Recurrent endometrial cancer: a retrospective study.

OBJECTIVE: The value of follow-up after treatment for endometrial cancer will be discussed. STUDY DESIGN: We evaluated our clinical experience, including mode of detection, of patients with recurrent endometrial cancer treated in the Erasmus Medical Centre in Rotterdam over a 20-year period. Clinical data and histopathological features from 64 patients were analyzed. Survival was analyzed with a Kaplan-Meier curve. RESULTS: Twenty-two patients had a local recurrence, 30 had a distant recurrence and 12 had simultaneous local and distant recurrent disease. Ninety-five percent of the local recurrences and 67% of the distant recurrences were detected within three years. Twenty-seven patients had a screen-detected recurrence, 34 had an interval screening recurrence and two had a chance finding recurrence. The overall survival rate at two years was 70% and at five years 53%. Patients with a screen-detected recurrence had a 5-year survival rate of 62%, while patients with interval screening and chance finding recurrences had a 5-year survival rate of 47%. CONCLUSION: A follow-up program in the first three years after primary treatment of endometrial cancer is useful in detecting recurrent disease. We have no reason to use a different program of follow-up in patients with low risk primary disease.

Stage III and IV endometrial cancer: a 20-year review of patients.

In advanced endometrial cancer, the importance of peritoneal cytology and optimal surgical cytoreduction remain subjects of discussion. We evaluated our clinical experience of 67 patients with FIGO stage III and IV endometrial cancer treated in the Erasmus Medical Centre in Rotterdam over a 20-year period with an emphasis on stage IIIA disease based on positive cytology only and optimal cytoreduction. Lymphadenectomy was not routinely performed and peritoneal cytology was examined in 74% of the patients. Stage IIIA disease was found in 33 patients, 10 of whom had positive cytology only. Analysis showed that incidence of recurrence and survival rates of patients with stage IIIA disease based on positive cytology only were comparable with stage IIIA disease based on other factors. In 50 patients, it was possible to remove all macroscopic tumor, whereas in 17 patients, an optimal cytoreduction was not achievable. The 2- and 5-year survival rates after optimal cytoreduction were 82.2% and 65.6%; where this could not be achieved, these figures were 50.8% and 40.6%. In advanced endometrial cancer patients, positive peritoneal cytology seems an important prognostic factor in stage IIIA disease if lymph node status is unknown. Survival is improved if optimal surgical cytoreduction is achievable.

Growth regulation and transcriptional activities of estrogen and progesterone in human endometrial cancer cells.

Estrogen-stimulated growth of the malignant human endometrium can be balanced by the differentiating properties of progesterone. To study the molecular basis behind this, gene expression profiling was performed using complementary DNA microarray analysis. In this study, the human endometrial cancer cell lines ECC-1 and PRAB-36 were used as models. The ECC-1 cell line, which expresses high levels of estrogen receptor alpha and is stimulated in growth by estrogens, was used to study estrogen regulation of gene expression. The Ishikawa sub-cell line PRAB-36, expressing both PRA and PRB, progesterone receptor isoforms, and inhibited in growth by progestagens, was used to study progesterone regulation of gene expression. Using these two well-differentiated human endometrial cancer cell lines, 148 estrogen- and 148 progesterone-regulated genes were identified. After functional classification, the estrogen- and progesterone-regulated genes could be categorized in different biologically relevant groups. Within the group of "cell growth and/or maintenance," 81 genes were clustered, from which a number of genes could be involved in arranging the cross talk that exists between estrogen and progesterone signaling. On the basis of analysis of the current findings, it is hypothesized that cross talk between estrogen and progestagen signaling does not occur by counterregulation of single genes, but rather at the level of differential regulation of different genes within the same functional families.

Gene expression profiling in human endometrial cancer tissue samples: utility and diagnostic value.

OBJECTIVE: Recently, gene expression profiling techniques have been used on several human cancers to classify tumor subgroups with a specific biological behavior, which were previously undetected by the conventional histopathologic staging systems. In the current study, the clinical usefulness and prognostic value of gene expression profiling in human endometrial carcinomas were studied. METHODS: A macro cDNA array, containing cDNAs of 588 genes selected from different areas of cancer research, was used to generate gene expression profiles of tumor tissue samples. The gene expression profiles of 12 endometrial cancers, 3 benign (e.g. noncancer) endometrial tissue samples and 3 myometrial tissue samples, taken from human surgical specimen, were compared. RESULTS: The efficacy to generate a gene expression profile of these tissue samples was 77%. The RNA samples could be randomly taken from the tissue samples and were highly reproducible. Cluster analysis of gene expression profiles of the different samples showed that the benign endometrial and the myometrial samples clustered separately from the tumor samples, indicating that the gene expression profiles were tissue specific and not patient specific. Cluster analysis of the tumor samples revealed two distinct tumor clusters. Ranking of the tumors in the two clusters showed high similarity with the histopathologic classification [International Federation of Gynecology and Obstetrics (FIGO) grading]. CONCLUSION: Classification of endometrial tumors on basis of their gene expression profiles showed similarity with the FIGO grading system.

Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method.

The recently developed cDNA expression array technique can be used to generate gene-expression fingerprints of tumour specimens. To gain insight into molecular mechanisms involved in the development and progression of cancer, this cDNA expression array technique could be a useful tool, however, no established methods for interpreting the results are yet available. We used the Atlas cancer cDNA expression array (Clontech, USA) for analysing total RNA isolated from four human endometrial carcinoma samples (two cell-lines and two tissue samples), one benign endometrial tissue sample and a human breast cancer cell-line, in order to develop a method for analysing the array data. The obtained gene-expression profiles were highly reproducible. XY-scatterplots and regression analysis of the logarithmic transformed data provided a practical method to analyse the data without the need of preceding normalization. Three genes (Decorin, TIMP3 and Cyclin D1) were identified to be differentially expressed between the benign endometrial tissue sample and the endometrial carcinoma samples (tissue and cell-lines). These three genes may potentially be involved in cancer progression. A higher degree of similarity in gene-expression profile was found between the endometrial samples (tissue and cell-lines) than between the endometrial samples and the breast cancer cell-line, which is indicative for an endometrial tissue-specific gene-expression profile.

Massive solitary metastasis of hepatocellular carcinoma in the ovary two years after liver transplantation.

Case report of a 47-year-old woman with a mass in the lower abdomen, was referred to us by the surgeon, two years after orthotopic liver transplantation for hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP), which was elevated at the time of initial diagnosis, was in the normal range. Frozen section examination during exploratory laparotomy showed appearances consistent with metastatic HCC in the ovary. This was confirmed at the final pathological examination. Definitive pathological conclusions were based on the findings of tumor cells arranged in trabecular and papillary aggregates, and the presence of bile-pigment, along with the patients history. This is the sixth case of metastatic HCC in the ovary being described in literature and the first case in which this metastasis was not accompanied by elevated AFP.

Differential gene expression in progesterone-sensitive and progesterone-insensitive endometrial carcinoma cells.

High doses of progesterone are used in the treatment of advanced and recurrent endometrial cancer. Unfortunately the response rate is relatively low: 10-30%. The mechanisms involved in the development of insensitivity to progesterone treatment of endometrial cancer tissue are largely unknown. As tumour development is thought to be associated with a cascade of genetic alterations, it can be expected that genetic changes are involved in the development of progesterone insensitivity in endometrial carcinomas. We therefore started an investigation to identify, isolate and characterise progesterone-regulated genes involved in progesterone-induced growth inhibition in endometrial carcinoma cells. Using differential display PCR eight progesterone-regulated cDNA clones were identified in endometrial carcinoma cell lines. Four of these progesterone-regulated cDNA clones were regulated in the for growth progesterone-sensitive cell line IK-3H12 and not regulated in the for growth-insensitive cell line ECC-1. This indicates that these four cDNA clones represent potentially important genes, which could be involved in inhibition of growth of endometrial carcinoma tissue by progesterone.

[The bikini incision: nice, but not without painful complications]. / De bikinisnede: mooi, maar niet zonder pijnlijke complicaties.

The low transverse abdominal incision, described by Pfannenstiel, is, mostly because of its decent scar, the incision of choice for most gynaecological operations. Making this incision, the ilioinguinal nerve and the iliohypogastric nerve can be involved. In many cases this causes a lasting numbness in the region around the scar. Some patients have a lasting, radiating, invalidating pain, which can be relieved surgically.

The low transverse Pfannenstiel incision and the prevalence of incisional hernia and nerve entrapment.

OBJECTIVE: The authors determined the prevalence of incisional hernia and nerve entrapment in patients with a low transverse Pfannenstiel incision. SUMMARY BACKGROUND DATA: The literature on the Pfannenstiel incision suggests an incisional hernia rate of 0.0% to 0.5%. However, in these series, physical examination, which is essential in the authors' view, was not performed. To the authors' knowledge, the prevalence of nerve entrapment after the Pfannenstiel incision is not known or has never been published. METHODS: All adult women, operated on between 1986 and 1992 using a Pfannenstiel incision and not having had another lower abdominal incision other than for laparoscopy, were invited for follow-up at the outpatient department. All patients were interviewed and subjected to a physical examination, with special interest to the presence of incisional hernia or nerve entrapment. RESULTS: In patients having had a Pfannenstiel incision, no incisional hernias were found. In patients also having had a laparoscopy, the incisional hernia rate was 3.5%. Nerve entrapment was found in 3.7%. The length of the incision was identified as a risk factor (p = 0.02). CONCLUSIONS: Incisional hernia is a rare complication of the Pfannenstiel incision. Complications of nerve damage, however, are not uncommon and should be recognized. When possible, nerves should be identified and preserved, especially when extending the incision more laterally.

Suspected idiopathic CD4+ T-lymphocytopenia in a young patient with vulvar carcinoma stage IV.

A case of a woman having a large invasive vulvar carcinoma is reported. Because of the early age of onset and recurrent pneumonia, immunodeficiency was suspected. There appeared to be a repetitive low CD4+ T-lymphocyte count, without evidence of HIV infection or other diseases or therapies known to be clearly associated with T-cell depletion. This is suspected for the rare disorder known as idiopathic CD4+ T-lymphocytopenia which is often associated with opportunistic infections. A case of suspected idiopathic CD4+ T-lymphocytopenia in a patient having an invasive vulvar carcinoma is described.

Anorectal manometry before, during and after estrogen replacement therapy.

The incidence of relaxation of the pelvic floor increases with age, and although a relation between prolapse and the decline of estrogens has been suggested, there is no objective evidence. Together with urodynamic measurements, anal manometry is one of the few ways of making an objective assessment of the strength of pelvic structures located in and near the pelvic floor. In order to study the role of estrogens, anal manometry was performed before, during and after estrogen replacement therapy with daily oral use of 0.625 mg conjugated estrogens for 6 months. Five postmenopausal women, who had not used estrogen replacement therapy in the past, were included in the study. None of the manometric parameters, including maximal anal resting pressure, maximal squeeze pressure and internal anal sphincter response, changed. It was concluded that estrogens have no effects on manometric parameters of the external sphincter and that anal manometry may not be the appropriate method to assess the effects of estrogens on the pelvic floor.

Magnetic resonance imaging (MRI) in endometrial carcinoma; preoperative estimation of depth of myometrial invasion.

BACKGROUND: The incidence of pelvic and aortic lymph node involvement in endometrial carcinoma depends on both tumor differentiation grade and myometrial invasion depth. It was evaluated whether magnetic resonance imaging (MRI) provides a preoperative technique to assess the depth of myometrial invasion. METHODS: The study includes 34 patients with an endometrial carcinoma. MRI (T5 Gyroscan, Philips) was made a few days before operation. Myometrial invasion was divided in four categories. Cervical invasion was classified as absent, superficial or deep. For comparison an in vitro MRI of the uterus was made directly after the operation. Histo-pathological examination of the uterus was used as a golden standard of the depth of myometrial invasion. RESULTS: The estimation by MRI of the myometrial invasion depth was correct in 25 out of 31 patients. In three patients estimation was not possible, because of bad image quality. In four patients the MRI underestimated the cervical invasion. CONCLUSIONS: Preoperative MRI in patients with an endometrial carcinoma can be used to estimate myometrial and cervical invasion. Therefore, in combination with the histological grading of the tumor, a preoperative MRI can be used to select patients at high risk of nodal involvement.

Dinoprostone priming of the cervix prior to termination of midgestation pregnancy with sulprostone.

OBJECTIVE: To determine if cervical ripening with the prostaglandin E2 analogue dinoprostone effectively shortens the induction-to-delivery interval in midpregnancy terminations with sulprostone. STUDY DESIGN: We retrospectively studied 100 women admitted for pregnancy termination at midgestation because of fetal anomalies between September 1989 and January 1993. Three regimens were used: 27 women received intramuscular sulprostone only, 29 women received intravenous sulprostone only, and 44 women received intravenous sulprostone after cervical priming with dinoprostone. Wilcoxon's rank sum test was used for statistical analysis. RESULTS: Dinoprostone priming did not significantly reduce the induction-to-delivery interval in either parous or nulliparous women. However, when divided into first and subsequent pregnancies, we found that primigravidae, but not multigravidae, had an induction-to-delivery interval that was significantly shorter by approximately 10.5 h when pretreated with dinoprostone. CONCLUSION: Dinoprostone priming of the cervix prior to termination of midgestation pregnancy with sulprostone (Nalador) effectively shortens the induction-to-delivery interval in women in their first pregnancy.

PIP: The authors retrospectively studied 100 women admitted for pregnancy termination at midgestation because of fetal anomalies between September 1989 and January 1993 to determine if cervical ripening with the prostaglandin E2 analog dinoprostone shortens the induction-to-delivery interval in midpregnancy terminations with sulprostone. 27 women received intramuscular sulprostone only, 29 women received intravenous sulprostone only, and 44 women received intravenous sulprostone after cervical priming with dinoprostone. Dinoprostone priming failed to significantly reduce the induction-to-delivery interval in neither parous nor nulliparous women. Dividing into first and subsequent pregnancies, however, it was found that primigravidae and not multigravidae women had an induction-to-delivery interval which was significantly shorter by approximately 10.5 hours when pretreated with dinoprostone. Dinoprostone priming of the cervix prior to termination of midgestation pregnancy with sulprostone (Nalador) therefore effectively shortens the induction-to-delivery interval in women during their first pregnancy.

[AIDS, also a gynecological diagnosis]. / AIDS, ook een gynaecologische diagnose.

In two women (aged 30 and 39), both addicted to heroin and HIV seropositive, cervical intraepithelial neoplasia and infiltrating squamous cell carcinoma of the cervix respectively were diagnosed. Treatment consisted of exconisation and radiotherapy respectively. Adding invasive cervical carcinoma to the AIDS-defining conditions and CIN II and CIN III to the symptomatic HIV-related conditions emphasis the importance of gynaecological care for HIV-infected women. Clear treatment guidelines for distinct patient groups still have to be defined.

Conus-cauda syndrome as a presenting symptom of endodermal sinus tumor of the ovary.

We report on a case of a 46-year-old woman with a conus-cauda syndrome due to an endodermal sinus tumor of the right ovary with multiple metastases in the spine and pelvic bone. Before removing the tumor surgically, combination chemotherapy was given to treat the metastases, which threatened to compromise the spinal cord.

Short-term results and long-term patients' appraisal of abdominal colposacropexy for treatment of genital and vaginal vault prolapse.

OBJECTIVE: To evaluate short-term results and long-term patients' satisfaction of abdominal colposacropexy performed for massive genital prolapse in our institute during a 14-year period. STUDY DESIGN: A retrospective analysis was performed of 101 consecutive women who underwent abdominal colposacropexy. The procedure consisted of retroperitoneal interposition of a Mersilene mesh between a prolapsed vaginal vault or uterus and the anterior surface of the sacrum. A questionnaire was used to evaluate patients' satisfaction after surgery. RESULTS: In the short-term there was an acceptable rate of complications of surgery, comparable with that reported in the literature. Prolapse-related complaints evaluated by questionnaire were markedly diminished after surgery. Pain and functional complaints were only partly improved in a subgroup of patients. Only 32% of the patients responded that they were fully cured after operation. CONCLUSIONS: Abdominal colposacropexy shows a particularly favorable result on prolapse-related complaints. Functional complaints and pain are not substantially relieved by this procedure. The complication rate of surgery is acceptable.

The incidence of cervical intraepithelial neoplasia among women with renal transplant in relation to cyclosporine.

OBJECTIVE: To evaluate the policy of an annual smear to screen renal transplant recipients for cervical intraepithelial neoplasia and invasive carcinoma and to determine the incidence of abnormal smears and CIN before and after the introduction of cyclosporine (1983). DESIGN: A retrospective study over the period 1971 to 1992. SUBJECTS: Postmenarchial women who received renal transplants and who were on immunosuppressive treatment for at least one month. MEAN OUTCOME MEASURES: Cytology and histology results. RESULTS: A total of 144 women who received renal transplantation were eligible for our study. Observation time varied from 1 to 227 months (median 59 months) with a mean for the group transplanted before 1983 (Group A) of 103 months, and for the group transplanted after 1983 (Group B) of 46 months. Of these women, 25 had an abnormal smear. Of these, 14 were confirmed by histology and repeated smears of the other 11 patients were negative. Within the 60 women in Group A with an abnormal smear, six had CIN I or CIN II, three had CIN III and one showed adenocarcinoma of the endometrium. Among the 84 women in Group B, four had CIN I or CIN II and none had CIN III. The overall incidence of abnormal cytology was 17.3%, with no invasive cervical carcinoma in this group. CONCLUSIONS: Our policy of screening is adequate. With the introduction of cyclosporine the incidence of abnormal cytology and histology has a tendency to decrease. However, the duration of risk is not comparable yet.