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Biomedical subjects
Publications and source records attributed to U Beller.
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BACKGROUND: Port-site metastasis (PSM) following laparoscopic surgery for cancer is being increasingly recognized as a potential problem; the majority of cases appear following laparoscopy for a pelvic mass that subsequently proved to be malignant or in the case of a disseminated intraperitoneal disease. The rare cases of PSM following laparoscopy for endometrial and cervical cancer have all been associated with the presence of regional lymph node metastasis or disseminated disease in the peritoneal cavity. We present here a case report of PSM in the absence of spread beyond the primary tumor. CASE: A 48-year-old woman with stage IA1 adenocarcinoma of the cervix was treated with laparoscopically assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic node dissection. The pathologic study revealed an endocervical adenocarcinoma confined to the cervix with negative lymph nodes. Nine months postoperatively, a cutaneous metastasis at the port-site was diagnosed. This was treated with wide local excision of the recurrence and the port-site track. Explorative laparotomy and para-aortic node sampling showed no evidence of recurrence elsewhere. CONCLUSION: This case emphasizes the risk for PSM in laparoscopic surgery performed for early stage disease.
OBJECTIVES: Type II endometrial carcinomas are estrogen-independent and have adverse histologic features and a substantially poorer prognosis. No risk factors have been identified. Interestingly, there is a striking clinical and histopathological similarity between serous papillary carcinomas of the ovary (OSPC), endometrium, and peritoneal cavity, suggesting a common oncogenic mechanism. Several common molecular alterations were found using molecular comparative analysis of OSPC and uterine serous papillary carcinoma (USPC). Germline mutations in the BRCA1 tumor suppressor gene predispose to breast and ovarian cancer but no association with sporadic endometrial cancer has been found. A family of Ashkenazi Jewish origin, in which one sister was first diagnosed with USPC and the second diagnosed with OSPC, led to the hypothesis that a BRCA mutation may contribute to USPC. METHODS: Genomic DNA from both patients as well as two unaffected siblings was analyzed for the three mutations common in Ashkenazi Jews. Loss of heterozygosity (LOH) analysis was performed on DNA extracted from USPC tumor tissue. RESULTS: Both affected sisters tested positive for BRCA1 5382insC germline mutation. LOH analysis confirmed the results. CONCLUSIONS: We present a breast-ovarian cancer family including two sisters with advanced serous papillary carcinomas of endometrial and ovarian origins, carrying the same BRCA1 mutation (5382insC). LOH analysis on USPC tumor DNA showed loss of the wild-type allele, suggesting a causal relationship between the germline BRCA1 mutation and USPC. We believe a study examining BRCA1 mutations in a large cohort of women with this high-risk endometrial carcinoma is warranted. A positive finding may have implications for surveillance and prophylactic surgery in carriers of BRCA1 mutations.
Female urinary stress incontinence diminishes the quality of life of about 5% of women. It is usually dealt with by surgery to correct the relaxed pelvic floor, the cause of the incontinence. Tension-free vaginal tape is used in a newly described procedure. It consists of the vaginal introduction of a prolene needle-guided mid-urethral sling. The procedure is easy to perform under local anesthesia, recovery is rapid, and results are similar to those of other effective operations. We report 44 patients who underwent this type of surgery. There were no significant complications. The early results were good and although the follow-up has been short, we believe that experience with this operation will play an important role in the treatment of urinary stress incontinence.
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To better understand the role of germline BRCA mutations in ovarian cancer in Ashkenazi Jews, we tested 29 consecutive patients admitted to our service for the three mutations common in this ethnic group. These mutations are 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2. Six patients had both breast and ovarian cancer, and 23 had ovarian cancer only. In the first group, all women had germline mutations, 2 with each mutation. Of 23 ovarian cancer patients, 11 were carriers (48%): 6 of 185delAG, 2 of 5382insC, and 3 of 6174delT. Regarding family history, of 13 women with no family history, 3 (23%) were carriers. Of 10 women with any family history of breast or ovarian cancer, 8 (80%) were carriers. We discuss possible explanations for this surprisingly high carrier rate, including a high proportion of familial disease coupled with lack of adequate family history, lower penetrance than previously expected, or increasing penetrance in recent generations due to nongenetic factors. Our data suggest that genetic testing is merited in all Ashkenazi women with ovarian cancer, regardless of family history.
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Germ-line BRCA1 and BRCA2 mutations account for most of familial breast-ovarian cancer. In Ashkenazi Jews, there is a high population frequency (approximately 2%) of three founder mutations: BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. This study examined the frequency of these mutations in a series of Ashkenazi women with ovarian cancer unselected for family history, compared with the frequency of these mutations in families ascertained on the basis of family history of at least two affected women. Penetrance was compared, both according to the method of family ascertainment (i.e., on the basis of an unselected ovarian cancer proband vs. on the basis of family history) and for the BRCA1 founder mutations compared with the BRCA2 6174delT mutation. There was a high frequency (10/22; [45%]) of germ-line mutations in Ashkenazi women with ovarian cancer, even in those with minimal or no family history (7/18 [39%]). In high-risk Ashkenazi families, a founder mutation was found in 59% (25/42). Families with any case of ovarian cancer were significantly more likely to segregate a founder mutation than were families with site-specific breast cancer. Penetrance was higher in families ascertained on the basis of family history than in families ascertained on the basis of an unselected proband, but this difference was not significant. Penetrance of BRCA1 185delAG and BRCA1 5382insC was significantly higher than penetrance of BRCA2 6174delT (hazard ratio 2.1 [95% CI 1.2-3.8]; two-tailed P = .01). Thus, the high rate of germ-line BRCA1/BRCA2 mutations in Ashkenazi women and families with ovarian cancer is coupled with penetrance that is lower than previously estimated. This has been shown specifically for the BRCA2 6174delT mutation, but, because of ascertainment bias, it also may be true for BRCA1 mutations.
OBJECTIVE: To determine the role of BRCA1 185delAG mutation in ovarian carcinogenesis. DESIGN: Genetic testing of a subset of cases from an ongoing study of ovarian cancer and of controls. SETTING: A community-based case-control incidence study. SUBJECTS: Seventy-nine patients with ovarian cancer, 62 hospitalized women without cancer (controls), and 120 healthy women participating in a fragile X screening program (also controls), examined for the presence of germline BRCA1 185delAG mutation. MAIN OUTCOME MEASURES: Polymerase chain reaction-amplified BRCA1 exon 2 fragments generated from patients' and controls' blood samples, analyzed by heteroduplex gel shift assay and direct sequence analyses. RESULTS: The 185delAG mutation was detected in 38.9% (7/18) of ovarian cancer patients with familial history, and 13.1% (8/61) of family history-negative ovarian cancer cases. Only 1 carrier was detected among the 120 healthy controls, and none in the hospital controls. A significant difference in mutation carrier rates between family history-negative cases and control groups of 120 and 62 subjects was identified (Fisher exact test, P=.001 and P=.003, respectively). The median age (+/-SE) at disease diagnosis was lower among both familial and family history-negative mutation carriers, as compared with mutation-negative, family history-negative cases--50 (+/-1.4) vs 60.5 (+/-3.5) years old, respectively (hazard ratio, 1.68; 95% confidence interval, 0.94-3.01). CONCLUSIONS: Our data are preliminary but suggest that BRCA1 185delAG germline mutation is frequent in Israeli ovarian cancer patients, irrespective of family history, and may confer an early-onset phenotype of ovarian cancer
Although diagnostic ultrasonography is playing an increasing role in the investigation of the patient with suspected ectopic pregnancy (EP), it has significant limitations in the very early stages of pregnancy. By sonographically exploring the intrauterine echoes in 45 cases of documented EP, we demonstrated a unique pattern in 28 cases (62.2%). A well-defined spheric structure forming an endometrial three-layer (ETL) pattern was seen, probably formed by a midline echo between the two adjacent edematous proliferative layers of the endometrium, the latter resembling the late proliferative endometrium. In 17 patients with a proved EP (37.8%), the ETL pattern was not demonstrated. However, the ETL was not demonstrated in all 40 cases of early intrauterine pregnancy and all 50 cases of miscarriage. These findings suggest a 100% specificity and a sensitivity of 62.2% for the ETL pattern in the diagnosis of EP.
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Women undergoing ultrasound scanning for the detection of ovarian cancer benefit psychologically from the examination, which has been shown to reduce levels of anxiety, depression, hostility and complaints about somatic symptoms. However, it is not completely clear what aspects of the ultrasound examination are responsible for these effects, and how these beneficial psychological effects vary under different circumstances. This study examined, in particular, the effect of various levels of feedback on patients' anxiety levels before and after ultrasound examination. Two hundred and seven women were randomly assigned to two different experimental conditions: high feedback and low feedback. The subjects' levels of anxiety (both trait and state anxiety) were measured immediately before and after the ultrasound examination. The women's individual risk factors for ovarian cancer were also recorded. This study showed a significant decrease in the level of trait anxiety following ultrasound scanning. The decrease in anxiety did not relate to the level of feedback provided to the patients, nor to the woman's degree of risk for ovarian cancer. The results are discussed in terms of possible implications for clinical care and the allocation of resources in the medical system.
The association of retropubic colposuspension for the treatment of urinary stress incontinence with genital prolapse has been reported previously. Described here is a case of an 83-year-old patient who had a colponeedle suspension and was readmitted because of genital prolapse 3 weeks after surgery. This case emphasizes the need for proper evaluation of the whole pelvic floor prior to any surgical treatment for urinary incontinence, and addition of appropriate surgical measures aimed to avoid later genital prolapse, if necessary.
A 39 year-old patient with long-standing diagnosis of pelvic endometriosis had been treated for over twenty years with oral contraceptives (OCs). A year prior to admission to the gynecological ward, an ultrasonographic examination revealed three hepatic lesions, which were not reported in previous liver sonography. These lesions progressed during OC use, over the next six months. Liver function tests were normal. Liver scan, CT and ultrasound imaging techniques supported the diagnosis of solid hepatic tumors. These lesions developed concomitantly to long-term use of OCs, therefore discontinuation of therapy was mandatory. Six months later, the patient was hospitalized due to pelvic pain. She underwent total abdominal hysterectomy and left salpingo-oophorectomy (the right adnexa had been removed years before). Due to the patient's young age, hormone replacement therapy was indicated. The preferred preparation was transdermal estradiol due to the fact that systemic absorption has no hepatic first-pass effect and therefore exerts minimal influence on liver enzymes and functions. Serial ultrasonographic examinations, performed while under treatment with transdermal estradiol, showed complete regression of the hepatic lesions over a period of two years. Our report demonstrates regression of multifocal hepatic tumors despite transdermal estradiol replacement therapy.
We present a case report of a 56 year old female suffering from recurrence of simultaneous endometrial and ovarian carcinomas, confined to distant neck and axillary lymph nodes. Resistance of the tumor to conventional chemotherapy and radiotherapy was followed by experimental Paclitaxel treatment which led to complete regression of all metastatic foci.