Vaginal birth after cesarean: what's new in the new millennium?

PURPOSE OF REVIEW: This brief review will focus exclusively on very recent developments and controversial aspects of vaginal birth after cesarean. Only papers published in 2001 or 2002 are included. RECENT FINDINGS: Recent studies have addressed the intrapartum management of vaginal birth after cesarean patients and the safety of trial of labor compared with elective repeat cesarean. SUMMARY: The recent trend has been towards a more cautious approach to vaginal birth after cesarean. Some are concerned that this trend may limit childbirth options for those women who wish to avoid repeat cesarean operations.     

Endometrial cancer: can nodal status be predicted with curettage?

OBJECTIVE: To determine whether histologic or molecular markers assessed in pretreatment curettage specimens predict nodal metastasis in endometrial cancer. METHODS: Phenotypic and molecular variables (ploidy, proliferating cell nuclear antigen, MIB-1, p53, HER-2/neu, and bcl-2) were analyzed in preoperative specimens from 82 patients with endometrial cancer who had lymph nodes dissected. These 82 patients had been selected from a total population of 283 patients with endometrial cancer, using a case-cohort design. Weighted logistic regressions were then used to determine significant predictors of positive lymph nodes, and results were estimated for the total population of 283 patients. RESULTS: Of the overall population, 12% of patients were estimated to have positive lymph nodes. Histologic subtype, p53, and bcl-2 each were significantly correlated (P <0.05) with lymph node status. With application of stepwise logistic regression, p53 was the only independent predictor of lymph node status. In addition, a statistical model predictive of positive lymph nodes was generated which incorporated the risk factors p53, bcl-2, and histologic subtype. CONCLUSION: In pretreatment curettage specimens, the presence of unfavorable levels of p53 or bcl-2 or of nonendometrioid histologic features, or combinations of those, significantly predicted lymph node status, thus facilitating the preoperative identification of patients at risk of lymph node metastases.     

Endometrial cancer – an update

Endometrial cancer incidence rates are continuing to rise and approximately 40 % of all cases being preventable. A major contributing factor to this is the current obesity epidemic. Surgery remains the cornerstone of treatment and minimal access techniques have established themselves as the gold-standard. Routine lymphadenectomy for all disease stages has not been demonstrated to benefit overall survival. Risk stratification and personalized approaches to patient treatment are becoming more of a necessity, especially in younger women who may wish to preserve their fertility. Genomic profiling is starting to change the way we consider endometrial cancer, which may help direct treatment modalities in the future. Priority setting the research agenda will help guide future research and allow us to further tackle this common gynaecological malignancy.     

Endometrial cancer arising in adenomyosis versus endometrial cancer coexisting with adenomyosis: are these two different entities?

Purpose

While adenomyosis is one of the most common benign histologic findings in hysterectomy specimens of endometrial cancer, demographics of endometrial cancer arising in adenomyosis (EC-AIA) has not been well elucidated. The aim of this study is to evaluate histopathological findings and disease-free survival (DFS) of EC-AIA in comparison to endometrial cancer coexisting with adenomyosis (EC-A).

Methods

EC-AIA cases were identified via a systematic literature search (n = 46). EC-A cases were identified from a historical cohort that underwent hysterectomy-based surgical staging in two institutions (n = 350). Statistical comparisons of the two groups were based on univariate and multivariate analyses.

Results

The EC-AIA group was significantly older than the EC-A group (58.9 versus 53.8, p = 0.002). As to tumor characteristics, 63.6% of EC-AIA cases reported tumor within the myometrium without endometrial extension. The EC-AIA group was significantly associated with more non-endometrioid histology (23.9 versus 14.8%; p = 0.002) and deep myometrial tumor invasion (51.6 versus 19.4%; p < 0.001) than EC-A. Tumor grade, stage, and nodal metastasis risk were similar (all, p > 0.05). In a univariate analysis, the EC-AIA group had a significantly decreased DFS compared to EC-A (5-year rates, 72.2 versus 85.5%, p = 0.001). After controlling for age, histology, tumor grade, and stage, EC-AIA remained an independent prognostic factor associated with decreased DFS compared to EC-A (adjusted-hazard ratio 2.87, 95% confidence interval 1.44–5.70, p = 0.031).

Conclusion

Our study demonstrated that EC-AIA has distinct tumor characteristics and a poorer survival outcome compared to EC-A. This suggests a benefit of recognition of this unique entity as an aggressive variant of endometrial cancer.

     

Environmental endocrine disruptors and breast cancer: new risk factors?

Human epidemiological studies and experimental animal data strongly suggest that xenobiotics with estrogenic activity may participate in to the increasing incidence of breast cancer, the most frequent cancer all around the world. Several reports have since 15 years reported positive correlations between blood or peritumoral adipose tissue levels of persistent organic compounds including organochloride pesticides and breast cancer risk. Moreover, fetal or perinatal exposition to low doses of such endocrine disruptors induce premalignant or malignant transformation of adult mammary gland in rodents. However, this environmental endocrine disrupter hypothesis still needs to be demonstrated. Further human studies are needed which will consider the exposition window, the association of several xenoestrogens, the molecular mechanisms involved and the possible individual genetic susceptibility in order to identify pertinent biomarkers and to define acceptable environmental concentration levels for agricultural or industrial chemical new products to be used.     

Endometrial cancer in morbidly obese women: Do racial disparities affect surgical or survival outcomes?

Objective

Endometrial cancer mortality disproportionately affects black women and whether greater prevalence of obesity plays a role in this disparity is unknown. We examine the effect of race on post-surgical complications, length of stay, and mortality specifically in a morbidly obese population.

Methods

Black and white women with endometrial cancer diagnosed from 1996 to 2012 were identified from the University Pathology Group database in Detroit, Michigan, and records were retrospectively reviewed to obtain clinicopathological, demographic, and surgical information. Analysis was limited to those with a body mass index of 40 kg/m² or greater. Differences in the distribution of variables by race were assessed by chi-squared tests and t-tests. Kaplan–Meier and Cox regression analyses were performed to examine factors associated with mortality.

Results

97 white and 89 black morbidly obese women were included in this analysis. Black women were more likely to have type II tumors (33.7% versus 15.5% of white women, p-value = 0.003). Hypertension was more prevalent in black women (76.4% versus 58.8%, p-value = 0.009), and they had longer hospital stays after surgery despite similar rates of open vs minimally invasive procedures and lymph node dissection (mean days = 5.4) compared to whites (mean days = 3.5, p-value = 0.036). Wound infection was the most common complication (16.5% in whites and 14.4% in blacks, p-value = 0.888). Blacks were more likely to suffer other complications, but overall the proportions did not differ by race. In univariate analyses, black women had higher risk of endometrial cancer-related death (p-value = 0.090). No racial differences were noted in adjusted survival analyses.

Conclusion

A more complete investigation, incorporating socio-demographic factors, is warranted to understand the effects of morbid obesity and race on endometrial cancer.     

Radical abdominal versus laparoscopic hysterectomy for stage IB cervical cancer: what's the point?

OBJECTIVE: To evaluate surgical morbidity and length of stay for type III radical abdominal hysterectomy performed in the private practice setting, and to compare these results with currently available data on laparoscopic radical hysterectomy. METHODS AND MATERIALS: One hundred seventy-five consecutive type III radical abdominal hysterectomies performed by the author in a uniform fashion over a ten-year period for patients with stage IB cervical cancer were evaluated. All surgeries were performed in private community hospitals in New Jersey. RESULTS: Type III radical abdominal hysterectomy performed in the private setting using the author's protocol resulted in lower surgical morbidity, equivalent hospital stay and resumption of normal activities, and much shorter operating times than laparoscopic radical hysterectomy. CONCLUSION: Laparoscopic radical hysterectomy provides no surgical or financial advantage over radical abdominal hysterectomy when the latter is performed in the private practice setting; results from laparoscopic surgery are inferior with respect to morbidity.     

Endometrial polyps in obese asymptomatic pre and postmenopausal patients with breast cancer: Is screening necessary?

Objective

To evaluate the prevalence of endometrial polyps in obese asymptomatic pre and postmenopausal patients with breast cancer and to know if a baseline pretamoxifen endometrial assessment should be taken into consideration in these women at high risk.

Methods

A cross-sectional study was carried out with 201 women with breast cancer. A diagnostic hysteroscopy was performed in all women. All formations suspected as polyps were removed. The prevalence of endometrial polyps was analyzed in all patients (n = 182) and in premenopausal (n = 49) and postmenopausal (n = 118) women with estrogen receptor (ER) positive breast cancer (BC) according to their body mass index (BMI) and other risk factors.

Results

Hysteroscopic evaluation was possible in 182 cases (90.5%). Of the total of women, 160 (87.9%) were ER(+)BC patients, 133 (73.1%) postmenopausal women and 41.5% were obese (BMI ≥ 30 kg/m²). Endometrial polyps were found in 52 cases (28.5%) (3 cases of simple hyperplasia harbored within a polyp). In premenopausal patients with ER(+)BC, there were no statistical differences in endometrial polyps according to their BMI (22.3% in non-obese women vs 31.7% in obese) while in all patients (26.4% in non-obese vs 44.0% in obese) and in postmenopausal women with ER(+)BC (25.9% in non-obese vs 48.6% in obese) there were statistical differences. In all women the relative risk (RR) of endometrial polyps in obese patients was 2.24 (1.01–4.83), in obese postmenopausal women with ER(+)BC was 2.75 (1.01–7.40) and in obese premenopausal patients with ER(+)BC was 1.42 (0.80–3.29).

Conclusions

Asymptomatic women with breast cancer have a high prevalence of baseline subclinical endometrial polyps and it is very high in obese postmenopausal patients with estrogen receptor positive breast cancer. Therefore, there may be a future role for baseline pretamoxifen screening of some sort for the obese asymptomatic postmenopausal patient, especially if they are elderly and ER positive.     

Bokhman Redux: Endometrial cancer “types” in the 21st century

In 1983 Jan V. Bokhman, M.D. published a landmark paper entitled “Two Pathogenetic Types of Endometrial Carcinoma” in which an enduring dualistic view of endometrial cancer was first proposed. “Type I” cancers are thought to represent estrogen driven mostly low grade endometrioid tumors strongly associated with obesity and other components of the metabolic syndrome. “Type II” cancers represent higher grade non-endometrioid tumors for which the latter associations are less significant. Basic tenets of this dichotomy including significant prognostic differences have been abundantly confirmed by later literature. The construct has in turn contributed a useful framework for decades of teaching and scientific advancement across disciplines. However, recent large epidemiologic studies indicate a more complex web of risk factors with obesity and hormones likely playing an important role across the entire endometrial cancer histologic and clinical spectrum. Moreover, high quality molecular data and refinements in pathologic classification challenge any simplistic classification of endometrial cancer. For example, the Cancer Genome Atlas (TCGA) recently defined four clinically distinct endometrial cancer types based on their overall mutational burden, specific p53, POLE and PTEN mutations, microsatellite instability and histology. Additionally, new histologic categories with clear prognostic implications have been accepted and it is becoming evident from an epidemiologic point of view that metabolic factors may play an important role in endometrial cancer overall. While Bokhman's intuitive dualistic model remains relevant when working with large registries and databases lacking granular information; most other efforts should integrate clinical, pathological and molecular specifics into more nuanced classifications.     

Endometrial pinopodes: some more understanding on human implantation?

Endometrial receptivity is a prerequisite for blastocyst implantation. During receptivity, the hairy-like epithelial cell microvilli transiently fuse to a single flower-like membrane projection called the 'pinopode'. Scanning electron microscopy in sequential endometrial biopsies shows that pinopodes appear about 1 week after ovulation, and they develop and regress within just 2 days. Interestingly, the cycle days when pinopodes appear can vary by up to 5 days between different individuals. On average, they occur on days 20-21 in natural cycles and earlier (days 19-20) in stimulated cycles. The abundance of pinopodes relates to implantation success and many patients with multiple implantation failures fail to produce pinopodes. Based on these findings, biopsies from candidate embryo recipients have been examined in mock cycles and pinopode numbers and timing of their appearance assessed. A similar cycle follows where embryos are replaced earlier or later, according to the reported timing of pinopode formation. If pinopodes are absent, the cycle can be modified. Accumulating evidence supports their clinical use as a marker to assess endometrial receptivity. Pinopode appearance, loss of steroid receptors and maximal expression of a(v)b(3) integrin, osteopontin and leukaemia inhibitory factor and receptor have been demonstrated in the same biopsy, showing a consistent association of pinopode appearance and other receptivity changes.     

Endometrial Biopsy in Low-Risk Women: Are We Over-Investigating?

The appropriate age at which to perform endometrial biopsy for abnormal uterine bleeding (AUB) is controversial. This study aimed to determine the prevalence of malignant and premalignant pathologies in women aged 41–49 years with AUB and without risk factors for endometrial cancer. Records of women who had undergone a biopsy at the gynaecology clinic of the Centre hospitalier de l'Université de Montréal between 2014 and 2018 were reviewed. Of the 209 women included in the study, 2 had atypical hyperplasia, which resolved without treatment, and 3 had hyperplasia without atypia. The remaining women had benign results, showing that the prevalence of malignant and premalignant endometrial pathologies is low in this subgroup of patients.     

Hysteroscopic Morcellation in Endometrial Cancer Diagnosis: Increased Risk?

Study ObjectiveOperative hysteroscopy requires elevated intrauterine pressures, which could lead to the spread of malignant cells into the peritoneal cavity. Currently, there is a paucity of data analyzing clinical outcomes in endometrial cancer after hysteroscopic morcellation with newer equipment. In this study, we sought to determine whether there are increased rates of positive peritoneal cytology, lymphovascular space invasion, or surgical upstaging in patients undergoing hysteroscopic morcellation compared with alternative endometrial biopsy methods.DesignA retrospective chart review of patients from 2013–2018 was performed. The exclusion criteria included biopsy at outside institution, stage IV endometrial cancer known before biopsy, and missing data regarding biopsy method and histology. Peritoneal cytology results, lymphovascular space invasion, and surgical staging were compared by method of biopsy and histology using chi-square and Kruskal-Wallis tests.SettingThe patients included in this study were accrued from the Karmanos Cancer Insittute in Detroit, Michigan.PatientsA total of 289 patients met the inclusion criteria: 184 patients were classified as low-grade (Fédération Internationale de Gynécologie et d'Obstétrique grades 1 and 2) and 105 as high-grade (Fédération Internationale de Gynécologie et d'Obstétrique grade 3, serous, clear cell, and carcinosarcoma) endometrial cancer.InterventionsFifty-three patients (18%) underwent hysteroscopy with morcellation. Alternative biopsy methods included hysteroscopy without morcellation, n = 81 (28%); endometrial biopsy, n = 112 (38.7%); and dilation and curettage, n = 43 (15%).Measurements and Main ResultsPositive peritoneal cytology was noted in 34 cases (12%) and negative cytology in 165 (57%). Cytology was not performed in 90 cases (31%). When comparing outcomes by histologic subtypes, no difference was seen in peritoneal cytology (p = .704 and .727 for low grade and high grade, respectively), stage (p = .773 and .053 for low grade and high grade, respectively) or lymphovascular space invasion (p = .400 and .142 for low grade and high grade, respectively).ConclusionOur study demonstrates that hysteroscopy with morcellation is a safe diagnostic method for low- and high-grade endometrial pathologic conditions and does not lead to increased dissemination of malignant cells, lymphovascular space invasion, or upstaging of patients.