An observational longitudinal study to evaluate miction, defecation, and sexual function after radical hysterectomy with pelvic lymphadenectomy for early-stage cervical cancer.

The objective of this study was to evaluate the problems with miction, defecation, and sexuality after a radical hysterectomy with or without adjuvant radiotherapy for the treatment of cervical cancer stage I-IIA. This study included an observational longitudinal study of self-reported bladder, defecation, and sexual problems with a baseline score. Ninety-four women were included in the study. An age-matched control group consisted of 224 women. The patients showed significantly more negative effects on sexual function compared with both the controls and their situation before the treatment throughout 24 months of follow-up. The problems included less lubrication, a narrow and short vagina, senseless areas around the labia, dyspareunia, and sexual dissatisfaction. Up to 12 months after the treatment, the patients complained significantly more of little or no urge to urinate and diarrhea as compared with the controls. Adjuvant radiotherapy did not increase the risk of bladder dysfunction, colorectal motility disorders, and sexual functions. We conclude that a radical hysterectomy for the treatment of early-stage cervical carcinoma is associated with adverse effects mainly on sexual functioning.

Pelvic exenteration as treatment of recurrent or advanced gynecologic and urologic cancer.

Pelvic exenteration is used as therapeutic option for advanced or recurrent cancer in the pelvis. We determined the complications of and the survival after pelvic exenteration. The study was performed as a retrospective cohort (n = 62) study from January 1, 1989, until January 1, 2000. Descriptive statistics were used. Survival was estimated according to the Kaplan-Meier life table. The operative mortality was 1.6%. Seventy-five percent of the patients had postoperative complications of which ileus and urinary tract infection were the most common. Late complications occurred in 83% of the patients. Recurrent disease was observed in 38% of the women, whereas 50% had died on January 1, 2000. Five-years disease-free and overall survival were 42% (confidence interval [CI] +/- 14%) and 46% (CI +/- 14%), respectively. Elderly patients (> 70 years old) do not experience more complications. Despite considerable morbidity, pelvic exenteration is a therapeutic option for survival, even for patients of 70 years and older.

Quality of life after pelvic exenteration.

OBJECTIVES: Pelvic exenteration, for gynecological and urological cancer, is an extensive and mutilating procedure. The 5-year survival rate is fairly good (40-60%), but little is known about the long-term quality of life. METHODS: In this retrospective cohort study, the quality of life was assessed using the EORTC QLQ-C30 (version 3.0) and the EORTC QLQ-OV28 questionnaires. RESULTS: Healthy females and those who underwent pelvic exenteration for a gynecological or urological malignancy reported comparable levels of emotional functioning and general quality of life. More physical, sexual, and social problems were, however, noted after exenteration. Younger patients and patients who underwent total pelvic exenteration had the most difficulty in adapting to daily life, disease, and treatment. They also had a worse body image, and the influence of the operation on their sex life was greater compared to other patient groups of this study. CONCLUSION: Despite the immense effect of pelvic exenteration on physical, sexual, and social functioning, women who underwent this procedure reported similar levels of emotional functioning and general quality of life compared to healthy women. Adaptation and the mechanism of response shift presumably play an important role.

Overall major histocompatibility complex class I expression is not downregulated in cervix cancer, as detected by immunoelectron microscopy.

Downregulation of major histocompatibility complex (MHC) class I molecules in cervix cancer has been proposed as a mechanism for cancer cells to escape immunodetection. By means of light microscopic immunohistochemistry, it has been shown that in 20-70% of cervix cancers MHC class I is downregulated. We have reinvestigated this phenomenon by quantitative immunogold analysis of MHC class I labeling on the plasma membrane of cervix epithelial cells in ten human squamous cancers and ten normal human cervices. We have not found a statistically significant difference in MHC class I expression between normal and cancer cells. The difference with published light microscopic data probably reflects the higher morphologic resolution and quantifiable immunoreactivity of the immunoelectron microscopy.

The value of abdominal CT scans in decision-making during chemotherapy in ovarian cancer.

OBJECTIVE: During chemotherapy of ovarian cancer many CT scans are performed to assess tumor response during treatment. The aim of this study was to determine the value of abdominal CT scan in the decision to continue chemotherapy or not, after the standard six cycles. METHODS: All ovarian cancer patients diagnosed between 1991 and 1997 were retrospectively included in the study. Clinical parameters, surgical results, diagnostic test results, and therapeutic strategies were collected from medical records. With logistic modeling those parameters were chosen that predicted best the chance of receiving additional chemotherapy. The chance of receiving further chemotherapy after six cycles based on these parameters was computed and compared to the chance based on CT scan results in addition to these parameters. Arbitrarily we defined a change of over 20% as meaningful. RESULTS: Eighteen of 50 included patients (36%) received over six cycles of chemotherapy; 29 patients (10%) were at low risk for receiving over six cycles, because they had an optimal debulking surgery and low levels of CA-125 at cycle six. The chance of receiving continued chemotherapy after taking into account positive tumor signs on CT-scan was 22%. This figure further increased to 33% if tumor presence was based on judgment of two CT scans. High-risk patients were patients with suboptimal debulking surgery or patients with an optimal debulking, but high CA-125 levels at cycle six (n = 21). Based on these parameters their chance of receiving additional chemotherapy was 71%, and after taking into account results of one or two CT-scans, the risks increased to 74% and 81%, respectively. CONCLUSION: CT scans are of no value in deciding the number of chemotherapy cycles in the initial treatment for ovarian cancer. They cost a lot of money, can add a lot of confusion, and offer no benefit over results of debulking surgery and CA-125 levels.

Pregnancy after EMA/CO for gestational trophoblastic disease: a report from The Netherlands.

OBJECTIVE: To investigate whether a desire for pregnancy changed after etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA/CO) treatment for gestational trophoblastic disease and whether the incidence of infertility and adverse pregnancy outcome differed from the general population. DESIGN: A cohort study was performed. Data were collected from hospital records and questionnaires. SETTING: The study was carried out in referral hospitals in The Netherlands. POPULATION: All women registered by the Dutch Working Party on Trophoblastic Disease and treated with EMA/CO were included. METHODS: A questionnaire was sent to all surviving patients treated with EMA/CO from 1986 until 1997. Women who underwent a hysterectomy were excluded from the study. MAIN OUTCOME MEASURE: Pregnancy outcome and pregnancy wish after chemotherapy. RESULTS: Fifty patients were treated with EMA/CO. In 86%, a complete remission was achieved. A questionnaire was sent to 33 patients. Response rate was 82% (27/33). After EMA/CO, 18 of the patients experienced a regular menstrual cycle. Three patients had an amenorrhoea. Fourteen patients had a pregnancy wish. Twelve patients conceived; 21 pregnancies occurred. Sixteen pregnancies were term deliveries. Two pregnancies ended in a miscarriage and two congenitally abnormal children were delivered prematurely. CONCLUSION: After EMA/CO, 86% of women with a pregnancy wish achieved pregnancy. However, women can be so anxious about a new pregnancy that they refrain from it. A causative relation between the two congenitally abnormal children and EMA/CO cannot be determined because of the small sample. The rate of miscarriages is not higher than in the general population. We can reassure patients that pregnancy after EMA/CO has a high probability of success and a favourable outcome. To diminish the fear of getting pregnant in some patients, psychosocial care should be considered in addition to medical care.

[Chronic radiation enteritis after irradiation of the lesser pelvis: surgical (im)possibilities]. / Chronische radiatie-enteritis na bestraling op het kleine bekken: chirurgische (on)mogelijkheden.

Three women aged 74, 59 and 36 years, had chronic complaints of abdominal pain, nausea, vomiting and diarrhoea, 1 to 8 years after radiotherapy for pelvic malignancies. Mechanical ileus due to fibrotic adhesions was found to be the cause; all three patients recovered after one or more operations. The prevalence of chronic radiation injury correlates with both radiation factors (volume) and patient characteristics. If possible, tumour recurrence needs to be excluded. Chronic intermittent ileus is the predominant symptom of chronic radiation injury. It often occurs within 2 years, but sometimes as long as 10 to 20 years after radiotherapy. Resection is warranted when short segments are affected. In other cases an intestinal bypass or stoma is the treatment of choice.

Update on the treatment of advanced cervical cancer.

In this review we discuss the most important issues concerning the treatment of advanced cervical cancer. Advances in the treatment of cervical cancer are made slowly, but recently the data from five important randomised studies gave rise to an important change in the standard treatment of this disease. For the new standard in advanced cervical cancer, it is clear that chemotherapy should be added to the radiation regimen for an optimal treatment. However, firm conclusions to which drugs or regimens cannot be drawn at this moment.

Preoperative selection of patients with low-stage endometrial cancer at high risk of pelvic lymph node metastases.

The goal of this study was to determine diagnostic accuracy of preoperative transvaginal sonography (TVS) to assess myometrial infiltration in patients with endometrial cancer and to determine the possibility of preoperatively selecting low-stage endometrial cancer patients at high risk of lymph node metastases. The depth of myometrial infiltration of endometrial cancer was assessed using TVS before or after curettage. Infiltration was classified as superficial if less than half of the myometrium was involved, otherwise it was classified as deep infiltration. Results were compared with the histology results of the definitive specimens. Patients were classified as high risk when they satisfied two of the following three criteria: 60 years of age or older; deep myometrial infiltration; and poorly differentiated or undifferentiated tumor. A total of 93 patients from 11 clinics were analyzed. The mean age was 66.1 years (SD +/- 11.4). The sonography and histology findings were in agreement in 69 of 93 patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of "deep infiltration" by preoperative TVS were 79% (95% CI 0.65-0.93), 72% (95% CI 0.61-0.83), 61% (95% CI 0.46-0.75), and 86% (95% CI 0.76-0.96), respectively. Combining tumor grade and myometrial infiltration in the hysterectomy specimen and age, 30 of 81 patients were classified as high-risk patients. Sensitivity and PPV, specificity, and NPV for preoperative diagnosis of high risk were 80% (95% CI 0.65-0.94) and 88% (95% CI 0.79-0.97), respectively. Preoperative assessment of myometrial tumor infiltration using just TVS is only moderately reliable in endometrial cancer patients. If the results of TVS, however, are combined with the patient's age and the degree of tumor differentiation in curettings, it is possible to preoperatively select endometrial cancer patients with a high risk of pelvic lymph node metastases with sufficient reliability.

Treatment of metastatic invasive moles in two husband-side sisters-in-law. Case reports and review of literature.

PURPOSE OF INVESTIGATION: The treatment of "high risk" persistent trophoblastic disease (PTD) consists of poly-chemotherapy. This policy probably will lead to overtreatment of some patients. Also, familiar molar pregnancies through the paternal line are unknown in the literature up till now. METHODS: We describe two cases of "high risk" PTD in two husband-side sisters-in-law, in which poly-chemotherapy was stopped after histology became available and showed invasive metastatic mole. CONCLUSION: It should be stressed that treatment decisions should be made based on the concept of "high" or "low" risk PTD, but if histology becomes available, chemotherapy might be less aggressive in cases of invasive mole. If invasive mole could be familiar through the paternal line remains unclear with the current knowledge of genetics in trophoblastic disease.

Benefits and side effects of lateral ovarian transposition (LOT) performed during radical hysterectomy and pelvic lymphadenectomy for early stage cervical cancer.

Ovarian function and ovarian cyst formation after radical hysterectomy and pelvic lymphadenectomy with lateral ovarian transposition (LOT) have been retrospectively examined in 54 patients with early stage cervical cancer (FIGO IB or IIA) with a follow-up of 3-7 years. Patients were divided into two groups: those without adjuvant pelvic radiotherapy (36 patients) and those with adjuvant pelvic radiotherapy (18 patients). Ninety-one percent (33/36) of the patients without adjuvant pelvic radiotherapy and 66% (12/18) of the patients with adjuvant pelvic radiotherapy remained without evidence of recurrent disease. Of the 36 patients who did not receive adjuvant pelvic radiotherapy, only two patients became postmenopausal (5.5%). However, of the 18 patients who also received adjuvant pelvic radiotherapy, 5 became postmenopausal (28%). There was a tendency to become postmenopausal if the scatter radiation dose at the transposed ovaries was 300 cGy or more, but our series is too small to allow a definite conclusion. This scatter radiation dose did not depend on the distance the ovaries were placed from the linea innominata, because of the variation in the level of the cranial border of the radiation field. Three out of 54 patients (5.5%) developed symptomatic ovarian cysts, of which 2 required surgical intervention because of pain symptoms. Remarkably, in one of them cyst formation occurred 5 years after surgery. Of the 3 patients with symptomatic ovarian cysts this was the only patient who received adjuvant pelvic radiotherapy. From these data it can be concluded that LOT protects ovarian function in most patients undergoing radical hysterectomy and pelvic lymphadenectomy for early stage cervical cancer, even if they receive adjuvant pelvic radiotherapy, with an acceptable risk of development of symptomatic ovarian cysts.

Familial ovarian cancer.

Familial ovarian cancer occurs in approximately 5% of all ovarian cancers. Since the relation between ovarian cancer and genetic heritage has drawn much attention lately, general gynaecologists will more and more be faced with the question how to survey patients from a family with the familial ovarian cancer syndrome. We describe a patient from a family with three daughters, of which two older sisters were known to have ovarian cancer. Although our patient was closely observed, a third-stage ovarian cancer developed. With this case in mind and after a review of the literature, we will in future closely survey patients from familial ovarian cancer families from their twentieth birthday on, and recommend prophylactic bilateral oophorectomy after child-bearing age. However, we are aware of the fact that it is impossible to diagnose ovarian cancer in a premalignant phase as yet, and the benefit of a close survey might be an earlier diagnosis and not prevention. Also, prophylactic oophorectomy does not prevent the occurrence of intra-abdominal malignancies histopathologically indistinguishable from ovarian cancer. Patients should be aware of these restrictions. If, in the future, the precise chromosomal defect in ovarian cancer families is localized, prevention of ovarian cancer, but not of intra-abdominal malignancies of the same histopathology, might be within reach.

Effects of mefenamic acid on menstrual hemostasis in essential menorrhagia.

Prostaglandin synthesis inhibitors decrease menstrual blood loss by 30% to 50% in patients with essential menorrhagia. To obtain insight into their mechanism of action, we measured menstrual blood loss in menorrhagic women, who were receiving mefenamic acid (500 mg, three times daily) (n = 6) or placebo (n = 5) in a double-blind way. In addition we studied the morphology of early menstrual hemostasis. The subjects' uteri were extirpated in the first 24 hours of menstruation, and light and electron microscopy were used to perform morphologic and morphometric studies. In the group treated with mefenamic acid mean menstrual blood loss was decreased by 40%. In uteri of the women treated with mefenamic acid hemostatic plugs were further transformed, and fewer vessels without a plug were observed than in uteri of the group receiving placebo. These data suggest that mefenamic acid may act through an improvement of platelet aggregation and degranulation and through increased vasoconstriction.

Menorrhagia. Current drug treatment concepts.

Since menorrhagia occurs in 9 to 14% of populations of healthy women, many general practitioners will encounter menorrhagia-related problems. Menorrhagia is difficult to objectify and the choice of treatment between the available drugs is not always an easy one. In this survey, the available knowledge on menorrhagia diagnosis, underlying pathophysiology and treatment, especially medicinal treatment, are discussed. Overall, a practical approach is emphasised. The desire for contraception as well as the underlying cause of menorrhagia determine the drug of choice in the treatment of menorrhagia. If contraception is desired, oral combination contraceptives and continuously dosed progestogens, orally or as a medicated intrauterine device (IUD), are the first choice drugs for essential menorrhagia, and for fibroid- and bleeding disorder-associated menorrhagia. If no contraception is desired, the first choice treatments are drugs that need to be administered only during menstruation, such as prostaglandin synthesis inhibitors or antifibrinolytics. Of these, antifibrinolytics reduce menstrual blood loss to the greatest extent, whereas prostaglandin synthesis inhibitors have the lowest incidence of side effects. Prostaglandin synthesis inhibitors also have the extra advantage of diminishing dysmenorrhoea. There is no place for ergometrine in the treatment of menorrhagia. No studies are available as yet on the combination of various drug treatment modalities, although such an evaluation would be desirable.

Polarized expression of major histocompatibility complex class I molecules in human endometrial and endocervical epithelial cells.

The localization of major histocompatibility complex (MHC) class I molecules in human endometrial and endocervical epithelial cells was studied with an immunogold technique on ultrathin cryosections. At the cell surface, MHC class I molecules are delivered solely to the basolateral plasma membrane in human epithelia. Therefore, only the basolateral domain of epithelial cells is capable of presenting antigen to MHC class I-restricted cytotoxic T cells.

Morphology of menstrual hemostasis in essential menorrhagia.

We performed a morphologic and morphometric study with light and electron microscopy on early menstrual hemostasis in five menorrhagic uteri and one control uterus, related the data to measured menstrual blood loss and compared the data with our previous study on normal menstruation. Menstrual blood loss ranged from 39 to 234 ml. Menorrhagic uteri contained large hemostatic plugs, protruding with a large part into the extravascular space. These plugs often consisted of loosely packed, poorly degranulated platelets with few fibrin fibers. Recanalized plugs, consisting of fibrin fibers and platelet remnants at the periphery of the vessel, were also observed in menorrhagic uteri. Using morphometry, we demonstrated a positive correlation between menstrual blood loss and the number of occlusive and nonocclusive hemostatic plugs, but not with other aspects of hemostatic plug formation such as the vessel area occluded by the plug, plug transformation, or intra- or extravascular localization of the plug. Vasodilation or endometrial height were not correlated with the amount of menstrual blood loss. These data suggest that essential menorrhagia is associated with fragile hemostatic plugs or with more extensive vessel damage.

Measured menstrual blood loss in women with a bleeding disorder or using oral anticoagulant therapy.

Bleeding disorders in women are associated with a high incidence of menorrhagia, but few objective data exist. Whether oral anticoagulant therapy in women is also associated with a higher incidence of menorrhagia is unknown. We measured menstrual blood loss in six women with various congenital or acquired bleeding disorders and in 11 women treated with oral anticoagulant therapy. Mean menstrual blood loss in women with a bleeding disorder was 219 ml (range, 60 to 568 ml); five women had menorrhagia. In women treated with oral anticoagulant therapy, mean menstrual blood loss was 98 ml (range, 9 to 239 ml), and five women had menorrhagia. Of the six women with normal menstrual blood losses, two had losses in the high normal range (60 to 80 ml). No correlation existed between anticoagulant state and menstrual blood loss. The data support the close association between bleeding disorders and menorrhagia and suggest that oral anticoagulants increase menstrual blood loss.

The alkaline hematin method for measuring menstrual blood loss--a modification and its clinical use in menorrhagia.

Direct measurement of menstrual blood loss is the only reliable basis of the diagnosis 'menorrhagia'. We describe modifications of the alkaline hematin method for measuring menstrual blood loss (MBL) which improve the recovery rate from 89 to 98% and make the method more suitable for routine laboratory use. Using this modified method, 5 out of 21 patients (24%) complaining of menorrhagia and scheduled for hysterectomy had an MBL less than 80 ml, which is the upper level of normal MBL.