Association between BRCA2 status and histologic variants (intraductal [IDC] and cribriform [CRIB] histology) in prostate cancer (PC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5579-5579
Author(s):  
Elena Castro ◽  
Daniela Correia Salles ◽  
Rebeca Lozano ◽  
Heather Thorne ◽  
Isabel Aragon ◽  
...  

5579 Background: IDC histology in PC has been suggested to associate with germline BRCA2 mutations (gBRCA2) in small series, leading to the potential recommendation of genetic testing for all PC patients with IDC in the primary tumor. Methods: We conducted a case-control study in which primary PC from 58 germline BRCA2 mutation carriers ( gBRCA2) and 116 from non-carriers (NC) were matched 1:2 by Gleason score and specimen type (core biopsy/prostatectomy). Samples were independently reviewed by two expert pathologists blinded to genetic status who established the presence of IDC and/or CRIB morphology with supportive immunohistochemical stains in a subset of cases. Next-generation sequencing, aCGH and/or FISH were used to assess for somatic mono-/bi-allelic BRCA2 alterations. PTEN protein loss was determined by IHC, and TMPRSS2-ERG was detected by FISH/qRT-PCR. Chi-square tests were used to compare the frequency of IDC and cribriform histology in gBRCA2 vs NC, as well as to assess the associations with other variables. Logistic regression models were built to identify independent factors associated with IDC and CRIB histology. Results: gBRCA2 cases were younger at diagnosis (median 61.3 vs 64, p < 0.01) and had T3-4 disease more often than NC cases (31% vs 10.5%, p < 0.01), but the two groups did not differ in any other clinical-pathologic characteristics. After independent histopathological review, 79 cases demonstrated IDC histology and 81 had CRIB histology. No differences in the prevalence of IDC (50% NC vs 36% gBRCA2, p = 0.09) or CRIB (43% NC vs 53% gBRCA2, p = 0.20) patterns were observed. The probability of IDC was higher in PC with bi-allelic BRCA2 alterations (OR 5.1, 95%CI 2.1-12.6), PTEN loss (OR 5.1, 95%CI 1.9-13.5) or both (OR 23.0, 95%CI 4.9-107.2) compared to those without these alterations. Bi-allelic BRCA2 alteration was also associated with higher probability of CRIB histology (OR 7.2, 95%CI 3.1-16.4). TMPRSS2-ERG fusions were not associated with IDC or CRIB histology. MVA confirmed the independent association of bi-allelic BRCA2 alteration (p < 0.01) and PTEN loss (p < 0.01) with IDC histology. Bi-allelic BRCA2 alteration (p < 0.01) and Gleason >8 (p < 0.01) were independent risk factors for CRIB histology. Conclusions: Primary PC with bi-allelic BRCA2 alterations was significantly associated with IDC and CRIB histology, independent of other clinical-pathologic factors (while gBRCA2 status alone was not). PTEN loss in primary PC was also independently associated with IDC, but not CRIB, histology.

2018 ◽  
Vol 40 (3) ◽  
pp. 249-250
Author(s):  
N A Chrysanthakopoulos ◽  
N S Dareioti

Aim: The present study aimed to investigate any possible association between ABO blood groups and lung cancer. Materials and Methods: The study was conducted on 122 lung cancer patients and 1,255 matched-healthy individuals that were reviewed retrospectively. Chi-square and logistic regression models were used for statistical analysis. Results: No significant difference between lung cancer patients and the control group was recorded regarding ABO blood types and the risk of lung cancer (p = 0.055, OR = 0.79, 95% CI 0.61–1.03). Male gender (p = 0.006, OR = 2.08, 95% CI 1.24–3.49) and smoking (p = 0.000, OR = 3.13, 95% CI 1.72–5.69) were significantly associated with the risk of lung cancer. Conclusion: No association between ABO blood types and the risk of lung cancer was observed.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5521-5521 ◽  
Author(s):  
Zhenlin Ju ◽  
Shannon Neville Westin ◽  
Russell Broaddus ◽  
Jie Li ◽  
Navdeep Pal ◽  
...  

5521 Background: Aberrations in the PI3K pathway, the central relay pathway of insulin signals, occur in the majority of endometrioid endometrial cancers. We explored the prognostic utility of PIK3CA, PIK3R1, and PTEN mutations, as well as PTEN protein loss, in the context of patient weight. Methods: Patients (pts) treated for endometrial cancer at a single institution between 2000 and 2009 were identified. Tumor DNA was extracted and exome sequencing performed using a 454 platform with confirmation of hot spot mutations by Sequenom. PTEN protein expression was determined by immunohistochemistry and reverse phase protein array (RPPA). RPPA for 135 relevant proteins was performed using a GeneTAC arrayer to create spot arrays. Slides were scanned, analyzed, and quantitated using Microvigene software. Results: One hundred eighty seven endometrioid endometrial cancer specimens were included. Median age was 61 yrs and median body mass index (BMI) was 33.5 kg/m2. The majority of pts had early stage (I/II) disease (74%) and grade 2 tumors (66%). There were no statistically significant associations between progression free survival (PFS) and PIK3CA, PIK3R1, PTEN mutation or loss. However, when stratified by BMI, PTEN loss was associated with a significantly improved PFS (p< 0.006) in obese (BMI > 30 kg/m2) pts. In contrast, PTEN loss was associated with a worse PFS (p<0.06) in non-obese (BMI < 30 kg/m2) pts. Further, PTEN loss in obese and non-obese pts resulted in distinct protein changes by RPPA, with canonical PI3K pathway activation observed only in the non-obese PTEN loss cohort. PTEN loss in obese pts was associated with decreased expression of CATENIN and phosphorylated FOXO3A. Conclusions: These data suggest the impact of PTEN loss on tumor biology and clinical outcomes must be interpreted in the context of BMI and provide potential explanation for prior discrepant findings on effect of PTEN status on prognosis in endometrial cancer. These data describe a clinically important interaction between metabolic state and tumor genetics that could potentially unveil the biologic underpinning of obesity-related cancers and may be relevant to ongoing clinical trials with PI3K pathway inhibitors.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 127-127 ◽  
Author(s):  
Filipe LF Carvalho ◽  
Tamara L Lotan ◽  
Sarah B. Peskoe ◽  
Jessica Hicks ◽  
Jennifer Good ◽  
...  

127 Background: Active surveillance is increasingly recommended for men with low-risk Gleason Score 3+3=6 (GS 6) prostate cancer. Yet, approximately one-third of patients with GS 6 cancer on biopsy are upgraded to higher GS at radical prostatectomy (RP). Previous studies have shown that clinical-pathologic parameters (age, prostate-specific antigen [PSA], prostate volume, extent of disease) are weak predictors of GS6 tumor upgrade. Our goal was to investigate the utility of PTEN as a molecular marker to predict upgrading in GS 6 biopsies. Methods: In a retrospective case-control study, 71 patients with GS 6 tumors on needle biopsy that were upgraded to GS 7 or higher cancer at RP (cases) were compared to 103 patients whose GS 6 tumors on needle biopsy were not upgraded at RP (controls). The most extensively involved needle core biopsy from each case was immunostained and scored for PTEN protein loss using a previously validated immunohistochemical (IHC) assay and binary scoring system. Confirmatory fluorescence in situ hybridization (FISH) was used to assess for PTEN gene deletion in biopsies with PTEN protein loss. The correlation of upgrading with PTEN loss and with clinical-pathologic variables was assessed by logistic regression. Results: Patients with upgraded cancers were older than controls (61.8 vs. 59.3 years), had higher mean pre-operative PSA levels (6.53 vs. 5.26 ng/mL), and a higher fraction of biopsy cores involved by tumor (0.42 vs, 0.36). However, of all pathologic variables, PTEN protein loss by IHC was most predictive of upgrading. Overall, PTEN protein loss was found in 18.3% (13 out of 71) of upgraded cases compared to 6.8% (7 out of 103) of controls (p=0.02). In the cases with PTEN protein loss, FISH confirmed homozygous PTEN deletion in 90% (9 out of 10) of upgraded tumors compared to 67% (4 out of 6) of interpretable not upgraded controls. On multivariate analyses, even after adjusting for age, preoperative PSA, clinical stage and race, GS 6 tumors with PTEN protein loss on biopsy were significantly more likely to be upgraded at RP compared to those without PTEN loss with odds ratio (OR) = 3.04 (1.08-8.55; p=0.035). Conclusions: In prostate needle biopsies, PTEN IHC may help distinguish men with low risk cancer from men with intermediate or higher risk cancers.


2021 ◽  
Author(s):  
Jingjin Zhang ◽  
Jinguo Chen ◽  
Hong Lin ◽  
Longxiang Huang ◽  
Shaoqing Ma ◽  
...  

Abstract Background: Acute acquired concomitant esotropia (AACE) is a relatively rare subtype of esotropia that can develop in older children (>5 years) and adults. The etiology of AACE is unknown, but there have been case studies describing risk factors. This study applied multiple regression analysis to explore risk factors and the impact of this subtype's surgical design esotropia and to gain insights into pathogenesis. Methods: Patients with Type III AACE and healthy controls, who were matched for age (±5 years) and refractive diopter (±1 D), were included in this study. All patients were treated between March 2018 to September 2020. We collected information on the number of hours spent performing near work per day, whether the patient wore glasses, and the refractive diopter of both the eyes. We also determined the deviation angles at both near- and far-vision in these individuals. Additionally, we measured the distance from the medial rectus insertion to the limbus in surgical patients.Results: Patients (n=51) with Type III AACE and sixty healthy control persons (n=60) were included in the study. We found that 99.96% of cases and 91.67% of controls had myopia. Among them, 60.8% of cases and 20.0% of controls did not wear glasses for near work. Twelve cases were treated with a prism, and thirty-nine were treated surgically. The average time devoted to near work per day was 7.24±1.91 (range: 4-12) hours and 3.7±1.29 (range: 2-7) in cases and controls, respectively. In univariate and multivariate logistic regression models, Type III AACE was significantly associated with increased hours of near work per day and near work without wearing glasses.Conclusions: Increased hours of near work per day and myopic patients performing near work without glasses are independent risk factors of Type III AACE. A satisfactory result can be obtained by optimizing the foot correction with the maximum and the most stable angles before operation.


2019 ◽  
Vol 2 (1) ◽  
pp. 39-44
Author(s):  
Ermawati Ermawati ◽  
Hafni Bachtiar

Prolap organ panggul merupakan kondisi yang mempengaruhi kualitas hidup wanita. Prolaps organ panggul ini dapat disebabkan oleh perlukaan sewaktu proses persalinan, proses penuaan, komposisi jaringan pada seorang wanita, batuk- batuk kronis, atau sering melakukan pekerjaan berat. Pengenalan dini prolaps terkait dengan prognosis pemulihan anatomik dan fungsional organ panggul. Hingga kini, penerapannya dalam dunia klinis belum banyak sehingga pelatihan dan pembelajaran lebih lanjut tentang pelvic organ prolapse quantification (POPQ) jelas diperlukan. Penelitian ini dilakukan dengan metode case control study di polikilinik Obgin RSUP. Dr. M. Djamil Padang mulai bulan September 2013 sampai jumlah sampel terpenuhi sebanyak 98 orang. Dengan 49 orang kelompok kontrol dan 49 orang kelompok kasus .Analisis dilakukan untuk menilai hubungan usia, paritas, pekerjaan dan indek massa tubuh dengan kejadian prolap organ panggul berdasarkan skor POPQ. Data disajikan dalam bentuk tabel. Data diuji dengan t test dan chi square test. Jika p<0,05 menunjukan hasil yang bermakna. Terdapat hubungan yang bermakna antara usia dengan kejadian prolap organ panggul dengan (p<0,05) dan OR 27,871.terdapat hubungan yang bermakna antara paritas dengan kejadian prolap organ panggul dengan (p<0,05) dan OR 52,970.Dari analisa statistik pekerjaan tidak bisa di uji secara statistik.indek massa tubuh tidak terdapat hubungan yang bermakna terhadap kejadian prolap organ panggul.(p>0,05)


2020 ◽  
Vol 4 (2) ◽  
pp. 107-119
Author(s):  
Swaidatul Masluhiya AF ◽  
Irma Irma

Masalah kesehatan masyarakat yang cukup seriuspada kelompok usia balita sampai saat ini adalah kejadian malnutrisi, hal iniberdampak pada gangguan pertumbuhan dan perkembangan fisik balita. Malnutrisi juga dapat menyebabkan balita menjadi rentan terhadap penyakit infeksi. Beberapa faktor penyebab malnutrisi diantaranya faktor makanan dan penyakit infeksi yang mungkin diderita anak, faktor ketahanan pangan dikeluarga, pola pengasuhan anak, pelayanan kesehatan dan kesehatan lingkungan. Tujuan penelitian ini adalah untuk mengetahui apakah sindrom penyakit tropis merupakan prediktor terjadinya gizi kurang pada balita. Penelitian ini termasuk penelitian observasional analitik dengan rancangan Case Control Study. Populasi dalam penelitian ini adalah seluruh pasangan ibu dan balita yang ada di daerah pesisir kecamatan Nambo Kota Kendari denganteknik simple randam sampling di dapatkan jumlah sampel  sebanyak 164 orang yang terdiri dari dua kelompok yaitu kelompok kasus dan kelompok kontrol dengan perbandingan 1:1. Data dianalisis secara statistik dengan uji Chi square pada tingkat kepercayaan 95% (α=0,05) dengan mempertimbangkan nilai Odd Ratio dan nilai Confidence Interval. Hasil penelitian ini menunjukan bahwa sindrom penyakit tropis (diare dengan р-value = 0,001 dan OR = 4,162, batuk – batuk dengan р-value = 0,001 dan OR = 3,552,ISPAnon pneumoni dengan р-value = 0,004 dan OR = 3,003) merupakan faktor prediktor terjadinya malnutrisi pada balita sedangkan infeksi cacing dengan р-value = 0,056 dan OR= 1,773 bukan merupakan faktor prediktor terjadinya malnutrisi pada balita di daerah pesisir Kecamatan Nambo Kota Kendari


Author(s):  
Valentino D’Onofrio ◽  
Agnes Meersman ◽  
Sara Vijgen ◽  
Reinoud Cartuyvels ◽  
Peter Messiaen ◽  
...  

Abstract Background There is a clear need for a better assessment of independent risk factors for in-hospital mortality, ICU admission, and bacteremia in patients presenting with suspected sepsis at the ED. Methods A prospective observational cohort study including 1690 patients was performed. Two multivariable logistic regression models were used to identify independent risk factors. Results SOFA score of ≥2 and serum lactate of ≥2mmol/L were associated with all outcomes. Other independent risk factors were individual SOFA variables and SIRS variables but varied per outcome. MAP&lt;70 mmHg negatively impacted all outcomes. Conclusion These readily available measurements can help with early risk stratification and prediction of prognosis.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mary Rezk-Hanna ◽  
Ian W. Holloway ◽  
Joy Toyama ◽  
Umme Shefa Warda ◽  
Lorree Catherine Berteau ◽  
...  

Abstract Background Tobacco smoking using a hookah (i.e., waterpipe) is a global epidemic. While evidence suggests that sexual minorities (SM) have higher odds of hookah use compared to heterosexuals, little is known about their hookah use patterns and transitions. We sought to examine transitions between hookah smoking and use of other tobacco and electronic (e-) products among SM adults aged 18 years of age and older versus their heterosexual counterparts. Methods We analyzed nationally representative data of ever and current hookah smokers from Wave 1 (2013–2014; ever use n = 1014 SM and n = 9462 heterosexuals; current use n = 144 SM and n = 910 heterosexuals) and Wave 2 (2014–2015; ever use n = 901 SM and n = 8049 heterosexuals; current use n = 117 SM and n = 602 heterosexuals) of the Population Assessment of Tobacco and Health Study. Comparisons between groups and gender subgroups within SM identity groups were determined with Rao-Scott chi-square tests and multivariable survey-weighted multinomial logistic regression models were estimated for transition patterns and initiation of electronic product use in Wave 2. Results Ever and current hookah smoking among SM adults (ever use Wave 1: 29% and Wave 2: 31%; current use Wave 1: 4% and Wave 2: 3%) was higher than heterosexuals (ever use Wave 1: 16% and Wave 2: 16%; current use Wave 1: 1% and Wave 2: 1%; both p < 0.0001). Among SM adults who reported hookah use at Wave 1, 46% quit hookah use at Wave 2; 39% continued hookah use and did not transition to other products while 36% of heterosexual adults quit hookah use at Wave 2 and 36% continued hookah use and did not transition to other products. Compared with heterosexuals, SM adults reported higher use of hookah plus e-products (Wave 2 usage increased by 65 and 83%, respectively). Conclusions Compared to heterosexuals, in addition to higher rates of hookah smoking, higher percentages of SM adults transitioned to hookah plus e-product use between 2013 and 2015. Results have implications for stronger efforts to increase awareness of the harmful effects of hookah as well as vaping, specifically tailored among SM communities.


2021 ◽  
Vol 10 (14) ◽  
pp. 3177
Author(s):  
Edyta Szymanska ◽  
Maciej Dadalski ◽  
Joanna Sieczkowska-Golub ◽  
Dorota Jarzebicka ◽  
Monika Meglicka ◽  
...  

Background: Infusion reactions (IRs) are the most common adverse events (AEs) of infliximab (IFX) treatment in patients with inflammatory bowel disease (IBD). Prophylactic premedication (PM) with corticosteroids or antihistamines prior to IFX infusions has been used in clinical practice, but its efficacy is not known. The aim of this study was to assess the influence of steroid PM on IR incidence in pediatric patients with IBD receiving IFX. Methods: We performed a case–control study that included pediatric patients with IBD receiving IFX. Patients were divided into four subgroups according to the agent and PM they received: Remicade (original drug) + PM, and two biosimilars—Reshma +/− PM, and Flixabi—PM. At our site, until 2018, PM with steroids was used as a part of standard IFX infusion (PM+); however, since then, this method has no longer been administered (PM−). IRs were divided into mild/severe reactions. Differences between subgroups were assessed with the appropriate chi-square test. Multivariate logistic regression was used to assess associations between PM and IR incidence, correcting for co-medication usage. Results: There were 105 children (55 PM+, 44 male, mean age 15 years) included in the study who received 1276 infusions. There was no difference between the PM+ and PM− subgroups, either in incidence of IR (18.2% vs. 16.0% of patients, p > 0.05) or in percentage of infusions followed by IR (2.02% vs. 1.02% of infusions, p > 0.5). The OR of developing IR when using PM was 0.34, and the difference in IRs ratio in PM+ and PM− patients was not statistically significant (95% CI, 0.034–1.9). There were 11/18 (61.1%) severe IRs (anaphylactic shock) reported in all patients (both PM+ and PM−). Conclusion: At our site, the incidence of IR was low, and PM did not decrease the incidence of IR in pediatric patients with IBD receiving IFX. These results indicate that PM with steroids should not be a standard part of IFX infusion to prevent IR.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyriaki Papantoniou ◽  
Gemma Castaño-Vinyals ◽  
Ana Espinosa ◽  
Michelle C. Turner ◽  
Vicente Martín-Sánchez ◽  
...  

AbstractSleep duration is a novel and potentially modifiable risk factor for cancer. We evaluated the association of self-reported sleep duration and daytime napping with odds of colorectal and gastric cancer. We included 2008 incident colorectal cancer cases, 542 gastric cancer cases and 3622 frequency-matched population controls, recruited in the MCC-Spain case–control study (2008–2013). Sleep information, socio-demographic and lifestyle characteristics were obtained through personal interviews. Multivariable adjusted logistic regression models were used to estimate odds ratios (OR) with 95% confidence intervals (CI) for cancer, across categories of sleep duration (≤ 5, 6, 7, 8, ≥ 9 hours/day), daytime napping frequency (naps/week) and duration (minutes/nap). Compared to 7 hours of sleep, long sleep was associated with increased odds of colorectal (OR≥9 hours: 1.59; 95%CI 1.30–1.94) and gastric cancer (OR≥9 hours: 1.95; 1.37–2.76); short sleep was associated with increased odds of gastric cancer (OR≤5 hours: 1.32; 0.93–1.88). Frequent and long daytime naps increased the odds of colorectal (OR6–7 naps/week, ≥30 min: 1.32; 1.14–1.54) and gastric cancer (OR6–7 naps/week, ≥30 min: 1.56; 1.21–2.02). Effects of short sleep and frequent long naps were stronger among participants with night shift-work history. Sleep and circadian disruption may jointly play a role in the etiology of colorectal and gastric cancer.


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