Postoperative radiotherapy in stage IB squamous cell cervical cancer.

OBJECTIVE: The purpose of the study was to evaluate postoperative whole pelvic radiation for high-risk patients with FIGO Stage IB cervical cancer. METHODS: One hundred and forty-eight patients with Stage IB squamous cell carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy. The low-risk group included patients without unfavorable prognostic factors who were treated only by surgery. The high-risk group included women with pelvic node metastases, with positive or close surgical margins, clinical tumor size > 4.0 cm, depth of stromal invasion > 1/3 the cervical wall, grade 3 tumor and presence of lymphovascular space involvement. High-risk patients received whole pelvic radiotherapy between two and four weeks after surgery. RESULTS: Seventy patients (47.3%) were low risk and 78 patients (52.7%) were high risk. Locoregional recurrences were diagnosed in nine cases (12.8%) in the surgery group and in 11 patients (14.1%) assigned to radiotherapy. The incidence of distant metastases was 2.8% in the surgery group and 6.4% in the surgery and radiotherapy group. Overall survival at five years was 88.6% in the low-risk group and 84.7% in the high-risk group. CONCLUSION: Five-year overall survival, locoregional and distant metastases were similar in the low-risk and high-risk groups of patients, thus emphasizing the value of whole pelvic radiation in patients with unfavorable prognostic factors in Stage IB cervical cancer.

Adenosquamous carcinoma of the uterine cervix--adjuvant chemotherapeutic treatment with paclitaxel and carboplatin; a case report.

Adenosquamous carcinoma of the uterine cervix is a rare mixture of malignant glandular and squamous epithelial elements. We present a case of a 56-year-old woman with Stage IV cervical carcinoma treated with paclitaxel and carboplatin chemotherapy after cytoreductive surgery. Solitary liver metastases were treated by ultrasound guided percutaneous sclerotherapy with 95% ethanol. For ten months the patient showed an objective response to the treatment with a good quality of life during that time. A year after the first, the second cytoreductive operation was performed and chemotherapy (paclitaxel, carboplatin, and epirubicin) followed. The patient died 20 months after establishing the diagnosis. Paclitaxel in combination with carboplatin as adjuvant chemotherapeutic treatment could be another promising agent for patients with advanced metastatic cervical adenocarcinoma.

Primary squamous cell carcinoma of endometrium: a case report.

A case of primary squamous cell carcinoma of the endometrium (PSCCE) in a virgin treated with surgery--abdominal hysterectomy and bilateral salpingo-oophorectomy, and followed by whole pelvic radiation is presented. The tumor recurred 12 months later and the patient then underwent relaparotomy and excision of recurrent tumor of the pelvis; right hemicolectomy and rectosigmoidectomy were done due to recurrence and metastasis of the primary tumor. After re-operation, six courses of cisplatin and 5-fluorouracil were given intravenously for cytotoxic effects at 3-week intervals. The patient's disease progressed despite therapy, and she died three months after the last cycle or 21 months after the first diagnosis was made.

Postoperative radiotherapy in stage I endometrial adenocarcinoma.

OBJECTIVE: To evaluate postoperative whole pelvic radiation for high-risk patients with Stage I endometrial adenocarcinoma. METHODS: One hunderd and twenty-two patients with irregular premenopausal or postmenopausal haemorrhage were included into the study. Fractional curettage was performed in all cases. When the pathohistological report confirmed endometrial adenocarcinoma, abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Low-risk patients include women with Stage IA tumours and Stage IB grade 1 or 2 histology. High-risk group include patients with Stage IB grade 3 tumours and Stage IC carcinomas. High-risk patients received whole pelvic radiotherapy between two and four weeks after surgery. RESULTS: Eighty-two patients (67.21%) were low-risk and forty patients (32.79%) were high-risk. In the low-risk group of patients, CA-125 was negative in ten cases and positive in 72 patients with a mean value of 30.12 +/- 12.42 U/ml serum. In the high-risk group of the patients, CA-125 was negative in two cases and positive in 38 patients with a mean value of 60, 48 +/- 20, 14 U/ml serum. Locoregional recurrences were diagnosed in four patients (4.87%) in the surgery group and in two patients (5.00%) assigned to radiotherapy. The incidence of distant metastases was 2.43% in the surgery group and 2.50% in the radiotherapy group. Overall survival at five years was 90.25% in the low-risk group and 87.50% in the high-risk group of patients. CONCLUSION: Five-year overall survival, locoregional and distant metastasis were similar in the low-risk and high-risk groups of patients. That emphasizes the value of whole pelvic radiation in patients with unfavourable prognostic factors in Stage I endometrial cancer.

Local estrogen treatment in patients with urogenital symptoms.

OBJECTIVES: Determination of the efficacy and safety of vaginally administered low dose (25 microg) micronized 17beta-estradiol in the management of patients with urogenital symptoms. METHODS: A total of 1612 patients with urogenital complaints were randomized to receive 25 microg of micronized 17beta-estradiol (n=828) or placebo (n=784) in a multicenter double-blind placebo-controlled study running for 12 months. Female patients were treated once a day over a period of 2 weeks, and then twice a week for the remaining of the 12 months with an active or placebo tablet. The assessment included full history-questionnaire, micturition diary, gynecologic and cystometric examination, transvaginal ultrasound, and serum 17beta-estradiol level determination. It was carried out at the beginning, and after 4 and 12 months of treatment. RESULTS: The overall success rate of micronized 17beta-estradiol and placebo on subjective and objective symptoms of postmenopausal women with vaginal atrophy was 85.5%, and 41.4%, respectively. A significant improvement of urinary atrophy symptoms was determined in vaginal ERT group as compared with the beginning of the study (51.9% vs. 15.5%, P=0.001). The maximal cystometric capacity (290 ml vs. 200 ml, P=0.023), the volume of the urinary bladder at which patients first felt urgency (180 vs. 140, P=0.048), and strong desire to void (170 ml vs. 130 ml, P=0.045) were significantly increased subsequent to the micronized 17beta-estradiol treatment. The number of patients with uninhibited bladder contractions significantly decreased following micronized 17beta-estradiol as compared with pretreatment values (17/30, P=0.013). Side effects were observed in 61 (7.8%) patients treated with low dose micronized 17beta-estradiol. Therapy with 25 microg of micronized 17beta-estradiol did not raise serum estrogen level nor stimulated endometrial growth. CONCLUSIONS: Local administration of 25 microg of micronized 17beta-estradiol is an effective and a safe treatment option in the management of women with urogenital complaints.

Serum CA-125 tumor marker in endometrial adenocarcinoma.

One hundred and seventy-four patients, mean age 61.23 +/- 9.41 years old, with irregular perimenopausal haemorrhage were included in the study. Fractional curettage was performed in all patients. When the pathohistologic findings were adenocarcinoma the concentration of CA-125 tumor marker was determined. Hysterectomy with bilateral salpingo-oophorectomy was determined. In 142 cases carcinoma was restricted to the uterus and in 32 patients extrauterine metastatic disease was found. In the former group CA-125 was positive in 130 patients with a mean value of 64.12 +/- 22.41 U/ml serum. In the latter group the cancer antigen was positive in 29 patients with a mean value of 244.82 +/- 68.11 U/ml. High production is associated with increased metastatic potential.

Adnexal masses in pregnancy: a review of eight cases undergoing surgical management.

OBJECTIVE: Our purpose was to determine maternal and foetal outcome in patients undergoing surgery for a pelvic mass in pregnancy. STUDY DESIGN: Maternal and foetal records (outcomes) of eight cases of adnexal masses associated with intrauterine pregnancy that required laparotomy or aspiration or that were diagnosed incidentally at the time of caesarean section were reviewed. The review was performed on patients who were seen with an adnexal mass in pregnancy from January 1994 to February 2001. We included patients with simple or complex masses > or = 6 cm that were persistent on ultrasonographic evaluation and patients with adnexal masses with complications (torsion, haemorrhage). We excluded cysts that spontaneously resolved by 16 weeks' gestation. RESULTS: Eight patients of 16,472 deliveries were identified with adnexal masses that satisfied the above criteria. Six patients underwent laparotomy in the first and/or the second trimester of pregnancy. In two of them emergency laparotomy were done due to torsion or haemorrhage as a complication of the adnexal masses. In all patients benign ovarian tumors were found. Two patients underwent transvaginal aspiration of simplex cysts due to subtorsion in the first trimester of gestation (negative results on cytological study). All of these eight patients had term deliveries. Two patients, due to obstetrical reasons, underwent caesarean section. CONCLUSION: The incidence of an adnexal mass during pregnancy in our population is consistent with what has been reported in the literature. We emphasize that transvaginal aspiration and drainage of symptomatic simplex cysts in the first trimester and percutaneous cysts in the second trimester can avert laparotomy. Our data support a randomised clinical study to determine optimal management of an adnexal mass in pregnancy.

Transabdominal chorionic villus sampling in the second and third trimesters of high-risk pregnancies.

Late chorionic villus sampling (placental biopsy) under ultrasound guidance was carried out in 800 (80 per cent) cases in the second trimester and 200 (20 per cent) cases in the third trimester of pregnancy. Out of 1000 placental biopsies, 250 (25 per cent) were performed because of suspicious ultrasonographic findings. Colour Doppler was used to investigate the uteroplacental and fetal vessels in 300 (30 per cent) pregnancies before and after late chorionic villus sampling (CVS). In the same group, mean serum alpha-fetoprotein (AFP) levels increased after sampling in 20 (6.7 per cent) patients. In 20 patients (2 per cent), complications between sampling and delivery were found. A placental haematoma measuring 0.5-1 ml was seen at the sampling site in 4 (0.4 per cent) patients in the second trimester of pregnancy and in 3 (0.3 per cent) in the third trimester. Two (0.2 per cent) demonstrated fever, but there were no instances of chorioamnionitis. There were only three (0.3 per cent) spontaneous abortions 4-6 weeks after late CVS. However, there was no correlation between AFP elevation, placental haematoma, Doppler measurements, and spontaneous abortion. Cytogenetic findings were obtained in 990 (99 per cent) of 1000 placental samplings. We found 60 (6.0 per cent) chromosomal abnormalities. In the group with suspicious ultrasonic findings (250 cases), we found significant oligohydramnios in 125 (50 per cent) and significant polyhydramnios in 60 (24 per cent), and 45 (18 per cent) had chromosomal abnormalities. Among the 60 patients with chromosomal abnormalities, ultrasonographic findings in 10 (16.7 per cent) were detected after the 20th week of pregnancy. There were no significant differences in mean pulsatility index (PI) in the uteroplacental and fetal vessels before and after late CVS. Preliminary data from five trisomic fetuses (three trisomy 21 and two trisomy 18) showed abnormally increased umbilical PI and abnormally decreased middle cerebral artery PI.

Ultrasonic fetal and placental tissue characterization and lung maturity.

OBJECTIVE: To determine a relationship between gestational age and the quantitative assessment of ultrasonic signs of placental tissue, fetal lung and liver tissue for determining fetal lung maturity in normal pregnancies and pregnancies with preeclampsia. METHODS: Placental, fetal lung and fetal liver tissue was examined by ultrasound in 240 normal and 60 preeclamptic pregnancies at 30-41 weeks' gestation. All patients underwent ultrasonically guided amniocentesis to obtain the lecithin-sphingomyelin ratio. The placentas of 160 patients after delivery were placed in water at body temperature for ultrasonic echo amplitude analysis. The coefficients of variation (the standard deviation divided by the mean value) of gray levels of the pixels in the region of interest obtained from images of the placenta, fetal liver and lung, were used to characterize the tissue in different groups during pregnancy. RESULTS: The coefficients of variation in mature fetuses were > 29% for placentas in vivo, > 34% for placentas in vitro, > 28% for liver tissue and > 30% for lung tissue. In mature fetuses the ratio of coefficients of variation of placental tissue in vivo against placental tissue in vitro was > 0.80, placental tissue in vivo against lung tissue > 0.90, lung tissue against liver tissue > 1.10 and placental tissue in vivo against liver tissue > 1.00. CONCLUSION: The placental and fetal lung tissue of preeclamptic patients tended to have higher coefficients of variation throughout pregnancy. These results were significantly higher when associated with low-birth-weight babies. There were no significant differences in fetal liver tissue between normotensive and preeclamptic groups.

Preoperative diagnosis of primary fallopian tube carcinoma by transvaginal ultrasound, cytological finding and CA-125.

Primary Fallopian tube carcinoma is rarely diagnosed preoperatively. We present the case of a 69-year-old woman with primary tubal carcinoma, which was diagnosed preoperatively on the basis of the cytological finding, characteristic features on transvaginal sonography, transvaginal color flow imaging and elevated CA-125. Transvaginal color Doppler imaging demonstrated the tumor revealed areas of neovascularization with characteristic low impedance (resistance index, 0.34 and pulsatility index, 0.62). Pathohistologic confirmation of the clearcell carcinoma has been done.

Transabdominal placental biopsy in the second and third trimester of pregnancy.

Transabdominal placental biopsy under ultrasound guidance was carried out in 260 cases in the second trimester and 50 cases in the third trimester of pregnancy. Placental tissue was aspirated using an 18 or 20 gauge needle. In a total of 310 placental biopsies in the second and third trimester, 100 were performed because of suspicious ultrasonographic findings. Placental biopsy is simple in the presence of severe oligohydramnios where fetal blood sampling is usually more difficult. Oligohydramnios and polyhydramnios were the ultrasonographic findings in 50% of cases and were found to be associated with 30% of abnormal chromosomal findings. There was one (0.3%) abortion within two weeks following placental biopsy. Placental biopsy did not affect the outcome of the pregnancy.

[The adenohypophyseal gonadotropins in patients with anorexia nervosa]. / Funkcija gonadotropina adeno-hipofize u bolesnica s anoreksijom nervozom.

In 13 patients with anorexia nervosa (AN), secondary amenorrhoea lasting eight to 25 months and the loss of body weight more than 25% were found. Estradiol concentrations (E2) were significantly lower in patients with anorexia nervosa than in nine patients in the control group (21.4 +/- 9.2 vs 96.5 +/- 25.8 pg/ml, p less than 0.01). LH concentrations were also significantly lower in AN than in the control group (6.8 +/- 3.2 vs 12.3 +/- 4.5 IU/L, p less than 0.01). A similar relationship was found in the FSH concentration (5.2 +/- 2.0 vs 9.4 +/- 3.5 Iu/L, p less than 0.05). A 100 ug LH-RH i.m. administration produced a significant rise of the LH concentration and a slightly smaller one of FSH in comparison with the basal concentrations, with a maximum rise after 60 minutes (LH after 60 minutes 76.4 +/- 16.5 IU/L, and FSH 24.0 less than 5.6 IU/L).

[Results of terminal salpingostomy and fimbrioplasty in distal occlusion and tubal phimosis]. / Rezultati terminalne salpingostomije i fimbrioplastike kod distalne okluzije i fimoze tuba.

Terminal salpingostomy and fimbrioplastics were performed in 108 patients by conventional surgical technique: 78 had bilateral occlusion of the abdominal orifice of the uterine tube with hydrosalpinx, 21 unilateral distal occlusion coupled with stenosis and perisalpingitis on the other side, and 9 bilateral stenosis and perisalpingitis. In all patients other causes of sterility were excluded. The duration of their sterility lasted 2-15 years, while their age ranged from 21 to 40 years. In 96 out 108 patients laparoscopy was applied immediately before operation. Out of 108 surgically treated patients, 22 conceived and gave birth to a child (20%), 2 had abortion (0.92%), and 7 conceived outside the uterus (3.7%). In 72 patients who did not conceive six months after operation, control hysterosalpingography was applied; it showed that 58 patients had one or both tubes unobstructed (80.5%), while bilateral reocclusion was found in 14 patients (19.4%). Hydrotubation was performed by a mixture of antibiotics and hydrocortisone 3-5 days following operation.

[Comparison of hysterosalpingographic and laparoscopic findings in tubal factor of sterility (author's transl)]. / Komparacija histerosalpingografije i laparoskopije kod tubarnog faktora neplodnosti.

Hysterosalpingographic and laparoscopic findings in 116 sterile women with the ovulatory cycle and the fertile spermiogram of their husbands were compared. Laparoscopy was performed in 65 patients in whom hysterosalpingography (HSG) revealed the occlusion of one or both tubes localized at the abdominal orifice, then in 23 women with unobstructed tubes and pertubal adhesions, and in 28 women in whom HSG findings were normal and who did not conceive at least 6 months after HSG. In 69% of cases the results of both methods were similar, whereas in 31% of cases laparoscopic findings, 18 laparoscopic findings showed significant by hysterosalpingography. Out of 28 normal HSG findings, 18 laparoscopic findings showed significant pathologic tubal changes. In unilateral occlusions HSG revealed peritubal adhesions in unobstructed tubes in 4 cases and laparoscopy in 18 out of 24 cases along with the agglutination of the fimbria and periovarian adhesions. In the whole group of the women examined, HSG revealed periadnexal adhesions in 39 (33%) and laparoscopy in 69 cases (59%).

[Yellow body function in bromocryptine induced early pregnancy in patients with hyperprolactinemia (author's transl)]. / Funkcija zutog tijela u ranoj trudnoci induciranoj bromokriptinom u bolesnica s hiperprolaktinemijom.

In six patients estrogens and gonadotropins were low and the prolactin concentration was increased (36-128 micrograms/l). Amenorrhea in all patients lasted 8-60 months, while galactorrhea was observed in five patients. By the X-ray of the sella turcica and neurologic and ophthalmologic examinations no signs of an intrasellar expansive process were revealed. The progesterone test was negative in four patients and the clomiphene test in all six patients. The LH-RH test (100 micrograms i. m.) showed the increased LH and FSH concentrations in all six patients. They all became pregnant in the course of the bromocryptine treatment (5-7.5 mg daily). Pregnanediol and prolactin concentrations were recorded every 14 days in the first 16 weeks of pregnancy, both in six patients and in eleven controls with spontaneous pregnancy. The pregnanediol concentrations proved somewhat higher in the control group than in patients having become pregnant under the bromocryptine therapy, but the differences are not statistically significant. However, the prolactin concentrations were significantly lower in controls than in pregnant women with the hyperprolactinemic anovulatory syndrome (p less than 0.01) in the sixth to the twelfth week of pregnancy.

[Improved pregnancy rates with ovulation stimulation using clomiphene and the effect of conjugated estrogens on the cervix]. / Poboljsanje stope zanosenja pri poticanju ovulacije clomiphenom ucinkom konjugiranih estrogena na cerviks.

From a larger group of women treated which clomiphene 25 patients were selected who failed to conceive in spite of an indirect evidence of the ovulatory response and adequate luteal phase. Seventeen of them, who showed a distinct suppression of preovulatory reaction according to a modified cervical score, were treated with combined clomiphene and conjugated estrogens. The cervical score, the cycle pattern and the pregnancy rate were compared with the results of the previous treatment. The improvement of the cervical score was noted in 74.4% of patients, 6 women became pregnant, and the pregnancy rate related to the number of ovulatory cycles was 13.9%. Criteria for the treatment presented are discussed.

[Cervical factor in sterile couples with an ovulatory cycle normospermia and patent tubes]. / Cervikalni faktkor u sterilinih brakova s ovulacijskim ciklusom, normozoospermijom i prohodnim tubama.

In 54 sterile married couples with a normal biophasic cycle, passable tubes, and normozoospermia, the properties of the cervical mucus were investigated. The biphasic cycle was determined according to the basal temperature curve, in which the hyperthermal phase lasts 12 days or more, the concentration of pregnanediol in the urine on the 22nd day of the cycle (6.4 mg/24h), estrogen on the 12th day of the cycle (78.4 micrograms/24h), and the LH concentration on the 13th day of the cycle (58.3 U/l). A positive crystallization test was found in 12 out of 54 patients and the postcoital test in 8 out of 54 patients. In 31 patients with the clinical symptoms of colpitis and cervicitis the culture of the cervical secretion showed pathogenic bacteria in 24 patients. Eighteen patients were subjected to conization previously. A positive crystallization test and a normal postcoital test were found only in 14 out of 17 patients following conization but in not single patient with cervicitis. After antibiotic therapy and stimulation with estrogens a restitution of the function of the cervical mucosa was observed in 25 patients, while 12 patients became pregnant. Inflammation proved to impair the normal function of the cervical mucosa, and if lasting long, it can lead to irreversible changes. Also surgery in cervix can result in the destruction and reduction of cervical glands and should therefore be strictly medically indicated and carefully performed, especially in nulligravidae.

Amenorrhea following oral contraception.

In 21 patients with amenorrhea after taking oral contraceptives, the urinary excretion of estrogens and the plasma concentrations of LH, FSH and prolactin were determined. In five of these women the amenorrhea was accompanied by galactorrhea. Ten of the 21 patients had had origomenorrhea before contraceptive therapy. The progesterone test was negative in 9 patients and clomiphene test was negative in 10 patients. The urinary excretion of estrogens and plasma LH and FSH values were low normal while the prolactin concentration in group A (amenorrhea without galactorrhea) amounted to 12.8 +/- 2.4 micrograms/l of plasma and in group B (amenorrhea with galactorrhea) to 85.4 +/- 15.8 micrograms/l (p < 0.01). The pituitary response to 100 micrograms synthetic LH-RH i.m. was similar to that found in the early follicular phase of the ovulatory cycle and showed that the pituitary was capable of synthesizing and secreting LH and FSH. Two of the three women from group A who wanted to become pregnant conceived under the therapy with Clomid and HCG. In all women from group B, in response to Parlodel (bromocriptine) therapy administered in 5-mg dose daily, the plasma concentration of prolactin decreased to a normal level, galactorrhea ceased within 15-62 days, and menstruation resumed within 38-75 days. In three women it is very probable that the cycle became biphasic, and a previously clomiphene negative patient became a clomiphene responder.