Proton pump inhibitors are not associated with fundic gland polyps - a systematic review that takes into consideration all known confounders.

Sporadic fundic gland polyps (FGPs) progress, albeit rarely, to dysplasia and cancer. Two meta-analyses, including 8 and 11 studies, concluded that proton pump inhibitors (PPIs) were associated with FGPs. Intervention is considered unnecessary when FGPs have a background of PPIs use. Both meta-analyses, however, disregarded known confounders: age, sex, endoscopy indications, study design (prospective or retrospective), duration of PPI use, and H. pylori infection. Confounders are known to invalidate meta-analyses. We followed PRIXMA guidelines and searched the literature for studies on FGPs in PPI-users and PPI-nonusers. In the 22 studies searched, we compared FGPs in PPI-users (n = 6534) and PPI-nonusers (n = 41 115). Heterogeneity was significant (Cochran Q = 277.8, P < 0.0001; I2 = 92.8%), annulling meta-analysis performed by blanket tallying. To offset the above confounders, we matched PPI-users and PPI-nonusers by (a) age and sex (n = 4300 and 29 307, respectively) and (b) their propensity scores derived from the confounders (n = 2950 and 4729, respectively). After both matching, FGPs were not significantly different between PPI-users and PPI-nonusers [odds ratio (OR) = 1.1, P = 0.3078; OR = 0.9, P = 0.3258, respectively]. Furthermore, FGP frequency did not correlate with increasing duration of PPI use (Pearson and Spearman correlation coefficients = 0.1162, 0.0386, P < 0.6064, 0.8646, respectively); it was not significantly different between any of the duration periods of observation, namely, <10, 10-20, 20-40, >40 months, nor was it significantly different between PPI-users and PPI-nonusers within each duration period (P > 0.05). We conclude that PPIs are not associated with FGPs, implying that a background history of PPI use is not a justification for nonintervention in the management of FGPs.

Proton Pump Inhibitor Associated Multiple Gastric Hyperplastic Polyps With Uncontrollable Bleeding: A Case Report.

BACKGROUND/AIM: The long-term use of proton pump inhibitors (PPIs) has been reported to be strongly associated with the development of fundic gland polyps (FGPs). Conversely, a few cases of gastric hyperplastic polyps (GHPs) associated with PPI use have been reported. We experienced a case of PPI-associated multiple GHPs with uncontrollable bleeding. CASE REPORT: A 64 year old man with a history of rheumatoid arthritis presented to the hospital with complaints of vertigo and black stools. Blood tests revealed anemia and hypoproteinemia. Esophagogastroduodenoscopy (EGD) showed blood and black residue accumulated in the stomach. The source of the bleeding was multiple hyperplastic polyps. Bleeding could be stopped even with fasting, and total blood transfusions amounted to 28 units of RBCs were required in 18 days. After the cessation of PPI, EGD showed that the polyps had almost disappeared. Pathological diagnosis of resected polyp was hyperplastic polyp, which was characterized by capillary hyperplasia and edema. Gastrin receptors were over-expressed in the foveolar epithelium and not in the capillaries. Methotrexate (MTX)-induced portal hypertensive gastroenteropathy was revealed during follow-up. We consider that the effect of portal hypertension may have caused the capillary hyperplasia. CONCLUSION: Although PPI-related polyps are usually fundic gland polyps and do not cause life-threatening adverse events, we experienced PPI-related GHPs in which hemostasis was difficult to control.

The association between duration of and indications for proton pump inhibitor use and risk of gastric polyps.

OBJECTIVES: The development of fundic gland polyps (FGPs) is the most common side effect of long-term proton pump inhibitor (PPI) use; however, the effect of drug use characteristics and their impact on the risk of other gastric polyp development remain unclear. We aimed to identify the influence of PPI administration, as well as its duration and dose, in the development of gastric polyps. METHODS: A prospective cohort study was conducted on consecutive patients who underwent gastroscopy between September 2017 and August 2019. Detailed characteristics of gastric polyps, Helicobacter pylori infection, and PPI use were analyzed. RESULTS: Among the 2723 patients included, gastric polyps (75% FGPs, 22% hyperplastic) were detected in 16.4%, and 60% were prescribed PPI. The risk of FGPs and hyperplastic polyps according to the duration of PPI use were as follows: 2-5 years [odds ratio (95% confidence interval); 2.86 (2.00-4.11) and 2.82 (1.69-4.78)]; 6-9 years [7.42 (5.03-11.01) and 2.32 (1.05-4.78)]; ≥10 years [14.94 (10.36-21.80) and 3.52 (1.67-7.03)]. Multivariate analysis confirmed that the risk of FGPs was 17.16 (11.35-26.23) for ≥10 years of PPI use. Portal hypertension-related conditions were associated with hyperplastic polyps [4.99 (2.71-9.20)]. CONCLUSION: Duration of and indications for PPI use are the most predictive factors for the development of gastric polyps. Prolonged PPI use increases the risk of polyp development and the number of patients with polyps, which may burden endoscopic practice. Highly selected patients may require particular care despite minimal risk of dysplasia and bleeding generally.

Long-term vonoprazan administration causes gastric fundic gland-type hyperplastic polyps and chronic bleeding.

A patient experienced gastric fundic gland-type hyperplastic polyps, consisting of foveolar epithelium and parietal cells, complicated with chronic bleeding due to long-term treatment with vonoprazan. The patient had progressive anemia, probably caused by bleeding from the polyps. After switching from vonoprazan to a histamine-2 (H2) receptor antagonist, the polyps markedly shrank and the anemia improved. Vonoprazan can produce reversible hyperplastic polyps and anemia. In case of anemia in patients receiving long-term vonoprazan, it is important to consider drug cessation or change to an H2 blocker.

Risk of Endometrial Polyps, Hyperplasia, Carcinoma, and Uterine Cancer After Tamoxifen Treatment in Premenopausal Women With Breast Cancer.

Importance: The association of tamoxifen use with the risk of uterine diseases, such as endometrial cancer, in premenopausal women with breast cancer remains controversial. However, many studies have reported an increased risk of uterine disease among postmenopausal tamoxifen users. Objective: To investigate the association of tamoxifen use with the risk of endometrial cancer and other uterine diseases in premenopausal women with breast cancer. Design, Setting, and Participants: A nationwide, population-based, retrospective longitudinal cohort study with an 18-year study period was conducted using data obtained from the Korean National Health Insurance Service. Participants included premenopausal women aged 20 to 50 years with breast cancer diagnoses between January 2003 and December 2018. Data were analyzed from April to December 2021. Exposures: Tamoxifen treatment. Main Outcomes and Measures: The incidence of uterine diseases, including endometrial cancer, hyperplasia, polyps, and other uterine cancers, was identified in the study cohort using insurance claim codes. The incidence of uterine diseases per 1000 person-years was compared between women receiving tamoxifen and those not treated with adjuvant hormone therapy. Multivariable Cox proportional hazard regression analysis was performed to determine the risk of each uterine disease. Results: Among 78 320 female participants with a mean (SD) age of 42.1 (6.1) years, 34 637 (44.2%) were categorized into the tamoxifen group and 43 683 (55.8%) were categorized into the control group. Among tamoxifen users, during the mean (SD) follow-up duration of 6.13 (4.15) years, the incidence of newly diagnosed endometrial polyps was 20.13 cases per 1000 person-years, that of endometrial hyperplasia was 13.49 cases per 1000 person-years, that of endometrial cancer was 2.01 cases per 1000 person-years, and that of other uterine cancers was 0.45 cases per 1000 person-years. The risk of endometrial cancer was higher in the tamoxifen group than in the control group (hazard ratio, 3.77; 95% CI, 3.04-4.66) after adjusting for age, body mass index, history of diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, gonadotropin-releasing hormone agonist treatment, and trastuzumab treatment. Conclusions and Relevance: In this longitudinal cohort study, premenopausal Korean women with breast cancer who received tamoxifen as adjuvant hormone therapy had a significantly increased risk of endometrial hyperplasia, polyps, carcinoma, and other uterine cancers compared with those who were not treated with adjuvant hormone therapy. These findings suggest that clinicians should consider the risk of uterine disease among tamoxifen users, including premenopausal women.

Gastric Hyperplastic Polyps Can Shrink After Discontinuation of Proton Pump Inhibitors: A Case Series Compared With Continuation of Proton Pump Inhibitors.

GOAL: This study investigated whether gastric hyperplastic polyps (GHPs) shrink after discontinuation of proton pump inhibitor (PPI) alone. BACKGROUND: Long-term use of PPIs has been reported to increase the incidence of GHPs, which sometimes bleed and cause anemia. We experienced a patient whose recurrent hemorrhagic GHPs associated with long-term use of PPIs had disappeared after discontinuation of PPIs. STUDY: This study was conducted retrospectively at Kyoto University Hospital. Patients with histologically confirmed GHPs who had been taking PPIs for >6 months and who had undergone a repeat endoscopy within 2 years were included. Polyp shrinkage was defined as the disappearance of polyps or a reduction of >50% in the long diameter of the largest polyp. RESULTS: Six patients who discontinued PPIs were compared with 17 patients who continued PPIs. Polyp shrinkage was significantly more frequent in the PPI-discontinuation group (5/6, 83%) than in the PPI continuation group (0/17, 0%) (P<0.001). In 2 patients in the PPI-discontinuation group, the polyps completely disappeared finally. CONCLUSION: These findings suggest that discontinuation of PPIs can shrink GHPs in patients using PPIs.

Fundic Gland Polyp With Parietal Cell Vacuolation Mimicking Signet Ring Cell Carcinoma.

Pseudo-signet ring parietal cell vacuolation has been described as a mimic of invasive signet ring cell carcinoma. Moreover, signet ring cell carcinoma has been described in a fundic gland polyp. This case demonstrates parietal cell vacuolation in a fundic gland polyp in a patient on a long-term proton pump inhibitor.

Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

BACKGROUND: Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. OBJECTIVES: To determine the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. SEARCH METHODS: We searched the following databases on 29 June 2020; The Cochrane Gynaecology and Fertility Group specialised register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO and Cumulative Index to Nursing and Allied Health Literature. We searched the Cochrane Breast Cancer Group specialised register on 4 March 2020. We also searched two trials registers, checked references for relevant trials and contacted study authors and experts in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of women with breast cancer on adjuvant tamoxifen that compared the effectiveness of the LNG-IUS with endometrial surveillance versus endometrial surveillance alone on the incidence of endometrial pathology. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer), diagnosed at hysteroscopy or endometrial biopsy. Secondary outcome measures included fibroids, abnormal vaginal bleeding or spotting, breast cancer recurrence, and breast cancer-related deaths. We rated the overall certainty of evidence using GRADE methods. MAIN RESULTS: We included four RCTs (543 women analysed) in this review. We judged the certainty of the evidence to be moderate for all of the outcomes, due to imprecision (i.e. limited sample sizes and low event rates). In the included studies, the active treatment arm was the 20 µg/day LNG-IUS plus endometrial surveillance; the control arm was endometrial surveillance alone. In tamoxifen users, the LNG-IUS probably reduces the incidence of endometrial polyps compared to the control group over both a 12-month period (Peto odds ratio (OR) 0.22, 95% confidence interval (CI) 0.08 to 0.64, I² = 0%; 2 RCTs, n = 212; moderate-certainty evidence) and over a long-term follow-up period (24 to 60 months) (Peto OR 0.22, 95% CI 0.13 to 0.39; I² = 0%; 4 RCTs, n = 417; moderate-certainty evidence). For long-term follow-up, this suggests that if the incidence of endometrial polyps following endometrial surveillance alone is assumed to be 23.5%, the incidence following LNG-IUS with endometrial surveillance would be between 3.8% and 10.7%.  The LNG-IUS probably slightly reduces the incidence of endometrial hyperplasia compared with controls over a long-term follow-up period (24 to 60 months) (Peto OR 0.13, 95% CI 0.03 to 0.67; I² = 0%; 4 RCTs, n = 417; moderate-certainty evidence). This suggests that if the chance of endometrial hyperplasia following endometrial surveillance alone is assumed to be 2.8%, the chance following LNG-IUS with endometrial surveillance would be between 0.1% and 1.9%. However, it should be noted that there were only six cases of endometrial hyperplasia. There was insufficient evidence to reach a conclusion regarding the incidence of endometrial cancer in tamoxifen users, as no studies reported cases of endometrial cancer. At 12 months of follow-up, the LNG-IUS probably increases abnormal vaginal bleeding or spotting compared to the control group (Peto OR 7.26, 95% CI 3.37 to 15.66; I² = 0%; 3 RCTs, n = 376; moderate-certainty evidence). This suggests that if the chance of abnormal vaginal bleeding or spotting following endometrial surveillance alone is assumed to be 1.7%, the chance following LNG-IUS with endometrial surveillance would be between 5.6% and 21.5%. By 24 months of follow-up, abnormal vaginal bleeding or spotting occurs less frequently than at 12 months of follow-up, but is still more common in the LNG-IUS group than the control group (Peto OR 2.72, 95% CI 1.04 to 7.10; I² = 0%; 2 RCTs, n = 233; moderate-certainty evidence). This suggests that if the chance of abnormal vaginal bleeding or spotting following endometrial surveillance alone is assumed to be 4.2%, the chance following LNG-IUS with endometrial surveillance would be between 4.4% and 23.9%. By 60 months of follow-up, there were no cases of abnormal vaginal bleeding or spotting in either group. The numbers of events for the following outcomes were low: fibroids (n = 13), breast cancer recurrence (n = 18), and breast cancer-related deaths (n = 16). As a result, there is probably little or no difference in these outcomes between the LNG-IUS treatment group and the control group.  AUTHORS' CONCLUSIONS: The LNG-IUS probably slightly reduces the incidence of benign endometrial polyps and endometrial hyperplasia in women with breast cancer taking tamoxifen. At 12 and 24 months of follow-up, the LNG-IUS probably increases abnormal vaginal bleeding or spotting among women in the treatment group compared to those in the control. Data were lacking on whether the LNG-IUS prevents endometrial cancer in these women. There is no clear evidence from the available RCTs that the LNG-IUS affects the risk of breast cancer recurrence or breast cancer-related deaths. Larger studies are necessary to assess the effects of the LNG-IUS on the incidence of endometrial cancer, and to determine whether the LNG-IUS might have an impact on the risk of secondary breast cancer events.

Risk Factors Associated with Endometrial Pathology in Premenopausal Breast Cancer Patients Treated with Tamoxifen.

PURPOSE: To evaluate factors associated with endometrial pathology during tamoxifen use in premenopausal breast cancer (BC) patients. MATERIALS AND METHODS: We reviewed the medical records of premenopausal BC patients treated with tamoxifen who underwent endometrial biopsy with or without hysteroscopy. Clinical characteristics were compared between women with endometrial pathology (endometrial hyperplasia or cancer) and those with normal histology or endometrial polyps. RESULTS: Among 284 endometrial biopsies, endometrial hyperplasia was diagnosed in 7 patients (2.5%), endometrial cancer was diagnosed in 5 patients (1.8%), normal histology was noted in 146 patients (51.4%), and endometrial polyp was present in 114 patients (40.1%). When comparing women with endometrial cancer (n=5) to women with normal histology, abnormal uterine bleeding was more common (p=0.007), and endometrial thickness was greater (p=0.007) in women with endometrial cancer. Chemotherapy for BC was also more common in patients with endometrial cancer (p=0.037). When comparing women with endometrial polyps and those with endometrial hyperplasia or cancer, the presence of abnormal uterine bleeding was more common in patients with endometrial hyperplasia or cancer (p<0.001); however, tamoxifen duration and endometrial thickness did not differ significantly between the two groups. CONCLUSION: In premenopausal BC patients treated with tamoxifen, abnormal uterine bleeding, increased endometrial thickness, and chemotherapy for BC were associated with the occurrence of endometrial cancer. These findings may provide useful information for gynecologic surveillance and counseling during tamoxifen treatment in premenopausal BC patients.

Enterotoxigenic Bacteroides fragilis infection exacerbates tumorigenesis in AOM/DSS mouse model.

The azoxymethane (AOM)/dextran sulfate sodium (DSS) murine model is commonly used to study colitis-associated cancer. The human commensal bacterium, enterotoxigenic Bacteroides fragilis (ETBF) secretes the Bacteroides fragilis toxin (BFT) which is necessary and sufficient to cause colitis. We report that BALB/c mice infected with WT-ETBF and administered three cycles of AOM/DSS developed numerous, large-sized polyps predominantly in the colorectal region. In addition, AOM/DSS-treated BALB/c mice orally inoculated with wild-type nontoxigenic Bacteroides fragilis (WT-NTBF) overexpressing bft (rETBF) developed numerous polyps whereas mice infected with WT-NTBF overexpressing a biologically inactive bft (rNTBF) did not promote polyp formation. Unexpectedly, the combination of AOM+ETBF did not induce polyp formation whereas ETBF+DSS did induce polyp development in a subset of BALB/c mice. In conclusion, WT-ETBF promoted polyp development in AOM/DSS murine model with increased colitis in BALB/c mice. The model described herein provides an experimental platform for understanding ETBF-induced colonic tumorigenesis and studying colorectal cancer in wild-type mice.

Case-control analysis of fundic gland polyps and proton-pump inhibitors. A pathologist's perspective. / Análisis de casos y controles de pólipos de glándulas fúndicas e inhibidores de bomba de protones. La perspectiva de un patólogo.

INTRODUCTION AND AIM: Adequately preserved slides and tissue blocks in pathology archives, when re-reviewed and associated with patient charts, are important tools to further assess prevalence changes and associations of certain pathologies. Our aim was to identify whether proton-pump inhibitor (PPI) use, dose, and duration of use were associated with gastric polyps and their phenotypes in a case-control study. METHODS: The slides from patients with a morphologic diagnosis of either hyperplastic polyps or fundic gland polyps were retrieved from the 1980, 1990, 2000, 2010, and 2016 surgical pathology files at a tertiary care hospital in Mexico City and re-evaluated. Cases were paired by age and sex with patients that underwent endoscopy and gastric mucosa biopsy in the same year, with no evidence of polyps. RESULTS: A total of 133 (3.8%) patients with gastric polyps were identified from 3,499 gastric biopsies taken in the abovementioned years and compared with 133 paired controls. Dyspepsia was more prevalent in the controls (p=0.002) and abdominal pain was more prevalent in the patients with gastric polyps (p=0.001). PPI use (OR 7.7, 95% confidence interval, 4.4-13.3) and taking more than one PPI medication (OR 4.9, 95% confidence interval, 1.09-22.3) were significantly associated with the presence of gastric polyps. The fundic gland phenotype in the oxyntic mucosa was more frequently associated with PPI use (p<0.042), with a continuous increase in its prevalence starting in the year 2000 (p=0.017 for trend). CONCLUSION: PPI administration for at least one year was associated with gastric fundic gland polyps.

Tamoxifen use as a malignancy risk factor in postmenopausal women with endometrial polyps.

OBJECTIVE: We analyzed tamoxifen use as a malignancy risk factor in women with endometrial polyps. METHODS: This retrospective study included 675 women who underwent hysteroscopic polypectomy in 2010 to 2015 at the University of Campinas. Women were divided into tamoxifen use (n = 169) and no tamoxifen use (n = 506) groups. The primary outcome was endometrial cancer prevalence. Dependent variables included age, parity, years since menopause, presence of abnormal uterine bleeding, endometrial pattern on hysteroscopy, and endometrial thickness. RESULTS: There were seven cases of endometrial cancer in the tamoxifen use group (4.14%) and 41 in the no tamoxifen use group (8.1%; P = 0.083). On performing multivariate analysis, tamoxifen use was not a risk factor for endometrial cancer (prevalence ratio 0.51, 95% confidence interval [CI] 0.23-1.14, P = 0.101). The no tamoxifen use group had an increased prevalence of malignancy when women presented with abnormal uterine bleeding (prevalence ratio 3.9, 95% CI 2.08-7.29, P < 0.001), age >60 years (prevalence ratio 2.1, 95% CI 1.12-3.93, P = 0.021), or nulliparous status (prevalence ratio 3.13, 95% CI 1.55-6.35, P = 0.002). The tamoxifen use group had increased prevalence of malignancy when women were >60 years (prevalence ratio 7.85, 95% CI 1.05-58.87, P = 0.006) or nulliparous (prevalence ratio 8.36, 95% CI 2.32-30.11, P < 0.001). CONCLUSION: Tamoxifen use was not related with a higher prevalence of endometrial cancer in women with endometrial polyps. Abnormal uterine bleeding, age > 60 years, and nulliparous status were associated with malignancy.

Synchronous Three Gastric Fundic Gland Polyps with Low-grade Dysplasia Treated with Endoscopic Mucosal Resection after Being Diagnosed to Be Tubular Adenocarcinoma Based on a Biopsy Specimen.

A 51-year-old woman had been taking proton pump inhibitor since August 2008. In May, 2016, endoscopic findings showed no atrophy and no intestinal metaplasia in the stomach, and multiple fundic gland polyps were identified in the stomach. A biopsy of a pedunculated polyp measuring 10 millimeters in diameter at the greater curvature of the middle gastric body demonstrated well differentiated tubular adenocarcinoma. In July 2016, we treated this lesion and two other semipedunculated polyps located near the first polyp and also measuring 10 mm in diameter by endoscopic mucosal resection. The final diagnosis of all lesions was a fundic gland polyp with low grade dysplasia and the cutting end was negative.

Proton-pump inhibitor-induced fundic gland polyps with hematemesis.

Fundic gland polyps (FGPs) are generally considered benign. Proton-pump inhibitors (PPIs) are used worldwide as first-line therapy for gastroesophageal reflux disease and nonsteroidal anti-inflammatory drug-induced ulcer treatment. Long-term use of PPIs increases the risk of FGP development. We report an extremely rare case of PPI-induced FGPs with hematemesis. A 37-year-old woman taking daily rabeprazole presented to the hospital with a complaint of hematemesis and tarry stools. Esophagogastroduodenoscopy (EGD) revealed > 20 pedunculated polyps in the gastric body and fundus. Histological examination showed multiple fragments of fundic gland mucosa with dilated glands. Based on these findings and the clinical history, FGPs were diagnosed. Rabeprazole use was discontinued. Repeat EGD performed 9 months later showed a significant decrease in the number and size of the polyps. FGPs are small polyps typically located in the gastric corpus and fundus. They are commonly reported in patients in their 60s and predominantly in females. We conclude that PPI use is a risk factor for the development of FGPs and hematemesis.

Pólipos de glândulas fúndicas: a histologia pode ser utilizada para prever uso de inibidores de bomba de próton? / Gastric fundic gland polyps: can histology be useful to predict proton pump inhibitors use?

ABSTRACT BACKGROUND: Fundic gland polyps allegedly increased in frequency in recent decades, and had attracted great attention due to possible association with prolonged proton pump inhibitor therapy. Prolonged use of this drug could cause parietal cell hyperplasia, obstruction of glandular lumen and cystic dilation of the gland. OBJECTIVE: This study aims to analyze clinical and pathological features of fundic gland polyps in patients with and without proton pump inhibitor therapy in a selected population from Brazil. METHODS: It was selected a sample of 101 Brazilian patients (78 females and 23 males), from a five years retrospective search of the files from a private pathology laboratory. The patients had an average age of 57 years and we included patients with a histological diagnosis of fundic gland polyp. The clinical data were obtained from their files and all histological slides were reviewed and examined with hematoxylin and eosin (HE) and Giemsa. RESULTS: Information about the use or non-use of proton pump inhibitors (PPI) was obtained in 84 patient files. In 17 cases we could not determine if PPI were used or not. Among those in which the information was available, a positive history of anti-acid therapy was observed in 63 (75.0%) patients. Parietal cell hypertrophy/hyperplasia and parietal cell protrusions were detected in most slides. Histological findings were identical in PPI users and PPI negative patients. Helicobacter pylori infection was detected in just two samples. Epithelial dysplasia or adenocarcinoma were not observed in our cases. Histopathological analysis of fundic gland polyps could not distinguish between PPI and non-PPI related cases. Parietal cell cytoplasmic protrusions, an alleged marker of prolonged acid suppression therapy, was detected in both groups. CONCLUSION: Histological features could not discriminate anti-acid therapy related fundic glands polyps in our patients.

RESUMO CONTEXTO: Os pólipos das glândulas fúndicas do estômago supostamente aumentaram em frequência nas últimas décadas e atraíram grande atenção devido à possível associação com a terapia prolongada com inibidores da bomba de prótons. O uso prolongado deste fármaco pode causar hiperplasia das células parietais, obstrução do lúmen glandular e dilatação cística da glândula. OBJETIVO: Este estudo tem como objetivo analisar os aspectos clínicos e patológicos dos pólipos das glândulas fúndicas em pacientes com e sem terapia com inibidores da bomba de prótons em uma população selecionada do Brasil. MÉTODOS: Foi selecionada uma amostra de 101 pacientes brasileiros (78 do sexo feminino e 23 do sexo masculino), a partir de uma pesquisa retrospectiva de cinco anos dos arquivos de um laboratório privado de patologia. Os pacientes tinham uma idade média de 57 anos e foram incluídos pacientes com diagnóstico histológico de pólipo das glândulas fúndicas. Os dados clínicos foram obtidos a partir de seus prontuários e todas as lâminas histológicas foram revisadas e examinadas com hematoxilina e eosina (HE) e Giemsa. RESULTADOS: Informações sobre o uso ou não uso de inibidores da bomba de próton (IBP) foram obtidas em 84 prontuários de pacientes. Em 17 casos, não foi possível determinar se o IBP foi usado ou não. Entre aqueles em que a informação estava disponível, observou-se uma história positiva de terapia com IBP em 63 (75,0%) pacientes. A hipertrofia das células parietais/hiperplasia e protrusões das células parietais foram detectadas na maioria das lâminas. Os achados histológicos foram idênticos em usuários de IBP e pacientes não usuários. A infecção por Helicobacter pylori foi detectada em apenas duas amostras. A displasia epitelial ou o adenocarcinoma não foram observados em nossos casos. A análise histopatológica dos pólipos das glândulas fúndicas não pôde distinguir entre os casos IBP e não relacionados ao IBP. As protuberâncias citoplasmáticas das células parietais, um suposto marcador de terapia prolongada de supressão de ácido, foram detectadas em ambos os grupos. CONCLUSÃO: Características histológicas não podem discriminar os pólipos das glândulas fúndicas relacionados à terapia anti-secretora em nossos pacientes.

Doenças imunomediadas em pacientes com doença celíaca e em seus familiares: um estudo comparativo entre idade e sexo / Immune mediated diseases in patients with celiac disease and their relatives: a comparative study of age and sex

ABSTRACT BACKGROUND: Up to 15% of other immune-mediated diseases (IMDs) can occur in patients with CD throughout their lives and are associated with multiple factors, including sex and sex hormone levels. Moreover, sex is associated with differences in clinical presentation, onset, progression, and outcomes of disorders. OBJECTIVE: To investigate the prevalence of IMDs at diagnosis in patients with celiac disease (CD) and their first-degree relatives and to compare the findings between female and male patients of different age. METHODS: A retrospective study including Brazilian patients with CD who visited the same doctor during January 2012 to January 2017 was performed. Demographic and medical history data were collected through self-administered questionnaires and medical charts of the patients. In total, 213 patients were examined at diagnosis: 52 males (mean age, 40.0 years) and 161 females (mean age, 41.4 years). The patients were divided into two groups according to sex and age. RESULTS: IMDs were observed in 60.2% of the female (97/161) and 42.3% of the male patients (22/52; P=0.22). However, the frequency of IMDs was significantly higher in females aged 51-60 years than in males with same age (P=0.0002). Dermatitis herpetiformis (DH) was significantly more prevalent in males (P=0.02), whereas atopy was more prevalent in females (P=0.02). IMDs observed in first-degree relatives were similar to those observed in patients (70.9%; P<0.001), with a higher number observed in female relatives. CONCLUSION: The frequency of IMDs in CD patients was similar in all age groups and both sexes, except women diagnosed with CD after 51 years of age presented with an increased frequency of IMDs compared with males. Dermatitis herpetiformis was more prevalent in males, whereas atopy was more prevalent in females. No difference was observed in the type of IMDs between the first-degree relatives of both sexes.

RESUMO CONTEXTO: Até 15% das outras doenças imunomediadas (DIMs) podem ocorrer em pacientes com doença celíaca ao longo de suas vidas e estão associados a múltiplos fatores, incluindo sexo e níveis de hormônios sexuais. Além disso, o sexo está associado a diferenças na apresentação, início, progressão e desfecho das doenças. OBJETIVO: Investigar a prevalência de DIMs ao diagnóstico de doença celíaca e em seus familiares de primeiro grau e comparar os resultados entre sexo feminino e masculino em diferentes idades. MÉTODOS: Estudo retrospectivo incluindo pacientes brasileiros com diagnóstico de doença celíaca que realizaram acompanhamento com o mesmo médico no período de janeiro 2012 a janeiro de 2017. Dados demográficos e histórico médico foram coletados através de um questionário auto administrado e prontuários médicos dos pacientes envolvidos. No total, 213 pacientes eram portadores de doença celíaca, dos quais 52 do sexo masculino (idade média 40,0 anos) e 161 do sexo feminino (idade média 41,4 anos). Os pacientes foram divididos em dois grupos de acordo com o sexo e idade. RESULTADOS: DIMs foram observadas em 60,2% das pacientes femininas (97/161) e 42,4% dos pacientes masculinos (22/52; P=0,22). Entretanto, a frequência de DIMs foi significantemente maior em pacientes do sexo feminino com idade entre 51-60 anos que em pacientes masculinos da mesma idade (P=0,0002). Dermatite herpetiforme apresentou maior prevalência no sexo masculino (P=0,02), enquanto atopia obteve maior prevalência nas pacientes do sexo feminino (P=0,02). DIMs observadas em familiares de primeiro grau foram similares as encontradas nos pacientes (70,9%; P<0,001), com um maior número observado em familiares femininos. CONCLUSÃO: A frequência de DIMs em pacientes com doença celíaca foi similar nos grupos etários e ambos sexos, exceto as mulheres com diagnóstico de doença celíaca após a idade de 51 anos, as quais apresentaram um aumento na frequência de DIMs em comparação com os pacientes do sexo masculino. Dermatite herpetiforme apresentou maior prevalência em pacientes do sexo masculino, enquanto que atopia foi mais prevalente no sexo feminino. Em relação ao sexo, não foi observada diferença no tipo de DIMs observada entre os familiares de primeiro grau.

Survivin Expression in Simple Endometrial Polyps and Tamoxifen-associated Endometrial Polyps.

Endometrial polyps are benign pathologies originating as localized overgrowths of basal endometrium. Risk factors include endogenous and exogenous estrogen excess and tamoxifen (TAM) exposure. Our main objective was to investigate the role of an apoptosis-inhibiting protein, survivin, in endometrial polyps. We performed a cross-sectional, analytical study; our samples were obtained from the archives of the Department of Pathology. Sixty samples were included, comprising 20 TAM polyps, 20 simple endometrial polyps, and 20 cases of simple endometrial hyperplasia without atypia not associated with TAM use. Immunohistochemical staining with rabbit monoclonal anti-human survivin, clone EP 119, was performed. Survivin staining score was highest in the endometrial polyp group and lowest in the TAM polyp group (P<0.001). There was no correlation between survivin staining score and the age of patient (r=0.09), TAM exposure (r=-0.02), nor endometrial thickness (r=0.25). Endometrial polyps are frequently associated with TAM. The low expression of the antiapoptotic marker survivin in TAM polyps but high expression in other polypoid endometrium illustrates that different mechanisms are responsible in the pathogenesis of endometrial polyps. It is possible that there is a direct effect of TAM on apoptosis or indirect effect through a progesterone-related mechanism.

GASTRIC FUNDIC GLAND POLYPS: CAN HISTOLOGY BE USEFUL TO PREDICT PROTON PUMP INHIBITORS USE?

BACKGROUND: Fundic gland polyps allegedly increased in frequency in recent decades, and had attracted great attention due to possible association with prolonged proton pump inhibitor therapy. Prolonged use of this drug could cause parietal cell hyperplasia, obstruction of glandular lumen and cystic dilation of the gland. OBJECTIVE: This study aims to analyze clinical and pathological features of fundic gland polyps in patients with and without proton pump inhibitor therapy in a selected population from Brazil. METHODS: It was selected a sample of 101 Brazilian patients (78 females and 23 males), from a five years retrospective search of the files from a private pathology laboratory. The patients had an average age of 57 years and we included patients with a histological diagnosis of fundic gland polyp. The clinical data were obtained from their files and all histological slides were reviewed and examined with hematoxylin and eosin (HE) and Giemsa. RESULTS: Information about the use or non-use of proton pump inhibitors (PPI) was obtained in 84 patient files. In 17 cases we could not determine if PPI were used or not. Among those in which the information was available, a positive history of anti-acid therapy was observed in 63 (75.0%) patients. Parietal cell hypertrophy/hyperplasia and parietal cell protrusions were detected in most slides. Histological findings were identical in PPI users and PPI negative patients. Helicobacter pylori infection was detected in just two samples. Epithelial dysplasia or adenocarcinoma were not observed in our cases. Histopathological analysis of fundic gland polyps could not distinguish between PPI and non-PPI related cases. Parietal cell cytoplasmic protrusions, an alleged marker of prolonged acid suppression therapy, was detected in both groups. CONCLUSION: Histological features could not discriminate anti-acid therapy related fundic glands polyps in our patients.