Recurrent ovarian dysgerminoma after laparoscopy.

To our knowledge, recurrent dysgerminoma at the site of tumor removal by laparoscopy in a patient with stage IA disease has not been previously reported. A woman with ovarian dysgerminoma treated by laparoscopy and tumor removed through the cul-de-sac recurred the 17 months later at the site of tumor removal. She was successfully treated with etoposide, bleomycin, and cisplatin chemotherapy with complete response. This case illustrates the potential for surgical site implant of an ovarian dysgerminoma; surgeons should follow strict guidelines when performing laparoscopic procedures for ovarian malignancies in order to prevent this type of incident.

Phase III randomized pilot study comparing interferon alpha-2b in combination with radiation therapy versus radiation therapy alone in patients with stage III-B carcinoma of the cervix.

This randomized pilot study was designed to determine whether the addition of interferon alpha-2b to standard radiation therapy offered an advantage in loco-regional control and survival over radiation therapy alone in a homogeneous group of patients with stage IIIB carcinoma of the cervix. Thirty-six patients were treated with a combination of interferon alpha-2b plus radiation therapy, and 38 patients were treated with radiation therapy alone. Patients with evidence of ureteral obstruction were excluded from the study. Evaluation of loco-regional response was determined by pelvic examination, cervical cytology, biopsies and CT scans when indicated. Survival time was measured from initiation of treatment to date of death or last follow-up. Patient characteristics were comparable between both study arms. The objective complete response rate was 67% in the combined therapy group and 55% in the radiation alone group (P = 0.454). With a median follow-up of 17 months for all patients and 31 months for live patients, 50% of the combined group survived vs. 39.5% of the radiation alone group (P = 0.424). We conclude that the addition of interferon alpha-2b to standard radiation therapy did not significantly improve loco-regional response or survival, although such a trend was noted. We encourage the design of a larger randomized study with sufficient power to detect meaningful differences to prove whether the tendency observed in the present investigation holds any promise to improve the outcome of these patients.

Cryopreservation of a small number of fresh human testicular spermatozoa and testicular spermatozoa cultured in vitro for 3 days in an empty zona pellucida.

It is known that the motility of human testicular sperm can be improved when they are cultured in vitro for a few days. The purpose of this study was to determine whether it is better to freeze human testicular spermatozoa on the day of biopsy (fresh) or after they were cultured for 3 days. A modified, single-sperm freezing technique was used in this study. The study consisted of two parts: (1) ejaculated spermatozoa were used to examine the influence of different concentrations of glycerol and synthetic serum substitute (SSS) on the survival rate after cryopreservation, and (2) the survival rates between cryopreserved fresh testicular spermatozoa (Group 1) and testicular spermatozoa that were cultured for 3 days before freezing (Group 2) were compared. Empty zonae pellucidae were obtained from mouse eggs. Five to 10 motile spermatozoa were selected and injected into an empty zona pellucida. For freezing, the zona pellucida with spermatozoa was transferred into a HEPES-buffered human tubal fluid containing different concentrations of glycerol and kept at room temperature for 10 to 15 minutes, and then loaded into a 0.25-ml-plastic straw. The straws were exposed to liquid nitrogen vapor for 2 hours and then plunged into liquid nitrogen. For thawing, the straws were taken out of liquid nitrogen and placed into a 37 degrees C waterbath for 25 to 30 seconds. There was no statistically significant difference in survival rates between 3% and 10% SSS with different glycerol concentrations. There was no statistically significant difference in the survival rates of spermatozoa between Group 1 and Group 2 after cryopreservation. It appears that in vitro culture of testicular spermatozoa before freezing does not increase survival rate.

Cyfra 21-1 marker in carcinoma of the cervix.

Cyfra 21-1 has been reported to be an effective tumor marker for epithelial carcinomas. The purpose of this investigation was to determine its value in evaluating response to treatment in patients with carcinoma of the cervix. Cyfra 21-1 levels were measured by immunoassay in the serum of 55 untreated patients with cervical cancer; a second sample was obtained in all of them after conventional treatment for association with clinical response. Pre-therapy levels were elevated in only 45% (25 of 55) of the patients, with a slight tendency to increase according to clinical stage: 33% (5/15) in stage I, 36% (8/22) in stage II and 67% (12/18) in stage III. In regards to association with response to therapy, and including patients with either normal or elevated pretreatment values, 46% (19/41) of women with a complete clinical response either persisted with or developed elevated levels after treatment completion. All 14 patients with persistent disease after therapy continued to have or developed elevated values. No patient with persistent disease had normal values after therapy, and all patients with negative values after treatment were truly complete clinical responders. The results of our study suggest that the test has a low sensitivity therefore and, despite our findings, a negative level after treatment may not be a safe indicator of disease-free status. On the other hand, an elevated post-treatment level is not a reliable indicator of persistence, proven by the fact that 46% of clinical responders fell in this category. Therefore, Cyfra 21-1 has a very limited role in correlating with response to treatment in carcinoma of the cervix.

Ultrarapid detection of sex chromosomes with the use of fluorescence in situ hybridization with direct label DNA probes in single human blastomeres, spermatozoa, amniocytes, and lymphocytes.

OBJECTIVE: To assess the ultrarapid fluorescence in situ hybridization (FISH) procedure with a 1-minute hybridization time for gender determination. DESIGN: Fluorescence in situ hybridization with direct label fluorescence DNA probes for chromosomes X and Y were tested with the use of different hybridization times and different cell types. SETTING: Hospital-based IVF program. INTERVENTION(S): The efficiency of the FISH procedure with different hybridization times was compared with the use of male lymphocytes. The same FISH procedure, but with only 1-minute hybridization, was carried out in human blastomeres, spermatozoa, uncultured amniocytes, male lymphocytes, and female lymphocytes. MAIN OUTCOME MEASURE(S): Percentages of nuclei with positive signals. RESULT(S): The percentages of nuclei with positive signals in lymphocytes with hybridization times of 1, 3, 4, 10, 30, and 45 minutes were 97%, 97%, 98%, 98%, 98%, and 98%, respectively. The percentages of nuclei with positive signals after FISH with a 1-minute hybridization time in single blastomeres, spermatozoa, amniocytes, male lymphocytes, and female lymphocytes were 94%, 96%, 96%, 98%, and 97%, respectively. CONCLUSION(S): Chromosomes X and Y of human blastomeres. spermatozoa, uncultured amniocytes, and lymphocytes can be detected rapidly with the use of this ultrarapid FISH procedure with a 1-minute hybridization time.

Feasibility study of repeated fluorescent in-situ hybridization in the same human blastomeres for preimplantation genetic diagnosis.

In order to increase the number of chromosomes examined in each blastomere, we have developed a repeated fluorescent in-situ hybridization (FISH) procedure by which six or more chromosomes can be analysed per blastomere of a human embryo. Three consecutive FISH procedures with directly-labelled fluorescent Vysis DNA probes were carried out for examination of chromosomes X, Y, 11, 13, 18 and 21 in the same blastomeres (n = 126) and lymphocytes (n = 164). Based on the initial number of nuclei, the percentages of nuclear loss and presence of signals were 3 and 92% respectively in blastomeres; 6 and 91% respectively in lymphocytes after the first FISH; 7 and 87% respectively in blastomeres and 10 and 86% respectively in lymphocytes, after the second FISH. These percentages were 13 and 78% respectively in blastomeres and 14 and 81% respectively in lymphocytes after the third FISH. The FISH procedure was repeated successfully in a couple for preimplantation genetic diagnosis of chromosomal aneuploidies in biopsied blastomeres of their embryos in our clinic. In conclusion, it is feasible to carry out repeated FISH procedures in the same blastomeres. Six or more chromosomes of a single blastomere may be examined using this procedure.

Potential use of repeated fluorescence in situ hybridization in the same human blastomeres for preimplantation genetic diagnosis.

OBJECTIVE: To assess the feasibility of repeated fluorescence in situ hybridization (FISH) procedures in the same nucleus of a human blastomere. DESIGN: Three consecutive FISH procedures were performed in the same human blastomere by using direct label fluorescence CEP and WCP probes (Vysis). SETTING: Hospital-based private IVF program. PATIENT(S): Twenty-eight infertile couples who underwent conventional IVF in our center. INTERVENTION(S): Embryos from oocytes with three pronuclei after in vitro insemination were used in this study. MAIN OUTCOME MEASURE(S): The rates of nuclear loss, present signals, and absent signal were examined. RESULT(S): In group 1, the rates of presence of signals were 94% after the first FISH, 92% after the second FISH, and 88% after the third FISH. In group 2, the rates of presence of signals were 96% after the first FISH, 93% after the second FISH, and 87% after the third FISH. There was no statistically significant difference in the rates of nuclear loss, present signals, and absent signal between three consecutive FISH procedures and between CEP and WCP probes. CONCLUSION(S): Six or more chromosomes of a single blastomere may be examined with use of this repeated FISH procedure, which may be important for preimplantation genetic diagnosis.

Prolactin disorders.

OBJECTIVE: To review the pathophysiology, clinical manifestations, current diagnostic procedures, and treatment options for disorders involving PRL production. Common clinical dilemmas are discussed in a pragmatic fashion to guide the practitioner. DESIGN: A world literature search of basic sciences and medical articles from the last three decades was performed using computerized MEDLINE. Recent endocrine and reproductive endocrine textbooks also were reviewed. Studies were selected for their degree of contribution to the basic sciences and clinical understanding of the disorder and for the quality of their study design and content. The information was summarized and grouped according to its relevance and application to specific sections of the manuscript. Studies were evaluated and critically used to support the views of the authors and to suggest specific clinical management strategies. RESULT(S): Disorders derived from abnormal PRL production are relatively common in clinical practice. Infertility, menstrual disorders, and galactorrhea are the most frequent manifestations encountered in women. Although frequently benign, the disorder occasionally may have severe consequences. CONCLUSION(S): An understanding of the underlying physiology and pathophysiology coupled with the awareness of the heterogeneous presentation of this disorder should help the clinician to approach it successfully.

[Defecation flowmetry. A new study technique for evaluating the evacuation function of the rectum]. / Defäkoflowmetrie. Eine neue Untersuchungstechnik zur Beurteilung der Entleerungsfunktion des Rektums.

In a prospective study carried out on 78 patients with chronic constipation (31, with slow transit, 47 with obstructive defecation disorders) the evacuation function of the rectum during defecation was assessed by defecoflowmetry. These patients were compared to a control group of normal volunteers (n = 32). The following parameters were evaluated: defecation and retention volume, defecation fraction, defecation time, maximum flow, mean flow rate and time to maximum flow. As expected, there was no difference in evacuation function between the group of patients with slow transit and the control group. Significant differences, however, existed between the two types of constipation, as well as between obstructive defecation disease and controls, regarding all parameters mentioned above. Evacuation function depends neither on rectal neck pressure nor on intrarectal pressure. In patients with obstructive defecation disorders, three subgroups were discernable: one with prolonged time of defecation and satisfactory evacuation, one with prolonged time of defecation and poor evacuation, and one small group of patients who were not able to defecate. Each group is based on a different underlying pathomechanism. We conclude that changes in evacuation function of the rectum refer either to volume or to time of defecation, or to both. Changes are found only in obstructive type constipation, not in slow transit constipation. Therefore, defeconflowmetry as a dynamic procedure can be used in screening for the classification of chronic constipation.

The effect of naproxen on fever in patients with advanced gynecologic malignancies.

The antipyretic action of naproxen has been reported as sufficiently selective for neoplasm-related fever such that the use of this agent has been recommended to distinguish neoplastic from infectious fever. The antipyretic effect of naproxen was evaluated in gynecologic oncology patients with advanced pelvic malignancies and fever without obvious source of infection (suspected neoplastic fever). Naproxen (250 mg orally every 8 hr) was given to 12 patients with (i) a daily temperature greater than 38.3 degrees C, (ii) fever for at least 3 days, (iii) no evidence of infection on physical exam, (iv) negative results of blood and urine cultures, and (v) a chest roentgenogram negative for pneumonia. Ten of the 12 patients initially received a minimum of 3 days of empiric antibiotic therapy without resolution of fever. Within 24 hr of starting naproxen therapy, 10 patients' (83%) fever responded: Eight patients (80%) had a complete lysis of fever and two had partial lysis (20%). Temperature response was accompanied by subjective improvement in patient malaise and fatigue. Naproxen therapy was continued for 5-7 days in these patients, and chemotherapy was administered to those patients scheduled to receive it. Two patients did not respond to naproxen therapy in 24 hr; thus, it was stopped and the fever workup was continued. Of these two patients, one was eventually diagnosed with bacteremia after multiple negative blood cultures and initially no response to antibiotics. Naproxen is clinically useful in the palliation of fever-related symptoms in gynecologic oncology patients with suspected neoplastic fever. Naproxen may also allow the limitation of extensive fever workups and prolonged empiric antibiotic therapy in these patients, and prevent delays in systemic therapy or supportive care.

Enzyme activities and maturation in unstimulated and exogenous gonadotropin-stimulated human oocytes.

With the advent of new techniques of human in vitro fertilization (IVF), identifying parameters of oocyte quality to allow selection of those most likely to fertilize becomes crucial. Morphology of oocytes, which correlates positively with biological performance, is the currently utilized classification criterion. However, biological links between form and function are tenuous, and underlying mechanisms remain elusive. We investigated whether biochemical activation is quantitatively associated with the stages of maturation in ova obtained from patients undergoing gynecologic surgery during unstimulated cycles and women undergoing IVF after exogenous gonadotropin stimulation. Changes in selected enzymes from protein, lipid, and carbohydrate metabolism (hexokinase, phosphoglucomutase, glycogen synthetase, uridine diphosphoglucose pyrophosphorylase, glucose-6-phosphate dehydrogenase, cytosolic thiolase, beta-hydroxyacyl-CoA dehydrogenase, alanine aminotransferase, and aspartate aminotransferase) were determined simultaneously, in individual oocytes, utilizing a highly sensitive biochemical methodology. Several enzyme activities paralleled maturation grade and were higher in stimulated oocytes after correction for grade. These biochemical findings quantify metabolic and functional changes that increase as ova mature, possibly contributing to their reproductive performance.

Operative laparoscopy in the management of tubal ectopic pregnancy.

One hundred and seventeen consecutive patients with diagnosis of ectopic pregnancy admitted to Temple University Hospital between October 1989 and March 1992 were divided into two groups. Group 1 consisted of 56 patients with operative laparoscopy and Group 2 consisted of 61 patients treated by laparotomy. The two groups were similar for age, race, parity, gestation, presentation, and location of the ectopic gestations. Fifty seven percent of patients in the laparoscopy group were treated by salpingectomy and 43% by salpingostomy, compared to 84% and 16% respectively in the laparotomy group. Mean operative time for laparoscopy was 58 min and 42 min for laparotomy. Complication rates were similar in the two sub-groups. Only two patients in the laparoscopy group required subsequent laparotomy, one to assure hemostasis and one, 5 weeks following surgery, for persistent trophoblastic disease. Operative laparoscopy was associated with a significantly shorter length of hospital stay (1.25 v. 4.39 days). This reflected in a lower cost of hospital stay ($10,105 vs. $13,608). The present data demonstrates that operative laparoscopy is not only safe and effective, but also more economical than open laparotomy in the treatment of ectopic pregnancies. This procedure is expected to replace laparotomy for the treatment of most cases of tubal ectopic pregnancy.

Distribution of tritiated cocaine in selected genital and nongenital organs following administration to male mice.

STUDY OBJECTIVE: To determine the distribution of cocaine administered to male mice in selected extragenital and genital organs and to investigate its possible binding to sperm. DESIGN: Twenty-seven sexually mature virus-free albino male mice were used in various experiments whereby following intravenous injection of tritiated cocaine hydrochloride, radioactivity was determined in several extragenital and genital organs, as well as sperm. RESULTS: Radioactivity was detected in all of the organs that were tested, and the highest concentrations per milligram of tissue were found in the kidney and epididymis. Removal of the sperm from the epididymis significantly reduced the radioactivity of the organ. The spermatozoa that were isolated on glass filters showed a linear correlation vs radioactivity (r = .93). CONCLUSIONS: Radioactivity is distributed to several organs, including the genital tract, and is found in association with sperm after in vivo administration of tritiated cocaine. These results may explain the mechanism underlying a male-mediated teratogenesis, which has been observed in animals that were exposed to cocaine, and they raise a possibility that the spermatozoa may carry cocaine into the oocyte during fertilization.

Management of the patient with an abnormal Papanicolaou smear.

Any patient with an abnormal Papanicolaou smear should undergo colposcopic evaluation. Histologic examination of tissue obtained by biopsy and by endocervical curettage is essential for a proper diagnosis. Conization of the cervix has very well-defined indications.

Mitomycin-C/5-FU and radiation therapy for locally advanced uterine cervical cancer.

To assess the feasibility and effectiveness of combined therapy on locally advanced cervical cancer, we entered 38 patients into a study. The patients were treated with mitomycin-C (10 mg/m2) on Days 1 and 30 and 5-FU (1000 mg/m2) on Days 1 to 4 and Days 30 to 33. In 5 weeks 4500-5000 cGy was given concurrently, followed by radioactive implants. Twenty-six patients had an early-stage disease (IB-IIB) and twelve had a late-stage disease (IIIB-IVA). Eighty-seven percent (33/38) of the patients had a tumor measuring 5 cm or more. The other 5 patients with a tumor size under 5 cm had biopsy-proven positive pelvic nodes; 2 of these 5 patients had a pretherapy hysterectomy. Tumor response, complete (CR) vs partial (PR), was assessed in 36 patients 3 months after completion of therapy. A CR was noted in 80% (29/36) of the patients. The PR status conferred a detrimental effect on the pelvic disease control (PDC), disease-free survival (DFS), and survival (S) while late stage correlated with the development of distant metastases (DM) and a poor DFS. PDC was obtained in 93% (27/29) of the patients who had a CR, as compared to only 43% (3/7) of those with a PR (P = 0.0228). The DFS and S rates were 59 and 77% for patients with a CR and 21 and 19% for those with a PR; respective P values were 0.0340 and 0.0002. Eleven percent (3/26) of the patients with an early stage developed DM, as compared to 50% (6/12) of those with late stage, (P = 0.0016). The DFS rates were 80 and 37% for patients with an early and late stage, respectively (P = 0.0141). Four patients developed transient neutropenia and one had transient thrombocytopenia. The second dose of mitomycin-C was omitted in 4 patients due to persistent neutropenia in 3 and to transfusion-related hepatitis in 1. Two percent (5/21) of the patients who had a staging laparotomy developed wound dehiscence. Three patients developed non-cancer-related small bowel obstruction requiring surgery. We concluded that this combined regimen was well tolerated. Although it was effective in controlling the cancer in the pelvis, this regimen failed to control DM in late-stage patients.

Prognosis of ovarian cancer developing in the residual ovary.

Elective oophorectomy at the time of hysterectomy for benign disease in women during their fifth decade is an important issue for both gynecologist and patient. It has been suggested that cancer developing in the residual ovary has a worse prognosis than the national average (L. McGowan, Obstet. Gynecol. 69, 386, 1987). In an effort to corroborate such finding, 36 women with epithelial ovarian cancer developing in the residual ovary after prior hysterectomy were compared to a group of 121 patients with epithelial ovarian cancer and no previous surgery. Analysis was made of age, stage at diagnosis, feasibility of cytoreductive surgery, and survival in both groups. Only age distribution was found to be significantly different between the two groups of patients (P less than 0.001). Neither FIGO staging or quality of cytoreductive surgery showed a statistically significant difference between both groups. At 3 years, 41% of the subjects with cancer in the residual ovary were alive, compared to 42% in the group without previous hysterectomy. The corresponding figures for 5-year survival are 34 and 27%, respectively (P = 0.939). On the basis of our findings we conclude that the overall prognosis for patients with ovarian cancer developing in the residual ovary does not appear to be any worse than that reported for ovarian cancer in general.