Is older age a poor prognostic factor in stage I and II endometrioid endometrial adenocarcinoma?

Objective

Prior studies have shown that age ≥ 70 years is associated with more aggressive non-endometrioid histology and worse survival in endometrial cancer. The purpose of this study is to assess if age is an independent poor prognostic factor in endometrioid histologies.

Methods

Under an IRB-approved protocol, we identified patients with surgical stage I to II endometrioid endometrial adenocarcinoma from 1995 to 2008 at two institutions. Patients were divided into two groups based on age at diagnosis: Group A (age 50-69 years) and Group B (age ≥ 70 years). All patients underwent hysterectomy, bilateral salpingoophorectomy, +/−pelvic/aortic lymphadenectomy and adjuvant therapy. Prognostic factors were evaluated by univariate and multivariate analyses.

Results

We identified 338 patients with stage IA to IIB endometrioid endometrial adenocarcinoma. The median age in Group A was 59 years (range 50-69) and Group B was 75 years (range 70-92). Patients in Group B were more likely to have hypertension (51% vs. 68%, p = 0.006) and coronary artery disease (9% vs. 18%, p = 0.03). There were no differences in progression-free or disease-specific survival, however, Group B had a worse overall survival (OS) (50.1 vs. 62.6 months, p = 0.03). On univariate analysis, age (p = 0.04), grade (p = 0.006), and coronary artery disease (p = 0.01) were associated with worse OS. After adjusting for grade and coronary artery disease, age was no longer a significant variable for OS (p = 0.17).

Conclusions

After adjusting for other poor prognostic factors, age ≥ 70 years alone may not be a significant variable affecting overall survival in patients with early stage endometrioid endometrial adenocarcinoma.     

May cathepsin D immunoreactivity be used as a prognostic factor in endometrial carcinomas? A comparative immunohistochemical study

OBJECTIVE: To investigate the prognostic value of immunohistochemical detection of cathepsin D and the association between cathepsin D and established prognostic factors in endometrial carcinoma. METHODS: Cathepsin D immunoreactivity was determined by an immunohistochemical technique in a series of 79 patients with surgical stage I-III primary endometrial carcinoma. RESULTS: Of 79 tissue specimens, 48 (61%) showed a positive reaction for cathepsin D. A significant correlation between cathepsin D and histological grade was found (P < 0.05). The other established clinicopathological prognostic factors were not associated with cathepsin D. There was not any significant difference in prognosis between the positive cases and negative cases for cathepsin D (P > 0.05). In the univariate analysis cathepsin D immunoreactivity did not show significant prognostic value for overall survival (P > 0.05). The multivariate analysis also showed that cathepsin D was not related to patient outcome (P = 0.24, relative risk = 0.34, 95% confidence interval = 0.05-2.09). CONCLUSIONS: Our results suggest that cathepsin D immunoreactivity may not be of prognostic value but more studies are needed to evaluate the relationship between its immunoreactivity in tumor cells and in other cells.     

Vascular endothelial growth factor (VEGF): can we use it as prognostic factor in endometrial cancer?

AIM: The aim of the study was to investigate if VEGF levels reflect the severity of endometrial cancer and the clinic relationship between microvasal density (MVD) and concentration of VEGF in tumor. METHODS: The study was conducted on 22 patients affected by endometrial cancer who were submitted to total abdominal radical hysterectomy plus bilateral salpingo-ophorectomy. VEGF (pg/mL) and MVD values were measured on histologic specimens of endometrial cancer obtained during the surgical treatment. The means and standard deviations of estimated values were calculated and a statistical comparison was effected by student t test for not coupled data. Pearson correlation test was used to analyze the eventual correlation among VEGF and MVD values in overall patients. RESULTS: We have documented that VEGF expression and MVD change according to FIGO stage, lympho-vascular infiltration and lymph node involvement. Pearson correlation test shows a good linear positive correlation in overall patients between VEGF and MVD values. CONCLUSIONS: Results obtained show a possible use of VEGF as prognostic factor in endometrial cancer. Confirmation of these data may permit both to identify high-risk patients, who must be treated with a more aggressive treatment, and to use an angiogenic therapy in endometrial cancer.     

The utilization of immunohistochemical prognostic factor in endometrial adenocarcinoma: is it cost effective?

This study investigated the relation between immunohistochemical prognostic factors and clinical stage and histopathological grade in endometrial adenocarcinoma. Twenty-seven patients with a mean age of 61 (38-74), who underwent radical surgery due to endometrial adenocarcinoma in our hospital between 1983-1998, were re-evaluated. For clinical staging FIGO criteria were used. Histopathological differentiation of the tumor was graded as good (grade 1), moderate (grade 2), and poor (grade 3). Estrogen and progesterone receptors, c-erb B2, UEA 1, Ki-67, PCNA and p53 were studied as immunohistochemical prognostic factors. There were no patients in stages IA and IIIB. Among the prognostic factors, PCNA was the most significantly stained marker, followed by c-erb B2, estrogen and progesterone receptors, regardless of the clinical stage and histopathological grade of the tumor. The least positivity was achieved with Ki-67. There was no significant difference when each prognostic factor was analysed with respect to clinical stage and histopathological grade. In our study no significant relation was found between the prognostic factors and the clinical stage and histopathological differentiation of the tumor. Therefore the cost effectiveness of the utilization of these factors should be reconsidered.     

Vulvar vestibulitis syndrome: an important factor in the evaluation of lifelong vaginismus?

The aim of the study was to investigate the prevalence of vulvar vestibulitis syndrome (VVS) in a sample of women suffering from lifelong vaginismus (N=91). Lifelong vaginismus is defined as "having a history of never having been able to experience penile entry of the vagina". The results with respect to VVS are compared with the results of women who are suffering from pain during intercourse (superficial dyspareunia) (N=84). Both patients groups were recruited from two treatment outcome studies. Using a standard physical examination, erythema was found in 77%, pain "on touch" in 69% and erythema and pain on the same location was seen in 56% of the patients with lifelong vaginismus. Furthermore, it was found that erythema (94%), pain (98%) and erythema and pain on the same location (92%) were more frequently found in patients with dyspareunia compared to women with lifelong vaginismus. It is concluded that pain is an integral part of the experiences in the majority of women with lifelong vaginismus.     

Is peritoneal cytology a prognostic factor of endometrial cancer confined to the uterus?

OBJECTIVE: The goal of this study was to investigate whether intraoperative peritoneal cytology serves as a prognostic factor in patients with the endometrial cancer limited to the disease confined to the uterus. METHODS: From patients with endometrial cancer treated at 2 facilities between 1988 and 2001, 307 patients were selected for retrospective investigation. To be included in this study, patients required (1) full surgical staging including total abdominal hysterectomy/bilateral salpingo-oophorectomy/retroperitoneal lymph node dissection/peritoneal cytology, (2) negative nodes, (3) disease localized to the uterus and (4) endometrioid subtype. RESULTS: The median duration of the follow-up period was 61 months (25th to 75th percentiles: 45 to 92 months). Peritoneal cytology was positive in 32 patients (10.4%). The 5-year survival rate of peritoneal-cytology-positive patients was 87%, significantly lower than that (97%) of cytology-negative patients (P = 0.011). The relationship between the clinicopathological factors including peritoneal cytology and the prognosis was investigated by univariate analysis, and peritoneal cytology positivity, age of 60 years or older, histologic grade (Grades 2 and 3), myometrial invasion of 1/2 or more and vascular invasion were significant prognostic factors (P < 0.05 in all). On multivariate analysis of these factors, peritoneal cytology positivity and histologic grade (Grade 2 and 3) were independent prognostic factors (P < 0.05 each). CONCLUSIONS: For the patients with endometrial cancer limited to the disease confined to the uterus in which accurate staging including retroperitoneal lymph node dissection was performed, peritoneal cytology may be an important prognostic factor.     

Morgagni hydatids: a new factor in infertility?

Purpose

To evaluate the effect of Morgagni hydatid (MH) on infertility by comparing women known to be fertile and infertile with respect to MH frequency.

Methods

The study was conducted in Gaziantep University Faculty of Medicine with the precipitation of total 455 patients. The 240 of them were pregnant to whom planned cesarean section (C/S) and the other 215 were infertile one who have undergone diagnostic laparoscopy. Fertile Group (Group 1) consisted of women whom have become spontaneously pregnant without any kind of infertility management. These are planned to undergo C/S with different indications. Infertile group (Group 2) consisted of women diagnosed as unexplained infertility and planned to undergo diagnostic laparoscopy according to ASRM 2006 guidelines. The frequency, number, and the bilaterality of the MH were evaluated during the C/S in fertile group and diagnostic laparoscopy in infertile group. SPSS was used for statistical analyses.

Results

The MH frequency was higher in Group 2 than Group 1 (P < 0.05). The bilaterality of MHs were significantly higher in Group 2 than Group 1 (P < 0.05).The number of the MHs were significantly higher in Group 2 than Group 1 (P < 0.05).

Conclusions

These findings suggest a possible effect of MH on fertility. The theory of MH disturbing tubal motility with respect to the pick-up and transport of ovum appears logical in this aspect.     

Computer-assisted embryo selection: a benefit in the evaluation of embryo quality?

Embryo selection is based on embryo developmental and morphological characteristics. Standard embryo evaluation has some disadvantages. New technology using multilevel images combined with a computer-assisted scoring system (CASS) has the potential to overcome these disadvantages. The aim of this study was to compare the value of a computer-assisted scoring system (CASS) versus a standard scoring system (SSS) in predicting implantation and live birth. This prospective study included 3185 embryos obtained during 502 IVF/intracytoplasmic sperm injection cycles with single-embryo transfer on day 3. Embryos were evaluated with two scoring systems: SSS and CASS. Logistic regression analyses were performed using implantation and live birth as outcomes. According to multiple regression analysis, implantation was influenced by number and size of blastomeres on day 3 using CASS and by all embryo parameters on day 3 using SSS. Combined analysis of both scoring systems revealed that implantation was affected by number and size of blastomeres using CASS and by the degree of embryo fragmentation using SSS. Using live birth as outcome, only the number of blastomeres on day 3, evaluated by SSS and CASS, was predictive. Prediction of implantation and live birth may be superior using CASS when compared with SSS.Embryo selection is currently based on embryo developmental and morphological characteristics of an embryo using a standard scoring system. This evaluation system is limited by a number of disadvantages. New technology using multilevel images combined with a computer-assisted scoring system has the potential to overcome these disadvantages. The aim of this study was to compare the value of such computer-assisted scoring system versus a standard scoring system in predicting implantation and live birth rate. This study included 3185 embryos obtained during 502 IVF or intracytoplasmic sperm injection cycles with single-embryo transfer on day 3. All the embryos were evaluated with two types of scoring systems: a standard scoring system and a computer-assisted scoring system. According to the statistical analysis, the implantation of an embryo was influenced by the number and size of blastomeres on day 3 when evaluated with the computer-assisted scoring system, and by all embryo parameters on day 3 using the standard scoring system. Combined analysis of both scoring systems revealed that implantation was affected by number and size of blastomeres using the computer-assisted scoring system and by the degree of embryo fragmentation using the standard scoring system. Live birth was influenced by the number of blastomeres on day 3 evaluated by both scoring systems. Prediction of embryo implantation and live birth was superior using the computer-assisted scoring system. In conclusion, a computer-assisted scoring system may be superior to a standard scoring system in the prediction of implantation and live birth.     

Endothelin-1: a key pathological factor in pre-eclampsia?

Endothelin (ET)-1 has been implicated in a diverse range of signalling events in a wide variety of target tissues. Given its potent vasoactive function and the prevalence of hypertension in pre-eclampsia, there has been extensive research on the role of ET-1 in this disorder. Indeed, ET-1 has been suggested to contribute to hypertension in pre-eclampsia. Recently, ET-1 has also been implicated in the induction of both oxidative stress and endoplasmic reticulum stress in pre-eclampsia; each of which has been proposed to contribute to many of the clinical manifestations of this disorder. ET-1 has been shown to activate key signalling molecules that lead to induction of these stress pathways. The use of ET-receptor antagonists could block oxidative and endoplasmic reticulum stress. Hence, further research into the role of ET-1 in pre-eclampsia may lead to the development of possible strategies to circumvent these stress pathways and the associated pathology that occurs in pre-eclampsia.Endothelin (ET)-1 has been implicated in a diverse range of signalling events in a wide variety of target tissues. Given its potent vasoactive function and the prevalence of hypertension in pre-eclampsia, there has been extensive research on the role of ET-1 in this disorder. Indeed, ET-1 has been suggested to contribute to hypertension in pre-eclampsia. Recently, ET-1 has also been implicated in the induction of both oxidative stress and endoplasmic reticulum stress in pre-eclampsia, each of which has been proposed to contribute to many of the clinical manifestations of this disorder. ET-1 has been shown to activate key signalling molecules that lead to induction of these stress pathways. The use of ET-receptor antagonists could block oxidative and endoplasmic reticulum stress. Hence, further research into the role of ET-1 in pre-eclampsia may lead to the development of possible strategies to circumvent these stress pathways and the associated pathology that occurs in pre-eclampsia.     

Taking a history in the evaluation of infertility: obsolete or venerable tradition?

Taking a relevant history that includes pelvic inflammatory disease or exposure to sexually transmitted diseases is not obsolete.     

Change in paternity: a risk factor for preeclampsia in multiparous women?

BACKGROUND: Preeclampsia is often thought of as being a disease of first pregnancies. The incidence of preeclampsia in subsequent pregnancies, after a previous normal pregnancy is lower. However, it has been reported that this beneficial effect of multiparity is lost with a change in paternity. The aim of this study was to assess the impact of change in paternity on the incidence of preeclampsia in Dutch multiparous pregnant women. METHODS: 364 Multiparous patients with hypertension (diastolic blood pressure > or = 100 mmHg) were identified in the obstetric database of the Academic Hospital Vrije Universiteit Amsterdam for the period 1989-1996. The diagnosis in their obstetrical history (Preeclampsia, HELLP-syndrome, chronic hypertension) was defined in a pragmatic way in view of the retrospective nature of the study. The control group consisted of 281 multiparous women from a midwife clinic, with normotensive pregnancies in the same period. Patients and controls were asked, by telephone, if the index pregnancy was from the same partner as the previous pregnancy and what the sex of the newborns had been in each pregnancy. Fisher's Exact test was used for statistical analysis and P < 0.05 was considered significant. RESULTS: The final study group consisted of 333 multiparous patients with hypertension. The control group consisted of 182 multiparous women without hypertension. The prevalence of new paternity was significantly higher (P < 0.0001) both for preeclamptic and HELLP patients in comparison with the controls, with an odds ratio of 8.6 (95%CI: 3.1-23.5) and 10.9 (95%CI: 3.7-32.3), respectively. CONCLUSION: This study confirms that change of partner raises the risk for preeclampsia in subsequent pregnancies. Immune maladaptation on the fetal maternal interface could be an underlying mechanism. Multiparous women with a new partner should be approached as being primigravid women.     

Antenatal detection of a single umbilical artery: does it matter?

The presence of a single umbilical artery is recognised as a soft marker for congenital anomalies, aneuploidy, earlier delivery and low birthweight. Most of the available data are derived from case series or highly selected populations and are therefore likely to be unrepresentative. In this retrospective case-comparison study, we firstly aimed to determine the incidence of a single umbilical artery in an unselected population and secondly to examine the clinical significance of this soft marker. Over a 40-month period, 107 cases were identified from a cohort of 35 066 births giving an incidence of 3.1 per 1000 total births and late pregnancy losses. The antenatal detection rate was only 30%. Compared to fetuses with normal cord vasculature, fetuses with a single umbilical artery were more likely to be delivered at an earlier gestation and to weigh less, were 1.7 times more likely to be delivered by a Caesarean section and 19% of the cases had a congenital anomaly. The perinatal mortality was 49.0 per 1000 total births, which was 6 times higher than the background hospital rate. The presence of a single umbilical artery is associated with a poorer perinatal outcome compared to that in fetuses with three vessels in the cord. Unfortunately, the antenatal detection rate is poor. Recognising the importance of this soft marker in counselling and management of pregnancies should provide the stimulus to improve detection rates.     

Hyperhomocysteinaemia: a risk factor for preeclampsia?

Preeclampsia represents one of the most frequent complications of pregnancy, however, little is known about its aetiology. Damage of the endothelial layer lining the blood vessel wall is thought to play an important role in the pathophysiology of preeclampsia, accordingly, mild hyperhomocysteinaemia has been reported to be more prevalent among preeclamptic women. Therefore, we investigated the role of hyperhomocysteinaemia in preeclampsia by measuring plasma levels of homocysteine and studying the prevalence of the 677(C-->T) polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, which may lead to reduced MTHFR enzyme activity and subsequently to higher plasma homocysteine levels.Plasma samples of 10 healthy non-pregnant women, 10 normotensive pregnant women, and 20 women with preeclampsia were analysed for total homocysteine levels by high performance liquid chromatography. Furthermore, 167 Dutch non-pregnant women previously hospitalised for preeclampsia and 403 population-based controls were analysed for the 677(C-->T) polymorphism by polymerase chain reaction followed by restriction fragment length polymorphism analysis (PCR/RFLP).In normotensive pregnancy homocysteine levels were lower compared with levels in healthy non-pregnant controls (8.4 versus 13.7micromol/l, P<0.001). Women with preeclampsia showed higher concentrations than women during normotensive pregnancy (13.3 versus 8.4micromol/l, P<0.02). However, levels of homocysteine in preeclampsia were comparable to those found in healthy non-pregnant women. PCR/RFLP showed no significant difference in the incidence of the 677(C-->T) polymorphism in the MTHFR gene between preeclamptic women with or without HELLP syndrome and controls (13 and 9% homozygous for the less common T-allele, respectively; OR 1.5, 95% CI 0.8-2.6, P=0.17).In contrast with previous reports, we cannot confirm that mild hyperhomocysteinaemia is a risk factor for preeclampsia. Pregnancy induced hyperhomocysteinaemia found in preeclampsia might better be explained by fluctuations in plasma volume than by the presence of the 677(C-->T) polymorphism in the MTHFR gene.