Introduction - University of Pittsburgh
9144001143000ENDOMETRIUM CHARACTERISTICS IN MORBIDLY OBESE BARIATRIC SURGERY CANDIDATES: AN EXPLANATORY ANALYSISbyAiym KaiyrlykyzyMD, Karaganda State Medical University, Kazakhstan, 2010Submitted to the Graduate Faculty ofEpidemiologyGraduate School of Public Health in partial fulfillment of the requirements for the degree ofMaster of Public HealthUniversity of Pittsburgh201400ENDOMETRIUM CHARACTERISTICS IN MORBIDLY OBESE BARIATRIC SURGERY CANDIDATES: AN EXPLANATORY ANALYSISbyAiym KaiyrlykyzyMD, Karaganda State Medical University, Kazakhstan, 2010Submitted to the Graduate Faculty ofEpidemiologyGraduate School of Public Health in partial fulfillment of the requirements for the degree ofMaster of Public HealthUniversity of Pittsburgh20149144000UNIVERSITY OF PITTSBURGHGRADUATE SCHOOL OF PUBLIC HEALTHThis essay is submittedbyAiym KaiyrlykyzyonApril 23, 2014and approved byEssay Advisor:Faina Linkov, PhD, MPH______________________________________Associate ProfessorDepartment of EpidemiologyGraduate School of Public HealthDepartment of Ob/Gyn and Reproductive SciencesSchool of MedicineUniversity of PittsburghEssay Reader:Ronald LaPorte, PhD______________________________________ProfessorDepartment of EpidemiologyGraduate School of Public HealthUniversity of Pittsburgh00UNIVERSITY OF PITTSBURGHGRADUATE SCHOOL OF PUBLIC HEALTHThis essay is submittedbyAiym KaiyrlykyzyonApril 23, 2014and approved byEssay Advisor:Faina Linkov, PhD, MPH______________________________________Associate ProfessorDepartment of EpidemiologyGraduate School of Public HealthDepartment of Ob/Gyn and Reproductive SciencesSchool of MedicineUniversity of PittsburghEssay Reader:Ronald LaPorte, PhD______________________________________ProfessorDepartment of EpidemiologyGraduate School of Public HealthUniversity of Pittsburghcenter4648200Copyright ? by Aiym Kaiyrlykyzy201400Copyright ? by Aiym Kaiyrlykyzy2014ABSTRACTcenter-221615Faina Linkov, PhD, MPHENDOMETRIUM CHARACTERISTICS IN MORBIDLY OBESE BARIATRIC SURGERY CANDIDATES: AN EXPLANATORY ANALYSISAiym Kaiyrlykyzy, MPHUniversity of Pittsburgh, 201400Faina Linkov, PhD, MPHENDOMETRIUM CHARACTERISTICS IN MORBIDLY OBESE BARIATRIC SURGERY CANDIDATES: AN EXPLANATORY ANALYSISAiym Kaiyrlykyzy, MPHUniversity of Pittsburgh, 2014Introduction: Endometrial cancer (EC) is the most prevalent gynecologic malignancy in the US and is strongly associated with obesity. With the increasing number of morbidly obese women of reproductive age, endometrial health and prevention of endometrial malignancies is a pressing public health concern. Objective: To explore the rate of endometrial pathology in a small cohort of cancer free, morbidly obese, female bariatric surgery candidates and to determine the success rate of Pipelle endometrial sampling in this group. Methods: Thirty-seven bariatric surgery candidates provided informed consent for endometrial sampling in an outpatient setting. Women were eligible to participate if they were considering bariatric surgery, had an intact uterus, had no history of EC, and had not undergone endometrial ablation. Endometrial samples were obtained using a Pipelle endometrial suction curette and processed at the Pathology Department of Magee-Womens Hospital. Results: We were unable to obtain samples from five women due to anatomical anomalies, such as cervical stenosis. Of the 32 collected samples, 8 were classified as insufficient to evaluate; therefore, 24 readable biopsies were analyzed. Of these 24, 1 was diagnosed as hyperplasia without atypia, 1 hyperplasia with atypia, 3 suggestive endometrial polyps, 1 endometrial tubal metaplasia, 5 normal secretory, 8 proliferative pattern, and 2 benign atrophic endometrial tissue. Four samples revealed hormonal effect likely due to pharmacologic treatment for uterine bleeding. While histologic evidence of unopposed estrogen was prevalent, no one presented with cancer. Thus, this study found an overall rate of subclinical pathology of 20% among women who could be sampled and an overall 35% Pipelle failure rate, including the 5 technically impossible biopsies suggesting morbidly obese patients may be difficult to evaluate with Pipelle biopsy. Conclusion: Morbidly obese women are at a higher risk of having undiagnosed endometrial pathology, at rates greater than previously reported. Results suggest the importance of additional research to more thoroughly examine relationships between levels of obesity and endometrial pathology, as well as to explore underlying mechanisms. This line of research may open new avenues for endometrial cancer prevention and control, and possibly revert this major public health problem. TABLE OF CONTENTS TOC \o "2-4" \h \z \t "Heading 1,1,Appendix,1,Heading,1" 1.0Introduction PAGEREF _Toc258006943 \h 11.1endometrial cancer PAGEREF _Toc258006944 \h 11.2endometrial cancer risk factors PAGEREF _Toc258006945 \h 31.2.1Hormonal imbalance and EC PAGEREF _Toc258006946 \h 31.2.2Obesity and EC PAGEREF _Toc258006947 \h 41.3endometrial sampling PAGEREF _Toc258006948 \h 61.4present study PAGEREF _Toc258006949 \h 62.0materials and methods PAGEREF _Toc258006950 \h 72.1study participants PAGEREF _Toc258006951 \h 72.2measurements PAGEREF _Toc258006952 \h 82.3statistical analysis PAGEREF _Toc258006953 \h 93.0results PAGEREF _Toc258006954 \h 104.0discussion PAGEREF _Toc258006955 \h 15bibliography PAGEREF _Toc258006956 \h 19List of tables TOC \h \z \c "Table" Table 1. Participant characteristics PAGEREF _Toc259135247 \h 10Table 2. Participant characteristics by Pipelle sampling success PAGEREF _Toc259135248 \h 12Table 3. Participant characteristics by histopathological analysis of endometrial biopsies PAGEREF _Toc259135249 \h 13List of figures TOC \h \z \c "Figure" Figure 1. Distribution of endometrial biopsy characteristics PAGEREF _Toc259135250 \h 13Introductionendometrial cancerCancer of the uterus (endometrial cancer, or EC) is the most common gynecological cancer in the US.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaW5rb3Y8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 1-3 The American Cancer Society estimates that at least 52,630 new cases of EC will be diagnosed, and about 8,590 women will die from EC in 2014. ADDIN EN.CITE <EndNote><Cite><RecNum>30</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>30</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">30</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors></contributors><titles><title>American Cancer Society</title></titles><volume>2013</volume><number>October 10</number><dates><pub-dates><date>01/17/2013</date></pub-dates></dates><urls><related-urls><url> 10</custom2></record></Cite></EndNote>3 Women have a one in 37 lifetime risk of developing EC. Seventy five present cases of EC are found in women aged 55 or over. ADDIN EN.CITE <EndNote><Cite><RecNum>30</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>30</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">30</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors></contributors><titles><title>American Cancer Society</title></titles><volume>2013</volume><number>October 10</number><dates><pub-dates><date>01/17/2013</date></pub-dates></dates><urls><related-urls><url> 10</custom2></record></Cite></EndNote>3 However, from 2006 to 2010, incidence rates of endometrial cancer increased by 1.5% per year among women younger than 50 years and by 2.6% per year among women 50 and older. Death rates for cancer of the uterine corpus for the same period increased by 1.5% per year among women younger than 50 and were stable among women 50 and older. ADDIN EN.CITE <EndNote><Cite><Year>2014</Year><RecNum>83</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>83</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">83</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors></contributors><titles><title>American Cancer Society: Cancer Facts and Figures</title></titles><volume>2014</volume><number>April 12</number><dates><year>2014</year></dates><pub-location>Atlanta, GA</pub-location><publisher>American Cancer Society</publisher><urls><related-urls><url> 12</custom2></record></Cite></EndNote>4 EC is more common in white women; however, black women have a poorer prognosis of cancer due to comorbidities, genetic alterations, and limited access to healthcare. As a result, they have later diagnostic, treatment disparities and higher mortality. ADDIN EN.CITE <EndNote><Cite><Author>Allard</Author><Year>2009</Year><RecNum>80</RecNum><DisplayText><style face="superscript">5</style></DisplayText><record><rec-number>80</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">80</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Allard, J. E.</author></authors></contributors><titles><title>Race disparities between black and white women in the incidence, treatment, and prognosis of endometrial cancer</title><secondary-title>Cancer control</secondary-title></titles><periodical><full-title>Cancer control</full-title></periodical><pages>53</pages><volume>16</volume><number>1</number><dates><year>2009</year></dates><publisher>H. Lee Moffitt Cancer Center and Research Institute</publisher><isbn>1073-2748</isbn><urls></urls></record></Cite></EndNote>5 The overall 5-year relative survival rate for blacks (61%) is lower compared to whites (84%). ADDIN EN.CITE <EndNote><Cite><Year>2014</Year><RecNum>83</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>83</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">83</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors></contributors><titles><title>American Cancer Society: Cancer Facts and Figures</title></titles><volume>2014</volume><number>April 12</number><dates><year>2014</year></dates><pub-location>Atlanta, GA</pub-location><publisher>American Cancer Society</publisher><urls><related-urls><url> 12</custom2></record></Cite></EndNote>4 There are two major types of endometrial cancer. Type I is a low-grade, well-differentiated tumor called endometrioid adenocarcinoma. It is the most common type of endometrial tumors that represents up to 80% of all EC and associated with endometrial tissue proliferation. ADDIN EN.CITE <EndNote><Cite><Author>Kurman</Author><Year>2010</Year><RecNum>33</RecNum><DisplayText><style face="superscript">6</style></DisplayText><record><rec-number>33</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">33</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kurman, Robert J.</author><author>McConnell, Thomas G.</author></authors></contributors><titles><title>Characterization and Comparison of Precursors of Ovarian and Endometrial Carcinoma: Parts I and II</title><secondary-title>International Journal of Surgical Pathology</secondary-title></titles><periodical><full-title>International Journal of Surgical Pathology</full-title></periodical><pages>181S-189S</pages><volume>18</volume><number>3 suppl</number><dates><year>2010</year><pub-dates><date>June 1, 2010</date></pub-dates></dates><urls><related-urls><url> Type II carcinomas are less common and often include squamous, serous papillary, or clear cells. This type of EC is poorly differentiated, grows quickly, and tends to aggressively spread to surrounding tissues and other organs through the lymph system and bloodstream. ADDIN EN.CITE <EndNote><Cite><RecNum>30</RecNum><DisplayText><style face="superscript">3,7</style></DisplayText><record><rec-number>30</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">30</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors></contributors><titles><title>American Cancer Society</title></titles><volume>2013</volume><number>October 10</number><dates><pub-dates><date>01/17/2013</date></pub-dates></dates><urls><related-urls><url> 10</custom2></record></Cite><Cite><Author>Horn</Author><Year>2007</Year><RecNum>72</RecNum><record><rec-number>72</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">72</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Horn, Lars-Christian</author><author>Meinel, Alexandra</author><author>Handzel, Romy</author><author>Einenkel, Jens</author></authors></contributors><titles><title>Histopathology of endometrial hyperplasia and endometrial carcinoma: An update</title><secondary-title>Annals of Diagnostic Pathology</secondary-title></titles><periodical><full-title>Annals of Diagnostic Pathology</full-title></periodical><pages>297-311</pages><volume>11</volume><number>4</number><keywords><keyword>Endometrial carcinoma</keyword><keyword>Endometrial hyperplasia</keyword><keyword>Type 1 and type 2 carcinoma</keyword><keyword>Microscopy</keyword><keyword>Surgical pathology</keyword></keywords><dates><year>2007</year><pub-dates><date>8//</date></pub-dates></dates><isbn>1092-9134</isbn><urls><related-urls><url> Even though both tumor types share similar risk factors such as parity, oral contraceptive use, age at menarche, diabetes, body mass index (BMI) has a greater impact on type I tumors than on type II tumors.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TZXRpYXdhbjwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+
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ADDIN EN.CITE.DATA 8Many studies of endometrial cancer are focused on endometrioid adenocarcinomas, because about 80% of EC cases are type I endometrial tumors. Type I EC an has estrogen driven mechanism and is associated with hyperplasia. ADDIN EN.CITE <EndNote><Cite><Author>Boruban</Author><Year>2008</Year><RecNum>68</RecNum><DisplayText><style face="superscript">9</style></DisplayText><record><rec-number>68</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">68</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Boruban, Melih C.</author><author>Altundag, Kadri</author><author>Kilic, Gokhan S.</author><author>Blankstein, Josef</author></authors></contributors><titles><title>From endometrial hyperplasia to endometrial cancer: insight into the biology and possible medical preventive measures</title><secondary-title>European Journal of Cancer Prevention</secondary-title></titles><periodical><full-title>European Journal of Cancer Prevention</full-title></periodical><pages>133-138 10.1097/CEJ.0b013e32811080ce</pages><volume>17</volume><number>2</number><keywords><keyword>biology</keyword><keyword>endometrial cancer</keyword><keyword>endometrial hyperplasia</keyword><keyword>prevention</keyword><keyword>00008469-200804000-00009</keyword></keywords><dates><year>2008</year></dates><isbn>0959-8278</isbn><urls><related-urls><url> Endometrial hyperplasia (EH) is a diagnostic category that includes a range of lesions and is characterized by an increased proliferation of endometrial cells. EH is a well-known precursor for EC, especially complex EH with atypia.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EYXVkPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 10-12 Timely diagnosis of EH is important, as approximately 30% of women with untreated complex hyperplasia with atypia progress to carcinoma. ADDIN EN.CITE <EndNote><Cite><Author>Lacey Jr</Author><Year>2009</Year><RecNum>71</RecNum><DisplayText><style face="superscript">12</style></DisplayText><record><rec-number>71</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">71</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lacey Jr, James V.</author><author>Chia, Victoria M.</author></authors></contributors><titles><title>Endometrial hyperplasia and the risk of progression to carcinoma</title><secondary-title>Maturitas</secondary-title></titles><periodical><full-title>Maturitas</full-title></periodical><pages>39-44</pages><volume>63</volume><number>1</number><keywords><keyword>Uterine cancer</keyword><keyword>WHO</keyword><keyword>Complex atypical hyperplasia</keyword><keyword>Cancer precursor</keyword><keyword>Progression risk</keyword></keywords><dates><year>2009</year><pub-dates><date>5/20/</date></pub-dates></dates><isbn>0378-5122</isbn><urls><related-urls><url> Some studies report increased risk for EC in women with hyperplasia depending on type (simple/complex) and presence of atypia as a primary criterion in predicting the likelihood of progression to carcinoma. ADDIN EN.CITE <EndNote><Cite><Author>Kurman</Author><Year>2010</Year><RecNum>33</RecNum><DisplayText><style face="superscript">6</style></DisplayText><record><rec-number>33</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">33</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kurman, Robert J.</author><author>McConnell, Thomas G.</author></authors></contributors><titles><title>Characterization and Comparison of Precursors of Ovarian and Endometrial Carcinoma: Parts I and II</title><secondary-title>International Journal of Surgical Pathology</secondary-title></titles><periodical><full-title>International Journal of Surgical Pathology</full-title></periodical><pages>181S-189S</pages><volume>18</volume><number>3 suppl</number><dates><year>2010</year><pub-dates><date>June 1, 2010</date></pub-dates></dates><urls><related-urls><url> Alternatively, Endometrial Intraepithelial Neoplasia (EIN), monoclonal premalignant endometrial glandular lesion, has been suggested as the precursor of the development of endometrioid-type endometrial adenocarcinoma. EIN has been opposed to EH, which was defined as anovulatory or persistent estrogen exposed endometria, and considered to be benign. ADDIN EN.CITE <EndNote><Cite><Author>Mutter</Author><Year>2000</Year><RecNum>86</RecNum><DisplayText><style face="superscript">13</style></DisplayText><record><rec-number>86</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">86</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mutter, George L.</author></authors></contributors><titles><title>Endometrial Intraepithelial Neoplasia (EIN): Will It Bring Order to Chaos?</title><secondary-title>Gynecologic Oncology</secondary-title></titles><periodical><full-title>Gynecologic Oncology</full-title></periodical><pages>287-290</pages><volume>76</volume><number>3</number><keywords><keyword>histopathology</keyword><keyword>endometrial carcinoma</keyword><keyword>endometrial hyperplasia</keyword><keyword>nomenclature</keyword></keywords><dates><year>2000</year><pub-dates><date>3//</date></pub-dates></dates><isbn>0090-8258</isbn><urls><related-urls><url> cancer risk factorsRisk factors for endometrial cancer may range from environmental factors to genetic predisposing contributors. Some risk factors are related to reproduction such as early age at menarche, late age at menopause and nulliparity. Others are more directly estrogen-related, such as use of unopposed estrogen replacement therapy, which is associated with an increased risk. ADDIN EN.CITE <EndNote><Cite><Author>Kaaks</Author><Year>2002</Year><RecNum>70</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>70</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">70</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kaaks, Rudolf</author><author>Lukanova, Annekatrin</author><author>Kurzer, Mindy S.</author></authors></contributors><titles><title>Obesity, Endogenous Hormones, and Endometrial Cancer Risk: A Synthetic Review</title><secondary-title>Cancer Epidemiology Biomarkers & Prevention</secondary-title></titles><periodical><full-title>Cancer Epidemiology Biomarkers & Prevention</full-title></periodical><pages>1531-1543</pages><volume>11</volume><number>12</number><dates><year>2002</year><pub-dates><date>December 1, 2002</date></pub-dates></dates><urls><related-urls><url> Environmental factors include lifestyle choices such as low physical activity, and sedentary lifestyle, which most likely lead to obesity. ADDIN EN.CITE <EndNote><Cite><RecNum>30</RecNum><DisplayText><style face="superscript">3</style></DisplayText><record><rec-number>30</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">30</key></foreign-keys><ref-type name="Web Page">12</ref-type><contributors></contributors><titles><title>American Cancer Society</title></titles><volume>2013</volume><number>October 10</number><dates><pub-dates><date>01/17/2013</date></pub-dates></dates><urls><related-urls><url> 10</custom2></record></Cite></EndNote>3 Epidemiological studies suggest that obesity has been linked to up to a five fold increase in EC risk. Although the mechanism of EC development is not clearly understood, studies show that a women’s hormonal balance plays an important role in the development of EC. ADDIN EN.CITE <EndNote><Cite><Author>Kaaks</Author><Year>2002</Year><RecNum>70</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>70</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">70</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kaaks, Rudolf</author><author>Lukanova, Annekatrin</author><author>Kurzer, Mindy S.</author></authors></contributors><titles><title>Obesity, Endogenous Hormones, and Endometrial Cancer Risk: A Synthetic Review</title><secondary-title>Cancer Epidemiology Biomarkers & Prevention</secondary-title></titles><periodical><full-title>Cancer Epidemiology Biomarkers & Prevention</full-title></periodical><pages>1531-1543</pages><volume>11</volume><number>12</number><dates><year>2002</year><pub-dates><date>December 1, 2002</date></pub-dates></dates><urls><related-urls><url> Additionally, the American Cancer Society Cancer Prevention Study II Nutrition Cohort examining measures of physical activity in relation to EC risk revealed a modest inverse association between physical activity and EC, after adjustment for BMI, suggesting that physical activity might have an independent effect on lowering EC risk. ADDIN EN.CITE <EndNote><Cite><Author>Patel</Author><Year>2008</Year><RecNum>78</RecNum><DisplayText><style face="superscript">15</style></DisplayText><record><rec-number>78</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">78</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Patel, Alpa V.</author><author>Feigelson, Heather Spencer</author><author>Talbot, Jeffrey T.</author><author>McCullough, Marjorie L.</author><author>Rodriguez, Carmen</author><author>Patel, Roshni C.</author><author>Thun, Michael J.</author><author>Calle, Eugenia E.</author></authors></contributors><titles><title>The role of body weight in the relationship between physical activity and endometrial cancer: Results from a large cohort of US women</title><secondary-title>International Journal of Cancer</secondary-title></titles><periodical><full-title>International Journal of Cancer</full-title></periodical><pages>1877-1882</pages><volume>123</volume><number>8</number><keywords><keyword>physical activity</keyword><keyword>exercise</keyword><keyword>sedentary behavior</keyword><keyword>endometrial cancer</keyword><keyword>prospective cohort</keyword></keywords><dates><year>2008</year></dates><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><isbn>1097-0215</isbn><urls><related-urls><url> This paper focuses on two major risk factors: estrogen unopposed by progesterone and obesity. Hormonal imbalance and ECEstrogen is a well-known endometrial growth factor, which can appear as either endogenous or exogenous. Before menopause estrogen that is produced by the ovaries is sufficiently counterbalanced by another female hormone – progesterone – during monthly menstrual cycles. After menopause, the ovaries stop producing estrogen and progesterone. The risk of developing EC increases when the balance between these two hormones shifts toward estrogen. Solid evidence suggest that the increased risk of EC is associated with unopposed estrogen ADDIN EN.CITE <EndNote><Cite><Author>Shapiro</Author><Year>1985</Year><RecNum>77</RecNum><DisplayText><style face="superscript">16</style></DisplayText><record><rec-number>77</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">77</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shapiro, Samuel</author><author>Kelly, Judith P.</author><author>Rosenberg, Lynn</author><author>Kaufman, David W.</author><author>Helmrich, Susan P.</author><author>Rosenshein, Neil B.</author><author>Lewis, John L.</author><author>Knapp, Robert C.</author><author>Stolley, Paul D.</author><author>Schottenfeld, David</author></authors></contributors><titles><title>Risk of Localized and Widespread Endometrial Cancer in Relation to Recent and Discontinued Use of Conjugated Estrogens</title><secondary-title>New England Journal of Medicine</secondary-title></titles><periodical><full-title>New England Journal of Medicine</full-title></periodical><pages>969-972</pages><volume>313</volume><number>16</number><dates><year>1985</year></dates><accession-num>2995807</accession-num><urls><related-urls><url>, either taken as hormone replacement after menopause or excess production of estrogen with lack of progesterone. In premenopausal women, polycystic ovarian syndrome (PCOS), also known as hyperandrogenism, has an important role in the development of EC, whereas in postmenopausal women, changes in estrogen metabolism induced by adipose tissue may be a central mechanism. Other hormone related factors linked to EC risk are null parity, prolonged exogenous estrogen use in birth control to prevent pregnancy or in menopausal hormone therapy, and insulin resistance. The later is also associated with PCOS and obesity, where elevated insulin levels and insulin like growth factor I causes high estrogen concentrations, which in the absence of sufficient progesterone leads to increased endometrial cell proliferation.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYWFrczwvQXV0aG9yPjxZZWFyPjIwMDI8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 9,14,17 Obesity and ECThe prevalence of obesity is rapidly increasing globally, in large part affecting western developed countries. It is estimated that nearly two-thirds of United States adults are overweight or obese. ADDIN EN.CITE <EndNote><Cite><Author>Flegal</Author><Year>2010</Year><RecNum>67</RecNum><DisplayText><style face="superscript">18</style></DisplayText><record><rec-number>67</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">67</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Flegal, K. M.</author><author>Carroll, M. D.</author><author>Ogden, C. L.</author><author>Curtin, L. R.</author></authors></contributors><titles><title>PRevalence and trends in obesity among us adults, 1999-2008</title><secondary-title>JAMA</secondary-title></titles><periodical><full-title>JAMA</full-title></periodical><pages>235-241</pages><volume>303</volume><number>3</number><dates><year>2010</year></dates><isbn>0098-7484</isbn><urls><related-urls><url> As the United States is experiencing the greatest rise in obesity rates, several large epidemiologic studies have demonstrated that obesity (body mass index, BMI >?30), and especially morbid obesity (BMI >?40), is associated with an increased rate of co-morbidities such as diabetes, high blood pressure, high cholesterol levels and overall poor health. ADDIN EN.CITE <EndNote><Cite><Author>Mokdad</Author><Year>2003</Year><RecNum>81</RecNum><DisplayText><style face="superscript">19</style></DisplayText><record><rec-number>81</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">81</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mokdad, A. H.</author><author>Ford, E. S.</author><author>Bowman, B. A.</author><author>et al.,</author></authors></contributors><titles><title>PRevalence of obesity, diabetes, and obesity-related health risk factors, 2001</title><secondary-title>JAMA</secondary-title></titles><periodical><full-title>JAMA</full-title></periodical><pages>76-79</pages><volume>289</volume><number>1</number><dates><year>2003</year></dates><isbn>0098-7484</isbn><urls><related-urls><url> Moreover, strong links between obesity and certain site cancers were found in epidemiological studies such as endometrial, colon, esophageal, kidney etc. ADDIN EN.CITE <EndNote><Cite><Author>Basen-Engquist</Author><Year>2011</Year><RecNum>82</RecNum><DisplayText><style face="superscript">20</style></DisplayText><record><rec-number>82</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">82</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Basen-Engquist, Karen</author><author>Chang, Maria</author></authors></contributors><titles><title>Obesity and Cancer Risk: Recent Review and Evidence</title><secondary-title>Current Oncology Reports</secondary-title><alt-title>Curr Oncol Rep</alt-title></titles><periodical><full-title>Current Oncology Reports</full-title><abbr-1>Curr Oncol Rep</abbr-1></periodical><alt-periodical><full-title>Current Oncology Reports</full-title><abbr-1>Curr Oncol Rep</abbr-1></alt-periodical><pages>71-76</pages><volume>13</volume><number>1</number><keywords><keyword>Neoplasm</keyword><keyword>Obesity</keyword><keyword>Overweight</keyword><keyword>Cancer risk</keyword><keyword>Intervention</keyword><keyword>Review</keyword><keyword>Insulin</keyword><keyword>Insulin-like growth factors</keyword><keyword>Sex steroid hormones</keyword><keyword>Adipokines</keyword><keyword>Hypoxia</keyword><keyword>Oxidative stress</keyword></keywords><dates><year>2011</year><pub-dates><date>2011/02/01</date></pub-dates></dates><publisher>Current Science Inc.</publisher><isbn>1523-3790</isbn><urls><related-urls><url> show that obesity is strongly associated with increased risk of EC, with morbidly obese women showing the most elevated risk. ADDIN EN.CITE <EndNote><Cite><Author>Pavelka</Author><Year>2004</Year><RecNum>59</RecNum><DisplayText><style face="superscript">21</style></DisplayText><record><rec-number>59</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">59</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pavelka, James C.</author><author>Ben-Shachar, Inbar</author><author>Fowler, Jeffrey M.</author><author>Ramirez, Nilsa C.</author><author>Copeland, Larry J.</author><author>Eaton, Lynne A.</author><author>Manolitsas, Tom P.</author><author>Cohn, David E.</author></authors></contributors><titles><title>Morbid obesity and endometrial cancer: surgical, clinical, and pathologic outcomes in surgically managed patients</title><secondary-title>Gynecologic Oncology</secondary-title></titles><periodical><full-title>Gynecologic Oncology</full-title></periodical><pages>588-592</pages><volume>95</volume><number>3</number><keywords><keyword>Obesity</keyword><keyword>Endometrial cancer</keyword><keyword>Lymphadenectomy</keyword></keywords><dates><year>2004</year><pub-dates><date>12//</date></pub-dates></dates><isbn>0090-8258</isbn><urls><related-urls><url> A large retrospective cohort study exploring the association of uterine cancer risk with BMI measurements in US women found a linear association such that each one unit increase in BMI was associated with an 11% increase in the likelihood of a diagnosis of uterine cancer. ADDIN EN.CITE <EndNote><Cite><Author>Ward</Author><RecNum>28</RecNum><DisplayText><style face="superscript">22</style></DisplayText><record><rec-number>28</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">28</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ward, Kristy K.</author><author>Roncancio, Angelica M.</author><author>Shah, Nina R.</author><author>Davis, Mitzie-Ann</author><author>Saenz, Cheryl C.</author><author>McHale, Michael T.</author><author>Plaxe, Steven C.</author></authors></contributors><titles><title>The risk of uterine malignancy is linearly associated with?body mass index in a cohort of US women</title><secondary-title>American Journal of Obstetrics and Gynecology</secondary-title></titles><periodical><full-title>American Journal of Obstetrics and Gynecology</full-title></periodical><number>0</number><keywords><keyword>cancer risk</keyword><keyword>endometrial cancer</keyword><keyword>obesity</keyword><keyword>overweight</keyword></keywords><dates></dates><isbn>0002-9378</isbn><urls><related-urls><url> A meta-analysis of prospective studies of BMI and incident EC revealed a risk ratio of 1.6 per each 5 units of BMI increase, indicating that a woman with a BMI higher than 42 kg/m2 (BMI hereafter reported without units) has an almost ten-fold increased risk of developing endometrial cancer compared to a normal weight woman. ADDIN EN.CITE <EndNote><Cite><Author>Crosbie</Author><Year>2010</Year><RecNum>29</RecNum><DisplayText><style face="superscript">23</style></DisplayText><record><rec-number>29</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">29</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Crosbie, Emma J.</author><author>Zwahlen, Marcel</author><author>Kitchener, Henry C.</author><author>Egger, Matthias</author><author>Renehan, Andrew G.</author></authors></contributors><titles><title>Body Mass Index, Hormone Replacement Therapy, and Endometrial Cancer Risk: A Meta-Analysis</title><secondary-title>Cancer Epidemiology Biomarkers & Prevention</secondary-title></titles><periodical><full-title>Cancer Epidemiology Biomarkers & Prevention</full-title></periodical><pages>3119-3130</pages><volume>19</volume><number>12</number><dates><year>2010</year><pub-dates><date>December 1, 2010</date></pub-dates></dates><urls><related-urls><url> Between 1999 and 2008 the prevalence of obesity increased slightly among women aged 20-39 and 40-59. ADDIN EN.CITE <EndNote><Cite><Author>Flegal</Author><Year>2010</Year><RecNum>67</RecNum><DisplayText><style face="superscript">18</style></DisplayText><record><rec-number>67</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">67</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Flegal, K. M.</author><author>Carroll, M. D.</author><author>Ogden, C. L.</author><author>Curtin, L. R.</author></authors></contributors><titles><title>PRevalence and trends in obesity among us adults, 1999-2008</title><secondary-title>JAMA</secondary-title></titles><periodical><full-title>JAMA</full-title></periodical><pages>235-241</pages><volume>303</volume><number>3</number><dates><year>2010</year></dates><isbn>0098-7484</isbn><urls><related-urls><url> With the number of obese women steadily increasing in the US over the past two decades, the prevalence of EC has also been on the rise since 2007.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Qb2xlZG5hazwvQXV0aG9yPjxZZWFyPjIwMDM8L1llYXI+
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ADDIN EN.CITE.DATA 24,25 Risk factors associated with EH are similar to those associated with EC, including increased BMI. ADDIN EN.CITE <EndNote><Cite><Author>Linkov</Author><Year>2008</Year><RecNum>51</RecNum><DisplayText><style face="superscript">26</style></DisplayText><record><rec-number>51</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">51</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Linkov, Faina</author><author>Edwards, Robert</author><author>Balk, Judith</author><author>Yurkovetsky, Zoya</author><author>Stadterman, Barbara</author><author>Lokshin, Anna</author><author>Taioli, Emanuela</author></authors></contributors><titles><title>Endometrial hyperplasia, endometrial cancer and prevention: Gaps in existing research of modifiable risk factors</title><secondary-title>European Journal of Cancer</secondary-title></titles><periodical><full-title>European Journal of Cancer</full-title></periodical><pages>1632-1644</pages><volume>44</volume><number>12</number><keywords><keyword>Uterus</keyword><keyword>Tumour markers</keyword><keyword>Risk factors</keyword><keyword>Diet</keyword><keyword>Obesity</keyword><keyword>Lifestyle</keyword><keyword>Endometrial carcinoma</keyword></keywords><dates><year>2008</year><pub-dates><date>8//</date></pub-dates></dates><isbn>0959-8049</isbn><urls><related-urls><url> Obese, premenopausal women are likely to have more anovulatory events with lower progesterone levels, and thus are at additional risk for endometrial proliferation ADDIN EN.CITE <EndNote><Cite><Author>Epplein</Author><Year>2008</Year><RecNum>32</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>32</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">32</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Epplein, Meira</author><author>Reed, Susan D.</author><author>Voigt, Lynda F.</author><author>Newton, Katherine M.</author><author>Holt, Victoria L.</author><author>Weiss, Noel S.</author></authors></contributors><titles><title>Risk of Complex and Atypical Endometrial Hyperplasia in Relation to Anthropometric Measures and Reproductive History</title><secondary-title>American Journal of Epidemiology</secondary-title></titles><periodical><full-title>American Journal of Epidemiology</full-title></periodical><pages>563-570</pages><volume>168</volume><number>6</number><dates><year>2008</year><pub-dates><date>September 15, 2008</date></pub-dates></dates><urls><related-urls><url>. Obese women (BMI 30-39.9) have a 4.6-fold increase in risk, and morbidly obese women (BMI ≥40) have a 23-fold increased risk of developing complex hyperplasia, compared to those with normal weight. ADDIN EN.CITE <EndNote><Cite><Author>Epplein</Author><Year>2008</Year><RecNum>32</RecNum><DisplayText><style face="superscript">27</style></DisplayText><record><rec-number>32</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">32</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Epplein, Meira</author><author>Reed, Susan D.</author><author>Voigt, Lynda F.</author><author>Newton, Katherine M.</author><author>Holt, Victoria L.</author><author>Weiss, Noel S.</author></authors></contributors><titles><title>Risk of Complex and Atypical Endometrial Hyperplasia in Relation to Anthropometric Measures and Reproductive History</title><secondary-title>American Journal of Epidemiology</secondary-title></titles><periodical><full-title>American Journal of Epidemiology</full-title></periodical><pages>563-570</pages><volume>168</volume><number>6</number><dates><year>2008</year><pub-dates><date>September 15, 2008</date></pub-dates></dates><urls><related-urls><url> Obesity increases the risk of EC in both postmenopausal and in premenopausal women. ADDIN EN.CITE <EndNote><Cite><Author>D.</Author><Year>2013</Year><RecNum>45</RecNum><DisplayText><style face="superscript">28</style></DisplayText><record><rec-number>45</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">45</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Caserta D.</author><author>Bordi G.</author><author>Scarani S.</author><author>Moscarini M.</author></authors></contributors><titles><title>Endometrial adenocarcinoma in a young woman</title><secondary-title>European Journal of Gyneacologic Oncology</secondary-title></titles><periodical><full-title>European Journal of Gyneacologic Oncology</full-title></periodical><pages>179-182</pages><volume>34</volume><number>2</number><dates><year>2013</year></dates><urls></urls><custom2>23781594</custom2></record></Cite></EndNote>28 One quarter of all EC cases occur in pre or perimenopausal women. ADDIN EN.CITE <EndNote><Cite><Author>Fader</Author><Year>2009</Year><RecNum>26</RecNum><DisplayText><style face="superscript">11</style></DisplayText><record><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">26</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fader, Amanda Nickles</author><author>Arriba, Lucybeth Nieves</author><author>Frasure, Heidi E.</author><author>von Gruenigen, Vivian E.</author></authors></contributors><titles><title>Endometrial cancer and obesity: Epidemiology, biomarkers, prevention and survivorship</title><secondary-title>Gynecologic Oncology</secondary-title></titles><periodical><full-title>Gynecologic Oncology</full-title></periodical><pages>121-127</pages><volume>114</volume><number>1</number><keywords><keyword>Endometrial cancer</keyword><keyword>Obesity</keyword><keyword>Quality of life</keyword><keyword>Epidemiology</keyword><keyword>Biomarkers</keyword><keyword>Prevention</keyword></keywords><dates><year>2009</year><pub-dates><date>7//</date></pub-dates></dates><isbn>0090-8258</isbn><urls><related-urls><url> Although the median age of EC onset in the US is 62 years of age, as the number of younger, obese women increases, EC may start to affect younger individuals.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXJsaW48L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 18,29 Recently, a case study in Hungary reported that young patients (less than 40 years of age) accounted for 4-5% of all EC in Hungary; 40% of reported cases were obese women. ADDIN EN.CITE <EndNote><Cite><Author>A.</Author><Year>2013</Year><RecNum>44</RecNum><DisplayText><style face="superscript">30</style></DisplayText><record><rec-number>44</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">44</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dudnyikova A. </author><author>Horváth K</author><author>Pete I.</author></authors></contributors><titles><title>Endometrial cancer in young patients: report of 17 cases</title><secondary-title>Magyar Onkolo?gia</secondary-title></titles><periodical><full-title>Magyar Onkolo?gia</full-title></periodical><pages>203-206</pages><volume>57</volume><number>3</number><edition>2013 Aug 9</edition><dates><year>2013</year><pub-dates><date>October 2013</date></pub-dates></dates><urls></urls><custom2> 24107826 </custom2><electronic-resource-num>doi: MagyOnkol.2013.57.3.203</electronic-resource-num><language>Hungarian</language></record></Cite></EndNote>30 endometrial sampling EC and EH are oftentimes discovered using Pipelle endometrial sampling in women who present with gynecologic symptoms, such as bleeding. A positive Pipelle biopsy can potentially save patients the time, cost, and inconvenience of a dilation and curettage (D&C). ADDIN EN.CITE <EndNote><Cite><Author>Ferry</Author><Year>1993</Year><RecNum>39</RecNum><DisplayText><style face="superscript">31</style></DisplayText><record><rec-number>39</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">39</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ferry, J.</author><author>Farnsworth, A.</author><author>Webster, M.</author><author>Wren, B.</author></authors></contributors><titles><title>The Efficacy of the Pipelle Endometrial Biopsy in Detecting Endometrial Carcinoma</title><secondary-title>Australian and New Zealand Journal of Obstetrics and Gynaecology</secondary-title></titles><periodical><full-title>Australian and New Zealand Journal of Obstetrics and Gynaecology</full-title></periodical><pages>76-78</pages><volume>33</volume><number>1</number><dates><year>1993</year></dates><publisher>Blackwell Publishing Ltd</publisher><isbn>1479-828X</isbn><urls><related-urls><url> However, many cases using the Pipelle device have been reported to yield insufficient tissue for making diagnoses, especially in women with a thin endometrium. ADDIN EN.CITE <EndNote><Cite><Author>Elsandabesee</Author><Year>2005</Year><RecNum>40</RecNum><DisplayText><style face="superscript">32</style></DisplayText><record><rec-number>40</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">40</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Elsandabesee, D</author><author>Greenwood, P</author></authors></contributors><titles><title>The performance of Pipelle endometrial sampling in a dedicated postmenopausal bleeding clinic</title><secondary-title>Journal of Obstetrics & Gynaecology</secondary-title></titles><periodical><full-title>Journal of Obstetrics & Gynaecology</full-title></periodical><pages>32-34</pages><volume>25</volume><number>1</number><dates><year>2005</year></dates><urls><related-urls><url> Previous studies reported various Pipelle failure rates to obtain sufficient sample ranging from 3% to 60.7%, with higher rates in postmenopausal women.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LaW08L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 33-37present studyPrevious studies reported that the prevalence of endometrial pathologies in untreated, asymptomatic, morbidly obese women is approximately 10%. ADDIN EN.CITE <EndNote><Cite><Author>Argenta</Author><Year>2013</Year><RecNum>27</RecNum><DisplayText><style face="superscript">38</style></DisplayText><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">27</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Argenta, P. A.</author><author>Kassing, M.</author><author>Truskinovsky, A. M.</author><author>Svendsen, C. A.</author></authors></contributors><titles><title>Bariatric surgery and endometrial pathology in asymptomatic morbidly obese women: a prospective, pilot study</title><secondary-title>BJOG: An International Journal of Obstetrics & Gynaecology</secondary-title></titles><periodical><full-title>BJOG: An International Journal of Obstetrics & Gynaecology</full-title></periodical><pages>795-800</pages><volume>120</volume><number>7</number><keywords><keyword>Bariatric surgery</keyword><keyword>endometrial cancer</keyword><keyword>endometrial hyperplasia</keyword><keyword>weight loss</keyword></keywords><dates><year>2013</year></dates><isbn>1471-0528</isbn><urls><related-urls><url> However, little is known about the overall prevalence of endometrial pathology in the general population of bariatric surgery patients, irrespective of a symptomatic status. Thus, the overall goal of this study was to collect endometrium specimens in a general cohort of cancer free, morbidly obese women considering bariatric surgery. The secondary goal of this paper was to evaluate the efficacy of Pipelle endometrial sampling success when used in women with a BMI >35.materials and methodsstudy participantsFemale bariatric surgery candidates (BMI >35) were recruited from the bariatric surgery clinic of Magee-Womens Hospital of the University of Pittsburgh Medical Center Health System (UPMC). Patients were approached if they were enrolled in a bariatric surgery program and were expected to undergo bariatric surgery (Roux-en-Y, Lap Band, or Sleeve Gastrectomy) within six months of recruitment. Exclusion criteria included: prior endometrial ablation, prior hysterectomy, severe inflammatory diseases such as rheumatoid arthritis, severe connective tissue disease, lupus, asthma controlled by medication, or refusal to consent to biopsy. Patients were not excluded on the basis of gynecologic symptoms such as bleeding, although the vast majority of patients were asymptomatic. Approval for this study was obtained from the University of Pittsburgh Institutional Review Board prior to the enrollment of any participants. All study-related procedures were performed at the Magee-Womens Hospital of UPMC Clinical and Translational Research Center (CTRC), an outpatient facility equipped to support various clinical and translational research, including bariatric surgery, and has trained and experienced clinical and/or research staff. measurementsEndometrial samples were obtained using a Pipelle endometrial suction curette and then forwarded to the Pathology Department of Magee-Womens Hospital for immediate processing and analysis. Specimens were formalin-fixed, embedded in paraffin, sectioned, and stained using standard hematoxylin and eosin stain preparation immediately after acquisition. Specimens were evaluated by two independent pathologists with expertise in gynecologic pathology; these pathologists were blinded to the patients’ health histories, age, BMI, or other characteristics. Pathologists were asked to categorize the tissues as: proliferative pattern, secretory pattern, simple hyperplasia (with or without atypia), complex hyperplasia (with or without atypia), or note any other pathologies, such as endometrial polyps, etc. During the study visit, a subset of consenting women also underwent a transvaginal ultrasound to determine endometrial thickness, which was measured to the nearest millimeter as a double-layer thickness at its thickest part in the longitudinal plane.Anthropometric measurements were collected by a registered research nurse at the CTRC. Waist and hip circumferences were measured to the nearest millimeter using a non-stretchable tape. Height was recorded to the nearest inch by a standardized, wall-mounted stadiometer. Weight, total body fat, and percent body fat were assessed by the foot-to-foot body composition Tanita analyzer, where participants wore light clothing and no shoes. Reproductive histories included: gravidity, parity, PCOS history, menstrual history, and desired fertility, and were obtained using a validated reproductive health questionnaire, which has previously been used in large, multi-center studies targeting bariatric surgery patients. ADDIN EN.CITE <EndNote><Cite><Author>Gosman</Author><Year>2010</Year><RecNum>43</RecNum><DisplayText><style face="superscript">39</style></DisplayText><record><rec-number>43</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">43</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gosman, Gabriella G.</author><author>King, Wendy C.</author><author>Schrope, Beth</author><author>Steffen, Kristine J.</author><author>Strain, Gladys W.</author><author>Courcoulas, Anita P.</author><author>Flum, David R.</author><author>Pender, John R.</author><author>Simhan, Hyagriv N.</author></authors></contributors><titles><title>Reproductive health of women electing bariatric surgery</title><secondary-title>Fertility and Sterility</secondary-title></titles><periodical><full-title>Fertility and Sterility</full-title></periodical><pages>1426-1431</pages><volume>94</volume><number>4</number><keywords><keyword>Bariatric surgery</keyword><keyword>obesity</keyword><keyword>women's health</keyword><keyword>pregnancy</keyword><keyword>infertility</keyword><keyword>polycystic ovary syndrome</keyword><keyword>contraception</keyword></keywords><dates><year>2010</year><pub-dates><date>9//</date></pub-dates></dates><isbn>0015-0282</isbn><urls><related-urls><url> Information on comorbidities was obtained from a general health questionnaire previously used in studies implemented by Lora Burke at the University of Pittsburgh School of Nursing.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdXJrZTwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 40,41statistical analysisDescriptive statistics were used to evaluate frequencies of various endometrial conditions. Continuous variables are reported as median (range), while categorical variables are presented as N (%). Fisher’s exact test and Wilcoxon rank-sum test were used to compare characteristics of women with successful Pipelle endometrial samples with those for whom readable samples were not obtained for categorical and continuous variables, respectively. This approach was also used to compare women with identified pathologies (e.g. hyperplasia with atypia, hyperplasia without atypia, or endometrial polyps) with women where no pathologies were identified. Differences in race, age, body composition, and other characteristics were evaluated for those groups. P-values less than 0.05 were considered statistically significant. Pipelle failure rate was calculated using the following formula: Pipelle failure rate= number of participants with insufficient sample + number of participants unable to gather sampletotal number of participants *100%resultsParticipant baseline characteristics are listed in Table 1. The median age of the patients was 39 years (range: 30 to 62 years), and the majority of women (73%) identified as white. The median BMI was 46.1 kg/m2 (range: 33.8-66.1). 36 women self-reported menopausal status; of these, 28 were premenopausal, 8 were postmenopausal. Among premenopausal women, five women reported bleeding between periods in the past 12 months compared to woman in postmenopausal status. Endometrial thickness in study participants ranged from 3.7 mm to 45.6 mm, with a median of 13.3 mm.Participants self reported a wide variety of comorbid conditions including hypertension (50%), diabetes (22%), thyroid disease (19%), and heart problems (5%). No one had reported previously diagnosed cancer. About 30% of women reported having either gall bladder stones or surgery for gall bladder stones, or both.Table SEQ Table \* ARABIC 1. Participant characteristicsVariableNMedian (range) or N (%)Age (years)3739 (30-62)Race (%) White4942 (85.7) Black497 (14.3)Preoperative BMI (kg/m2) Total Body Mass (kg)Body fat (%)Waist circumference (cm)3732323446.1 (33.8-66.1)65.15 (40-112.2)50.5 (45.3-67.2)126.3 (101.1-167.6)Waist-Hip ratio340.9 (0.74-1.01)Menopausal Status Not reported371 (2.7%) Premenopausal28 (75.7%) PostmenopausalEndometrial thickness (mm)178 (21.6%)13.3 (3.7-45.6)Number of prior pregnancies243 (1-12)Note. Continuous variables described by medians (ranges); categorical variables described by n (%). Sample sizes vary due to missing dataThe reproductive health questionnaire revealed that 73% of participants had ever been pregnant. The median gravidity among this population was 3 pregnancies, ranging from 1 to 12. For most (67%) of the study participants first pregnancy ended with live births, 24% had miscarriages, and 9% reported other outcomes. About 25% of women are planning a pregnancy in the next year or two. Out of all women who filled out reproductive history questionnaire, 15 (40.6%) women had irregular periods, and seven women (18.9%) had been diagnosed with PCOS by their healthcare provider, 6 of whom were premenopausal women. History of hormone use was self-reported by 6 (16.2%) women, 3 of whom specified using birth control and 1 woman who used hormone replacement therapy (HRT). Although 37 participants provided written, informed consent for endometrial sampling in an outpatient setting, we were unable to gather samples from 5 women due to stenosis of the cervix or anatomical challenges associated with body hiatus that did not allow locate the cervix. Of the 32 samples obtained, 24 were readable and 8 were classified as insufficient to perform histopathological analysis. There was an overall 35% failed Pipelle rate, including the 5 technically impossible biopsies (13.5%). No significant differences in participants’ profiles were found when comparing groups with successful and failed Pipelle sampling (see Table 2) Table SEQ Table \* ARABIC 2. Participant characteristics by Pipelle sampling successVariableSuccessful Pipelle samplingN=24Failed Pipelle samplingN=13P-value*Age (years)37.5 (30-62)40 (32-58)0.244Preoperative BMI (kg/m2)46.3 (35.7-66.1)45.7 (33.8-58.8)0.445Waist circumference (cm)127 (109-167.6)122 (101-154.5)0.607Waist-Hip ratio0.9 (0.8-1)0.9 (0.74-1.01)0.887Body fat (kg)Body fat (%)67.05 (40-107.5)51.3 (45.3-67.2)56.5 (45.6-112.2)48 (45.6-57.8)0.1730.586Menopausal status0.177 Not reported1 (4.2%)0 Premenopausal20 (83.3%)8 (61.5%) Postmenopausal3 (12.5%)5 (38.5%)Note. Continuous variables described by medians (ranges); categorical variables described by n (%)* p-values are based on Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical variables. The distribution of endometrial characteristics can be found in Figure 1. The most common finding was a proliferative pattern endometrium (33.3%), but a range of different endometrial characteristics was observed, including 2 patients with hyperplasia and 3 patients with a polyp, for a total of 5 patients (20.9% of those with successful Pipelle sampling) having an abnormal endometrium. Both samples with hyperplasia were identified in premenopausal women. No participants had evidence of endometrial cancer. Five women have presented with normal secretory endometrial tissue. Figure SEQ Figure \* ARABIC 1. Distribution of endometrial biopsy characteristicsTable 3 presents the analysis of groups based on the obtained endometrial biopsy results (presence of pathology [abnormal endometrium] vs. no pathology [normal endometrium]). Patients with abnormal endometrium had marginally higher preoperative BMIs and body fat mass, and were significantly more likely to have irregular periods (80% vs. 31.6%, p=0.029). No other significant differences were found. Logistic regression did not reveal a significant association between BMI and presence of endometrial pathology (adjusting for race and age).Table SEQ Table \* ARABIC 3. Participant characteristics by histopathological analysis of endometrial biopsiesVariableNormal endometriumN=19Abnormal endometrium N=5P-value*Age (years)38 (31-62)35 (30-57)0.454Race1.000 White6 (31.6%)1 (20%) Black13 (68.4%)4 (80%)Preoperative BMI (kg/m2)Waist circumference (cm)45.5 (35.7-63.9)125.3 (109-167.6)52.2 (44.8-66.1)134.6 (127-155)0.0590.063Waist-Hip ratio0.9 (0.8-0.99)0.93 (0.85-1.0)0.481Body fat mass (kg)Body fat (%)64.9 (40-99.8)50.4 (45.3-60.4)81.4 (67.6-107.5)54.2 (46.7-67.2)0.0490.206Menopausal status1.000 Not reported01 (20%) Premenopausal16 (84.2%)4 (80%) Postmenopausal3 (15.8%)0Number of prior pregnancies2 (0-6)2 (0-12)0.797Irregular periods0.029 Not reported1 (5.3%)1 (20%) Yes6 (31.6%)4 (80%) No12 (63.1%)0PCOS0.210 Not reported1 (5.3%)1 (20%) Yes3 (15.8%)2 (40%) No15 (78.9%)2 (40%)Hormone use0.535 Not reported 1 (5.3%)1 (20%) Yes5 (26.3%)0 No13 (68.4%)4 (80%)Note. Continuous variables described by medians (ranges); categorical variables described by n (%)* p-values are based on Wilcoxon rank sum test for continuous variables and Fisher’s exact test for categorical variablesdiscussionThe results of this exploratory prospective investigation suggest that morbidly obese women may be at high risk of harboring endometrial pathology. With over 20% of bariatric surgery candidates in the current sample showing evidence of endometrial hyperplasia and endometrial polyps combined, it appears that these women may potentially benefit from receiving additional Ob/Gyn follow up care after bariatric surgery. This rate of pathology is a surprising finding for this relatively young population; higher than previously reported in samples recruited in other clinical settings. ADDIN EN.CITE <EndNote><Cite><Author>Viola</Author><Year>2008</Year><RecNum>53</RecNum><DisplayText><style face="superscript">42</style></DisplayText><record><rec-number>53</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">53</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Viola, Alexandre S.</author><author>Gouveia, Daniela</author><author>Andrade, Liliana</author><author>Aldrighi, Jose M.</author><author>Viola, Carolina F. M.</author><author>Bahamondes, Luis</author></authors></contributors><titles><title>Prevalence of endometrial cancer and hyperplasia in non-symptomatic overweight and obese women</title><secondary-title>Australian and New Zealand Journal of Obstetrics and Gynaecology</secondary-title></titles><periodical><full-title>Australian and New Zealand Journal of Obstetrics and Gynaecology</full-title></periodical><pages>207-213</pages><volume>48</volume><number>2</number><keywords><keyword>cancer</keyword><keyword>endometrium</keyword><keyword>hyperplasia</keyword><keyword>obesity</keyword><keyword>overweight</keyword></keywords><dates><year>2008</year></dates><publisher>Blackwell Publishing Asia</publisher><isbn>1479-828X</isbn><urls><related-urls><url> Thus, additional research in determining high-risk subgroups among obese women is an important step toward implementing and justification of the screening in these subgroups. Additionally, results of the present study suggest that Pipelle endometrial sampling failure rate in morbidly obese populations may be higher than in general gynecologic settings, which has important implications for clinical care. Pipelle biopsies and D&C have previously been reported to have almost equal success rates in the diagnosis of endometrial pathologies. ADDIN EN.CITE <EndNote><Cite><Author>Demirkiran</Author><Year>2012</Year><RecNum>54</RecNum><DisplayText><style face="superscript">34</style></DisplayText><record><rec-number>54</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">54</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Demirkiran, Fuat</author><author>Yavuz, Evrim</author><author>Erenel, Hakan</author><author>Bese, Tugan</author><author>Arvas, Macit</author><author>Sanioglu, Cevdet</author></authors></contributors><titles><title>Which is the best technique for endometrial sampling? Aspiration (pipelle) versus dilatation and curettage (D&C)</title><secondary-title>Archives of Gynecology and Obstetrics</secondary-title><alt-title>Arch Gynecol Obstet</alt-title></titles><periodical><full-title>Archives of Gynecology and Obstetrics</full-title><abbr-1>Arch Gynecol Obstet</abbr-1></periodical><alt-periodical><full-title>Archives of Gynecology and Obstetrics</full-title><abbr-1>Arch Gynecol Obstet</abbr-1></alt-periodical><pages>1277-1282</pages><volume>286</volume><number>5</number><keywords><keyword>Pipelle endometrial biopsy</keyword><keyword>Dilatation curettage</keyword><keyword>Endometrial hyperplasia</keyword><keyword>Endometrium cancer</keyword><keyword>Endometrial sampling</keyword></keywords><dates><year>2012</year><pub-dates><date>2012/11/01</date></pub-dates></dates><publisher>Springer-Verlag</publisher><isbn>0932-0067</isbn><urls><related-urls><url> Despite the failure rate, curettage and biopsy (Pipelle) are recommended techniques for diagnosing endometrial precancers with good evidence of efficacy and substantial clinical benefit.The finding that over 10% of bariatric surgery candidates had endometrial polyps is interesting and warrants further investigation. While endometrial polyps are generally benign, a recent meta-analysis revealed that women with polyps are at higher risk of developing cancer. ADDIN EN.CITE <EndNote><Cite><Author>Lee</Author><Year>2010</Year><RecNum>36</RecNum><DisplayText><style face="superscript">43</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">36</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lee, Stephanie Cruz</author><author>Kaunitz, Andrew M.</author><author>Sanchez-Ramos, Luis</author><author>Rhatigan, Ronald M.</author></authors></contributors><titles><title>The Oncogenic Potential of Endometrial Polyps: A Systematic Review and Meta-Analysis</title><secondary-title>Obstetrics & Gynecology</secondary-title></titles><periodical><full-title>Obstetrics & Gynecology</full-title></periodical><pages>1197-1205 10.1097/AOG.0b013e3181f74864</pages><volume>116</volume><number>5</number><keywords><keyword>00006250-201011000-00027</keyword></keywords><dates><year>2010</year></dates><isbn>0029-7844</isbn><urls><related-urls><url> According to observational data, vaginal bleeding and postmenopausal status also increases the risk of developing endometrial malignancy. ADDIN EN.CITE <EndNote><Cite><Author>Lee</Author><Year>2010</Year><RecNum>36</RecNum><DisplayText><style face="superscript">43</style></DisplayText><record><rec-number>36</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">36</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lee, Stephanie Cruz</author><author>Kaunitz, Andrew M.</author><author>Sanchez-Ramos, Luis</author><author>Rhatigan, Ronald M.</author></authors></contributors><titles><title>The Oncogenic Potential of Endometrial Polyps: A Systematic Review and Meta-Analysis</title><secondary-title>Obstetrics & Gynecology</secondary-title></titles><periodical><full-title>Obstetrics & Gynecology</full-title></periodical><pages>1197-1205 10.1097/AOG.0b013e3181f74864</pages><volume>116</volume><number>5</number><keywords><keyword>00006250-201011000-00027</keyword></keywords><dates><year>2010</year></dates><isbn>0029-7844</isbn><urls><related-urls><url> This study is interesting because the sample was predominantly made up of premenopausal women without vaginal bleeding. This study is one of the first studies to evaluate the presence of endometrial pathology, specifically focusing on women who are morbidly obese. Although the sample size was relatively small, participants were generally representative of bariatric surgery practice at our institution and were racially representative of the two major ethnic groups in the area. Conventionally, BMI is widely used to define obesity because of the difficulties in measuring body fat directly and the inability to evaluate body fat distribution. It has been reported that abdominal fat mass distribution is related to endometrial thickness, whereas the occurrence of EC relates to the amount but not the distribution of adipose tissue.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYXJtaW5nPC9BdXRob3I+PFllYXI+MjAwMzwvWWVhcj48
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ADDIN EN.CITE.DATA 44,45 Thus, our results are consistent with prior findings and strengthen the argument that BMI and body fat mass are potential indicators of elevated risk for endometrial pathologies. While this study has many strengths, including the investigation of a novel population using a validated approach, several limitations warrant mention. First, the data on endometrial thickness are limited. We were not able to control for changes in thickness through the menstrual cycle, which are known to occur in healthy asymptomatic women. This is important because the endometrium can reach thickness of 16 mm during the secretory phase in premenopausal women. ADDIN EN.CITE <EndNote><Cite><Author>Nalaboff</Author><Year>2001</Year><RecNum>52</RecNum><DisplayText><style face="superscript">46</style></DisplayText><record><rec-number>52</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">52</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nalaboff, Kenneth M.</author><author>Pellerito, John S.</author><author>Ben-Levi, Eran</author></authors></contributors><titles><title>Imaging the Endometrium: Disease and Normal Variants</title><secondary-title>RadioGraphics</secondary-title></titles><periodical><full-title>RadioGraphics</full-title></periodical><pages>1409-1424</pages><volume>21</volume><number>6</number><dates><year>2001</year></dates><accession-num>11706213</accession-num><urls><related-urls><url> Our sample of bariatric surgery candidates appropriately included pre and postmenopausal women, as well as cycling women who were in different phases of their cycle. The number of women with transvaginal ultrasounds also included only half the study sample, limiting interpretation of the study results. Second, the modest size of the study did not allow us to evaluate the possible impact of modifiable variables (e.g. use of birth control) on the risk of abnormal endometrial histology. Findings of this study have potential implications for fertility preservation in morbidly obese women. While hysterectomy is a common treatment for women with hyperplasia, both women in our study who were diagnosed with hyperplasia were in their early thirties, and indicated that fertility is still desired. Timely diagnosis of hyperplasia in morbidly obese populations and appropriate counseling about conservative vs. surgical hyperplasia management might help these women to preserve fertility. Also, obesity can affect ovulation and the chances of pregnancy through hyperandrogenism and oligo-anovulation, which is attributed to increased aromatization of androgens to estrogens in the peripheral adipose tissue of obese and overweight women. Thus, obese premenopausal women with PCOS should not be neglected if fertility is desired. Despite morbid obesity, five women in the study sample had some evidence of an ovulation presenting secretory pattern tissue on biopsy. These initial findings suggest that Ob/Gyn and primary healthcare providers should pay special attention to the endometrial health of morbidly obese women, especially those who want to preserve fertility. It appears that morbidly obese women are at higher risk of harboring undiagnosed endometrial pathology at higher rates than previously suspected. As weight loss may improve endometrial health, bariatric surgery is very appealing in terms of exploring endometrial changes occurring with weight loss. ADDIN EN.CITE <EndNote><Cite><Author>Argenta</Author><Year>2013</Year><RecNum>27</RecNum><DisplayText><style face="superscript">38</style></DisplayText><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">27</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Argenta, P. A.</author><author>Kassing, M.</author><author>Truskinovsky, A. M.</author><author>Svendsen, C. A.</author></authors></contributors><titles><title>Bariatric surgery and endometrial pathology in asymptomatic morbidly obese women: a prospective, pilot study</title><secondary-title>BJOG: An International Journal of Obstetrics & Gynaecology</secondary-title></titles><periodical><full-title>BJOG: An International Journal of Obstetrics & Gynaecology</full-title></periodical><pages>795-800</pages><volume>120</volume><number>7</number><keywords><keyword>Bariatric surgery</keyword><keyword>endometrial cancer</keyword><keyword>endometrial hyperplasia</keyword><keyword>weight loss</keyword></keywords><dates><year>2013</year></dates><isbn>1471-0528</isbn><urls><related-urls><url> Recent study by Argenta et al. showed promising results that bariatric surgery induced weight loss might correct estrogen and progesterone imbalance thought estrogen levels reduction. Additionally, study showed that obese women with endometrial pathology have different profile of hormone receptors expression from whose without pathology, suggesting possible stratification of the risk of developing endometrial pathology. ADDIN EN.CITE <EndNote><Cite><Author>Argenta</Author><Year>2014</Year><RecNum>85</RecNum><DisplayText><style face="superscript">47</style></DisplayText><record><rec-number>85</rec-number><foreign-keys><key app="EN" db-id="pp2x0fw5d9sd5fetpesv0wz3dxssdexapsp5">85</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Argenta, Peter</author><author>Svendsen, Charles</author><author>Elishaev, Esther</author><author>Gloyeske, Nika</author><author>Geller, Melissa A.</author><author>Edwards, Robert P.</author><author>Linkov, Faina</author></authors></contributors><titles><title>Hormone receptor expression patterns in the endometrium of asymptomatic morbidly obese women before and after bariatric surgery</title><secondary-title>Gynecologic Oncology</secondary-title></titles><periodical><full-title>Gynecologic Oncology</full-title></periodical><pages>78-82</pages><volume>133</volume><number>1</number><keywords><keyword>Obesity</keyword><keyword>Bariatric surgery</keyword><keyword>Endometrial cancer</keyword><keyword>Endometrial hyperplasia</keyword><keyword>Estrogen receptor (ER)</keyword><keyword>Progesterone receptor (PR)</keyword></keywords><dates><year>2014</year><pub-dates><date>4//</date></pub-dates></dates><isbn>0090-8258</isbn><urls><related-urls><url> Thus, a better understanding of endometrial pathology mechanisms linked to obesity may have important implications for developing effective and timely interventions to prevent and control EC and possibly revert this major public health issue.bibliography ADDIN EN.REFLIST 1.Linkov F, Taioli E. 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