Malignancy risk factors and prognostic variables of pancreatic mucinous cystic neoplasms in Chinese patients.

BACKGROUND: Pancreatic mucinous cystic neoplasms (MCNs) represent one of the precursor lesions of pancreatic ductal adenocarcinoma, and their detection has been facilitated by advances in preoperative imaging. Due primarily to the rarity of MCNs, however, there is limited knowledge regarding the prognostic variables and high-risk factors for malignant transformation. A more comprehensive and nuanced approach is necessary to fill this gap and provide a basis for improved treatment decisions and patient outcomes. AIM: To investigate the high-risk factors associated with malignant MCNs and to explore the prognostic factors of MCN with associated invasive carcinoma (MCN-AIC). METHODS: All cases of resected MCNs from a single high-volume institution between January 2012 and January 2022 were retrospectively reviewed. Only cases with ovarian-type stroma verified by progesterone receptor staining were included. Preoperative features, histological findings and postoperative course were documented. Multivariate logistic regression was employed to investigate variables related to malignancy. Survival analysis was performed using the Kaplan-Meier curve, and the prognostic factors were assessed to evaluate the postoperative course of patients with MCN-AIC. RESULTS: Among the 48 patients, 36 had benign MCNs, and 12 had malignant MCNs (1 high-grade atypical hyperplasia and 11 MCN-AIC). Age, tumour size, presence of solid components or mural nodules and pancreatic duct dilatation were identified as independent risk factors associated with malignancy. The follow-up period ranged from 12 mo to 120 mo, with a median overall survival of 58.2 mo. Only three patients with MCN-AIC died, and the 5-year survival rate was 70.1%. All 11 cases of MCN-AIC were stage I, and extracapsular invasion was identified as a prognostic factor for poorer outcomes. CONCLUSION: The risk factors independently associated with malignant transformation of MCNs included age, tumour size, presence of solid components or mural nodules, and pancreatic duct dilatation. Our study also revealed that encapsulated invasion was a favourable prognostic factor in MCN-AIC patients.

The faith of non-surveilled pancreatic cysts: a bicentric retrospective study.

BACKGROUND: Incidental discovery of pancreatic cystic neoplasms (PCLs) is a common and steadily increasing occurrence. The aim of this study was to investigate a cohort of patients presenting with incidentally detected PCLs which were not included in a surveillance protocol, and to compare their risk of malignant evolution with that of systematically surveilled lesions. MATERIALS AND METHODS: A population of PCLs which did not receive surveillance over a period >10 years (population A) was selected at the Medical University of Vienna. A group of "low risk" branch duct intraductal papillary mucinous neoplasm ≤15 mm in size upon diagnosis undergoing a regular follow-up of at least 5 years at the University of Verona was selected as control (population B). The incidence of pancreatic cancer (PC), cumulative risk of PC and disease-specific survival were compared. RESULTS: Overall, 376 patients with non-surveilled PCLs were included in study group A and compared to 299 patients in group B. This comparison resulted in similar incidence rates of PC (1.6% vs 1.7%, p = 0.938), a strong similarity in terms of disease-specific mortality rates (1.3% vs 0.3%, p = 0.171) and the 5- and 10-year cumulative risk of PC (≅ 1% and 2%, p = 0.589) and DSS (≅ 100% and 98%, p = 0.050). CONCLUSION: The "price to pay" for a negligence-based policy in the population of non-surveilled PCLs was reasonable, and the incidence of PC was comparable to that reported for a population of low-risk cysts enrolled to a standardized surveillance protocol.

An Update on Endocrine Mucin-producing Sweat Gland Carcinoma: Clinicopathologic Study of 63 Cases and Comparative Analysis.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.

Incidence and potential predictors of thromboembolic events in epithelial ovarian carcinoma patients during perioperative period.

OBJECTIVE: To assess the incidence and the risk factors of venous thromboembolism (VTE) in patients with epithelial ovarian carcinoma (EOC) during the perioperative period. METHODS: A retrospective analysis was conducted on the patients with epithelial ovarian cancer treated in our hospital, between January 2017 and July 2019, and a comprehensive review of the medical documentation was performed to collect relevant data. We then analyzed the related factors of the thrombosis in the EOC patients, using univariate and multivariate analysis to identify significant risk factors for VTE, and bootstrap resampling method was used to verify the multivariate analysis results. The ROC curve methods were conducted to evaluate the diagnostic value for the prediction of VTE. RESULTS: We analyzed 233 cases of patients with EOC, of whom the incidence of VTE was 11.16%. According to multivariate and 5000 bootstrap samples analysis, preoperative D-dimer levels (>4.215 µg/ml, p = 0.041 and p = 0.032) and comorbid of cerebral infarction (p < 0.001 and p < 0.001) had statistical significance in predicting VTE events; bootstrap analysis also found the Alb, CA125, OCCC had statistical significance. While According to multivariate and 5000 bootstrap samples analysis, age (>50.5 years old, p = 0.019 and p = 0.002) and nonoptimal debulking surgery (p = 0.007 and p = 0.002) showed significance in predicting VTE after surgery; bootstrap analysis also found the D-dimer levels (>4.215 µg/ml) and tuberculosis had statistical significance. CONCLUSION: More effective thromboprophylaxis and pre-test assessment is necessary for EOC patients. For prediction VTE events, D-dimer levels (>4.215 µg/ml) were the independent predictors before operation. Age and debulking surgery were the independent predictors post operation.

Association between pelvic inflammatory disease, infertility, ectopic pregnancy and the development of ovarian serous borderline tumor, mucinous borderline tumor and low-grade serous carcinoma.

OBJECTIVE: Risk factors for ovarian borderline tumors and low-grade serous carcinoma (LGSC) are poorly understood. The aim of this study was to examine the association between infertility, pelvic inflammatory disease (PID), endometriosis, ectopic pregnancy, hysterectomy, tubal ligation and parity and the risk of serous borderline tumor (SBT), mucinous borderline tumor (MBT) and LGSC. METHODS: This was a population-based cohort study using linked administrative and hospital data. Participants were 441,382 women born between 1945 and 1975 who had been admitted to hospital in Western Australia between 1 January 1980 and 30 June 2014. We used Cox regression to estimate hazard ratios (HRs). RESULTS: We observed an increased rate of SBT associated with infertility, PID and ectopic pregnancy (HRs and 95% CIs were, respectively, 1.98 (1.20-3.26); 1.95 (1.22-3.10) and 2.44 (1.20-4.96)). We did not detect an association between any of the factors under study and the rate of MBT. A diagnosis of PID was associated with an increased rate of LGSC (HR 2.90, 95% CI 1.21-6.94). CONCLUSIONS: The association with PID supports the hypothesis that inflammatory processes within the upper gynaecological tract and/or peritoneum may predispose to the development of SBT and LGSC.

Características de la neoplasia quística mucinosa del páncreas en pacientes atendidos en un Hospital Nacional del Perú / Characteristics of pancreatic mucinous cystic neoplasm in patients treated at a National Hospital in Peru

RESUMEN Con el objetivo de analizar las características clínico, patológicas y quirúrgicas de la Neoplasia Quística Mucinosa de páncreas (NQM), se realizó un análisis de los pacientes del servicio de Cirugía de Páncreas, Bazo y Retroperitoneo del Hospital Nacional Guillermo Almenara Irigoyen en Lima, Perú desde enero del 2009 hasta octubre del 2018. La presencia del estroma ovárico se usó como criterio diagnóstico de NQM. De diez pacientes con edad promedio de 47,8 años, nueve fueron mujeres, las lesiones estuvieron localizadas en el páncreas distal, el tamaño tumoral promedio fue de 88,6 mm. En todos los pacientes se realizó una pancreatectomía distal siendo tres laparoscópicas, no hubo reoperaciones ni fallecidos, dos pacientes tuvieron carcinoma invasor asociado. En conclusión, la presentación de NQM es mayor en mujeres de edad media siendo la localización en el páncreas distal y el porcentaje de malignidad bajo. La cirugía laparoscópica es una alternativa de manejo.

ABSTRACT In order to analyze the clinical, pathological, and surgical characteristics of pancreatic mucinous cystic neoplasm (MCN), an analysis of the patients from the Pancreas, Spleen, and Retroperitoneal Surgery Service of the Guillermo Almenara Irigoyen National Hospital in Lima, Peru, was performed from January 2009 to October 2018. The presence of ovarian stroma was used as a diagnostic criterion for MCN. From ten patients with an average age of 47.8 years, nine were women; the lesions were located in the distal pancreas, and the average tumor size was 88.6 mm. All patients underwent a distal pancreatectomy, three of which were laparoscopic; there were no reoperations or deaths; two patients had associated invasive carcinoma. In conclusion, the frequency of MCN is higher in middle-aged women, being the location in the distal pancreas and the percentage of malignancy is low. Laparoscopic surgery is a disease management option.

Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4-21% in reproductive aged women. Recently, the Ovarian Cancer Association Consortium (OCAC) reported a decreased risk of invasive ovarian cancer among women with self-reported PCOS. However, given the limitations of self-reported PCOS, the validity of these observed associations remains uncertain. Therefore, we sought to use Mendelian randomization with genetic markers as a proxy for PCOS, to examine the association between PCOS and ovarian cancer. METHODS: Utilizing 14 single nucleotide polymorphisms (SNPs) previously associated with PCOS we assessed the association between genetically predicted PCOS and ovarian cancer risk, overall and by histotype, using summary statistics from a previously conducted genome-wide association study (GWAS) of ovarian cancer among European ancestry women within the OCAC (22 406 with invasive disease, 3103 with borderline disease and 40 941 controls). RESULTS: An inverse association was observed between genetically predicted PCOS and invasive ovarian cancer risk: odds ratio (OR)=0.92 [95% confidence interval (CI)=0.85-0.99; P = 0.03]. When results were examined by histotype, the strongest inverse association was observed between genetically predicted PCOS and endometrioid tumors (OR = 0.77; 95% CI = 0.65-0.92; P = 0.003). Adjustment for individual-level body mass index, oral contraceptive use and parity did not materially change the associations. CONCLUSION: Our study provides evidence for a relationship between PCOS and reduced ovarian cancer risk, overall and among specific histotypes of invasive ovarian cancer. These results lend support to our previous observational study results. Future studies are needed to understand mechanisms underlying this association.

Assessing endometrial cancer risk among US women: long-term trends using hysterectomy-adjusted analysis.

BACKGROUND: Commonly reported incidence rates for endometrial cancer fail to take into account both the large number of hysterectomies performed each year and the dynamic change in hysterectomy rate over the past decade. Large racial differences in premenopausal hysterectomy rates between Black and White women in the United States likely affect calculation of race-based risk. OBJECTIVES: The objectives of the study were to determine how the long-term trends in Black-White differences in endometrial cancer incidence and histology type have changed over time for women at risk. STUDY DESIGN: Using longitudinal Surveillance, Epidemiology, and End Results data from 1997 to 2014 and state-level hysterectomy prevalence from the Behavioral Risk Factor Surveillance System, we calculated hysterectomy-adjusted incidence rates of endometrial cancer and the proportion of high vs low-risk endometrial cancer, by race, over time. RESULTS: In women older than 50 years who have not had a hysterectomy, endometrial cancer incidence is 87 per 100,000 from 1997 to 2014. Among White women endometrial cancer incidence changed from 102 (1997-2001) to 86 (2012-2014) cases per 100,000, with a nonsignificant decreasing linear trend (adjusted risk ratio, 0.95; 95% confidence interval, 0.91-1.00; p=0.05). In contrast, incidence for Black women was 88 (1997-2001), 101 (2002-2006), 100 (2007-2011), and 102 (2012-2014) cases per 100,000 with no decreasing trend (adjusted risk ratio, 1.02; 95% confidence interval, 0.96-1.10, P = .449). High-risk histology increased among both groups (White: adjusted risk ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .015; Black: adjusted risk ratio, 1.06; 95% confidence interval, 1.02-1.10, P = .007). Racial difference in the proportion of high-risk disease remained stable. CONCLUSION: Updated hysterectomy-adjusted incidence demonstrates that endometrial cancer is the second most common cancer among women older than 50 years with a uterus and that endometrial cancer has been more common among Black women compared with White women in the United States since 2002. A clinical approach of proactive communication and routine screening for early symptoms in the perimenopausal and menopausal years, especially among Black women, is warranted. These findings can also inform equitable distribution of research funding for endometrial cancer and serve to promote public awareness of this common cancer.

Trends and characteristics of epithelial ovarian cancer in Japan between 2002 and 2015: A JSGO-JSOG joint study.

OBJECTIVE: To examine the trends of epithelial ovarian cancer histologic subtypes in Japan. METHODS: A nationwide retrospective registry study was performed between 2002 and 2015 (Japan cohort, n = 48,640). Trends were also examined in The Surveillance, Epidemiology, and End Results Program (US cohort, n = 49,936). Time-specific proportional changes of four major histological subtypes (serous, clear cell, endometrioid, and mucinous) were examined. RESULTS: The Japan cohort had more stage I disease (44.1% versus 24.9%) and less stage IV disease (10.0% versus 23.1%) than the US cohort (P < 0.001). The Japan cohort had more non-serous histology, particularly clear cell carcinoma (26.9% versus 8.4%), than the US cohort (P < 0.001). In the Japan cohort, proportion of clear cell carcinoma increased significantly from 23.4% to 29.1% between 2002 and 2010 (P < 0.001). Among stage I disease, clear cell carcinoma increased significantly in the Japan cohort from 32.9% to 40.3% between 2002 and 2015 (P < 0.001), whereas mucinous carcinoma increased significantly in the US cohort from 15.0% to 24.8% (P = 0.01). In 2015, clear cell carcinoma was most common among women aged <50 years from the Japan cohort (30.2%) versus serous carcinoma in the US cohort (50.8%). In the Japan cohort, the peak age was 75 years for serous, 57 for clear cell, and 45 for endometrioid carcinoma (P < 0.001). Mucinous carcinoma decreased until 43 years and increased again after age 73 years (P < 0.001). CONCLUSION: Characteristics of epithelial ovarian cancer in Japan are largely different compared to the US. In Japan, clear cell carcinoma has increased significantly in recent years to account for nearly 30% of epithelial ovarian cancer.

[Characteristics of pancreatic mucinous cystic neoplasm in patients treated at a National Hospital in Peru]. / Características de la neoplasia quística mucinosa del páncreas en pacientes atendidos en un Hospital Nacional del Perú.

In order to analyze the clinical, pathological, and surgical characteristics of pancreatic mucinous cystic neoplasm (MCN), an analysis of the patients from the Pancreas, Spleen, and Retroperitoneal Surgery Service of the Guillermo Almenara Irigoyen National Hospital in Lima, Peru, was performed from January 2009 to October 2018. The presence of ovarian stroma was used as a diagnostic criterion for MCN. From ten patients with an average age of 47.8 years, nine were women; the lesions were located in the distal pancreas, and the average tumor size was 88.6 mm. All patients underwent a distal pancreatectomy, three of which were laparoscopic; there were no reoperations or deaths; two patients had associated invasive carcinoma. In conclusion, the frequency of MCN is higher in middle-aged women, being the location in the distal pancreas and the percentage of malignancy is low. Laparoscopic surgery is a disease management option.

Con el objetivo de analizar las características clínico, patológicas y quirúrgicas de la Neoplasia Quística Mucinosa de páncreas (NQM), se realizó un análisis de los pacientes del servicio de Cirugía de Páncreas, Bazo y Retroperitoneo del Hospital Nacional Guillermo Almenara Irigoyen en Lima, Perú desde enero del 2009 hasta octubre del 2018. La presencia del estroma ovárico se usó como criterio diagnóstico de NQM. De diez pacientes con edad promedio de 47,8 años, nueve fueron mujeres, las lesiones estuvieron localizadas en el páncreas distal, el tamaño tumoral promedio fue de 88,6 mm. En todos los pacientes se realizó una pancreatectomía distal siendo tres laparoscópicas, no hubo reoperaciones ni fallecidos, dos pacientes tuvieron carcinoma invasor asociado. En conclusión, la presentación de NQM es mayor en mujeres de edad media siendo la localización en el páncreas distal y el porcentaje de malignidad bajo. La cirugía laparoscópica es una alternativa de manejo.

An analysis of the association between statin use and risk of endometrial and ovarian cancers in the Women's Health Initiative.

BACKGROUND: Statins have anti proliferative activity in vitro against endometrial and ovarian cancer and can affect levels of reproductive hormones. We analyzed data from the Women's Health Initiative (WHI) to assess whether statins are associated with risk of endometrial and ovarian cancer. METHODS: The WHI study included 161,808 postmenopausal women in which incident cases of endometrial (n = 1377) and ovarian cancer (n = 763) were identified over an average of 10.8 (SD + 3.3) years. Information on statin use and risk factors was collected at baseline and follow-up. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of statin use and risk of endometrial and ovarian cancer. All statistical tests were two-sided. RESULTS: Statins were used at baseline by 7.5% women and by up to 25% at year nine. The multivariable adjusted HR for risk of endometrial cancer for baseline statin use was 0.74, 95% C.I. 0.59-0.94 and for ovarian cancer was 1.15, 95% C.I. 0.89-1.50. In time-dependent models, statins were not associated with endometrial cancer (HR 0.91, 95% C.I. 0.76-1.08) however there was an increased risk of ovarian cancer (HR 1.30, 95% CI 1.04-1.62), largely attributed to the effect of the hydrophilic statin, pravastatin (1.89, 95% CI 1.24-2.88). CONCLUSIONS: There was a reduction in risk of endometrial cancer among statin users at baseline but not in time-dependent models. Pravastatin use was associated with an increased risk of ovarian cancer. Analyses of larger numbers of cases are needed to evaluate these findings.

Birth weight and the risk of histological subtypes of ovarian and endometrial cancers: Results from the Copenhagen School Health Records Register.

BACKGROUND: Studies of birth weight associations with ovarian and endometrial cancer risks are limited with inconsistent results, and none has evaluated associations by histologic subtype. We utilized prospectively collected birth weight information to investigate the association with risk of ovarian and endometrial cancers overall and by histologic subtype. METHODS: 162,559 girls, born from 1930 to 1989, from the Copenhagen School Health Records Register (CSHRR) were followed prospectively via linkage with the Danish health registers. Ovarian (n=666) and endometrial (n=694) cancers were identified from 1978 to 2014. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Women with lower (2.0-3.25 vs. 3.26-3.75kg) and higher (3.75-5.5 vs. 3.26-3.75kg) birth weights had increased risks of ovarian cancer overall [HR (95% CI): 1.27 (1.06-1.52); 1.51 (1.21-1.87), respectively] and serous ovarian cancers [1.54 (1.19-1.98); 1.98 (1.47-2.67), respectively]. A decreased risk of Type II endometrial tumors was suggested per kilogram increase in birth weight [HR (95% CI): 0.63 (0.40-1.00)]. CONCLUSIONS: Our results suggest that both lower and higher birth weights were associated with increased ovarian cancer risk and associations were particularly strong for serous ovarian cancer, the most common subtype. Birth weight was not associated with most types of endometrial cancer.

Perineal Talc Use and Ovarian Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: It has been posited that there is an association between perineal talc use and the incidence of ovarian cancer. To date, this has only been explored in observational studies. OBJECTIVES: To perform a meta-analysis to evaluate the association between perineal talc use and risk of ovarian cancer. METHODS: Studies were identified using six electronic databases. Observational studies involving at least 50 cases of ovarian cancer were eligible for inclusion. We analyzed the association between ovarian cancer, including specific types, and any perineal talc use, long-term (>10 years) use, total lifetime applications, and use on diaphragms or sanitary napkins. A subgroup analysis was performed, stratifying by study design and population. RESULTS: We identified 24 case-control (13,421 cases) and three cohort studies (890 cases, 181,860 person-years). Any perineal talc use was associated with increased risk of ovarian cancer (OR = 1.31; 95% CI = 1.24, 1.39). More than 3600 lifetime applications (OR = 1.42; 95% CI = 1.25, 1.61) were slightly more associated with ovarian cancer than <3600 (OR = 1.32; 95% CI = 1.15, 1.50). An association with ever use of talc was found in case-control studies (OR = 1.35; 95% CI = 1.27, 1.43), but not cohort studies (OR = 1.06; 95% CI = 0.90, 1.25). However, cohort studies found an association between talc use and invasive serous type ovarian cancer (OR = 1.25; 95% CI = 1.01, 1.55). We found an increased risk of serous and endometrioid, but not mucinous or clear cell subtypes. CONCLUSIONS: In general, there is a consistent association between perineal talc use and ovarian cancer. Some variation in the magnitude of the effect was found when considering study design and ovarian cancer subtype.

Prevalence and outcomes of cystic lesions of the transplant pancreas: The University of Wisconsin Experience.

Literature on the behavior of cystic lesions in pancreas transplants is scarce, and hence a better understanding is warranted. Data on recipients and their respective donors that underwent simultaneous kidney and pancreas, pancreas transplant alone, and pancreas after kidney between 1994 and 2015 were reviewed (n = 1185). Cystic lesions of the transplant pancreas developed in 22 patients (1.8%): 12 pseudocysts, 2 cysts/remnants, 4 intraductal papillary mucinous neoplasms (IPMN), 2 adenocarcinomas, 1 low-grade intraepithelial pancreatic neoplasia, and 1 case of polycystic kidney disease. The median size was 3.6 cm (1.6-5.5 cm), and occurred at a median time of 65.5 months (2-183 months) posttransplant. The median age of the graft at time of diagnosis was 42 years (25.7-54.5), with 17 of 22 grafts (77%) functioning at time of diagnosis. Triggers for investigation were elevations in pancreatic enzymes, re-admissions for abdominal pain, and incidentalomas. High-resolution imaging and diagnostic biopsy/aspiration with ancillary tests were the main diagnostic tests. Most pseudocysts were managed by percutaneous drainage, and although no firm inference can be made from such a small series, we have observed that the behavior and management of IPMN and adenocarcinoma in the pancreas graft appears congruent to that of the native pancreas.

Long-term Risk of Pancreatic Malignancy in Patients With Branch Duct Intraductal Papillary Mucinous Neoplasm in a Referral Center.

BACKGROUND & AIMS: Little is known about the development of branch duct intraductal papillary mucinous neoplasms (BD-IPMNs). We evaluated long-term outcomes of a large cohort of patients with BD-IPMNs to determine risk of malignancy and define a subset of low-risk BD-IPMNs. METHODS: We performed a retrospective analysis of data from 577 patients with suspected or presumed BD-IPMN under surveillance at the Massachusetts General Hospital. Patients underwent cross-sectional imaging analysis at 3 months or later after their initial diagnosis. The diagnosis of BD-IPMN was based on the presence of unilocular or multilocular cysts of the pancreas and a non-dilated main pancreatic duct (<5 mm). We collected demographic, clinical, and pathology data. Cysts were characterized at the time of diagnosis and during the follow-up period. Follow-up duration was time between initial cyst diagnosis and date of last visit or death for patients without development of pancreatic cancer, date of surgery for patients with histologically confirmed malignancy, or date of first discovery of malignancy by imaging analysis for patients with unresectable tumors or who underwent neoadjuvant treatment before surgery. The primary outcome was risk of malignancy, with a focus on patients followed for 5 years or more, compared with that of the US population, based on standardized incidence ratio. RESULTS: Of the 577 patients studied, 479 (83%) were asymptomatic at diagnosis and 363 (63%) underwent endoscopic ultrasound at least once. The median follow-up time was 82 months (range, 6-329 months) for the entire study cohort; 363 patients (63%) underwent surveillance for more than 5 years, and 121 (21%) for more than 10 years. Malignancies (high-grade dysplasia or invasive neoplasm) developed after 5 years in 20 of 363 patients (5.5%), and invasive cancer developed in 16 of 363 patients (4.4%). The standardized incidence ratio for patients with BD-IPMNs without worrisome features of malignancy at 5 years was 18.8 (95% confidence interval, 9.7-32.8; P < .001). One hundred and eight patients had cysts ≤1.5 cm for more than 5 years of follow-up; only 1 of these patients (0.9%) developed a distinct ductal adenocarcinoma. By contrast, among the 255 patients with cysts >1.5 cm, 19 (7.5%) developed malignancy (P = .01). CONCLUSIONS: In a retrospective analysis of patients with BD-IPMNs under surveillance, their overall risk of malignancy, almost 8%, lasted for 10 years or more, supporting continued surveillance after 5 years. Cysts that remain ≤1.5 cm for more than 5 years might be considered low-risk for progression to malignancy.

Frequency of "incidental" serous tubal intraepithelial carcinoma (STIC) in women without a history of or genetic risk factor for high-grade serous carcinoma: A six-year study.

Objective The purpose of this study was to determine the prevalence of incidentally discovered serous tubal intraepithelial carcinoma in women without a genetic risk for or history of high grade serous carcinoma (HGSC) in the gynecologic tract. METHODS: All pathology reports at our institution that included bilateral salpingectomies from January 2006-December 2011 were examined in women >50years old in which the entire tube or the distal one-third was examined histologically with the complete (proximal and distal fallopian tube) or modified (distal one third of the tube) SEE-FIM protocol. Cases were divided into: Group 1, a history of or known risk factors (BRCA1 or BRCA2 mutations) for HGSC and Group 2, those without these attributes for whom a STIC would be unexpected (incidental). Women undergoing unspecified "risk-reducing" procedures were included in Group 1. RESULTS: Of 4051 identified total, 2268 had complete examination of the distal fallopian tube and were age 50 or above. Of these, 1747 were in group 2. Two STICs were identified (0.1%), one associated with a grade 2 endometrial endometrioid adenocarcinoma and one with a low-grade ovarian serous carcinoma in the setting of a serous borderline tumor. CONCLUSIONS: Incidental STICs in women over age 50 are uncommon. However, the significance of lesser tubal atypias (0.3% in this study), risk of STIC in women with no epithelial pathology and the risk imposed by coexisting endometrioid neoplasia are unclear and require further study.

Time trends in the incidence of hysterectomy-corrected overall, type 1 and type 2 endometrial cancer in Denmark 1978-2014.

OBJECTIVE: To investigate time trends in the incidence of overall, type 1 and type 2 endometrial cancer in Denmark 1978-2014, correcting for hysterectomy. METHODS: Based on the Danish Cancer Registry and the Danish National Patient Registry we calculated hysterectomy-corrected incidence rates of overall, type 1 and type 2 endometrial cancer. Separate analyses for women <55years (defined as pre- and perimenopausal age) and women aged ≥55years (defined as postmenopausal age) and analyses allowing for different time trends before and after the study period midyear 1996 were performed. Log-linear Poisson models were used to estimate annual percentage change (APC) in incidence with 95% confidence intervals (CI). RESULTS: The overall incidence of endometrial cancer decreased slightly from 1978 to 1995, but in the last two decades of the study period the incidence has been stable (APC=0.16; 95% CI: -0.19; 0.50). In the study period (1978-2014) type 1 endometrial cancer incidence decreased slightly (APC=-0.67; 95% CI:-0.83; -0.52), whereas the incidence of type 2 endometrial cancer increased substantially (APC=4.85; 95% CI: 4.47; 5.23). The decrease in type 1 endometrial cancer was most pronounced before 1996 in women younger than 55 years (APC=-2.79; 95% CI: -3.65; -1.91), while the largest increase in type 2 endometrial cancer was observed after 1996 (APC=6.42; 95% CI: 5.72; 7.12). CONCLUSIONS: Over a period of more than 35 years, the incidence of type 1 endometrial cancer decreased, mainly in pre- and perimenopausal women, while type 2 endometrial cancer incidence increased.

A nationwide study of ovarian serous borderline tumors in Denmark 1978-2002. Risk of recurrence, and development of ovarian serous carcinoma.

OBJECTIVE: Absolute risk and risk factors for recurrence and ovarian serous carcinoma following ovarian serous borderline tumors (SBTs) is not well-established. METHODS: We included all women with SBTs in Denmark, 1978-2002. Diagnoses were confirmed by centralized pathology review and classified as atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Implants were classified as noninvasive or invasive. Medical records were collected and reviewed, and follow-up was obtained. Subsequent diagnoses were also confirmed by centralized pathology review. We examined absolute risk and risk factors for recurrent APST and serous carcinoma using Cox regression. RESULTS: The absolute serous carcinoma risk after, respectively, 5 and 20years was 5.0% and 13.9% for noninvasive LGSC, and 0.9% and 3.7% for APST. Serous carcinoma risk was significantly higher following noninvasive LGSC compared with APST among stage I patients/patients without implants (HR=5.3; 95% CI: 1.7-16.3), whereas no significant association with tumor type was found in advanced stage patients/patients with implants. Advanced stage - notably invasive implants - bilaterality, surface involvement, and residual disease increased serous carcinoma risk. However, women with stage I APST also had a higher risk than the general population. CONCLUSIONS: This largest population-based cohort of verified SBTs revealed that women with noninvasive LGSC are significantly more likely to develop serous carcinoma than women with APST, which could not entirely be explained by invasive implants. Although invasive implants was a strong risk factor for serous carcinoma, even women with stage I APST were at increased risk compared with the general population.

The nature of early-stage endometrial cancer recurrence-A national cohort study.

BACKGROUND AND AIMS: The aim of the study was to present a comprehensive analysis of disease recurrence in a large Danish cohort of women with early-stage endometrial cancer treated according to national guidelines. METHODS: All women diagnosed with stage I or II endometrial cancer in 2005-2009 were included in a population-based historical cohort derived from the Danish Gynaecological Cancer Database. Disease recurrence up to 3 years after the primary diagnosis was identified using national registers and hospital charts. Follow-up on survival ended on 31st December 2014. We evaluated the predictive value of clinico-pathological and sociodemographic variables using multivariate logistic regression. RESULTS: Recurrence within 3 years of the primary treatment was diagnosed in 183 (7%) of the included 2612 women. Site of recurrence significantly impacted on overall survival as the 5-year survival rate was 64.8% for women with vaginal recurrence and 17.5% in women with distant recurrence. Factors predictive of recurrence included the International Federation of Gynaecology and Obstetrics (FIGO) stage (OR: IB = 1.91, stage II = 3.91), Charlson comorbidity index of 3 (OR 1.86), non-endometrioid histology (OR 1.81) and being outside of the workforce (OR 1.81). Vaginal recurrence was predicted by FIGO stage only (OR: IB = 1.88, II = 2.79), while extra-vaginal recurrence was predicted by FIGO stage (OR: IB = 2.12, II = 3.31), Charlson comorbidity index of 3 (OR 1.88) and non-endometrioid histology (OR 2.51). CONCLUSIONS: Future research should seek to understand the underlying mechanisms of the identified predictive factors to improve recurrence prediction and to reduce morbidity and mortality.

The association between reproductive and hormonal factors and ovarian cancer by estrogen-α and progesterone receptor status.

OBJECTIVE: We assessed the association between reproductive and hormonal factors and ovarian cancer incidence characterized by estrogen receptor-α (ERα) and progesterone receptor (PR) status. METHODS: Tissue microarrays were used to assess ERα and PR expression among 197 Nurses' Health Study (NHS), 42 NHSII and 76 New England Case-Control Study (NECC) ovarian cancer cases. NHS/NHSII cases were matched to up to 4 controls (n=954) on diagnosis date and birth year. NECC controls (n=725) were frequency matched on age. Cases were considered receptor positive if ≥1% of tumor cells stained positive. Associations by ERα and PR status were assessed using polytomous logistic regression. p-Value for heterogeneity was calculated using a likelihood ratio test. RESULTS: 45% of ovarian tumors were PR(+), 78% were ERα(+) and 45% were ERα(+)/PR(+), while 22% were ERα(-)/PR(-). Postmenopausal status was associated with an increased risk of PR(-) tumors (OR: 2.07; 95%CI: 1.15-3.75; p-heterogeneity=0.01) and age at natural menopause was inversely associated with PR(-) tumors (OR, per 5years: 0.77; 95%CI: 0.61-0.96; p-het=0.01). Increasing duration of postmenopause was differentially associated by PR status (p-het=0.0009). Number of children and tubal ligation were more strongly associated with ERα(-) versus ERα(+) tumors (p-het=0.002 and 0.05, respectively). No differential associations were observed for oral contraceptive or hormone therapy use. CONCLUSIONS: Postmenopausal women have an increased risk of developing PR(-) ovarian tumors compared to premenopausal women. The associations observed for ovarian cancer differ from those seen for breast cancer suggesting that the biology for tumor development through ERα and PR pathways may differ.