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1.
Ann Surg ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33443907

RESUMO

OBJECTIVE: The aim of this study was to evaluate which mesh type yields lower recurrence and complication rates after ventral hernia repair. SUMMARY BACKGROUND DATA: More than 400,000 ventral hernia repairs are performed annually in the United States. Although the most effective method for repairing ventral hernias involves using mesh, whether to use biologic mesh versus synthetic mesh is controversial. METHODS: Single-blind, randomized, controlled, pragmatic clinical trial conducted from March 2014 through October 2018; 165 patients enrolled with an average follow up of 26 months. Patients were randomized 1:1 to have their ventral hernias repaired using either a biologic (porcine) or synthetic (polypropylene) mesh. The primary study outcome measure was hernia recurrence at 2 years. RESULTS: A total of 165 patients (68 men), mean age 55 years, were included in the study with a mean follow-up of 26 months. An intention-to-treat analysis noted that hernias recurred in 25 patients (39.7%) assigned to biologic mesh and in 14 patients (21.9%) assigned to synthetic mesh (P = 0.035) at 2 years. Subgroup analysis identified an increased rate of hernia recurrence in the biologic versus the synthetic mesh group under contaminated wound conditions (50.0% vs 5.9%; P for interaction = 0.041). Postoperative complication rates were similar for the 2 mesh types. CONCLUSIONS: The risk of hernia recurrence was significantly higher for patients undergoing ventral hernia repair with biologic mesh compared to synthetic mesh, with similar rates of postoperative complications. These data indicate that the use of synthetic mesh over biologic mesh to repair ventral hernias is effective and can be endorsed, including under contaminated wound conditions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02041494.

2.
Mult Scler Relat Disord ; 48: 102696, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360264

RESUMO

BACKGROUND: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) is a CNS demyelinating disease distinct from neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis. Some patients with MOGAD exhibit a highly-relapsing and steroid-dependent disease course for which optimal treatment is unknown. Interleukin-6 (IL-6) plays an important pathobiologic role in NMOSD with aquaporin-4 antibodies and preliminary data suggest similar mechanisms of CNS damage may occur in MOGAD. OBJECTIVE: To summarize our experience with and all current literature on the use of tocilizumab, an IL-6 inhibitor, for highly-relapsing MOGAD along with the underlying immunopathologic rationale. METHODS: This is a single-center report from a U.S. military tertiary referral hospital of all patients with clinically, radiographically, and serologically confirmed MOGAD who were treated with tocilizumab compiled with data from five other case series/reports from tertiary referral centers. The main outcomes of interest were reduction in annualized relapse rate and required dose of oral prednisone for symptomatic management. RESULTS: Ten total patients with relapsing MOGAD who were treated with intravenous or subcutaneous tocilizumab were identified. At our institution, a 20 year-old female with a 9-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab. In 28 months of follow up, she had no clinical relapses and was able to discontinue corticosteroids. Another 35 year-old female at our institution with a 10-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab for 6 months. Tocilizumab therapy was associated with relapse freedom, resolution of eye pain, and ability to discontinue corticosteroids. When compiled with data from all other case reports of relapsing MOGAD treated with tocilizumab, there have been zero clinical or radiographic relapses in 10 patients over an average treatment duration of 28.6 months. CONCLUSIONS: Tocilizumab is an IL-6 inhibitor that may be a promising therapeutic option for patients with relapsing MOGAD that has not responded to other immunotherapies. Our results support a key role for IL-6-related mechanisms in MOGAD disease activity. Its safety and tolerability profile, both in our own experience and based on its use for other FDA approved conditions, may even justify its use a first line therapy in select patients. Further research is needed to establish the safety and efficacy of IL-6 inhibition in MOGAD.

3.
Toxicol Pathol ; : 192623320975841, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33297858

RESUMO

With advancements in whole slide imaging technology and improved understanding of the features of pathologist workstations required for digital slide evaluation, many institutions are investigating broad digital pathology adoption. The benefits of digital pathology evaluation include remote access to study or diagnostic case materials and integration of analysis and reporting tools. Diagnosis based on whole slide images is established in human medical pathology, and the use of digital pathology in toxicologic pathology is increasing. However, there has not been broad adoption in toxicologic pathology, particularly in the context of regulatory studies, due to lack of precedence. To address this topic, as well as practical aspects, the European Society of Toxicologic Pathology coordinated an expert international workshop to assess current applications and challenges and outline a set of minimal requirements needed to gain future regulatory acceptance for the use of digital toxicologic pathology workflows in research and development, so that toxicologic pathologists can benefit from digital slide technology.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33176013

RESUMO

BACKGROUND: The Laparoscopic Approach to Cervical Cancer (LACC) trial is the first phase III randomised, multicentred trial to compare oncologic outcomes associated with open radical hysterectomy vs minimally invasive surgery (MIS) for treatment of early cervical cancer. AIM: To evaluate our surgical experience in patients with early cervical cancer. METHODS AND MATERIALS: The Lifehouse Gynaecologic Oncology database was queried based upon the eligibility criteria of the LACC study and included all FIGO 2009 stage (1A1 with lymph vascular space invasion, 1A2, 1B1) cervical cancer women from 2008-2018. Patients were also included in our study if they had abdominal radical trachelectomy (ART), laparoscopic radical hysterectomy (TLRH) and robotic radical trachelectomy (RRT). RESULTS: Forty-six women were identified with four exclusions. Thirty-seven women had stage 1B1 disease, 24 had a squamous cell carcinoma, 15 had an adenocarcinoma and three had an adenosquamous carcinoma of the cervix. Of the 42 eligible patients, 32 underwent an open abdominal approach (26 total abdominal radical hysterectomy (TARH), six ART) and ten a MIS approach (nine TLRH and one RRT) with a mean follow-up of 4.8 years. All 42 women had a pelvic lymph node dissection, eight women had nodal metastases and 16 patients received adjuvant chemoradiation. Two of the nine women in the laparoscopic radical hysterectomy group had a recurrence. Both had adenocarcinoma, stage 1B1 disease. There were no recurrences in the TARH group or radical trachelectomy groups. CONCLUSION: Our data, albeit limited in number, have reflected the results of the LACC trial that MIS was associated with a lower disease-free survival than open radical hysterectomy.

5.
BMJ Open ; 10(11): e037163, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33148724

RESUMO

OBJECTIVES: To explore the time trend and geographical distribution of childhood leukaemia incidence over the territory of the Italian region of Sardinia. SETTING: All hospitals departments, diagnostic centres and social security agencies in Sardinia were regularly screened in 1974-2003 to identify, register and review the diagnoses of incident cases of haematological malignancies (HM). PARTICIPANTS: The whole child population aged 0-14 resident in Sardinia. PRIMARY AND SECONDARY OUTCOME MEASURES: Incidence and time trend of childhood HM and childhood acute lymphoblastic leukaemia (ALL) over the study period, and use of Bayesian methods to plot the probability of areas with excess incidence on the regional map. RESULTS: Overall, 675 HM cases, including 378 ALL cases, occurred among children aged 0-14 years resident in Sardinia in 1974-2003, with an incidence rate of 6.97×10-5 (95% CI 6.47 to 7.51) and 3.85×10-5 (95% CI 3.48 to 4.26), respectively. Incidence of HM and ALL showed an upward trend along the study period especially among females. Three communes out of the 356 existing in 1974, namely Ittiri, Villa San Pietro and Carbonia, stand out as areas with excess incidence of HM and ALL in particular and another, Carloforte, for ALL only. CONCLUSIONS: Our results might serve as convincing arguments for extending the coverage of routine cancer registration over the whole Sardinian population, while prompting further research on the genetic and environmental determinants in the areas at risk.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33034043

RESUMO

BACKGROUND: Current guidelines recommend that resolution of a complete molar pregnancy (CMP) can only be confirmed once a negative ß-human chorionic gonadotropin (ß-hCG) has been maintained for six months following uterine surgical evacuation. However, multiple studies have found that the risk of developing gestational trophoblastic neoplasia (GTN) once a negative ß-hCG had been obtained is negligible, which suggests that a shorter follow-up may be reasonable. AIM: To determine the trend in ß-hCG following diagnosis of a CMP and the incidence of GTN, in a single unit. MATERIALS AND METHODS: All patients presenting to the tertiary hospital, Royal Prince Alfred Hospital Early Pregnancy Assessment Service (RPAH EPAS), with a histopathological diagnosis of a CMP between 2010 and 2017 were included. Data collected included age, parity, ß-hCG at diagnosis, subsequent ß-hCG levels, incidence of GTN and treatment required. RESULTS: Sixty-seven patients were diagnosed with CMP between January 2010 and July 2017 through RPAH EPAS. The mean age of women diagnosed with a CMP was 33 years. None of the 40 patients who spontaneously achieved a negative ß-hCG and completed their six months follow-up had a subsequent rise in ß-hCG. The median number of days from surgical evacuation to normalisation of ß-hCG was 55.5 days. Sixteen out of 67 patients who had a CMP required further management for persistent GTN. None of these patients achieved a negative ß-hCG prior to further management. CONCLUSIONS: Consideration could be made to decreasing the period of ß-hCG monitoring for women who achieve a spontaneous negative ß-hCG following surgical evacuation of a CMP.

7.
Surg Innov ; : 1553350620957802, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894031

RESUMO

Background. Esophagogastroduodenoscopy (EGD) is an important tool in the evolving specialty of acute care surgery (ACS). Understanding the types of nonelective EGDs performed by ACS groups is important for the development of ACS programs and the training of future general surgeons. Methods. We conducted a retrospective review of all EGDs performed by ACS surgeons at a single urban academic center over a 5-year period (January 2013-December 2018). Results. A total of 495 EGDs were performed, of which 129 (26%) were urgent, nonelective procedures. Patients who underwent urgent EGD were younger than those who underwent elective procedures (median 55 vs 60 years, P = .03), had higher American Society of Anesthesiologists (ASA) classes (median ASA 3 vs 2, P = .0002), and longer hospital stays (median 5 days vs 0 days, P < .0001). The most common indications for urgent endoscopies were the management of leak, dysphagia, or stenosis in patients with a history of foregut surgery, followed by the management of esophageal perforation. The success rate of endoscopic therapy was high (median 88%, interquartile range (IQR) 78-89%). However, some patients required multiple interventions (median 1, IQR 1-3), and patients treated for leaks were less likely to be successfully treated with endoscopic therapy alone than patients treated for other indications (success rate 65% vs 88%, P = .003). Conclusions. Our experience suggests that EGD has an important role in current ACS practice and that endoscopic management is safe and effective in a range of urgent surgical scenarios. Future ACS surgeons should be facile with endoscopic techniques.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32935336

RESUMO

BACKGROUND: Australian Cervical Screening Program guidelines no longer recommend colposcopy and cytology at six months following treatment of cervical intraepithelial neoplasia (CIN2/3) and a co-test of cure can be performed at 12 months without colposcopy. AIMS: To determine the usefulness of six-month colposcopy and cytology and routine colposcopy with co-testing at 12 months in detecting persistent or recurrent disease in patients treated for CIN2/3. MATERIALS AND METHODS: We conducted a review of all patients with histologically proven CIN2/3 who underwent a cervical excisional procedure between March 2012 and March 2017 in one specialised centre. RESULTS: We examined 1215 cases and 750 remained after exclusions for analysis. At six months (722 cases, 96.2%) seven of 42 (16.7%) patients with high-grade cytology had a high-grade colposcopy and 24 of 42 (57.1%) had a normal colposcopy. Persistent CIN2/3 was diagnosed in 12 cases (1.7%) and only 1/3 had a high-grade colposcopy. Cytology was more useful than colposcopy in detecting persistent disease. At 12 months (638 cases, 85%) routine colposcopy at the time of co-testing had a high false positive rate with all high-grade changes negative on biopsy and co-test. Recurrent CIN2/3 was diagnosed in five cases, and four had normal colposcopy at co-testing. CONCLUSIONS: There may be a delay in detection of persistent/recurrent CIN2/3 in a small number of cases without six-month colposcopy and cytology; however, it is not likely to negatively impact overall clinical outcome. Co-testing at 12 months following treatment of CIN2/3 without colposcopy is safe and routine colposcopy at collection of the co-test can be omitted.

9.
J Robot Surg ; 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737804

RESUMO

Surgery is the mainstay treatment for endometrial cancer and complex atypical endometrial hyperplasia. These conditions are more common in the obese women and as such these patients pose additional risks and challenges to surgery. Laparoscopic hysterectomy (LH) is preferred over open surgery in obese patients as it reduces surgical morbidity. However, more recently, robotic-assisted hysterectomy (RH) has been used in morbidly obese patients to overcome the limitations of conventional laparoscopy. To compare the surgical outcomes of morbidly obese patients undergoing LH or RH for endometrial cancer or complex atypical hyperplasia. A retrospective analysis of morbidly obese patients (BMI > 40 kg/m2) who underwent LH or RH for endometrial cancer or complex atypical hyperplasia at the Chris O'Brien Lifehouse Gynaecological Oncology Unit from 2015 to 2019 was performed. Data was collected from the prospectively maintained gynaecology oncology database and descriptive analysis was performed. 33 (51.6%) underwent LH and 31 (48.4%) had RH. More LHs were performed 2015-2017 period, whereas there were more RHs performed in 2018-2019 period (p = 0.01). The difference between theatre time use and operating time for LH surgery compared to RH was significantly shorter (45.7 for LH versus 61.9 min for RH, p = 0.009). RH was performed more commonly when BMI was > 50 kg/m2 (p = 0.02). There has been an increase in the use of RH in morbidly obese patients, particularly for women with a BMI > 50 kg/m2.

10.
Expert Opin Pharmacother ; 21(12): 1399-1405, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32543241

RESUMO

INTRODUCTION: In recent years there has been a dramatic rise in available disease-modifying therapies for the treatment of relapsing multiple sclerosis (MS). Dimethyl fumarate (DMF) is an oral drug approved by the FDA for relapsing MS with unique immunomodulatory and cytoprotective effects. AREAS COVERED: Herein, the authors provide the reader with a review of the literature obtained via a PubMed database search and provide their expert opinion on the use of DMF in clinical practice. The article details DMF's mechanism of action, long-term data on efficacy, tolerability and safety. EXPERT OPINION: Since approval, growing experience with DMF in clinical practice demonstrates a combination of efficacy, ease of administration along with an acceptable safety profile. The authors believe that DMF is a valuable long-term treatment option in patients with relapsing MS. However, long-term follow up studies are needed to provide further data on progressive multifocal leukoencephalopathy (PML) risk stratification for MS patients on treatment with DMF. Indeed, despite the strong association with lymphopenia, not all patients with DMF associated PML experienced prolonged overall lymphopenia, suggesting that additional predictive metrics are still needed.


Assuntos
Fumarato de Dimetilo/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Administração Oral , Ensaios Clínicos como Assunto , Fumarato de Dimetilo/administração & dosagem , Fumarato de Dimetilo/efeitos adversos , Fumarato de Dimetilo/farmacocinética , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacocinética , Leucopenia/induzido quimicamente , Assistência de Longa Duração , Esclerose Múltipla Recidivante-Remitente/imunologia , Resultado do Tratamento
11.
HPB (Oxford) ; 22(10): 1496-1503, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32340857

RESUMO

BACKGROUND: Ampullary stenosis following Roux-en-Y gastric bypass (RYGB) is increasingly encountered. We describe cases of biliary obstruction from ampullary stenosis and choledocholithiasis to illustrate the associated diagnostic and interventional challenges with this condition. METHODS: We reviewed medical records of patients with prior RYGB who underwent a biliary access procedure or surgery for non-malignant disease from January 2012-December 2018. RESULTS: We identified 15 patients (4 male, 11 female; mean age 53.7 years) who had RYGB on average 11.7 years (range 1-32) years before diagnosis of biliary obstruction. Fourteen patients reported abdominal pain, 5 had nausea/emesis, 12 had elevated liver function tests, and 6 had ascending cholangitis. Mean common bile duct (CBD) diameter at presentation was 16.9 mm (range 4.0-25.0 mm). Operations included 3 transduodenal ampullectomies (2 with biliary bypass), 2 CBD explorations with stone extraction, 1 laparoscopic cholecystectomy alone, 1 Whipple procedure, 1 balloon enteroscopy with sphincterotomy, and 7 transgastric endoscopic retrograde cholangiopancreatography. All ampulla pathology was benign in patients who underwent resection. At follow-up (mean 15.4 months; range 0.23-44.5 months), 12/15 (80%) reported symptom resolution or improvement. DISCUSSION: Ampullary stenosis after RYGB presents challenges for diagnostic evaluation and intervention, often requiring multi-disciplinary expertise. The underlying pathology remains to be elucidated.

12.
Genet Epidemiol ; 44(5): 442-468, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32115800

RESUMO

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.


Assuntos
Neoplasias da Mama/genética , Estudo de Associação Genômica Ampla , Receptores Estrogênicos/metabolismo , Neoplasias da Mama/metabolismo , Estrogênios/metabolismo , Feminino , Predisposição Genética para Doença , Genômica , Humanos , Medição de Risco , Transcriptoma , Proteínas de Transporte Vesicular/genética
13.
Aust N Z J Obstet Gynaecol ; 60(2): 278-283, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32065384

RESUMO

BACKGROUND: Salpingectomy may damage ovarian reserve by direct vascular interruption to the ovary or thermal vascular injury from electrosurgery. It is plausible that this risk may increase in the context of salpingectomy conducted for ectopic pregnancy due to the distension of the fallopian tube and vascular changes associated with pregnancy. AIM: To report anti-Müllerian hormone (AMH) concentrations before and after laparoscopic salpingectomy for ectopic pregnancy as an indicator of change in ovarian reserve. MATERIALS AND METHODS: Women aged 18-44 years scheduled for salpingectomy for tubal ectopic pregnancy were prospectively recruited. Serum AMH concentrations were measured immediately prior to surgery, then repeated four months post-operatively. In all cases, salpingectomy was conducted laparoscopically using bipolar electrosurgery and mechanical scissors. A group of women scheduled for uterine curettage for first trimester miscarriage was recruited to ensure any observed change in AMH concentration in the women undergoing salpingectomy was secondary to surgery, rather than an effect of pregnancy. RESULTS: Paired pre- and post-operative serum AMH concentrations were obtained from 32 women with tubal ectopic pregnancy. The mean age of the women was 33.6 ± 4.6 years. There was no significant difference in the median pre- and post-operative AMH concentrations (13.00 pmol/L (range 5-67 pmol/L) vs 15.25 pmol/L (range 3-96 pmol/L), P = 0.575). Median AMH concentrations also remained stable in women experiencing a first trimester miscarriage (10.40 pmol/L (range 3.9-37.8 pmol/L) vs 13.67 pmol/L (range 2.8-30.5 pmol/L), P = 0.185). CONCLUSION: Laparoscopic salpingectomy using electrosurgery and mechanical scissors does not damage ovarian reserve. AMH concentrations do not fluctuate from baseline in the first trimester of pregnancy.


Assuntos
Reserva Ovariana , Gravidez Ectópica/cirurgia , Salpingectomia , Adolescente , Adulto , Hormônio Antimülleriano/sangue , Feminino , Humanos , Laparoscopia , Gravidez , Estudos Prospectivos , Adulto Jovem
14.
Bone ; 131: 115115, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31689523

RESUMO

CONTEXT: The gut hormones peptide YY (PYY) and ghrelin mediate in part the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. However, preclinical data suggest these hormones also affect the skeleton and could contribute to postoperative bone loss. OBJECTIVE: We investigated whether changes in fasting serum total PYY and ghrelin were associated with bone turnover marker levels and loss of bone mineral density (BMD) after RYGB. DESIGN, SETTING, PARTICIPANTS: Prospective cohort of adults undergoing RYGB (n=44) at San Francisco academic hospitals. MAIN OUTCOME MEASURES: We analyzed 6-month changes in PYY, ghrelin, bone turnover markers, and BMD by dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT). We calculated the uncoupling index (UI), reflecting the relative balance of bone resorption and formation. RESULTS: Postoperatively, there was a trend for an increase in PYY (+25pg/mL, p=0.07) and a significant increase in ghrelin (+192pg/mL, p<0.01). PYY changes negatively correlated with changes in spine BMD by QCT (r=-0.36, p=0.02) and bone formation marker P1NP (r=-0.30, p=0.05). Relationships were significant after adjustments for age, sex, and weight loss. No consistent relationships were found between ghrelin and skeletal outcomes. Mean 6-month UI was -3.3; UI correlated with spine BMD loss by QCT (r=0.40, p=0.01). CONCLUSIONS: Postoperative PYY increases were associated with attenuated increases in P1NP and greater declines in spine BMD by QCT. Uncoupling of bone turnover correlated with BMD loss. These findings suggest a role for PYY in loss of bone mass after RYGB and highlight the relationship between intestinal and skeletal metabolism.

16.
Br J Cancer ; 121(2): 180-192, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31213659

RESUMO

BACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.


Assuntos
Estatura , Índice de Massa Corporal , Genes BRCA1 , Genes BRCA2 , Heterozigoto , Análise da Randomização Mendeliana , Mutação , Neoplasias Ovarianas/etiologia , Adulto , Idoso , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Modelos de Riscos Proporcionais
18.
Surg Obes Relat Dis ; 15(6): 964-968, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31076368

RESUMO

BACKGROUND: Obesity and high breast density both increase breast cancer risk but paradoxically are inversely related. Bariatric surgery decreases breast cancer risk, but its impact on mammographic breast density is not well understood. OBJECTIVES: We investigated how mammographic density changes after bariatric surgery and whether this change is related to weight loss. SETTING: University of California, San Francisco Medical Center. METHODS: We reviewed records from 349 prospectively collected patients who underwent bariatric surgery between 2013 and 2015 and identified 42 women with pre- and postoperative screening mammograms within 1.5 years of surgery. We recorded body mass index (BMI), height and Breast Imaging Reporting and Data System density and calculated BMI loss and total weight loss. Data were analyzed in Stata 14.2. RESULTS: Average age was 54.2 years, mean preoperative BMI was 43.8 kg/m2, mean BMI lost was 30.9%, and total weight loss was 31.1% at 1.3 years. Over one-third had a change in mammographic breast density, which increased 93.3% of the time (P < .001). Amount of weight loss was not associated with a density change. Patients with the lowest mammographic density preoperatively were most likely to have a density change (P = .02). CONCLUSIONS: Most women with a mammographic change had an increase in breast density, despite bariatric surgery being associated with reduced breast cancer risk. Baseline breast density was associated with a density change, but amount of weight loss was not. These findings suggest the metabolic effects of bariatric surgery have an effect on breast parenchyma independent of absolute BMI reduction or weight loss.


Assuntos
Cirurgia Bariátrica/estatística & dados numéricos , Densidade da Mama/fisiologia , Mamografia/estatística & dados numéricos , Obesidade/cirurgia , Perda de Peso/fisiologia , Índice de Massa Corporal , Peso Corporal/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Surg Obes Relat Dis ; 15(6): 864-870, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31060907

RESUMO

BACKGROUND: Gallstone disease occurs more commonly in the obese population and is often diagnosed during the preoperative evaluation for bariatric surgery. OBJECTIVES: This study analyzed outcomes of laparoscopic gastric bypass (LGB) and laparoscopic sleeve gastrectomy (SG), with and without cholecystectomy (LC), using data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program. SETTING: Patients reported to Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program participating centers in the United States and Canada in 2015. METHODS: All cases of LGB and SG, with and without LC, were analyzed. A 1:1 propensity-matched cohort was created for both SG and LGB, with and without concomitant LC. Multivariate logistic regression stratified by procedure was used to identify predictors of major complications after SG and LGB, using concomitant LC as a predictor. We also constructed a model for surgical site infections (SSIs) for SG group. RESULTS: Of 98,292 sleeve operations, 2046 (2%) had concomitant LC. Of 44,427 bypass operations, 1426 (3%) had concomitant LC. For the sleeve group, concomitant LC increased operative time by an average of 27 minutes but did not affect length of stay, mortality, or major complications. Concomitant LC was associated with increased SSI (1% versus .4%) and need for reoperation (1.6% versus .7%) in univariate models. After adjusting for other predictors, concomitant LC was associated with increased risk for SSI (odds ratio 2.5, confidence interval 1.0-5.9, P = .04). For the bypass group, concomitant LC increased operative time by an average of 28 minutes to the operation, and postoperative length of stay averaged ∼5 hours longer (2.4 versus 2.2 d, P = .03). Thirty-day complications were similar between the groups. On multivariate analysis, concomitant LC was not a significant risk factor for major complications. Only operative time was an independent factor for major complications. CONCLUSIONS: Concomitant LC with laparoscopic sleeve gastrectomy or gastric bypass did not affect mortality or risk of major complication. For sleeve patients, concomitant LC was associated with a .6% increased risk (.4% to 1.0%) of SSI. Concomitant LC with laparoscopic sleeve gastrectomy or gastric bypass is safe when indicated for gallstone disease.


Assuntos
Colecistectomia , Gastrectomia , Derivação Gástrica , Laparoscopia , Adulto , Colecistectomia/efeitos adversos , Colecistectomia/métodos , Colecistectomia/estatística & dados numéricos , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Gastrectomia/estatística & dados numéricos , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Derivação Gástrica/estatística & dados numéricos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco
20.
Nat Commun ; 10(1): 1741, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988301

RESUMO

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Feminino , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Locos de Características Quantitativas
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