Hereditary and sporadic ovarian cancer: genetic testing and clinical implications (review).

The two most common forms of hereditary ovarian cancer are: the breast ovarian cancer syndrome, and ovarian cancer associated with HNPCC (hereditary nonpolyposis colorectal cancer) syndrome. Studies have shown that these diseases may be associated with mutations in a number of tumor suppressor genes, mainly BRCA1 and BRCA2. Malfunction of the protein products of these genes have also been found to be involved in sporadic ovarian cancer, which makes up the majority of ovarian cancer cases. HNPCC-ovarian cancer associated families reveal frequent mutations in at least four genes (hMSH2, hMLH1, hPMS1, and hPMS2) involved in the repair of mismatched DNA. With ovarian cancer being such an important health issue, the push is on to design reliable screening tests to detect defective inherited or somatic alleles in individual carriers. So far, most progress has been demonstrated in those patients with family histories of the disease who are at increased risk. The ramifications of such research may impact a variety of scientific, clinical, legal, ethical, and psychosocial issues. In addition to current treatment modalities, positive results of these tests may indicate the need for increased clinical surveillance, prophylactic treatment, and genetic counseling of patients on an individual basis. It remains to be seen whether the technology can be made reliable enough to not only benefit high-risk individuals but also the general population.

Use of lonidamine to potentiate the effect of cisplatin and carboplatin on platinum resistant human ovarian cancer cells.

Lonidamine (LND), an indazole-3-carboxylic-acid derivative, is a new, relatively non-toxic, chemotherapeutic agent. LND, which interferes with energy metabolism, has been shown to potentiate the antineoplastic effects of chemotherapeutic agents and radiation. In this study, we evaluated the effect of LND in combination with cisplatin (DDP) or carboplatin (CARBO) on platinum resistant ovarian cancer cells. The ovarian cancer cell line BG-1 was selected as platinum resistant cell line, defined as cell line with survival fraction >50% at 0.5 peak plasma concentration (PPC). Cells were treated during the proliferative phase of cell growth with DDP and CARBO using doses between 0.1 and 1x (x = PPC). PPC of DDP = 2.5 mu g/ml, PPC of CARBO = 28 mu g/ml. Cells were also treated with LND at doses varying between 10 and 100 mu g/ml (PPC 20-50 mu g/ml). Drugs were used as single agents and in combination. Experiments were performed by treating the cells with DDP or CARBO for 90 min and with LND continuous exposure or 90 min only. The ATP cell viability assay was used to assess the antiproliferative effect of the drugs tested. Experiments were repeated at least 3 times. The synergistic interaction formula for anticancer agents and the t-test were used for the analysis of the results. LND was shown to be effective when used in continuous exposure only (IC50 = 0.58). The IC50 of DDP was 1.1 and the IC50 of CARBO was 0.64. Significant dose related antiproliferative effect of LND alone, as well as DDP and CARBO cytotoxicity potentiation was observed (p<0.05). LND was shown to have synergistic effect when combined with platinum compounds to treat ovarian cancer cells at doses of 20 and 30 mu g/ml. These doses are achievable in patients. LND, a relatively new antineoplastic agent with good clinical tolerance, has been shown to synergistically potentiate the antiproliferative effect of platinum compounds on platinum resistant ovarian cancer cells. LND is an agent of potential use for the treatment of ovarian cancer patients in combination with DDP or CARBO.

Ovarian cancer in women with prior hysterectomy: a 14-year experience at the University of Miami.

Between 1977-1990, 755 women were evaluated and treated for ovarian cancer at the University of Miami/Jackson Memorial Medical Center. Ninety-five of them (12.6%) had previously undergone hysterectomy with preservation of one or both ovaries. Sixty women (7.9%) had undergone hysterectomies after the age of 40. Review of the literature reveals a 4.5-14.1% incidence of prior hysterectomy in women developing ovarian cancer. Prophylactic oophorectomy in women undergoing hysterectomy at age 40 or older would have prevented 138 of 2632 cases (5.2%) of ovarian cancer in a combined literature series. Applied nationally, such an approach could be expected to prevent over 1000 cases of ovarian cancer annually. We recommend routine prophylactic oophorectomy in all women undergoing hysterectomy after the age of 40. This strategy would have prevented 60 cases of ovarian cancer treated at the University of Miami during the past 14 years.

Gestational trophoblastic disease in a fifty-one year old woman.

Molar pregnancy has always been of interest to physicians because of the diagnostic and management challenges it presents. Its occurrence in patients older than 50 years of age is rare and misdiagnosis is common. A 51 year old black female presented to the gynecology emergency room with vaginal bleeding for twenty days. She was diagnosed with a molar pregnancy by a pelvic ultra-sound. Prior to presenting to the emergency room she had a negative work-up for hyperthyroidism, including a biopsy of a benign thyroid nodule and was also started on Inderal for new onset hypertension. She underwent a primary hysterectomy and subsequently required five courses of actinomycin D for plateauing of the BhCG. The different forms of presentation of gestational trophoblastic disease should be kept in mind so that the diagnosis can be made promptly and appropriate treatment started early, especially in patients with advanced age.

Use of interferon and medroxyprogesterone acetate for the treatment of endometrial cancer.

Endometrial cancer is a hormone sensitive tumor. Response rate to progestational therapy is related to steroid receptor expression of the tumor. Interferons have been shown to enhance hormonal receptors. In this study the effect of four different interferons and medroxyprogesterone acetate (MPA), on three human endometrial cancer cell lines (AE-7, HEC-1A and HEC-1B), was studied. The ATP cell viability assay was used to measure the antiproliferative activity of the agents used. Synergistic effect was noted only when interferons and MPA were used in combination for the treatment of AE-7, which is the only cell line with a high baseline level of progesterone receptors. These observations indicate that the use of interferons and MPA may have a role for the treatment of endometrial cancer patients with progesterone receptor positive cells.

Advanced mucinous adenocarcinoma in pregnancy.

The incidence of masses in pregnancy is estimated to occur in 1/81 to 1/2,500 pregnancies. The development of colorectal carcinoma during pregnancy is a more rare event, with less than 30 cases above the peritoneal reflection reported in the last 70 years. The differential diagnosis of mucinous adenocarcinoma of ovarian vs. gastrointestinal origin is often difficult. We report a pregnant patient affected by advanced colorectal cancer, who presented with an asymptomatic unilateral adnexal mass on ultrasound. A 28-year old woman was referred to our hospital after a routine ultrasound examination at 26 weeks gestation showing a right adnexal mass. At elective exploratory laparotomy, the patient was found to have metastatic mucinous adenocarcinoma. Diagnostic and treatment choices of such a cancer in a pregnant patient were explored. The final diagnosis of colorectal cancer was made only at the time of a subsequent emergency laparotomy. The goal of an obstetrician/gynecologist and other care givers of pregnant patients, is to achieve a healthy mother and child. Unfortunately, physicians may unwillingly sacrifice the health of the mother by denying or delaying her procedures or treatments simply because she is pregnant. It is especially important in the case of adnexal masses and their related pathology, due to the difficulty in detection and management of such cases during pregnancy, that doctors actively assume the responsibility of assuring that pregnant patients receive the proper care they need.

Urinary diversion in gynecologic oncology.

Urinary diversion in gynecology is performed primarily in conjunction with cancer surgery, but at times, it is required for women with intractable urinary fistulas or other urologic disorders. After 1950, ileal conduits replaced ureterosigmoidostomies as the most widely used form of urinary diversion. Transverse colon conduits have gained popularity because these nonirradiated bowel segments offer less risk for postoperative urinary leaks and small bowel complications associated with bowel and ureteral anastomoses. In 1978, Kock et al described the use of detubularized segments of ileum and the intussuscepted nipple valves to create a continent pouch that is still advocated by urologists in some centers. Ileocolonic continent pouches, originally suggested in 1908, have received considerable attention in the past 10 to 15 years because of ease of construction, lower revision rates, and higher continence rates compared with the Kock ileal pouches. At the Division of Gynecologic Oncology at the University of Miami, the authors have been using the Miami pouch as the preferred form of continent urinary diversion since 1988, with acceptable results. Women who need urinary diversion can be offered at least two major choices: (1) the traditional bowel (ileum or colon) conduit, which requires an external ostomy appliance, or (2) a continent pouch, such as the Miami ileocolonic reservoir. In choosing between non-continent and continent conduits, the patients must be made aware that the continent pouches are available in only a few centers in the United States and carry a slightly higher risk for complications because of the relatively higher complexity. Nonetheless, data strongly suggest that most of these complications can be managed noninvasively and that these patients retain a closer to normal quality of life. The age, disease status, and general health of the woman and the likelihood of her long-term survival after diversion weigh heavily in the final decision.

Radical hysterectomy for cervical cancer: hysterectomy before pelvic lymphadenectomy or vice versa?

The technique for radical abdominal hysterectomy (RAH) and lymphadenectomy (LND) for patients with cervical cancer has been well described. Whether RAH should be performed before or after pelvic lymph node dissection (PLND) is a controversial issue. This study compared the two procedures performed at the same institution. Patients treated with type III RAH for cervical cancer stage IB-IIA at our institution between 1987 and 1995 were included in this study. Only patients who underwent para-aortic lymph node dissection (PALND) first, followed by PLND and then RAH (Group A) or RAH and then PLND (Group B) were included. Clinical and surgical information including intraoperative and postoperative complications was collected. Operative reports were used to identify the patients who had RAH performed before PLND or vice versa. Data analysis was obtained using unpaired t-test with significance set at P < 0.05. Complete information was obtained for 314 patients. The results of Group A (157 patients) and Group B (157 patients) were as follows: mean age = 45.3 and 44.8 (P = 0.73); mean weight = 149 and 149 lb.; mean length of stay = 10 and 8 days (P < 0.0001); mean operative time = 230 and 172 mins (P = 0.004); mean estimated blood loss (EBL) = 1,238 and 1098 cc (P = 0.21); mean number of PALN removed = 7 and 6 (P = 0.06); mean number of PLN removed = 28 and 26 (P = 0.24). No statistical difference in major intraoperative and postoperative complications was observed. The most common complication was postoperative fever (53/157 in Group A and 49/157 in Group B). Radical hysterectomy can be safely performed either before or after PLND. The number of pelvic lymph nodes removed, as well as the EBL and the intraoperative complications are similar and are not affected by the operative time. The surgeon should decide the sequence of the procedures accordingly to his/her personal preference.

Evaluation of the Pfannenstiel incision for radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy.

Radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy (RAH/P + PAL) has classically been described through a low midline vertical incision. Transverse incisions have been used with good results for various pelvic surgical procedures. Hesitancy has been encountered when utilizing these transverse incisions in gynecologic oncology patients. In most studies, muscle-splitting transverse incisions seem to be of equal efficacy as midline vertical incisions in regards to surgical exposure and clinicopathologic data obtained and are known to be superior in cosmesis and postoperative morbidity. A retrospective chart review was performed to identify 25 patients who underwent RAH/P + PAL for stage I carcinoma of the cervix from 1990 to 1998 through a nonmuscle splitting (Pfannenstiel) abdominal incision. All patients were seen and had follow-up in the Division of Gynecologic Oncology, University of Miami School of Medicine/Jackson Memorial Medical Center (Miami, FL). Data were collected on various clinical and surgical parameters including height/weight, operative time, blood loss, number of lymph nodes obtained, length of hospital stay, and postoperative complications. Analysis of the data revealed that operative time and average blood loss were within acceptable parameters. The yield at lymphadenectomy for pelvic and para-aortic lymph nodes was also respectable. Postoperative complications were minimal and there were no wound complications reported. Therefore, the Pfannenstiel incision can be safely utilized in a select group of patients undergoing RAH/P + PAL.

Gynecologic laparoscopy.

Laparoscopic techniques are slowly gaining acceptance in gynecologic oncology. Usage in early stage endometrial and ovarian cancer and in the evaluation of suspicious adnexal masses is increasing, but large prospective series have not been performed. Laparoscopic procedures carry a steep learning curve and there are a limited number of centers currently performing these procedures for oncologic indications. It seems clear, however, that for the well-selected patient, in experienced hands, laparoscopic procedures in gynecologic oncology offer many potential benefits.

Brachial plexus lesions in hemiplegics.

Nine hemiplegic patients with muscular atrophy in the paralysed upper limb have been subjected to a clinical and electrophysiological investigation. In all but one case with circumscribed muscular atrophy in the shoulder girdle or the small hand muscles electromyography showed evidence for denervation. The findings are consistent with traction neuropathy on the brachial plexus and its branches in spastic or hypermobile shoulder joints.

[The significance of exteropropioception (tactile-kinesthetic system) for verbal and nonverbal behavior following brain lesions]. / Die Bedeutung der Extero-Propriozeption (taktil-kinästhetisches System) für das verbale und nichtverbale Verhalten nach Hirnläsion.

Brain performance is organized by complex feedback networks. Lesions disrupt and short-circuit the older phylogenetic behaviour. Recovery takes place by bridging over, essentially induced by sensory input. Given its plurality, exteroproprioception is the most powerful modality of input. A model of its stimulation ("guidance of movements in problem-solving every day tasks") reaching attention and cooperation of heavily injured patients is summarized, and arguments in favour of it are advanced.

[Cyclic sciatica and extrauterine endometriosis]. / Zyklische Ischialgie und extrauterine Endometriose.

Cyclic sciatica caused by ectopic endometriosis is an unusual cause of compression of a lumbar root, of the sciatic nerve or its plexus. A 38-year-old patient is presented with a history of menstruation associated with right-sided sciatica, which gradually developed over a 2 1/2-year period into disabling constant pain and a lumboradicular syndrome with signs of S1-root involvement. Suggested compression of the sciatic nerve by ectopic endometriosis in the sciatic notch region could be confirmed by CT and MR, by prompt response to hormonal suppression of ovarian function and by regression of the radiological findings. If the history of cyclic pain, local tenderness on deep palpation and the onset of referred pain in the buttock had been observed at the beginning, unnecessary and costly medico-technical procedures delaying diagnosis and treatment (including unnecessary physiotherapy) could have been avoided. Cyclic sciatica is discussed in a review of literature, and possibilities of treatment are discussed.

Surgical management of advanced and recurrent cervical cancer.

Since the early 1940s, the incidence of cervical cancer has dramatically decreased due in large part to the work of Papanicolaou and Traut. Successful treatment can now be done using simple or radical surgical intervention for early invasive lesions and radiation therapy for more advanced lesions. However, despite current advances in screening and early treatment, local recurrences still happen and are difficult to treat. The natural history of cervical cancers is that of a slowly growing, locally invasive tumor. As such, it lends itself to radical surgical resection in selected patients prior to distant metastasis. Current advances in intraoperative and postoperative monitoring, as well as improved surgical techniques and devices, have decreased the morbidity and mortality of radical surgical procedures to acceptable levels. Current data associated with these procedures for advanced or recurrent cervical cancer are described.