Late effects in patients with Fanconi anemia following allogeneic hematopoietic stem cell transplantation from alternative donors.

Hematopoietic stem cell transplantation (HSCT) is curative for hematological manifestations of Fanconi anemia (FA). We performed a retrospective analysis of 22 patients with FA and aplastic anemia, myelodysplastic syndrome or acute myelogenous leukemia who underwent a HSCT at Memorial Sloan Kettering Cancer Center and survived at least 1 year post HSCT. Patients underwent either a TBI- (N=18) or busulfan- (N=4) based cytoreduction followed by T-cell-depleted transplants from alternative donors. Twenty patients were alive at time of the study with a 5- and 10-year overall survival of 100 and 84% and no evidence of chronic GvHD. Among the 18 patients receiving a TBI-based regimen, 11 (61%) had persistent hemochromatosis, 4 (22%) developed hypothyroidism, 7 (39%) had insulin resistance and 5 (27%) developed hypertriglyceridemia after transplant. Eleven of 16 evaluable patients (68%), receiving TBI, developed gonadal dysfunction. Two patients who received a TBI-based regimen died of squamous cell carcinoma. One patient developed hemochromatosis, hypothyroidism and gonadal dysfunction after busulfan-based cytoreduction. TBI appears to be a risk factor for malignant and endocrine late effects in the FA host. Multidisciplinary follow-up of patients with FA (including cancer screening) is essential for early detection and management of late complications, and improving long-term outcomes.

Treatment of menorrhagia in women undergoing hematopoietic stem cell transplantation.

The management of uterine bleeding in female transplant patients over a 3-year period at our institution was reviewed. A total of 33 females who had undergone allogeneic hematopoietic stem cell transplant were identified as having received gynecologic consultation for the diagnosis of menorrhagia. Hormone therapy achieved a resolution of symptoms in 32 (97%) of the patients, and 26 (79%) required only one hormone regimen. Following resolution of symptoms, transition to standard-dose oral contraceptive pills as maintenance therapy prevented recurrent menorrhagia due to high circulating estrogen levels. Alternatives for patients who are unable to tolerate oral administration and those with hepatotoxicity are also discussed.

Screening for ovarian cancer: what we know, what we need to know.

The majority of women with ovarian cancer present with advanced-stage disease. Women with early-stage ovarian cancer have a much better chance of achieving a cure than do women with late-stage disease. This difference makes screening for ovarian cancer, with the hope of detecting it in its presymptomatic state, an attractive concept. Unfortunately, efforts to demonstrate that screening for ovarian cancer in the general population can decrease mortality have been disappointing. Current screening techniques do not have high enough sensitivity and specificity to be applied to the general population, because the low prevalence of the disease in the general population leads to very low positive predictive values for the available screening tests. However, applying current screening strategies to certain high-risk populations (women who carry mutations in the BRCA1 or BRCA2 genes, or with strong family histories of breast/ovarian cancer) is a reasonable approach and may result in acceptably high positive predictive values. This article discusses the results of screening studies using serum CA-125, sonography, other serum markers, and combinations of these tests. Screening for women of average risk is not recommended, although such women should be encouraged to participate in clinical trials whose end points are either the demonstration of the impact of screening on mortality, or the development of novel screening strategies. Screening with twice yearly transvaginal sonography and serum CA-125 testing is recommended for women at high risk for ovarian cancer, although prospective data are needed regarding the impact of such screening on stage of cancer detected, quality of life, and psychological distress, as well as the costs--both personal and societal--of screening.

Adnexal masses in women with breast cancer: US findings with clinical and histopathologic correlation.

PURPOSE: To correlate ultrasonographic (US), clinical, and histopathologic findings in patients with breast cancer who underwent surgery for adnexal masses evident at US. MATERIALS AND METHODS: A database search yielded 54 patients with breast cancer and with adnexal masses at US and histopathologic examinations. Clinical, US, and histopathologic findings were correlated. RESULTS: Forty (74%) patients had benign adnexal masses, and 14 (26%) had malignant masses; three patients had both benign and malignant ovarian masses. Seven patients had primary ovarian cancer, and seven had breast metastases to the ovary. All breast metastases to the ovary were bilateral solid masses at histopathologic examination and occurred in women with stage IV breast carcinoma at the time of US. Eleven ovaries with breast metastases were solid at US. The remaining three ovaries with breast metastases had cystic components at US because of hemorrhage or coexistent benign ovarian cysts. Four of seven patients with primary ovarian carcinoma had bilateral ovarian tumors, and seven of 11 ovarian carcinomas were predominantly cystic at US. No patient with primary ovarian carcinoma had stage IV breast cancer. CONCLUSION: In this small series, half the ovarian malignancies in patients with breast cancer were primary ovarian carcinomas and half were breast metastases to the ovary. Breast metastases to the ovary most frequently are bilateral solid masses at US and are associated with stage IV disease at the time of US.

Management of menopausal symptoms in the cancer patient.

In the decades since hormone replacement therapy (HRT) was introduced, there has never been more controversy surrounding it than at present. Physicians and patients are faced with many questions regarding risk and few definitive answers. This article will discuss the current health benefits associated with hormone replacement, including its beneficial effects on the cardiovascular system, osteoporosis, vasomotor symptoms, colon cancer risk, and Alzheimer's disease. Epidemiologic evidence suggesting an association between HRT, estrogen in particular, and breast cancer will also be discussed. Currently, there is no definitive evidence of a link between HRT and breast cancer risk, particularly with short-term use. Yet, only about 15% of women who would benefit from such therapy actually use it. This is due, in part, to concerns regarding breast cancer risk. For the breast cancer survivor, the current dictum is that estrogen replacement is contraindicated. For these patients and those who choose not to start HRT, the list of adequate, currently available alternatives for the many menopausal symptoms is still insufficient. Because of the known beneficial effects of HRT, its extension to patients with a history of hormone-dependent cancer may be indicated. However, randomized, controlled trials must be performed to assess the potential risks in these patients.

Predictors of distant recurrence in clinical stage I or II endometrial carcinoma treated by combination surgical and radiation therapy.

A retrospective analysis of 201 patients with clinical Stage I or II endometrial carcinoma treated by combined surgery and radiation therapy from January 1976 to December 1992 is reported. The aim of the study was to determine predictors, if any, for distant recurrence. Twenty-eight patients (13.9%) in our series developed a recurrence. The most common sites were peritoneal carcinosis (28.6%), bones (28.6%), and lungs (21.4%). Seventy-eight percent appeared within 3 years, and actuarial survival rates at 12, 36, and 60 months after recurrence were 39.2, 14.2, and 7.1%, respectively. An analysis of predictive factors significant for the development of distant recurrence was performed. Significant factors by univariate analysis were age (P = 0.019), stage (P = 0.02), grade (P = 0.014), depth of myometrial invasion (P = 0.007), lymph node involvement (P < 0.001), and peritoneal cytology (P = 0.006). A multivariate analysis of these variables showed that lymph node involvement was the strongest predictor for distant recurrence.

Etiology, prognosis and management of nuchal cystic hygroma: 25 new cases and literature review.

OBJECTIVE: To develop an algorithm for the prenatal management of patients when a cystic hygroma is diagnosed by ultrasonography. METHODS: We report a personal series of 25 cases diagnosed between 10 and 23 weeks gestation and a review of the literature comprising a total of 999 cases. We focused on the etiologies and the value of various prognostic factors in the management of cystic hygromas. These include karyotype, alpha-fetoprotein levels, sonographic findings in the fetus and within the hygroma itself, and natural history. RESULTS: According to the literature, fetal chromosomal abnormalities were associated with cystic hygromas in 62% of the cases. Turner's syndrome remains the most common (33%) but Down's syndrome, Trisomy 18 and Trisomy 13 are not rare (15, 7 and 2%). Others have Mendelian abnormalities. The prognosis remains gloomy. The literature reports that only 9% of cases result in healthy children with normal karyotypes. The remaining 91% are either terminated (89%) or liveborn (2%), but with chromosome abnormalities or various malformations. CONCLUSION: The prognostic factors associated with a poor outcome are an abnormal karyotype and associated structural malformations. Resolution of the hygroma by 20 weeks gestation suggests a good prognosis, but is not definitive. All other factors evaluated do not appear to be of prognostic value at this time. Careful analysis of these prognostic factors is very important to identify the small percentage of normal children and to advise parents effectively for a future pregnancy.