (1 per 17 368). The positive predictive values were 32% (95% CI 16–52), 80% (28–99), and 50% (7–93), respectively. Mutational analysis detected predominantly missense mutations associated with a late-onset phenotype. Interpretation The combined overall proportion of infants carrying a mutation for lysosomal storage disorders was higher than expected. Neonatal screening for lysosomal storage disorders is likely to raise challenges for primary health-care providers. Furthermore, the high frequency of late-onset mutations makes lysosomal storage disorders a broad health problem beyond childhood. Funding Austrian Ministry of Health, Family, and Women.
Pancreatic endocrine tumors (PETs) have long fascinated clinicians and investigators despite their relative rarity. Their clinical presentation varies depending on whether the tumor is functional or ...not, and also according to the specific hormonal syndrome produced. Tumors may be sporadic or inherited, but little is known about their molecular pathology, especially the sporadic forms. Chromogranin A appears to be the most useful serum marker for diagnosis, staging, and monitoring. Initially, therapy should be directed at the hormonal syndrome because this has the major initial impact on the patient's health. Most PETs are relatively indolent but ultimately malignant, except for insulinomas, which predominantly are benign. Surgery is the only modality that offers the possibility of cure, although it generally is noncurative in patients with Zollinger–Ellison syndrome or nonfunctional PETs with multiple endocrine neoplasia-type 1. Preoperative staging of disease extent is necessary to determine the likelihood of complete resection although debulking surgery often is believed to be useful in patients with unresectable tumors. Once metastatic, biotherapy is usually the first modality used because it generally is well tolerated. Systemic or regional therapies generally are reserved until symptoms occur or tumor growth is rapid. Recently, a number of newer agents, as well as receptor-directed radiotherapy, are being evaluated for patients with advanced disease. This review addresses a number of recent advances regarding the molecular pathology, diagnosis, localization, and management of PETs including discussion of peptide-receptor radionuclide therapy and other novel antitumor approaches. We conclude with a discussion of future directions and unsettled problems in the field.
Somatostatin receptor (SSTR) PET has demonstrated a significant improvement over conventional imaging (CI) in patients with neuroendocrine tumors (NETs). SSTR PET should replace 111In-pentetreotide ...scintigraphy (OctreoScan; Mallinckrodt) in all indications in which the latter is currently being used. These appropriate use criteria (AUC) are intended to aid referring medical practitioners in the appropriate use of SSTR PET for imaging of patients with NETs. The indications were evaluated in well-differentiated NETs. Of the 12 clinical scenarios evaluated, 9 were graded as appropriate: initial staging after the histologic diagnosis of NET, evaluation of an unknown primary, evaluation of a mass suggestive of NET not amenable to endoscopic or percutaneous biopsy, staging of NET before planned surgery, monitoring of NET seen predominantly on SSTR PET, evaluation of patients with biochemical evidence and symptoms of a NET, evaluation of patients with biochemical evidence of a NET without evidence on CI or a prior histologic diagnosis, restaging at time of clinical or laboratory progression without progression on CI, and new indeterminate lesion on CI with unclear progression. Representatives from the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the American College of Radiology (ACR), the American Society of Clinical Oncology (ASCO), the North American Neuroendocrine Tumor Society (NANETS), the European Association of Nuclear Medicine (EANM), the Endocrine Society, the Society of Surgical Oncology, the National Comprehensive Cancer Network (NCCN), the American College of Physicians (ACP), the American Gastroenterological Association (AGA), and the World Conference on Interventional Oncology (WCIO) assembled under the auspices of an autonomous workgroup to develop the following AUC.
Summary Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and ...biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at >75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specificity necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours.
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