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Background: To present a diagnostic evaluation and treatment strategy for serous adenocarcinoma of the ovary discovered during an in vitro fertilisation (IVF) sequence, and report on reproductive outcome after tumour resection and embryo transfer., Case Presentation: Cycle monitoring in IVF identified an abnormal ovarian lesion which was subjected to ultrasound-guided needle aspiration. Cytology suggested malignancy, and unilateral oophorectomy was performed after formal staging. After surgery, the patient underwent an anonymous donor oocyte IVF cycle which established a viable twin intrauterine pregnancy. No recurrence of cancer has been detected in the >72 month follow-up interval; mother and twin daughters continue to do well., Conclusion: Suspicious adnexal structures noted during controlled ovarian hyperstimulation for IVF warrant assessment, and this report confirms the role of aspiration cytology in such cases. If uterine conservation is possible, successful livebirth can be achieved from IVF if donor oocyes are utilised, as described here.

The aim of this study was to use the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay to determine the response of 17 endometrial and 27 cervical tumours to cytotoxic drugs. Tumour samples were taken at surgery and cultured using the explant technique. Cells were incubated with chemotherapy drugs. The MTS cytotoxicity assay was carried out to ascertain the response to the drugs and correlated retrospectively to the clinical outcome. Tumours of similar stage and grade displayed heterogeneity in their responses to the drugs. A total of 88 of 90 tumours (97.8%), including data from an earlier study of 44 ovarian tumour samples yielded chemosensitivity data. A total of 45 specimens were evaluable for in vitro-in vivo correlations. In vitro sensitivity was associated with clinical response in 26 of 30 patients and in vitro resistance with progressive disease or death in 14 of 15 patients. A randomised prospective trial should be carried out to validate chemosensitivity/resistance testing., (Copyright 2002 International Society for Preventive Oncology)

The response of ovarian serous papillary adenocarcinomas to various cytotoxic drugs was examined using the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) cytotoxicity assay. Thirty tumors were collected and organized into four groups according to histologic grade and FIGO stage: stage III, grade 2; stage III, grade 3; stage IV, grade 2; and stage IV, grade 3. The MTS chemosensitivity assay was performed on each tumor to examine the response to cisplatin, paclitaxel, hycamtin and the combination of cisplatin and paclitaxel. Ovarian adenocarcinomas of similar stage and grade displayed varying responses to the same drug. A lower concentration of the drug was often as effective as the peak plasma concentration. For some specimens combination therapy was more effective for inhibiting tumor growth, and for others single-agent therapy gave a better response. A chemosensitivity/resistance profile is recommended before deciding on appropriate chemotherapy.

The purpose of this study is to report our experience with weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease. Treatment was begun at a dose of 40 mg/m2 and escalated weekly by 5-10 mg/m2, depending upon response and tolerance, to a maximum dose of 60 mg/m2. Remission was induced with weekly intramuscular methotrexate alone in 12 (60%) of 20 patients in 2-12 (median 8) weeks. The remaining 7 patients had a complete response to alternate chemotherapy. There were no major toxicities. Although the results of the present study are less favorable in terms of response, the overall published results using weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease indicate that it is comparable in efficacy to other first-line treatments while having the advantages of convenience, low cost, and low toxicity.

Invasion and metastasis require the destruction of the extracellular matrix and basement membranes to facilitate growth or migration of tumor cells into vascular and lymphatic spaces. These processes are mediated by proteolytic enzymes. Malignant cells produce urokinase which is a protease known to enhance the invasiveness of many tumor cells. The relationship between urokinase and various prognostic factors was investigated in 16 patients with epithelial ovarian cancer. Tissue concentrations of urokinase were measured in tumor cytosols using enzyme-linked immunoassays. Urokinase levels were lower in ovarian tumors of low malignant potential (median 9.5, range 3.5-18.3 pg/mg protein, n = 4) than invasive cancers (median 44.6, range 16.1-210.6 pg/mg protein, n = 12), p < 0.01. In the invasive carcinomas urokinase levels did not vary significantly with tumor stage or cell type. Grade 3 tumors had higher levels of urokinase (median 120.4, range 21.4-397.1 pg/mg protein, n = 6) than grade 1 and 2 tumors (median 29.2, range 16.1-51.8 pg/mg protein, n = 6), p < 0.05. Urokinase levels were higher in recurrent (median 120.4, range 51.8-210.6 pg/mg protein, n = 4) than in primary (median 29.2, range 16.1-97.1 pg/mg protein, n = 8) tumors, p < 0.05. These results support the hypothesis that urokinase plays a role in invasion and metastasis of ovarian epithelial cancers and suggest that tissue levels of urokinase may have prognostic value.

This is an evaluation of our experience with colorectal reanastomosis on a gynecologic oncology service. A retrospective review was carried out on all patients who underwent colorectal resection and reanastomosis on the gynecologic oncology service from October 1, 1987 to September 30, 1992. Thirty-nine procedures were performed: Nine patients underwent sigmoidectomy alone, 20 also underwent cytoreduction, and 10 also underwent exenteration. Thirty-eight percent of the patients had undergone prior radiotherapy. The level of anastomosis above the anal verge was 3-5 cm in 9 patients, 6-9 cm in 20 patients, and 10-14 cm in 10 patients. Sixteen had a protective colostomy which included 13 of the 15 patients with prior radiotherapy. Thirteen of the protective colostomies were taken down, although three of these required a second permanent colostomy. Three other patients required colostomy at a later date, one of whom developed a rectovaginal fistula 10 days following exenteration for postradiation recurrent carcinoma of the cervix. A total of 30 of the 37 evaluable patients (81%) had an ultimately functional colorectal reanastomosis. Problems related to colorectal function included stricture (4), fistula (4), chronic diarrhea (3), tenesmus (1), and fecal incontinence (1). Colorectal anastomosis is a worthwhile endeavor in selected patients with gynecologic cancer.

The pudendal thigh is a sensate fasciocutaneous flap supplied by the posterior labial artery. We report on the results of pudendal thigh flaps used for vaginal reconstruction in eight patients at the time of pelvic exenteration (6) and radical vaginectomy (2). Patients were interviewed and results were assessed 5 to 19 months after surgery. The flaps were raised in the thigh creases just lateral to the hair bearing area of the labia majora and included skin, subcutaneous tissues, deep fascia of the thigh, and the epimysium of the adductor muscles. Flap sizes varied from 9 x 4 cm to 15 x 6 cm. Bilateral flaps were used in seven patients. The flaps were technically easy to perform. Partial (apical) flap necrosis occurred in four patients. One patient developed complete necrosis of bilateral flaps, followed by an enterovaginal fistula. One patient whose flaps did not necrose developed a rectovaginal fistula at the site of rectal reanastomosis. The functional results are disappointing. The only patient having successful vaginal intercourse had a unilateral flap reconstruction following lower vaginectomy in a nonirradiated pelvis. No patient with bilateral flaps or prior pelvic irradiation has had successful coitus. Other long-term sequelae include vulvar pain (2), chronic vaginal discharge (2), hair growth (4), and protrusion of the flaps (2). These vulvovaginal symptoms discourage patients and their partners from genital contact. Breaching the integrity of the vulva to construct a neovagina that is likely to be unsuitable for sexual intercourse may deprive women of their only potential for normal genital sexual responsiveness. Techniques of vaginoplasty require continued assessment.

Separate vulvar and groin incisions have significantly reduced the morbidity of vulvar cancer surgery. We describe a patient with FIGO stage II squamous vulvar cancer, who developed an ipsilateral tumor recurrence in the skin bridge between the vulva and the groin within 7 months of modified radical vulvectomy and bilateral inguinofemoral lymphadenectomy, using triple incisions. The recurrence was treated by wide local excision alone and she remains free of disease 2 years later. Although rare, the potential for failing to excise tumor emboli in the lymphatics of the skin bridge must be recognized when the triple incision technique is used in the surgical treatment of vulvar cancer.

In order to prevent the complications of long-term nasogastric suctioning and increase patient comfort, we have been using gastrostomy tubes (G-tubes) in gynecologic oncology patients who are deemed to be at risk for protracted postoperative bowel dysfunction. This study describes our patient selection criteria and evaluates the results with 35 MIC (Medical Innovation Corporation, Milpitas, CA) gastrostomy tubes inserted between September 1, 1992 and April 30, 1993. The procedure is technically easy and adds approximately 10 min to operating time. The tubes were well tolerated by the patients over periods ranging from 5 to 135 days. All tubes were used for postoperative gastric drainage and in addition, eight tubes were used for short-term enteral feeding. One patient with short bowel syndrome continued enteral nutritional supplementation at home. Twenty patients were discharged with their G-tubes in situ. Five of these patients required continuous gastric drainage because of obstruction of gastric emptying or small bowel by advanced tumor, and four of them were taking full liquids orally prior to discharge from the hospital. Gastrostomy tubes are convenient adjuncts to postoperative care of the gynecologic oncology patient and afford palliation with few complications to patients dying with bowel obstruction.

Objective: The purpose of this study was to investigate the role of fibrinolysis in the pathogenesis of essential menorrhagia., Study Design: We measured fibrinolytic activity and the concentration of the fibrinolytic activators, tissue plasminogen activator, and plasminogen activator inhibitor type 1 in endometrial extracts at various stages of the menstrual cycle in patients with normal menstrual loss (< or = 80 ml per cycle) and essential menorrhagia (> 80 ml per cycle). Tissue plasminogen activator activity was assayed by measuring the rate of conversion of Glu-plasminogen to plasmin with a chromogenic plasmin substrate. Enzyme-linked immunoassays were used to measure tissue plasminogen activator and plasminogen activator inhibitor type 1 antigen levels., Results: Women with essential menorrhagia had higher endometrial tissue plasminogen activator activity in the menstrual phase compared with controls (p < 0.01). Endometrial tissue plasminogen activator antigen levels were higher in both the late secretory (p < 0.01) and menstrual (p < 0.001) phases in essential menorrhagia than in the normal group. Endometrial plasminogen activator inhibitor type 1 was significantly higher in essential menorrhagia only in the menstrual phase (p < 0.01)., Conclusion: The premenstrual rise in tissue plasminogen activator antigen production with delayed increase in plasminogen activator inhibitor type 1 is the probable cause of the greater endometrial tissue plasminogen activator activity that occurs during menstruation in women with essential menorrhagia.

There have been five previous well-documented cases of metastatic vulvar basal cell cancer in the literature. We now present the sixth case-an 86-year-old patient with vulvar basal cell cancer metastatic to an ipsilateral groin node. She was treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy and remains free of disease 1 year later.

Fibrinolytic activity of the menstrual fluid is increased in dysfunctional uterine bleeding (DUB). We measured the effect of tranexamic acid on the menstrual blood loss and endometrial fibrinolytic enzymes in women with DUB (> 80 ml menstrual loss/cycle). Endometrial biopsies were taken between 24 and 36 hours after the onset of menstruation. Enzyme activity was assayed by measuring the rate of conversion of Glu-plasminogen to plasmin, using a chromogenic plasmin substrate. Antigen levels were measured using an enzyme linked immunoassay (ELISA) technique. Tranexamic acid reduced menstrual blood loss by 58% (p < 0.05). Endometrial tissue plasminogen activator activity and antigen and plasminogen activator inhibitor--type 1 antigen levels were significantly decreased by tranexamic acid. The effect of tranexamic acid on the fibrinolytic enzymes at local endometrial level may be responsible for its success in the treatment of menorrhagia.

There is a demand on gynecologic oncology services for semipermanent cannulization of central veins to improve the quality of life in cancer patients by circumventing the need for frequent peripheral venous punctures. Central venous thrombosis and sepsis are the major complications with these lines. We reviewed our experience with the externalized Groshong catheters and subcutaneously implanted Hickman ports in 104 gynecologic oncology patients requiring either chemotherapy (56), hyperalimentation (5), or supportive care (43). All devices were inserted under the supervision of one primary gynecologic oncologist. Groshong catheters and Hickman ports remained in place for a median of 68.5 and 210 days, respectively (P < 0.001). Thrombosis occurred in association with 4.8% of catheters and was exclusive to the Groshong catheters. Line sepsis occurred in 32% of Groshong catheters and 16.2% of Hickman ports (P = 0.04). Infection rates were not higher in dual-lumen compared to single-lumen Groshong catheters. Staphylococcus epidermidis was the comments isolate in line infections. The majority of lines were salvaged despite infectious complications. Malfunction of the catheter was equally common in both groups (10.5-13.5%), but was complete, necessitating replacement of only 2.9% of lines. The Groshong catheters took less time to insert (P < 0.003). The externalized Groshong catheter remains a useful alternative to the subcutaneously implanted ports, especially when relatively short-term use is anticipated, but gynecologic oncologists should be aware that there is an increased frequency of complications with the externalized catheter.

Background: The majority of ureteric injuries associated with an operation are the result of gynecologic surgery. Thus, gynecologists must be aware of this risk and appreciate that ureteric injury can present late and in an unusual manner., Case: A 26-year-old woman presented with gross abdominal distention 4 months after total abdominal hysterectomy. Ultrasonography demonstrated a large volume of ascitic fluid and a complex cyst arising from the left ovary. Serum blood urea nitrogen and creatinine were normal. Laparotomy showed a mass of 1-2-cm cysts (urinomas) on the pelvic peritoneum and tubo-ovarian surfaces and a right hydroureter with a right ureteric fistula at the level of the ureteric tunnel. A ureteroneocystostomy was performed., Conclusion: Ureteroperitoneal fistula with urinary ascites is a rare complication of pelvic surgery. Intravenous urography or computed tomography scan would have helped establish the diagnosis.

We report three cases of abdominal wall metastases from ovarian cancer after laparoscopy. The implants occurred at the site of insertion of laparoscopy trocars. One patient had an implant of serous papillary carcinoma of low malignant potential at the trocar sites after laparoscopic oophorectomy. Laparoscopic surgery is inappropriate in patients with malignant ascites or when preoperative or intraoperative findings are suggestive of ovarian cancer.

Background: Plasminogen activators (PA) play an important role in the mediation of pathologic processes, including cancer invasion. Levels of urokinase are increased in malignant endometrium compared with normal endometrium. The role of PA inhibitors (PAI) in the malignant process is not known., Methods: PAI-1 (endothelial type inhibitor) and PAI-2 (placental type inhibitor) in extracts of malignant (n = 14) and normal (n = 7) postmenopausal endometrium were measured. The results were correlated with the standard prognostic variables in endometrial carcinoma, namely, stage, histologic grade, depth of myometrial invasion, and estrogen receptor status of the tumor., Results: PAI-1 was not detectable in normal endometrium and was present in small quantitities (0.11-1.54 ng PAI-1/mg protein) in 4 of 14 specimens of malignant endometrium. PAI-2 was present in 4 of 7 normal and all (14 of 14) malignant endometrial cytosols. PAI-2 levels were higher in Stage II and III compared with Stage I cancers (P < 0.05) and in malignant endometrium that invaded the myometrium to more than half its depth compared with those with less than 50% invasion (P < 0.05). No significant correlation was found between PAI-2 and estrogen receptor levels (r = -0.32)., Conclusions: Endometrial adenocarcinoma has higher levels of PAI-2 than does normal postmenopausal endometrium. Highest levels of PAI-2 were found in the poorer prognostic categories of endometrial cancer.

The efficacy of single agent chemotherapy with methotrexate in low risk gestational trophoblastic disease is well established, but efforts to reduce toxicity and patient time and cost continue. Twenty-five patients with nonmetastatic postmolar gestational trophoblastic disease were seen by the Division of Gynecologic Oncology at the University of South Florida between February 1986 and December 1991. Patients were treated with either weekly intramuscular methotrexate 40 mg/M2 (Group 1, n = 13) or alternating doses of intramuscular methotrexate 1 mg/kg and folinic acid 0.1 mg/kg over eight consecutive days with an eight- day interval (Group 2, n = 12). Patient age, body weight and pre-treatment beta-hCG values were similar in the two groups. One patient defaulted from treatment and was lost to follow-up. All other patients were cured. Complete remission was achieved with primary chemotherapy in nine (69%) patients in Group 1 and nine (75%) in Group 2. All patients with pre-treatment beta-hCG of 650 mIU/ml or less responded to primary therapy whereas 50% of those with higher levels required second-line therapy. When secondary and tertiary treatment were included, the duration of treatment was similar in both groups. Remission was achieved at significantly lower levels of methotrexate in group 1 patients (p < 0.001). No major toxicities occurred. Side effects were gastrointestinal and myelosuppressive and occurred in 2.5% and 15.6% of treatment cycles in Groups 1 and 2, respectively (p < 0.01). Weekly methotrexate is an equally effective and less toxic regimen than eight-day methotrexate-folinic acid in nonmetastatic postmolar gestational trophoblastic disease.

We analysed 98 consecutive instrumental rotational deliveries of babies weighing > 2,500 grams in primiparae. Our aim was to compare the use of Kjelland's forceps with vacuum delivery with regard to efficacy and safety. The vaginal delivery rate was similar with Kjelland's forceps (96%) and vacuum (90%). The vacuum cup failed to effect rotation in 14% and 77% required forceps delivery after vacuum rotation. The vacuum took longer to effect delivery (P < 0.01). Women delivered with Kjelland's forceps had higher pain scores in the puerperium. There were no perinatal deaths. Low Apgar scores and cord arterial pH values of less than 7.20 were recorded more frequently after vacuum rotation (p < 0.05). Babies delivered with Kjelland's forceps sustained more physical trauma. The incidence of asphyxial encephalopathy was the same in both groups. We would recommend a more selective approach to the use of both rotational vacuum and Kjelland's forceps in primiparae.

One hundred and ninety-four primiparae with lumbar epidural analgesia established during the first stage of labour were discouraged from pushing until the fetal head was visible at the perineum or until three hours had elapsed since full dilation of the cervix. The outcome in this group was compared with a similar group in whom pushing was commenced as soon as the second stage was diagnosed. The observed increase in spontaneous deliveries did not reach statistical significance. There was a reduction in non-rotational forceps (p less than 0.05), but no change occurred in the incidence of rotational forceps deliveries. The high rates of oxytocin augmentation in these primiparous labours may account for the failure of delayed pushing to increase the spontaneous delivery rate in our population.