Endometrial cancer is a malignancy of the endometrium (the inner lining of the uterus, or womb) and is the most common gynaecological cancer, and accounts for 13% of all cancers in women. It is most frequently in women over age 50. A know risk factor is prior oestrogen-replacement therapy (however, oestrogen replacement also lowers risk of heart disease). Symptoms can include pelvic pain, and blood-soaked discharge - though these are also common symptoms related to menopausal changes.
PubMed Central search for free-access publications about Endometrial Cancer MeSH term: Endometrial Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
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Postawski K, Przadka-Rabaniuk D, Piersiak T 8-oxo-7,8-dihydroguanine level - the DNA oxidative stress marker - recognized by fluorescence image analysis in sporadic uterine adenocarcinomas in women. Ginekol Pol. 2013; 84(1):44-50 [PubMed]
OBJECTIVES: In the case of carcinogenesis in human endometrium no information exists on tissue concentration of 8-oxo-7,8-dihydroguanine, the DNA oxidative stress marker This was the main reason to undertake the investigation of this DNA modification in human uterine estrogen-dependent tissue cancers. MATERIAL AND METHODS: In order to estimate the level of oxidative damage, 8-oxo-7,8-dihydroguanine was determined directly in cells of tissue microscope slides using OxyDNA Assay Kit, Fluorometric. Cells were investigated under confocal microscope. Images of individual cells were captured by computer-interfaced digital photography and analyzed for fluorescence intensities (continuous inverted 8-bit gray-scale = 0 [black]-255 [white]). Fluorescence scores were calculated for each of 13 normal endometrial samples and 31 uterine adenocarcinoma specimens. Finally the level of the oxidative stress marker was also analyzed according to histological and clinical features of the neoplasms. RESULTS: The obtained data revealed that: 8-oxo-7,8-dihydroguanine levels were higher in uterine adenocarcinomas than in normal endometrial samples (48,32 vs. 38,64; p<0,001); in contrast to normal endometrium there was no correlation between age and DNA oxidative modification content in uterine cancer; highest mean fluorescence intensity was recognized in G2 endometrial adenocarcinomas; level of 8-oxo-7,8-dihydroguanine does not depend on Body Mass Index (BMI) and cancer uterine wall infiltration or tumor FIGO stage. CONCLUSIONS: Our study indicates that accumulation of the oxidized DNA base may contribute to the development of endometrial neoplasia, however oxidative DNA damage does not seem to increase with tumor progression.
Santeufemia DA, Lumachi F, Basso SM, et al. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy as salvage treatment for a late wound recurrence of endometrial cancer. Anticancer Res. 2013; 33(3):1041-4 [PubMed]
Endometrial cancer (EC) is usually diagnosed at an early stage, when surgery-alone may be curative, but 20-25% of patients with EC have higher-risk early-stage disease requiring radiation therapy alone or in combination with chemotherapy, in addition to surgery. Most EC relapses are either pelvic or distant metastases and occur within the first three years after hysterectomy. Laparotomy wound recurrences of EC are extremely rare, and only a few cases have been previously reported. We describe the unusual case of a late wound recurrence from an EC surgically removed 10 years previously which was successfully treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) after response to a hormonal therapy. Ten years after abdominal hysterectomy and bilateral salpingo-oophorectomy, on computed tomographic (CT) scan, a 70-year-old woman exhibited an abdominal mass of 3.5 cm, strictly adherent to the abdominal rectal muscle. CT-guided biopsy revealed estrogen- and progesterone receptor-positive metastasis from EC and the patient was treated with megestrole acetate. The whole body (18)F-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET)/CT showed a marked metabolic response at the single metastatic site, with no further metastases, and the patient underwent surgical resection of the mass followed by immediate HIPEC perfusion with cisplatin. No residual macroscopic disease was present at the end of surgery and no complications occurred during the hospital stay. At 12-month follow-up, the patient is alive without evidence of disease. Although this approach is still being investigational for peritoneal recurrence of EC, our report confirms its feasibility and its promising results in highly selected patients.
Huang CY, Ho CM, Chen YL, et al. Impact of lymphadenectomy in uterine endometrioid carcinoma. Eur J Surg Oncol. 2013; 39(4):350-7 [PubMed]
AIMS: To investigate the role of lymphadenectomy in uterine endometrioid carcinoma based on the 2009 FIGO staging system. METHODS: Using an institution-maintained cancer registry database, all patients who were treated surgically for endometrial cancer from 1991 to 2008 in two medical centers were analyzed. Kaplan-Meier and Cox proportional hazards methods were used to determine the role of lymphadenectomy. RESULTS: From 961 women with uterine endometrioid carcinoma, 680 underwent lymphadenectomy and 281 did not. Young age, early-stage disease, low-grade tumor, and lymphadenectomy were favorable independent prognostic factors. The five-year disease-specific survival (DSS) of stages IA, IB, II, and III, and the two-year DSS of stage IV patients who underwent lymphadenectomy were 97.8%, 88.3%, 91.5%, 70.5%, and 32.1%, respectively, compared to 98.7%, 70.0%, 73.3%, 42.9%, and 16.6% in those without lymphadenectomy (p > 0.05 for stage IA; p < 0.01 for stages IB-IV, log-rank test). In high-risk patients (i.e., poorly-differentiated, outer-half myometrial invasion, and stages II-IV), more extensive lymph node resection was associated with an improved five-year DSS, from 71.3% (1-10 nodes removed) and 85.3% (11-20 nodes removed) to 86.8% (>20 nodes removed) (p = 0.02, log-rank test). For stage IIIC-IV patients with nodal metastasis, the extent of node resection also significantly improved the five-year DSS, from 34.4% (1-10 nodes removed) and 62.4% (11-20 nodes removed) to 79.6% (>20 nodes removed) (p = 0.04, log-rank test). CONCLUSIONS: Lymphadenectomy improves the survival of patients with uterine endometrioid carcinoma stage IB to stage IV. The extent of lymphadenectomy also improves the survival of high-risk patients and those with nodal disease.
Kalin A, Merideth MA, Regier DS, et al. Management of reproductive health in Cowden syndrome complicated by endometrial polyps and breast cancer. Obstet Gynecol. 2013; 121(2 Pt 2 Suppl 1):461-4 [PubMed]
BACKGROUND: Cowden syndrome is an autosomal-dominant condition associated with mutations in the tumor suppressor gene PTEN. Gynecologic malignancies are common with a 5-10% risk of endometrial cancer and 25-50% risk of breast cancer. CASE: A 37-year-old woman with a history of breast cancer, other neoplasms, and multiple skin lesions was diagnosed with Cowden syndrome after a germline PTEN mutation was identified. The endometrium had high glucose uptake on positron emission tomography scan and was irregularly thickened on ultrasonography; biopsy revealed endometrial polyps and simple hyperplasia. Fifteen months later, hysteroscopy again confirmed numerous benign endometrial polyps. CONCLUSION: Recurrent, multiple endometrial polyps portend a high risk of endometrial cancer in women with Cowden syndrome. Monitoring for malignancy and consideration of hysterectomy after childbearing is completed is warranted.
Al-Loh S, Al-Hussaini M Undifferentiated endometrial carcinoma: a diagnosis frequently overlooked. Arch Pathol Lab Med. 2013; 137(3):438-42 [PubMed]
Undifferentiated endometrial carcinoma (UEC) is a relatively uncommon neoplasm with only few studies published thus far. It has always been a diagnostic challenge because of the lack of proper definition cited in most of the standard textbooks. Recently however, a few studies have highlighted the clinicopathologic features of UEC. The distinctive morphology of UEC was noted by the group from MD Anderson Cancer Center, which enabled them to establish the defining criteria. It appears to be more aggressive than endometrial endometrioid adenocarcinoma, FIGO (International Federation of Gynecology and Obstetrics) grade 3, its main differential diagnosis. Proper recognition of this entity is important owing to its aggressive behavior.
Park JY, Nam JH, Kim YT, et al. Poor prognosis of uterine serous carcinoma compared with grade 3 endometrioid carcinoma in early stage patients. Virchows Arch. 2013; 462(3):289-96 [PubMed]
Difference in prognosis between grade 3 endometrioid carcinoma (G3EC) of the endometrium and uterine serous carcinoma (USC) is controversial. In this study, we further evaluated the difference in prognosis, if any, between G3EC (n = 61) and USC (n = 47) on a total of 565 patients with endometrial cancer. In addition, meta-analysis was performed using data from seven previous publications (n = 8,637) and from the Asan Medical Center (n = 108). Regarding the cases from our institution, USC tended to occur in older patients (≥65 years) than G3EC (P = 0.011). Deep myometrial invasion (more than or equal to half) was more frequently identified in G3EC (36/61, 59.0 %) than in USC (17/47, 36.2 %) (P = 0.021). Between patients with early stage G3EC and USC (stages I and II), there were no significant differences in any clinicopathological parameter, but there was a significant difference in overall survival (P = 0.017) that was not found in advanced stage (P = 0.588). USC was an independent prognostic factor for poor overall survival (hazard ratio, 6.125; P = 0.030) in early stage patients. In the meta-analysis on 5-year survival in patients with early stage cancers, which also included our study results, a higher relative risk (1.92, 95 % CI 1.62-2.27) was demonstrated in USC than in G3EC (P < 0.001). In conclusion, our study reveals that USC is associated with a poorer prognosis compared with G3EC, only in patients with early stage carcinoma, suggesting that different treatment strategies should be considered according to the histologic type in order to improve treatment outcome.
Humphrey P, Cornes P, Al-Booz H Vaginal vault brachytherapy in endometrial cancer: verifying target coverage with image-guided applicator placement. Br J Radiol. 2013; 86(1023):20120428 [PubMed] Article available free on PMC after 01/03/2014
OBJECTIVE: This quality assurance study assesses whether CT image-guided verification has led to improvements in the technique when compared with previous studies. METHODS: The CT images were studied from a cohort of 105 consecutive patients with endometrial cancer having adjuvant brachytherapy to the vaginal vault in 2010. Images were taken at first insertion, checked for air gaps and treatment delivered. Images were later transferred to the planning system and air gaps between vaginal mucosa and vaginal cylinder were measured. Comparisons were made with the 2008 results from this centre and the literature series. RESULTS: Images from two patients were not assessable owing to artefacts from hip replacements. Air gaps >2 mm were seen in 11/103 patients. Repositioning or use of a larger cylinder reduced air gaps to 7/103 patients. In total, 96/103 patients (over 93%) were able to achieve good vaginal contact throughout the treatment volume. This shows a significant improvement in applicator positioning in our centre since 2008 and also a significant improvement over the total data published in 2010 (Pearson χ(2) test=46.19; p<0.0001). CONCLUSION: The vaginal cylinder technique with CT imaging was proven to be effective for 96/103 patients. It is necessary to consider whether there is a better technique for the few patients with air gaps >2 mm. ADVANCES IN KNOWLEDGE: For the vast majority of patients, this technique is well tolerated, without the need for analgesia, and will continue to be the first choice technique in this centre.
Elshaikh MA, Cattaneo R, Shah M, et al. Endometrial carcinoma in the baby boomer generation. Tumor characteristics and clinical outcome. Anticancer Res. 2013; 33(2):619-24 [PubMed]
BACKGROUND: Baby boomers (BB) entering retirement represent a significant burden on medical resources. The unique lifestyle characteristics engendered by the BB may lead to different endometrial cancer characteristics that bear understanding. We sought to characterize BB with endometrioid carcinoma after hysterectomy and compare the results to those of prior to the baby boomers (PB). PATIENTS AND METHODS: After reviewing our prospectively maintained database of 1,450 patients with endometrial cancer, we identified 595 patients who underwent hysterectomy for 1988 International Federation of Gynecologic Oncology (FIGO) stage I-II uterine endometrioid carcinomas, who were born between 1926 and 1964. Their medical records were reviewed in this Institutional review board (IRB)-approved study. Patients with non-endometrioid carcinoma and those who received preoperative therapy were excluded. Patients were defined as BB (born 1946-1964) or PB (born in 1926-1945). The two groups were compared regarding patients' demographics, tumor characteristics and survival. Following a univariate analysis, multivariable modeling was carried out using Cox regression analysis. RESULTS: All patients underwent hysterectomy with a minimum of two years' follow-up. There were 234 patients (39%) in the BB group and 361 patients (61%) in the PB group. Median follow-up for the study cohort was 56 months. BB had higher body mass index (p=0.027), lower tumor grade (p=0.002), earlier FIGO stage (p=0.023), higher number of dissected lymph nodes (p=0.008), less lymphvascular space involvement (p=<0.034), less utilization of adjuvant therapy (p=<0.001), and younger age at diagnosis (p=0.002). However, there was no significant difference found between the BB and PB in regards to local control, disease-specific survival and overall survival. For the study cohort, FIGO stage and tumor grade were independent predictors of recurrence-free and disease-specific survival. There was a trend towards shorter overall survival for the PB women (p=0.063). CONCLUSION: Although tumor characteristics were more favorable in the BB group of women, local control and survival end-points were not statistically different compared to those of the PB group. As more BB are diagnosed with endometrial carcinoma, further research is warranted to further elucidate the characteristic differences in endometrial carcinoma, if any, in this generation.
Puljiz M, Puljiz Z, Vucemilo T, et al. Prognostic significance of matrix metalloproteinases 2 and 9 in endometrial cancer. Coll Antropol. 2012; 36(4):1367-72 [PubMed]
We investigated the prognostic significance of matrix metalloproteinases 2 (MMP 2) and 9 (MMP 9) in endometrial cancer (EC). The expression of MMP 2 and MMP 9 was analyzed immunohistochemically in 73 primary EC patients. In most cases, the gelatinases were predominantly localized to epithelial cell of tumor origin. In univariate analysis histological type, tumor grade, FIGO (1988) surgical stage and high stromal MMP 2 expression were identified as a significant determinant for EC recurrence, while epithelial MMP 2 expression and epithelial and stromal MMP 9 expression were not. Multivariate analysis revealed a subgroup of patient age > or = 63.6 years with endometrioid adenocarcinoma and papillary serous carcinoma, all FIGO (2009) stage I disease where strong staining of stromal MMP 2 increase risk of EC recurrence (p = 0.037).
Win AK, Lindor NM, Winship I, et al. Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome. J Natl Cancer Inst. 2013; 105(4):274-9 [PubMed] Article available free on PMC after 20/02/2014
BACKGROUND: Lynch syndrome is an autosomal dominantly inherited disorder caused by germline mutations in DNA mismatch repair (MMR) genes. Previous studies have shown that MMR gene mutation carriers are at increased risk of colorectal, endometrial, and several other cancers following an initial diagnosis of colorectal cancer. We estimated cancer risks following an endometrial cancer diagnosis for women carrying MMR gene mutations. METHODS: We obtained data from the Colon Cancer Family Registry for a cohort of 127 women who had a diagnosis of endometrial cancer and who carried a mutation in one of four MMR genes (30 carried a mutation in MLH1, 72 in MSH2, 22 in MSH6, and 3 in PMS2). We used the Kaplan-Meier method to estimate 10- and 20-year cumulative risks for each cancer. We estimated the age-, country-, and calendar period-specific standardized incidence ratios (SIRs) for each cancer, compared with the general population. RESULTS: Following endometrial cancer, women carrying MMR gene mutations had the following 20-year risks of other cancer cancers: colorectal cancer (48%, 95% confidence interval [CI] = 35% to 62%); cancer of the kidney, renal pelvis, or ureter (11%, 95% CI = 3% to 20%); urinary bladder cancer (9%, 95% CI = 2% to 17%); and breast cancer (11%, 95% CI = 4% to 19%). Compared with the general population, these women were at statistically significantly elevated risks of colorectal cancer (SIR = 39.9, 95% CI = 27.2 to 58.3), cancer of the kidney, renal pelvis, or ureter (SIR = 28.3, 95% CI = 11.9 to 48.6), urinary bladder cancer (SIR = 24.3, 95% CI = 8.56 to 42.9), and breast cancer (SIR = 2.51, 95% CI = 1.17 to 4.14). CONCLUSIONS: Women with Lynch syndrome who are diagnosed with endometrial cancer have increased risks of several cancers, including breast cancer.
Terada KY, Black M, Terada LH, et al. Survival of endometrial cancer patients with lymphatic invasion and deficient mismatch repair expression. Gynecol Oncol. 2013; 129(1):188-92 [PubMed]
OBJECTIVE: This study examines patients under the age of 70 with endometrial cancer and lymphatic invasion or lymph node metastases. Survival of patients with loss of tumor mismatch repair expression is compared to survival of patients with normal mismatch repair expression. METHODS: This is a retrospective review of patients treated from 1998-2009 for carcinoma of the endometrium. All patients with lymphatic invasion, including lymph node metastases, had immunohistochemical staining of the primary tumor for loss of expression of the mismatch repair genes MLH1, PMS2, MSH6, and MSH2. Overall survival and disease specific survival were compared using Kaplan-Meier plots. RESULTS: Sixty-six patients were identified for inclusion; 26 demonstrated loss of mismatch repair expression and 40 demonstrated normal mismatch repair expression. Overall survival and disease specific survival were significantly better in the group with defective mismatch repair expression. Subgroup analysis of FIGO stage 3C patients also showed significantly better survival in patients with deficient mismatch repair expression. CONCLUSION: For patients with endometrial cancer and lymphatic invasion, patients demonstrating loss of mismatch repair expression in the primary tumor appear to have a significantly better survival than patients with normal mismatch repair expression. Further investigation appears warranted to examine a possible role of mismatch repair expression as a prognostic marker for high risk patients with endometrial cancer.
Ko EM, Funk MJ, Clark LH, Brewster WR Did GOG99 and PORTEC1 change clinical practice in the United States? Gynecol Oncol. 2013; 129(1):12-7 [PubMed]
OBJECTIVE: To assess the practice of adjuvant radiation (RT) for endometrial cancer in the United States following the publication of the Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC1), and Gynecologic Oncology Group-Adjuvant Radiation for Intermediate Risk Endometrial Cancers (GOG99). METHODS: A retrospective cohort study using the NCI SEER database compared the use of RT pre and post publication of PORTEC1 (1996-99 v 2000-03) and GOG 99 (2000-03 v 2004-07). Criteria for intermediate (IR) and high-intermediate (HIR) risk categories as defined by PORTEC1 and GOG99 were applied. Chi-squared statistics and adjusted multivariable Poisson models were used. RESULTS: RT did not increase for HIR (RR 1.05, 95%CI 0.99, 1.11) or IR groups (RR 1.0, 95% CI 0.95, 1.05) following GOG99 publication, or for HIR (RR 1.01, 95% CI 0.86, 1.19) or IR groups (RR 0.88, 95% CI 0.77-1.00) following PORTEC1 publication. Radiation rates changed heterogeneously across the country without a discernible pattern of cause. Among radiated patients, brachytherapy use increased, whereas external beam use decreased after GOG99 publication. CONCLUSIONS: As the debate regarding the utility of adjuvant radiation in early stage endometrial cancer continues, we found that overall, clinicians had not adopted GOG99 or PORTEC1 results into their clinical practice in the years immediately after publication. However, we did identify significant variation in practice by geographic location. Given that barely half the women deemed highest risk for recurrence received radiation, these findings illustrate that clinical practice reflects the continued controversy surrounding adjuvant radiation in the treatment of endometrial cancer.
Perissinotti A, Paredes P, Vidal-Sicart S, et al. Use of SPECT/CT for improved sentinel lymph node localization in endometrial cancer. Gynecol Oncol. 2013; 129(1):42-8 [PubMed]
OBJECTIVE: To assess the usefulness of adding SPECT/CT to planar images for pre-surgical sentinel lymph node (SLN) identification in endometrial cancer (EC), a technique that could have an important clinical impact on the staging, treatment, and prognosis of EC patients. METHODS: We compared the planar and SPECT/CT lymphoscintigraphic images of 44 patients with high-risk EC who underwent sentinel lymph node procedure (SLN) using an injection technique recently developed at our center known as TUMIR (Transvaginal Ultrasound Myometrial Injection of Radiotracer). 148 MBq (4 mCi) of 99mTc-nanocolloid were injected, guided by transvaginal ultrasound imaging. Planar and SPECT/CT images were performed in all 44 patients. RESULTS: SLNs were seen on planar images in 32 cases (73%) and in 34 cases (77%) using SPECT/CT. A total of 88 SLNs were depicted by planar lymphoscintigraphy while SPECT/CT visualized a total of 110 SLNs. SPECT/CT changed the assessment of the SLNs visualized in planar lymphoscintigraphy in 26 cases, either by modifying the number and/or the location of the SLNs detected. External iliac chain was the most frequent location of SLN detection (71%) in the 34 cases. Fifteen of these patients (44%) showed para-aortic SLNs. One case had exclusive para-aortic drainage (3%) that was only visualized by SPECT/CT. In another case, SPECT/CT was able to localize the only pelvic metastatic lymph node not visualized by planar images. CONCLUSIONS: SPECT/CT combined with planar imaging improves preoperative SLN detection and provides valuable anatomic information that enhances the presurgical stage of the SLN technique in endometrial cancer.
Feng Z, Gan H, Cai Z, et al. Aberrant expression of hypoxia-inducible factor 1α, TWIST and E-cadherin is associated with aggressive tumor phenotypes in endometrioid endometrial carcinoma. Jpn J Clin Oncol. 2013; 43(4):396-403 [PubMed]
OBJECTIVE: Intratumoral hypoxia promotes angiogenesis, invasion and epithelial-mesenchymal transition, a pivotal event in tumor metastasis. TWIST is a master regulator of multiple developmental processes and has recently been shown to be the key factor responsible for cancer metastasis via the inhibition of E-cadherin expression, a hallmark of epithelial-mesenchymal transition. This study aimed to determine the expression of hypoxia-inducible factor 1α, TWIST and E-cadherin in patients with endometrioid endometrial carcinoma and to examine their clinical significance in endometrioid endometrial carcinoma progression. METHODS: Using immunohistochemical and tissue microarray approaches, we evaluated the expression of hypoxia-inducible factor 1α, TWIST and E-cadherin in normal endometrial (n = 35), atypical hyperplasia (n = 28) and endometrioid endometrial carcinoma samples (n = 124). Furthermore, we statistically analyzed the association between these markers, as well as their correlation with clinicopathologic variables. RESULTS: The expression of hypoxia-inducible factor 1α and TWIST were markedly increased, whereas E-cadherin was decreased, as lesions progressed from normal endometrium to atypical hyperplasia to carcinoma (P < 0.01). Among various clinical parameters, the expression of hypoxia-inducible factor 1α and TWIST was strikingly elevated with aggressive tumor characteristics, including higher pathologic grade, deep myometrial invasion and lymph node involvement (P < 0.05). More importantly, overexpression of hypoxia-inducible factor 1α positively correlated with enhanced TWIST expression in endometrioid endometrial carcinoma samples (r = 0.249, P < 0.01); however, statistical analysis showed a negative relationship between TWIST upregulation and E-cadherin downregulation (r = -0.183, P = 0.042). CONCLUSIONS: These results demonstrated for the first time that the hypoxia-inducible factor 1α/TWIST/E-cadherin pathway may play a critical role in invasion and metastasis of endometrioid endometrial carcinoma. The combined evaluation of these markers may be useful in predicting aggressive phenotypes and thus prognosis in patients with endometrioid endometrial carcinoma.
Felix AS, Cook LS, Gaudet MM, et al. The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium. Br J Cancer. 2013; 108(3):727-34 [PubMed] Article available free on PMC after 19/02/2014
BACKGROUND: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. METHODS: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. RESULTS: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01). CONCLUSION: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.
Sawicki S, Kobierski J, Cytawa W, Wydra D Sentinel lymph node detection with the use of SPECT-CT in endometrial cancer--analysis of two cases. Ginekol Pol. 2012; 83(9):703-7 [PubMed]
On the basis of two cases we discuss the important issues regarding the sentinel lymph node detection biopsy (SLNB) in endometrial cancer with combined cervical administration of the radiocolloid and the subserosal blue dye injection. The first patient (endometrioid adenocarcinoma G2, invasion > 50% myometrium) had 4 SLNs detected. Three were both hot and blue (detected on SPECT-CT). The fourth, paraaortic SLN was blue only. None of the lymph nodes contained metatstases. The second patient (endometrioid adenocarcinoma G1, invasion > 50% myometrium) had 4 SLNs detected. Three were blue (but two of them had also very low radioactivity). The fourth SLN was hot only. Blue only node contained macrometastasis. In the past patients underwent cervical amputation. Diverse distribution of each tracer confirms the advantages of the combined tracers administration in SLNB. The radiotracer is the crucial component--uptake was present in 6 of 8 SLNs. Although the blue dye is more a complimentary method, its suberosal injection significantly increases the safety of the SLNB procedure. In the first case we have detected blue only SLN in paraaortic region which otherwise would be missed using the cervical approach only. More importantly in the second case the tracer uptake was very limited due to the previous surgery and the blue dye administration allowed correct SLNs detection (including the metastatic node). Presented clinical cases confirms that the combined cervical and subserosal tracers administration together with preoperative SPECT-CT constitute an optimal SLN detection method and correctly provides information about the regional lymph node status.
Halkia E, Kalinoglou N, Spiliotis J Surgical management of endometrial cancer. A critical review. J BUON. 2012 Oct-Dec; 17(4):637-43 [PubMed]
Endometrial cancer (EC) is a common gynecological malignancy. Prognosis depends on 3 main factors: histological subtype, depth of invasion into the myometrium and lymph node involvement. Surgery remains the gold standard of treatment for this cancer. The aim of this article was to review the surgical approach and the new techniques along with the clarification of some controversial aspects concerning the management of advanced disease stages and the role of lymph node dissection. Surgery of EC remains the treatment of choice in the management of early stage disease. The role of lymph node dissection remains controversial.
Luomaranta A, Leminen A, Loukovaara M Prediction of lymph node and distant metastasis in patients with endometrial carcinoma: a new model based on demographics, biochemical factors, and tumor histology. Gynecol Oncol. 2013; 129(1):28-32 [PubMed]
OBJECTIVE: To develop a model that might predict the probability of lymph node and distant metastasis (stages IIIC-IV) in endometrial carcinoma. METHODS: We studied 774 patients with endometrial carcinoma treated in a single institution. Demographic factors, biochemical factors and preoperative tumor characteristics, identified as potential risk factors for advanced carcinoma in unadjusted analyses, were used to create a logistic regression model with lymph node and distant metastasis as the dependent variable. Statistically significant odds ratios in the regression model were rounded to the nearest whole number. These rounded values were the estimated weights for each factor that were summed to generate a score that might predict the probability of stage IIIC-IV carcinoma. RESULTS: Biochemical factors and preoperative tumor characteristics predicted lymph node and distant metastasis in the regression model, whereas demographic factors were without effect. The score combining weighted risk factors was: (2 × leukocytosis)+(3 × thrombocytosis)+(7 × elevated CA125)+(4 × high-risk histology). The area under curve (AUC) for this total score was 0.823, with 71.6% sensitivity, 75.2% specificity, 25.9% positive predictive value, and 95.7% negative predictive value, using 6 as cut-point. After excluding stage IV carcinomas from the dataset, the AUC was 0.813 for the total score in predicting nodal involvement (P=0.82 vs. total score in predicting stage IIIC-IV carcinomas in the complete dataset). CONCLUSIONS: Based on the high negative predictive value, this prediction model could be applied for identifying patients who may not benefit from lymphadenectomy for endometrial carcinoma staging.
Wang ZQ, Wang JL, Shen DH, et al. Should all endometrioid uterine cancer patients undergo systemic lymphadenectomy? Eur J Surg Oncol. 2013; 39(4):344-9 [PubMed]
OBJECTIVE: To evaluate the potential benefits of systemic pelvic and para-aortic lymphadenectomy in endometrioid uterine cancer patients. METHODS: We conducted a retrospective study on 244 cases of endometrioid uterine cancer that involved surgery in the Center of Gynecologic Oncology, Peking University People's Hospital, Beijing, from January 2000 to May 2008. We conducted staging for each case to ensure accordance with FIGO 2009 surgical staging criteria. Clinical data, including histology, age at diagnosis, surgical procedure, adjuvant therapy, date of death or last follow-up, and date and sites of recurrence were collected for each patient. RESULTS: Among 244 endometrioid uterine cancer patients, 207 cases (84.8%) underwent systemic pelvic lymphadenectomy. Among these cases, pelvic lymph nodes in 17 cases (8.2%) exhibited tumor metastasis. Systemic aortic lymphadenectomy was performed in 127 cases (52.0%) among 244 total patients. Five cases (3.9%) exhibited positive aortic lymph nodes, of which four exhibited positive pelvic lymph nodes. We investigated the impact of positive retroperitoneal lymph nodes on staging: 4 (4/161, 2.5%), 6 (6/29, 20.7%), 6 (6/35, 17.1%), 1 (1/8) and 1 (1/6) case changed to stage IIIc from stage Ia, Ib, II, IIIa, and IIIb, respectively. Tumor-free and overall survival did not differ between patients who underwent pelvic lymphadenectomy or not (P > 0.05). Tumor-free survival improved in stage Ib pelvic lymphadenectomy patients (P = 0.040); para-aortic lymphadenectomy did not improve patient survival in all stages (P > 0.05). CONCLUSION: Systemic lymphadenectomy is not warranted in stage Ia endometrioid uterine cancer.
Grigoriadis C, Androutsopoulos G, Zygouris D, et al. Synchronous squamous cell carcinoma of the endometrium and endometrioid adenocarcinoma of the ovary. Eur J Gynaecol Oncol. 2012; 33(6):666-8 [PubMed]
BACKGROUND: Synchronous primary endometrial and ovarian cancers are relatively uncommon in general population. The etiology and pathogenesis of this phenomenon remains unclear. The authors' aim was to present a case of synchronous squamous cell carcinoma of the endometrium and endometrioid adenocarcinoma of the ovary and review current literature. CASE: The patient, a 64-year-old, nulliparous postmenopausal Greek woman presented with a complaint of abdominal pain and abnormal uterine bleeding. Preoperative computer tomography (CT) of the abdomen and pelvis, and abdominal ultrasound (U/S) revealed an intra-abdominal three cm mass with solid components between the left ovary and small bowel. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH+BS), total omentectomy, pelvic and para-aortic lymph node dissection, and removal of the implant at the serosa of small bowel. Histopathology revealed Stage IA endometrial cancer squamous type and Stage IIIC ovarian cancer of endometrioid-type. Postoperatively the patient underwent adjuvant chemotherapy and radiotherapy. Follow-up of 22 months after initial surgery revealed no evidence of recurrence. CONCLUSION: The reason for better median overall survival of patients with synchronous primary endometrial and ovarian cancers is not intuitively obvious. Perhaps favourable clinical outcome may be related with the detection of patients at early stage and low-grade disease with an indolent growth rate.
Capobianco G, Pili F, Contini M, et al. Analysis of epidermal growth factor receptor (EGFR) status in endometrial stromal sarcoma. Eur J Gynaecol Oncol. 2012; 33(6):629-32 [PubMed]
PURPOSE: Endometrial stromal sarcomas (ESSs) are rare neoplasms, which are currently treated by surgery, whereas effective adjuvant therapies have not yet been established. Recently, epidermal growth factor receptor (EGFR) expression has been described in ESS, and a potential role of EGFR-targeted adjuvant therapies has been proposed. The aim of this study was to analyze EGFR status in an ESS series and to evaluate their potential role as molecular targets. MATERIALS AND METHODS: EGFR status was investigated in a total of ten cases of ESS, which included seven low-grade ESS and three undifferentiated ESS cases. EGFR expression levels were assessed by immunohistochemistry, and gene amplification analysis was performed with dual-color fluorescence in situ hybridization (FISH). RESULTS: Nine out of ten ESS cases showed positive immunostaining, whereas FISH analysis demonstrated constantly negative results. CONCLUSIONS: This study confirmed that EGFR is frequently overexpressed in ESS. FISH analysis did not show EGFR amplification in any of the tumors, therefore EGFR expression in ESS should be related to different genetic mechanisms.
Okazawa M, Ueda Y, Enomoto T, et al. A retrospective analysis of endometrial carcinoma cases surgically treated with or without para-aortic lymph node dissection followed by adjuvant chemotherapy. Eur J Gynaecol Oncol. 2012; 33(6):620-4 [PubMed]
PURPOSE: To analyze the efficacies of para-aortic node (PAN) dissection for patients undergoing surgery and adjuvant chemotherapy for endometrial carcinomas. METHODS: At the Osaka University Hospital and the Kaizuka City Hospital in Osaka, Japan, either pelvic lymph nodes (PLN) plus para-aortic lymph nodes (PAN) or PLN-only dissections were performed for endometrial carcinomas. An adjuvant chemotherapy using paclitaxel, epirubicin, and carboplatin was conducted for all such patients. A retrospective comparison of the efficacy of PAN dissection was conducted. RESULTS: Disease-free and overall survivals and frequency of PAN involvement at the first recurrence did not exhibit a statistically significant difference between the PLN-only group and the PLN + PAN group. Operation time was significantly longer in the PLN + PAN group than the PLN-only group, and the total blood loss was also significantly greater in the PLN+PAN group. CONCLUSION: PAN dissection may be omitted, without adverse effect on prognosis, for endometrial carcinoma patients with recurrence risks who undergo adjuvant chemotherapy using platinum, anthracycline and taxane derivatives.
OBJECTIVE: This study aimed to determine the clinically important prognostic factors for loco-regional or distant recurrence in early-stage endometrial cancer. MATERIALS AND METHODS: This study complied with the Declaration of Helsinki, and the local ethics committee approved the study. Cases who underwent primary surgery of early-stage endometrial cancer at the Institution from 2000 to 2012 were reviewed retrospectively. Patients who did not detect recurrence were classified as group 1 (n = 200); those who detected recurrence were classified as group 2 (n = 23). Clinically prognostic factors were evaluated by univariate analyses. RESULTS: The average age for group 2 (LUSI) was 63.8 years (p = 0.0001). Patients with grade 3 histology were all detected within group 2 (p = 0.0001). Endometrioid adenocarcinoma displaying squamous differentiation was found with a rate of 58.3% in group 2 (p = 0.0001). Lower uterine segment involvement (LUSI) and lymphovascular space invasion (LVSI) rates were 86.9% in group 2 (p = 0.0001). The rate of tumor size > 2 cm was 56.6% in group 2 (p = 0.0001). The median depth of myometrial invasion (DMI) was 5.1 mm (p = 0.034) and the average in myometrial thickness was 14.5 mm in group II (p = 0.0001). The percentage of myometrial invasion was 35.8% in Group II (p = 0.0001). Tumor free-distance was 9.4 mm in group II (p = 0.0001). CONCLUSION: Age and clinicopathological parameters of the tumours are significant predictors for recurrence in early-stage endometrial cancer.
Goto T, Takano M, Aoyama T, et al. Prognosis of high-grade endometrial cancer: a comparison of serous-type and clear cell type to grade 3 endometrioid-type. Eur J Gynaecol Oncol. 2012; 33(6):579-83 [PubMed]
OBJECTIVE: To evaluate prognosis of high-grade endometrial cancers, comparing serous (SC) and clear cell (CCC) types to grade 3 endometrioid carcinoma (ECG3). METHODS: Among patients with endometrial cancer treated in two decades, medical records of patients with high-grade endometrial cancer were retrospectively investigated. RESULTS: Of 447 endometrial cancers, 107 (24%) high-grade endometrial cancers were identified, with the increasing incidence in the last decade (28% vs 19%; p = 0.026). There were 24 SC, 14 CCC and 69 ECG3. Median age was 62, 68, and 61 years, respectively, with the CCC type showing an elder age than the ECG3 type (p = 0.012). The rates of patients with Stage IIIc-IV, lymph node assessment or complete resection at primary surgery, and post-operative chemotherapy were not significantly different; however, response rate to first-line chemotherapy in patients with measurable disease was lower in SC than ECG3 (3 / 11, 27% vs 14 / 19, 74%; p = 0.037), regardless of regimens. Five-year overall survival (OS) was 40%, 71%, and 71% respectively, and five-year progression-free survival (PFS) was 25%, 71%, and 61%, respectively, showing SC with worse prognosis than ECG3 on both OS (p = 0.026) and PFS (p = 0.0028). According to the multivariate analysis, age > or = 70, Stage IIIc-IV and incomplete resection were independent prognostic factors on poor OS, whereas SC, Stage IIIc-IV and incomplete resection were on poor PFS. CONCLUSIONS: The increasing trend of high-grade endometrial cancer and different outcomes according to histological subtypes, especially poor PFS and chemotherapeutic response in SC, were suggested.
Leitao MM, Khoury-Collado F, Gardner G, et al. Impact of incorporating an algorithm that utilizes sentinel lymph node mapping during minimally invasive procedures on the detection of stage IIIC endometrial cancer. Gynecol Oncol. 2013; 129(1):38-41 [PubMed]
OBJECTIVE: To determine whether the frequency of cases diagnosed with stage IIIC endometrial cancer is affected by the incorporation of a modified surgical lymph node assessment. METHODS: Since 2008, we have increasingly utilized a modified nodal assessment using an algorithm that incorporates SLN mapping. For this analysis, we identified all cases of newly diagnosed endometrial cancers undergoing a minimally invasive staging procedure not requiring conversion to laparotomy from 1/1/08 to 12/31/10. Procedures were categorized as standard, modified, and hysterectomy only. Differences were based on time period: 2008 (Y1), 2009 (Y2), and 2010 (Y3). Appropriate statistical tests were used. RESULTS: We identified a total of 507 cases. The distribution of cases was 143 (Y1), 190 (Y2), and 174 (Y3). Tumor grade (P=0.05) and high-risk histologies (P=0.8) did not differ during the 3 time periods. A standard staging procedure was performed in the following cases: Y1 (93/143; 65%), Y2 (66/166; 35%), and Y3 (40/164; 23%) (P<0.001). Median operative times were as follows: Y1 (218 min), Y2 (198 min), and Y3 (176.5 min) (P<0.001). The median numbers of total lymph nodes removed among cases with at least 1 node retrieved were: Y1 (20); Y2 (10); Y3 (7) (P<0.001). Cases diagnosed as stage IIIC were as follows: Y1 (10/143; 7%), Y2 (15/166; 7.9%), and Y3 (13/164; 7.5%) (P=1.0). CONCLUSIONS: The incorporation of a modified staging approach utilizing the SLN mapping algorithm reduces the need for standard lymphadenectomy and does not appear to adversely affect the rate of stage IIIC detection.
Kang S, Todo Y, Odagiri T, et al. A low-risk group for lymph node metastasis is accurately identified by Korean gynecologic oncology group criteria in two Japanese cohorts with endometrial cancer. Gynecol Oncol. 2013; 129(1):33-7 [PubMed]
OBJECTIVE: The Korean Gynecologic Oncology Group (KGOG) recently proposed new pre-operative criteria to identify a low-risk group for lymph node metastasis in endometrial cancer. The aim of this study was to test whether the good performance of the criteria can be reproducible in diverse clinical settings. METHODS: From two Japanese hospitals, 319 patients with endometrial cancer who underwent systemic lymphadenectomy were retrospectively reviewed. In one hospital, para-aortic lymphadenectomy was routinely performed, but it was selectively performed in the other hospital. The performance of the criteria was determined by adjusting the false-negative rate (FNR) at the given prevalence of nodal metastasis of 10% using Bayes' theorem. RESULTS: Nodal metastasis rate of the study population was 12.9%. The KGOG low-risk criteria identified 181 of 319 patients as a low-risk group (51%), and three false-negative cases were found (1.9%). Despite a significant difference in the nodal metastasis rate (18.2% and 8.8%, P=.012) and the surgical policy for para-aortic lymphadenectomy (100% and 48.9%, P<.001) between the two hospitals, KGOG criteria consistently showed a very low adjusted FNR at the prevalence of 10% in both hospitals (1.8% vs. 1.1%, respectively). Among the entire study population, the adjusted FNR was 1.4% (95% confidence interval, .5% to 4.3%), which was similar to the FNR of 1.3% in our previous study. CONCLUSION: The KGOG low-risk criteria accurately identified a low-risk group for lymph node metastasis with acceptable false negativity regardless of diverse clinical settings.
Rahman MT, Nakayama K, Ishikawa M, et al. Fatty acid synthase is a potential therapeutic target in estrogen receptor-/progesterone receptor-positive endometrioid endometrial cancer. Oncology. 2013; 84(3):166-73 [PubMed]
OBJECTIVE: In the current study we investigated the clinicopathological significance of fatty acid synthase (FASN) expression and its relationship with estrogen receptor (ER) and progesterone receptor (PR) in endometrioid endometrial cancer. METHODS: FASN expression in endometrioid endometrial cancer was assessed by immunohistochemistry using 108 paraffin-embedded tissue specimens and clinical data collected from a retrospective chart review. The specific FASN inhibitor C75 was used to analyze the relationship between FASN expression and cell growth as well as ER/PR expression in endometrioid endometrial cancer cell lines. RESULTS: Positive FASN immunostaining was observed in 77.8% (84/108) of the tumors analyzed. Deep myometrial invasion was significantly and inversely correlated with positive FASN expression (p = 0.024). Positive ER (p = 0.018) and PR status (p = 0.012) was significantly correlated with positive FASN expression. Patients with positive FASN expression in endometrioid endometrial cancer tissues tended to have a favorable progression-free/overall survival (p = 0.127 and p = 0.087, respectively). Ishikawa cells with high FASN expression also showed high expression of ER/PR, while HEC1B cells had low expression levels of both FASN and ER/PR. FASN inhibition by C75 (10 µM) significantly reduced ER/PR expression compared with control dimethyl sulfoxide treatment of Ishikawa cells. The growth of Ishikawa cells having positive FASN and ER/PR expression was significantly inhibited in the presence of C75 or FASN small-interfering RNA compared to HEC1B cells that lacked FASN and ER/PR expression. CONCLUSION: The current findings suggest that there may be cross talk between the ER/PR and FASN signaling pathways that modulate ER/PR activation and could play a role in endometrioid endometrial cancer pathogenesis.
Antunes A, Andrade LA, Pinto GA, et al. Is the immunohistochemical expression of proliferation (Ki-67) and apoptosis (Bcl-2) markers and cyclooxigenase-2 (COX-2) related to carcinogenesis in postmenopausal endometrial polyps? Anal Quant Cytol Histol. 2012; 34(5):264-72 [PubMed]
OBJECTIVE: To evaluate the pattern of Ki-67, Bcl-2 and COX-2 expression in the glandular epithelium and stroma of malignant and benign endometrial polyps in postmenopause. STUDY DESIGN: A total of 390 postmenopausal women underwent surgical hysteroscopy; women with endometrial polyps were included. Polypoid lesions were histologically classified as benign, premalignant or malignant lesions. Ki-67, Bcl-2 and COX-2 expression were evaluated by immunohistochemistry according to percentage of stained cells, staining intensity, and final score. RESULTS: The prevalence of malignancy in endometrial polyps was 7.1% and was associated with postmenopausal bleeding. The final score showed that only mean COX-2 expression was higher in malignant polyps both in the glandular epithelium (6.1 +/- 2.5) (p < 0.001) and stroma (2.4 +/- 3.0) (p < 0.01). There was a higher Bcl-2 expression, especially in the glandular epithelium, with no differences between benign polyps and premalignant/malignant polyps. Ki-67 expression was low in both benign polyps and premalignant/malignant polyps. CONCLUSION: Polyps in postmenopause have a high COX-2 expression that is higher in malignant polyps than in benign polyps. There was no difference in Ki-67 and Bcl-2 expression between malignant polyps and premalignant/malignant polyps.
Liu JJ, Hazra A, Giovannucci E, et al. One-carbon metabolism factors and endometrial cancer risk. Br J Cancer. 2013; 108(1):183-7 [PubMed] Article available free on PMC after 15/01/2014
BACKGROUND: This is the largest prospective cohort analysis to assess how dietary factors involved in one-carbon metabolism are associated with endometrial cancer incidence, using 26 years of follow-up data from the Nurses' Health Study. METHODS: The prospective cohort analysis of one-carbon metabolism dietary factors used the Cox proportional hazards model, and incorporated 788 incident endometrial cancer events from 1980 to 2006. Genotyping and unconditional logistic regression were performed on 572 endometrial cancer cases and their matched controls to examine 29 mostly non-synonymous single-nucleotide polymorphisms involved in one-carbon metabolism. RESULTS: There were no significant dose-response relationships between intake of any of the one-carbon metabolism dietary factors and endometrial cancer incidence, but alcohol consumption of <1 drink a day was significantly protective (hazard ratio: 0.80; 95% CI: 0.68, 0.94). Those with the MTHFR 677 TT or MTHFR 1298 CC genotype had more protective associations for many of the dietary factors and endometrial cancer, but statistical power was limited in this analysis. CONCLUSION: Dietary levels of folate, choline, methionine, vitamin B2, vitamin B6 or vitamin B12 do not appear to influence endometrial cancer incidence. Moderate alcohol intake may protect against developing endometrial cancer.
Arem H, Park Y, Pelser C, et al. Prediagnosis body mass index, physical activity, and mortality in endometrial cancer patients. J Natl Cancer Inst. 2013; 105(5):342-9 [PubMed] Article available free on PMC after 06/03/2014
Background Higher body mass index (BMI) and inactivity have been associated with a higher risk of developing endometrial cancer, but the impact on endometrial cancer survival is unclear. Methods Among incident endometrial cancer case subjects in the National Institutes of Health-AARP Diet and Health Study, we examined associations of prediagnosis BMI (n = 1400) and physical activity (n = 875) with overall and disease-specific 5- and 10-year mortality. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for tumor characteristics, treatment, and other risk factors. All statistical tests were two-sided. Results Compared with women with a BMI in the range of 18.5 to less than 25kg/m(2), the hazard ratios for 5-year all-cause mortality were 1.74 (95% CI = 1.13 to 2.66) for BMI in the range of 25 to less than 30kg/m(2), 1.84 (95% CI = 1.17 to 2.88) for BMI in the range of 30 to less than 35kg/m(2), and 2.35 (95% CI = 1.48 to 3.73) for BMI greater than or equal to 35kg/m(2) (P trend < .001). Higher BMI was also statistically significantly associated with poorer endometrial cancer-specific but not cardiovascular disease 5-year mortality. Hazard ratio estimates for 10-year all-cause and endometrial cancer-specific mortality as related to BMI were similar to 5-year hazard ratio estimates, whereas 10-year cardiovascular disease mortality became statistically significant (HR = 4.08; 95% CI = 1.56 to 10.71 comparing extreme BMI groups). More physical activity was related to lower all-cause 5-year mortality (HR = 0.57, 95% CI = 0.33 to 0.98 for >7 hours/week vs never/rarely), but the association was attenuated after adjustment for BMI (HR = 0.64, 95% CI = 0.37 to 1.12). No association was observed between physical activity and disease-specific mortality. Conclusions Our findings suggest that higher prediagnosis BMI increases risk of overall and disease-specific mortality among women diagnosed with endometrial cancer, whereas physical activity lowers risk. Intervention studies of the effect of these modifiable lifestyle factors on mortality are needed.
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