Small cell neuroendocrine carcinoma of the endometrium and laparoscopic staging: a clinicopathologic study of a case and a brief review of the literature.

Small cell neuroendocrine (NE) carcinoma is one of the most aggressive tumors that arise in the female genital tract. Small cell carcinoma of the endometrium (SCCE) is an extremely rare disease. Because of its rarity, the only clinical reports are limited to case studies, and therefore, clinical behavior and optimal treatment modalities are not well defined. To the best of our knowledge, we present the first case of SCCE staged by laparoscopic approach. A 54-year-old parous woman admitted with intermittent vaginal spotting. On physical examination, she had a 4- x 3-cm mass fungating out of the cervical os. Magnetic resonance imaging showed an endometrial mass of 25 x 30 x 50 mm in dimensions, invading less than 50% of the depth of the myometrium at the uterine fundus. Pathologic examination revealed undifferentiated malign NE tumor of endometrium of small cell type. The patient underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and laparoscopic pelvic and para-aortic lymphadenectomy. The disease was surgically staged as IB. Histologically, tumor cells were monotone, with scanty, ill-defined cytoplasm and hyperchromatic nuclei. Immunohistochemically, tumor showed positive immunoreactivity for P16, neuron-specific enolase, and synaptophysin. She underwent pelvic external radiation and brachytherapy postoperatively. Patient has no evidence of disease after 26 months of follow-up. Small cell NE carcinoma of the endometrium is an extremely rare and aggressive disease. With the availability of skilled endoscopic surgeons, laparoscopic management of women, even with SCCE in early stage, can be a feasible option.

Nifedipine therapy for preterm labor: effects on placental, fetal cerebral and atrioventricular Doppler parameters in the first 48 hours.

OBJECTIVE: To assess the effect of nifedipine tocolysis on Doppler parameters of the uterine, umbilical and fetal middle cerebral arteries and atrioventricular valves in the first 48 h of therapy. METHODS: Doppler waveforms of uterine, umbilical and middle cerebral arteries and both atrioventricular valves were measured from 28 pregnant women and fetuses prior to and during nifedipine therapy for preterm labor. Maternal and fetal heart rates (FHR), maternal systolic and diastolic blood pressure, and the Doppler pulsatility index (PI) of the uterine, umbilical and middle cerebral arteries were measured. The cerebroplacental ratio (middle cerebral artery PI/umbilical artery PI) was calculated. The total time velocity integrals (TVIs) of tricuspid and mitral valves and their E- and A-wave peak velocity ratio (E/A) were measured. Friedman repeated-measures analysis of variance was used to compare the variables before and after nifedipine therapy. If significant differences were found, Wilcoxon's signed ranks test was used to analyze the difference between the two variables. A P-value of < 0.05 was considered significant. RESULTS: Nifedipine maintenance was associated with a significant decline in maternal systolic and diastolic blood pressure after 24 h, while maternal heart rate and FHR were unaffected. The uterine artery PI had decreased significantly at 24 and 48 h, while the umbilical artery PI did not change significantly. The middle cerebral artery PI had decreased significantly at 24 and again at 48 h. A significant fall in the cerebroplacental Doppler ratio was maintained beyond 24 h. The mean E/A values, TVIs and TVI x FHR values at 24 and 48 h were unchanged from the baseline values. CONCLUSIONS: Nifedipine maintenance tocolysis is associated with a significant decline in uterine artery and middle cerebral artery Doppler indices 24 h after the first dose. Fetal cardiac diastolic function is unaffected and the significant redistribution observed after 24 h is likely to be attributable to altered cerebral blood flow.

The short-term effect of nifedipine tocolysis on placental, fetal cerebral and atrioventricular Doppler waveforms.

OBJECTIVE: To evaluate the effect of nifedipine on placental and fetal middle cerebral and atrioventricular Doppler waveforms. METHODS: Doppler waveforms of uterine (UtA), umbilical (UA) and middle cerebral (MCA) arteries and both atrioventricular valves were measured from 21 pregnant women/fetuses prior to and during nifedipine therapy for preterm labor. Maternal and fetal heart rates (FHR), maternal systolic and diastolic blood pressure, the Doppler pulsatility index and systolic/diastolic ratio of the UtA, UA and MCA were measured. The total time velocity integrals (TVI) of tricuspid and mitral valves and their E-wave/A-wave (E/A) TVI ratios were measured. Wilcoxon signed pairs test was used to compare the differences in Doppler parameters before and at 3 h after nifedipine loading up to a maximum dose of 40 mg. RESULTS: Fetal arterial and UtA Doppler parameters were not different before and after nifedipine therapy. Blood flow across the atrioventricular valves and the TVI were equally unaffected by nifedipine. The TVI x FHR product was also unchanged following nifedipine therapy. CONCLUSIONS: In women with otherwise uncomplicated pregnancies, nifedipine loading and tocolysis are generally well tolerated by the mother. Placental and fetal cerebral arterial blood flow, fetal systolic and diastolic cardiac function and downstream distribution of fetal cardiac output are unaffected by nifedipine loading. These results apply to women with unchanged vital parameters. Further studies are necessary to show long-term effects of nifedipine therapy and may help to refine choice of tocolytic agents.

Should advanced age alone be considered a contraindication to systemic lymphadenectomy in gynecologic oncologic patients? A university hospital experience in Turkey.

In this case-control study, we aimed at analyzing the effect of pelvic and paraaortic lymphadenectomy on intraoperative and postoperative morbidity and mortality rates in a series of elderly patients (age >/= 65 years) with gynecologic malignancies. We examined preexisting medical conditions, surgical data, intraoperative and postoperative morbidity and mortality in 37 patients aged 65 years or older with endometrial and ovarian carcinoma who underwent pelvic and paraaortic lymphadenectomy. Control group consisted of patients between 60 and 64 years with similar malignancies. The number of patients with hypertension (P = 0.03), minor (P = 0.01) and major cardiac problems (P = 0.03), chronic obstructive lung disease (P = 0.02), and history of cerebrovascular disease (P = 0.04) were significantly higher in the study group than that in control. The median operative time was significantly shorter (160 min) in the study group than that (191 min) in control (P = 0.004). There were no significant differences between the groups with regard to blood loss, intraoperative and postoperative blood transfusion, preoperative and postoperative hemoglobin levels, yielded lymph nodes, and postoperative stay. Minor and major intraoperative and postoperative complications were not different between the groups. In these elected elderly patients, we demonstrate that pelvic and paraaortic lymph node dissection can be performed with an acceptable morbidity and mortality. We should perform pelvic and paraaortic lymphadenectomy in the older aged patients and advanced aged should not be considered a contraindication.

Risk factors for pelvic surgery.

One hundred and eighty four women who had corrective surgery for stress incontinence, genital prolapse or both were compared with two hundred and ninety women who had no surgery for these conditions. Patients and controls did not differ in terms of age, height, weight or body mass index. Younger age at first delivery (20.1+/-4.1 vs 22.8+/-4.9, p<0.000) and a smoking history (33.2% vs 23%, p<0.015) were found as risk factors for the study group. Women who underwent surgery had greater gravidity (4.85+/-2.9 vs 3.87+/-2.5, p<0.001), greater parity (3.03+/-1.9 vs 2.19+/-1.3, p<0.000), were less often nulliparous (2.2% vs 7.9%, p<0.008), less likely to have had a cesarean delivery (1.1% vs 9%, p<0.001) and more likely to have had a vaginal delivery (97.3% vs 85.9%, p<0.000) than the control group. The study group have had larger neonates on average (3800+/-416 vs 3373+/-637 gm's, p<0.000) and had greater use of forceps or vacuum extractor for at least one delivery (17.9% vs 7.6%, p<0.001). Highly significant relationship was found between the risk of having corrective surgery and the number of children born vaginally. Women who had 4 or more vaginal deliveries had 11.7 times more risk of urinary incontinence or genital prolapse.

The effect of ascites, mass volume, and peritoneal carcinomatosis on serum CA125 levels in patients with ovarian carcinoma.

The aim of this study is to investigate the effects of ascites, ovarian mass volume, and peritoneal carcinomatosis on serum CA125 levels in patients with nonmucinous epithelial ovarian carcinoma. Serum CA125 levels were determined by a commercial enzyme immunoassay kit in a series of 98 patients with stage I-IV nonmucinous epithelial ovarian carcinoma. Amounts of ascites were determined in each patient with ascites. Ovarian mass volumes were calculated in 22 patients with stage I disease without ascites. Peritoneal carcinomatosis was detected in 35 ovarian cancer patients. Serum CA125 levels were compared among the patients with different clinical conditions. Serum CA125 levels were significantly higher in cases of ovarian cancer with ascites when compared with those without ascites (P < 0.01). Abnormal levels of serum CA125 were found in 80% of all patients; these abnormal levels were detected in 92% and 97% of the patients with ascites and with peritoneal carcinomatosis, respectively. A positive correlation between serum CA125 levels and ascites amounts was found in patients with ascites (P < 0.01, r = 0.74). However, there was no correlation between ovarian mass volumes and levels of serum CA125 in patients having stage I disease but no ascites (P = 0.5, r = 0.15). Our results showed that serum CA125 levels might be affected by the amount of ascites and the presence of peritoneal carcinomatosis but not with ovarian mass volume. However, these findings need to be confirmed in more and larger studies. These results may be beneficial in the management of ovarian carcinoma patients with elevated CA125 levels.

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.

Omentectomy, peritoneal biopsy and appendectomy in patients with clinical stage I endometrial carcinoma.

The aim of this study was to evaluate whether omentectomy, appendectomy, and peritoneal biopsy should be a routine part of staging surgery in endometrial carcinoma. Data of 97 patients who had been diagnosed with clinical stage I endometrial carcinoma were reviewed. Associations in the data obtained, pelvic and para-aortic lymph node status, depth of myometrial invasion, grade, and histology were investigated. The chi-square (chi2) test was used for statistical analysis. Of 97 patients, six (6%) had omental metastases, which was microscopic in four. There was a statistically significant relationship between omental metastasis and tumor grade (P < 0.01). Deep myometrial invasion was significantly more common in patients with omental metastases. Tumor was found in one of 55 appendectomy specimens (2%). Omentectomy may be included in surgical staging in patients with deeply invasive or grade 3 endometrial cancer because of the possibility of omental metastasis in spite of what appears to be stage I disease in laparotomy. In other cases, omentectomy and appendectomy and biopsies from peritoneal sites should be performed in the presence of grossly suspicious disease.

Estrogen and progesterone receptor manipulations in castrated rat uterus models and the clinical adaptation.

To investigate the influence of tamoxifen, danazol and triptorelin (a GnRH agonist) on estrogen and progesterone receptors of rat endometrium, 44 castrated Sprague-Dawley rats were divided into four equal groups, and each group received either no treatment or one of the agents. After administration of the agents, estrogen and progesterone receptor levels, detected by immunohistochemical methods, were compared with the controls. Estrogen and progesterone receptors were significantly higher in the tamoxifen group than the controls (p<0.05), but this was not noticed in the triptorelin group (p>0.05). Receptor levels were higher in the danazol group than the controls, but it was significant only in the estrogen receptors. Among the 3 groups, receptor levels were higher than in the control group. There was not any correlation among the estrogen and progesterone receptor levels in all groups. Steroid receptor manipulations can be used in the treatment of gynecologic cancer, but further investigations are needed.

Borderline ovarian tumours: retrospective analysis of twenty-one cases.

Twenty-one borderline ovarian tumour cases, diagnosed and treated in our oncology section between 1986 and 1996, were retrospectively analysed. Thirty-three percent of the cases had serous tumours and the rest (66.6%) were mucinous, 57.1% of the mucinous tumours were the intestinal type and the remaining 42.9% were the endocervical type. When all the cases were analysed, the average age was 45.4+/-18.6 years, the average follow-up period was 5.5+/-2.6 years. The preoperative average CA125 level was 55.1+/-51.9 U/mL, and for CA19.9 it was 48.2+/-47.8 U/mL. Of the patients 85.7% were stage I and 14.3% state III. There were not any significant differences between the serous, intestinal-type mucinous and endometroid-type mucinous tumours regarding tumour volumes (p>0.05). When serous and mucinous tumours were compared according to the tumour markers, CA125 levels were significantly higher in the serous tumours (p=0.04) and CA19.9 levels were significantly higher in the mucinous tumours (p=0.02). All of the patients are under our follow-up and are in remission, except one, who died in the third year of the treatment because of chronic renal failure unrelated to the ovarian pathology.

PIP: Tumors of low malignant potential represent approximately 15% of epithelial ovarian tumors and tend to occur at a younger age than malignant neoplasia. This paper presents a retrospective analysis of the 21 borderline ovarian tumors diagnosed and treated at Dokuz Eylul University in Izmir, Turkey, in 1986-96. The average age at presentation was 45.4 +or- 18.6 years. The diagnosis was made by exploratory laparotomy and frozen section. 7 tumors (33.3%) were serous and 14 (66.6%) were mucinous. 8 borderline mucinous tumors (57.1%) were intestinal type and 6 (42.9%) were endocervical. The average preoperative cancer marker level was 55.1 +or- 51.9 U/ml for CA125 and 48.2 +or- 47.8 U/ml for CA19.9. CA125 levels were significantly higher in serous tumors (p = 0.04) while CA19.9 measurements were significantly higher in mucinous tumors (p = 0.02). 18 tumors (85.7%) were stage I and 3 (14.3%) were stage III. There were no significant differences in tumor volume between serous, intestinal-type mucinous, and endometroid-type mucinous tumors. Women with stage I tumors who wanted to preserve their fertility underwent unilateral salpingo-oophorectomy; total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed in the remaining cases. Women with stage III tumors received 6 rounds of first-line adjuvant chemotherapy followed by second-look laparotomy. 1 patient died in the third year of treatment as a result of chronic renal failure unrelated to the ovarian pathology; the remaining women, who have been followed an average of 5.5 +or- 2.6 years, are in remission.

Umbilical coiling index: is it a marker for the foetus at risk?

The aim of this study was to determine the relationship between the number of coils in the umbilical cord and perinatal outcome. The umbilical cords and delivery records of 147 liveborn neonates were prospectively studied. The umbilical coiling index (UCI) of each cord was calculated by dividing the total number of complete umbilical vascular coils by the umbilical cord length. Subjects with UCIs below the 10th percentile, above the 90th percentile, and between the 10th and 90th percentiles were defined as hypocoiled, hypercoiled, and normocoiled, respectively. Several different parameters were used to measure neonatal outcome. The mean UCI was 0.20 +/- 10 (SD). No relationship was noted between UCI and maternal age, gravidity, parity, oligohydramnios, or birth weight. When we compared the hypocoiled group (n = 30) with the normocoiled group (n = 87), we detected a statistically significantly higher incidence of meconium staining, interventional delivery, apgar scores, fetal blood pH and intrapartum fetal heart rate disturbances. As a result, we concluded that the UCI has a strong relationship with perinatal outcome and may be used antenatally as a marker for identifying the fetus at risk.

[Does the incidence of premature labor vary according to the season?]. / L'incidence de l'accouchement prématuré varie-t-elle selon les saisons?

To investigate the epidemiology of premature delivery, in particular regarding potential seasonal influences, a retrospective medical-record study was conducted in 3345 women who delivered prematurely over a six-year period (1988-1993). The control group was composed of 53,162 women who carried their pregnancies to term. Each study subject had delivered at least one liveborn baby, prematurely or at full term. The premature delivery rate (ratio of premature over term deliveries) was highest in May through July and decreased significantly in January and February (p < 0.05). Premature delivery rates were similar in primiparas and multiparas (p > 0.05) and were not influenced by the gender of the fetus (p > 0.05). In conclusion, premature delivery rates vary across seasons, suggesting an influence of weather conditions.