Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans. AIMS: To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations. METHODS: We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations with prescribed PPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within the UK Biobank using self-reported medication use and cancer-registry recorded primary liver cancer. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. RESULTS: In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2103 controls. In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use of PPIs was associated with increased liver cancer risk (adjusted OR 1.80, 95% CI 1.34, 2.41 and adjusted HR 1.99, 95% CI 1.34, 2.94 respectively). There was little evidence of association with H2RA use (adjusted OR 1.21, 95% CI 0.84, 1.76 and adjusted HR 1.70, 95% CI 0.82, 3.53 respectively). CONCLUSIONS: We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research.

Microscopic colitis: a population-based case series over a 9-year period in Northern Ireland.

AIM: We report clinicopathological experience of microscopic colitis (MC) in a population-based case series in Northern Ireland over a 9-year period. METHOD: The pathology laboratory information system within a large teaching centre serving two healthcare trusts was interrogated for cases coded between 2008 and 2016 as collagenous colitis (CC) or lymphocytic colitis (LC). Demographic, clinical and follow-up information was collected from healthcare records. RESULTS: A total of 326 new diagnoses of MC were identified, an average annual incidence of 6.7 per 100 000 population. The average annual incidence of CC and LC was 5.0 and 1.7 per 100 000 population, respectively. For coding reasons it is likely that LC data are incomplete. Of 191 cases diagnosed by specialist gastrointestinal pathologists, 141 patients had CC and 50 patients had LC. Both CC and LC predominantly involved women aged 60-79. Some 15% demonstrated endoscopic abnormalities. Endoscopic sampling protocols varied widely: 30% of individuals with CC and 32% of those with LC had the right and left colon sampled separately, with histology concordant in 95% of cases. Of the 191 cases, only one case (of LC) was refractory to treatment; the rest exhibited a clinical response. Only 35 patients had follow-up endoscopy and biopsies, and three of each diagnosis showed persistent disease on histology. CONCLUSION: Overall, CC and LC are benign conditions with similar demographics, clinical associations, management and outcomes. Separate sampling of the right and left colon is advised at colonoscopy if this diagnosis is being considered, but left colonic sampling, which can be performed at flexible sigmoidoscopy, will diagnose the vast majority of cases.

Heller's myotomy and pneumatic dilatation in the treatment of achalasia: a population-based case-control study assessing long-term quality of life.

Long-term health-related quality-of-life (HRQL) outcomes have not been widely reported in the treatment of achalasia. The aims of this study were to examine long-term disease-specific and general HRQL in achalasia patients using a population-based case-control method, and to assess HRQL between treatment interventions. Manometrically diagnosed achalasia cases (n = 120) were identified and matched with controls (n = 115) using a population-based approach. Participants completed general (SF-12) and disease-specific (Achalasia Severity Questionnaire [ASQ]) HRQL questionnaires, as appropriate, in a structured interview. Mean composite scores for SF-12 (Mental Component Summary score [MCS-12] and Physical Component Summary score [PCS-12]) and ASQ were compared between cases and controls, or between intervention groups, using an independent t-test. Adjusted mean differences in HRQL scores were evaluated using a linear regression model. Achalasia cases were treated with a Heller's myotomy (n = 43), pneumatic dilatation (n = 44), or both modalities (n = 33). The median time from last treatment to HRQL assessment was 5.7 years (interquartile range 2.4-11.5). Comparing achalasia patients with controls, PCS-12 was significantly worse (40.9 vs. 44.2, P = 0.01), but MCS-12 was similar. However, both PCS-12 (39.9 vs. 44.2, P = 0.03) and MCS-12 (46.7 vs. 53.5, P = 0.004) were significantly impaired in those requiring dual treatment compared with controls. Overall however, there was no difference in adjusted HRQL between patients treated with Heller's myotomy, pneumatic dilatation or both treatment modalities. In summary, despite treatment achalasia patients have significantly worse long-term physical HRQL compared with population controls. No HRQL differences were observed between the treatment modalities to suggest a benefit of one treatment over another.

Oral presentation of histoplasmosis in an immunocompetent patient: a diagnostic challenge.

Histoplasmosis is a rare systemic fungal infection, primarily affecting the pulmonary system. Oral lesions are usually a manifestation of the disseminated form of the disease and most frequently observed in severely immunocompromised patients, such as those with advanced human immunodeficiency virus infection and/or frank acquired immune deficiency syndrome. The clinical presentation of the oral lesions may be difficult to distinguish from oral squamous cell carcinoma. The histopathological features are usually characteristic, but occasionally the organisms are scanty and not readily identified, which can preclude obtaining the correct diagnosis and ensuring appropriate management. Histoplasmosis is an unusual and rare cause of chronic non-healing ulceration in the oral cavity. A case of histoplasmosis involving the oral cavity in an immunocompetent patient is reported, which was not recognized, resulting in the inappropriate management of the condition.

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study.

BACKGROUND: Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. OBJECTIVES: To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. METHODS: Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. RESULTS: Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. CONCLUSIONS: Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study.

Areca nut chewing in an expatriate population in Sydney: report of two cases.

Areca nut (betel nut) consumption occurs in a variety of forms, either on its own or with the addition of a number of products. This habit is prevalent in the Indian Subcontinent and South-East Asia. Recent immigration statistics indicate that 30% of new arrivals in Australia are from these geographical regions and are known to perpetuate this custom long after migration. The objective of this paper is to highlight the variety of oral presentations that may occur as a result of areca nut consumption in these particular demographic subgroups. Dental practitioners must be familiar with the wide spectrum of oral lesions that may present in this setting. More significantly, they must be aware that some of these lesions possess the potential for malignant transformation and hence require more specific management. Best practice mandates that dental practitioners in a multicultural society must: (1) be capable of recognizing the expatriate populations in which this custom is widely practised; (2) incorporate this particular line of questioning into the routine risk factor analysis that is undertaken for every patient from these particular sub-populations; and (3) institute appropriate referral and follow-up of these lesions if required.

The spatial and temporal expression of calretinin in developing rat molars (Rattus norvegicus).

Calretinin is a 29-kDa calcium-binding protein abundantly expressed in central and peripheral neural tissues. The aim here was to determine its expression during various stages of odontogenesis. Five categories of embryonic (E) and postnatal (P) rats at various ages (E17, E18, E20, P0, and P7), both male and female, were used to represent the various stages of molar tooth development. The heads of the experimental animals were harvested at the appropriate time and each was cut mid-sagittally and coronally to locate the tooth germs. Selected sections were stained immunohistochemically with polyclonal rabbit anticalretinin at a concentration of 1:25 after microwave irradiation. The results showed that calretinin is distributed widely in epithelium-derived tissues during odontogenesis in rat molar tooth germs. It was expressed focally in the dental lamina, outer enamel epithelium, stellate reticulum and stratum intermedium at different stages. In contrast, it was expressed diffusely and intensely in the inner enamel epithelium and presecretory ameloblasts, although it was discontinuous over the cusp tips. In the secretory ameloblasts, the staining was less intense, being restricted to the cytoplasm, including Tomes' processes. This distribution suggests that calretinin may play a part in enamel formation.

Nucleolar organizer regions (AgNORs) in odontogenic cysts and ameloblastomas.

The aim of this study was to determine whether nucleolar organizer regions (AgNORs) may be of value in distinguishing various odontogenic cysts from the unicystic ameloblastoma. Histological sections were prepared from fifteen cases each of odontogenic keratocyst, residual cyst, dentigerous cyst, unicystic ameloblastoma and conventional ameloblastoma. In each case intra-nuclear AgNOR dots were counted in 100 consecutive basal nuclei. Statistical comparison of the least squares means showed that those areas of unicystic ameloblastomas lined by characteristic epithelium had a significantly lower AgNOR count than the other groups (P < 0.05). The dentigerous cysts had significantly higher AgNOR counts than the residual cysts and unicystic ameloblastomas (P < 0.05). These differences may or may not be indicative of variations in metabolic, proliferative or transcriptional activity. We conclude that AgNOR counts are not of diagnostic significance and cannot be used to distinguish the various odontogenic cysts from one another nor from the unicystic ameloblastoma.