Minimally invasive surgery for endometrial cancer: Does operative start time impact surgical and oncologic outcomes?

Objective

Recent literature in ovarian cancer suggests differences in surgical outcomes depending on operative start time. We sought to examine the effects of operative start time on surgical outcomes for patients undergoing minimally invasive surgery for endometrial cancer.

Methods

A retrospective review was conducted of patients undergoing minimally invasive surgery for endometrial cancer at a single institution between 2000 and 2011. Surgical and oncologic outcomes were compared between patients with an operative start time before noon and those with a surgical start time after noon.

Results

A total of 380 patients were included in the study (245 with start times before noon and 135 with start times after noon). There was no difference in age (p = 0.57), number of prior surgeries (p = 0.28), medical comorbidities (p = 0.19), or surgical complexity of the case (p = 0.43). Patients with surgery starting before noon had lower median BMI than those beginning after noon, 31.2 vs. 35.3 respectively (p = 0.01). No significant differences were observed for intraoperative complications (4.4% of patients after noon vs. 3.7% of patients before noon, p = 0.79), estimated blood loss (median 100 cc vs. 100 cc, p = 0.75), blood transfusion rates (7.4% vs. 8.2%, p = 0.85), and conversion to laparotomy (12.6% vs. 7.4%, p = 0.10). There was no difference in operative times between the two groups (198 min vs. 216.5 min, p = 0.10). There was no association between operative start time and postoperative non-infectious complications (11.9% vs. 11.0%, p = 0.87), or postoperative infections (17.8% vs. 12.3%, p = 0.78). Length of hospital stay was longer for surgeries starting after noon (median 2 days vs. 1 day, p = 0.005). No differences were observed in rates of cancer recurrence (12.6% vs. 8.8%, p = 0.39), recurrence-free survival (p = 0.97), or overall survival (p = 0.94).

Conclusion

Our results indicate equivalent surgical outcomes and no increased risk of postoperative complications regardless of operative start time in minimally invasive endometrial cancer staging, despite longer length of hospital stay for surgeries beginning after noon.     

The risk of premalignant and malignant pathology in endometrial polyps: should every polyp be resected?

AIM: There is no wide consensus in the literature on the clinical significance and management of symptomatic and asymptomatic polyps. Aims of the study are to evaluate frequency of premalignant and malignant histo-pathologic features in endometrial polyps resected hysteroscopically and identify clinical parameters able to predict final histopathologic diagnosis. METHODS: Clinical data and pathologic report of 90 consecutive operative hysteroscopies performed on women with endometrial polyps were collected. Frequency of premalignant and malignant histopathologic features on the polyps were calculated and relation to clinical risk factors analyzed. RESULTS: The frequency of premalignant and malignant histopathologic features in polyps was 6.7% and 2.2% respectively. Owing to the small sample size no statistical analysis to detect clinical risk factor for premalignant or malignant histopathologic features could be performed. CONCLUSION: Frequency of premalignant and malignant histopathologic features in symptomatic and asymptomatic patients is not negligible. Reported clinical risk factors for malignant degeneration of endometrial polypoid lesions are the same as those reported for endometrial cancer and are very common in patients with endometrial polyps. Every endometrial polyp should be resected.     

Does hysteroscopy produce intraperitoneal spread of endometrial cancer cells?

Hysteroscopy is the tool of choice for the evaluation of the endometrial cavity, including the assessment of abnormal uterine bleeding (AUB). The combination of endometrial biopsy and diagnostic hysteroscopy could replace dilation and curettage in most patients. However, hysteroscopy might disseminate endometrial cells into the peritoneum, thereby potentially raising the stage and decreasing the survival of a patient with endometrial cancer. The purpose of this article is to explore the dilemma of whether hysteroscopy produces intraperitoneal spread of endometrial cancer cells, and, if the answer is yes, what is the prognostic significance of isolated malignant cells in the peritoneal cavity. We conducted a literature search using MEDLINE using the following key words: hysteroscopy, endometrial carcinoma, and dissemination for the years 1980 through 2001. Retrospective data shows a correlation between fluid-based hysteroscopy and the presence of cancer cells in the peritoneal cavity. It cannot, however, be determined whether positive peritoneal washings are the result of hysteroscopy or whether the endometrial cells are found in the peritoneum as a result of other mechanism. Because no prospective, randomized studies have been performed on the dissemination of cancer cells by diagnostic hysteroscopy, no definite conclusions can be made concerning the risk of diagnostic hysteroscopy. In addition, the prognostic significance of isolated malignant cells in the peritoneal cavity of women with endometrial cancer is unclear. Although there might be an increased risk of peritoneal contamination by cancer cells after hysteroscopy, there is currently no evidence that these patients face worse prognosis than patients who have undergone other diagnostic procedures.     

Does the localisation of tumour at stage I endometrial endometrioid adenocarcinoma have an impact on invasion of the tumour and individualisation of the surgical procedure?

OBJECTIVE: To detect whether the localisation of the tumour has an impact on the dissemination of the tumour and whether or not surgical procedures should be individualized according to the localisation of the tumour. MATERIAL METHOD: 106 clinically surgically stage I endometrial endometrioid carcinoma cases treated multi-institutionally at Gulhane Military Medical Academy (GATA) and Dr. Zekai Tahir Burak (ZTB) Women's Health Education and Research Hospital Gynecologic Oncology Units in the last five years were evaluated retrospectively. The tumours localised near the internal cervical os and not invading the cervical canal were accepted as lower uterine segment (LUS) localisation and the corporal location as upper uterine segment (UUS) localisation. RESULTS: Tumour localisation was more frequent in the upper segment than LUS (85.9% vs 14.1%). There was no statistically significant difference between only endometrial and only serous invasion rates. Myometrial invasion less than one-half was significantly higher in the UUS group than the LUS group (p < 0.05). Lymph vascular space involvement rate was significantly higher in the LUS group (60%, 9/15) than the UUS group (23 %, 21/91), (p < 0.01). Positive peritoneal cytology rate was 20% (3/15) in the LUS group and 6.6% (6/91) in the UUS group (p > 0.05). CONCLUSION: Patients with LUS involvement should be considered as high-risk patients. Thus more expanded surgery must be taken into consideration. In this study a limitation was the low number of patients with LUS involvement. Larger prospective studies are necessary to confirm our results.     

Does metoclopramide exposure alter endometrial receptivity and decrease pregnancy rates?

Objective: The aim of this study was to investigate the effect of metoclopramide on endometrial receptivity with an immunohistochemical investigation of integrin β3 expression in pregnant rats.

Materials and methods: In the present study, the pregnant mice administrated by different doses of metoclopramide were used to explore the effect of metoclopramide on embryo implantation, especially on the endometrial receptivity.

Results: The statistical results showed that the number of implanted embryos was gradually declining along the increasing dose of metoclopramide. When the administrated dose of metoclopramide was 3?mg/kg per day, great changes were observed in the exposed uterine morphology and down-regulated integrin β3 were also found in high dose metoclopramide-exposed mice.

Conclusion: Metoclopramide exposure, especially in high doses may alter endometrial receptivity by effecting integrin expression on decidual tissue which can decrease pregnancy rates. This drug should only be recommended for use during pregnancy when benefit outweighs the risk.     

Is there a relationship between endometrial polyps and obesity,diabetes mellitus,hypertension?

Objective

The purpose of our study was to evaluate the relationship between endometrial polyps and obesity, diabetes mellitus (DM) and hypertension (HT).

Materials and methods

202 patients who applied to our gynecology clinic with complaints of infertility, recurrent pregnancy loss and abnormal uterine bleeding, diagnosed to have endometrial polyps by hysteroscopy, were compared with 79 patients without polyps, retrospectively. The relationships between risk factors and presence of a polyp and polyp size were analyzed.

Results

The mean age of cases with endometrial polyps was significantly greater than the controls. The mean body mass index (BMI) of the cases with polyps was also significantly greater than the controls. There was no significant difference between groups with respect to prevalence of DM or HT.

Conclusion

This study suggests that obesity is an independent risk factor in the development of endometrial polyps. Clinicians should be aware in terms of endometrial polyps in the assessment of patients with BMI ≥30. There was no relationship between HT or DM with presence of polyps.     

What is the optimal minimally invasive surgical procedure for endometrial cancer staging in the obese and morbidly obese woman?

ObjectiveThirty-three percent of U.S. women are either obese or morbidly obese. This is associated with an increased risk of death from all causes and is also associated with an increased risk of endometrial carcinoma. We sought to compare minimally invasive surgical techniques for staging the obese and morbidly obese woman with endometrial cancer.Materials and methodsConsecutive robotic endometrial cancer staging procedures were collected from 2005–2007 and were compared to consecutive laparoscopic cases (2000–2004). Demographics including age, weight, body mass index (BMI), operative time, estimated blood loss, lymph node retrieval, hospital stay and complications were collected and compared.ResultsDuring the study period, there were 36 obese and 13 morbidly obese women who underwent surgery with the DaVinci® robotic system and 25 obese and 7 morbidly obese women who underwent traditional laparoscopy. For both the obese and morbidly obese patient, robotic surgery was associated with shorter operative time (p = 0.0004), less blood loss (p < 0.0001), increased lymph node retrieval (p = 0.004) and shorter hospital stay (p = 0.0119).ConclusionsRobotic surgery is a useful minimally invasive tool for the comprehensive surgical staging of the obese and morbidly obese woman with endometrial cancer. As this patient population is at increased risk of death from all causes, including post-operative complications, all efforts should be made to improve their outcomes and minimally invasive surgery provides a useful platform by which this can occur.     

Does size matter? Tumor size and morphology as predictors of nodal status and recurrence in endometrial cancer

OBJECTIVE: To determine whether tumor size or morphology is predictive of extrauterine disease and/or recurrence risk in endometrial cancer and therefore guide decisions about the necessity of complete surgical staging and adjuvant therapy. METHODS: All women with surgically treated endometrial carcinoma between 1 January 1990 and 1 January 2000 were eligible. 345 patients were eligible for retrospective chart review. Univariate and multivariate logistic regression models were used to determine the predictors of nodal metastasis and recurrence. RESULTS: As tumor size increased, the risk of nodal metastasis increased. However, a risk of nodal metastasis remained even with small lesions less than or equal to 2 cm (6.3% risk). Patients with tumor size greater than 2 cm had a 26.3% incidence of nodal metastasis. In univariate analysis, the odds ratio (OR) for tumor size as a predictor of extrauterine disease was 1.4 (95% CI 1.2-1.6). In multivariate analysis, tumor size was not statistically significant. Only the lesions greater than or equal to 8 cm confer a risk that approaches previously identified well-known predictors. Tumor size was not found to be a statistically significant predictor of recurrence OR 1.3 (1.0-1.8). CONCLUSIONS: Tumor size correlates with extrauterine disease, but it is not an independent prognostic variable. Although the risk of extrauterine disease increases with tumor size, the risk of nodal metastases remains even for those patients with very small tumors, underscoring the need for routine complete surgical staging. Tumor size does not appear to be an independent predictor of recurrence.     

Expression of the inhibin/activin subunits alpha (α), beta-A (βA) and beta-B (βB) in benign human endometrial polyps and tamoxifen-associated polyps

Background Inhibins (INH) are dimeric glycoproteins, composed of an alpha subunit (INH-) and one of two possible beta subunits (INH-A or INH-B). They have substantial roles in human reproduction and in endocrine-responsive tumours. Therefore, the aims of this study were to determine the frequency and tissue distribution of INH-, INH-A and INH-B in normal human endometrium and glandular-cystic endometrial polyps, and polyps caused by tamoxifen use.Materials and methods Tissue samples were obtained from women in the proliferative, early secretory and late secretory phase as well as glandular-cystic polyps and endometrial polyps associated with tamoxifen use (n=5 each). Immunohistochemistry with specific monoclonal antibodies, a semi-quantitative analysis and statistical evaluation was performed.Results INH-, INH-A and INH-B were primarily observed in glandular and luminal epithelial cells, with a variant staining intensity in stromal cells. INH- in glands was significantly higher during the early secretory phase (p<0.05) and the late secretory phase (p<0.01) than in the proliferative phase with a significant difference between the early secretory and the late secretory phases (p<0.01). INH-A expression was significantly higher during the late secretory than the proliferative phase (p<0.05) and the late secretory than the early secretory phase (p<0.05), with no significant differences for INH-B. Glandular-cystic polyps showed significantly lower expression of INH- and INH-A than the late secretory endometria (p<0.05 and p<0.01 respectively). Additionally, tamoxifen-associated polyps also demonstrated a significantly lower expression of INH- and INH-A than late secretory endometria (p<0.01 and p<0.01 respectively). No statistical differences were observed between tamoxifen-associated and glandular-cystic polyps.Discussion INH-, INH-A and INH-B were expressed in normal endometrium and endometrial polyps. A cyclical expression of INH- and INH-A in normal glands may reflect a functional and hormone-dependent role in human endometrium. Significant differences in staining reaction between the late secretory endometria and polyps suggest that this tissue remains in the proliferating state rather than the secretory state. Therefore, endometrial polyps may be tumours of dysregulation with mainly proliferating characteristics, being unable to synchronise with normal endometrium.     

Tamoxifen and endometrial cancer. Is screening necessary? A review of the literature

Tamoxifen is a selective oestrogen receptor modulator (SERM) with anti-oestrogenic activity in the breast and oestrogenic effects in various tissues such as the endometrium, bone and cardiovascular territory. As adjuvant hormone therapy, it has a clear beneficial effect in patients with breast cancer, reducing relapses, contralateral breast cancer and mortality. Its most important secondary effect is a greater rate of occurrence of endometrial cancer. Although the risk/benefit ratio is clearly positive, the follow-up on these patients is still an issue. In women with metrorrhagia, it is clear that an endometrial sample must be obtained for histological examination and the best procedure today is hysteroscopic-directed biopsy. Nevertheless, the need to screen asymptomatic patients is not universally accepted. The vaginal ultrasound scan gives a great number of false positives. This entails more aggressive and more expensive procedures such as hysteroscopic-directed biopsy, meaning greater expense and more complications. As a result, the cost/benefit ratio is not very favourable. The rate of occurrence of endometrial cancer in 1026 tamoxifen-treated patients with breast cancer in our hospital between 1999 and 2001 was 1.25%. Two cases were diagnosed in asymptomatic patients. In this article, we analyse the literature on the need to screen patients on tamoxifen and about the most appropriate diagnostic protocol.     

How should we assess the safety of IVF technologies?

Clinical IVF treatment was established over 30 years ago through pioneering work by Edwards and Steptoe and other teams around the world and is now considered routine treatment. However, the pace of scientific and technological advances means that IVF practitioners can now access an increasing array of new and invasive technologies. The examples are many but include: extended embryo culture, development of media to include growth factors, developments in genetic screening, use of time-lapse technology and the advent of vitrification of embryos and oocytes. In parallel, wider scientific and medical advances are raising our awareness of the potential impact of assisted reproduction technology on areas such as embryonic development, gene expression and genomic imprinting and the developmental origins of health and disease. A recently suggested paradigm for assessing new technologies in IVF includes development in animal models such as rodents and large animals, preclinical research with human gametes and embryos donated to research, prospective clinical trials in IVF and, finally, follow-up studies of IVF children. In this paper, we describe efforts to address key areas of this pathway, namely preclinical research using human gametes/embryos and long-term, follow-up studies of the health of assisted reproduction children.VIDEO LINK: http://sms.cam.ac.uk/media/1401011