Resection of recurrent ovarian or fallopian tube carcinoma involving the liver

OBJECTIVES: Patients who develop recurrent ovarian of fallopian tube carcinoma involving the liver often have disease refractory to chemotherapy and carry a poor prognosis. The impact of aggressive resection in this patient population is unclear. METHODS: From 1/1988 to 9/2001, 24 patients with recurrent ovarian or fallopian tube carcinoma who underwent complete gross resection or optimal debulking of their hepatic metastases and disease at other sites were identified from prospective databases at a single institution. RESULTS: The median age of patients was 53 years old, and the median interval between primary diagnosis and liver resection was 69 months. All patients had primary resection or cytoreduction and chemotherapy as part of their initial treatment. Subsequent hepatic resections included trisegmentectomy (2), lobectomy (2), segmentectomy (17), and wedge resection (3). Additional resection of disease outside the liver was performed in 18 patients (75%). Twenty-one patients (88%) had removal of all gross disease, and three patients (13%) had optimal tumor debulking to less than 1 cm. Eighteen patients recurred with sites of initial recurrence, including the abdomen and pelvis (14), spine/paraspinal region (2), lung (1), and liver (1). Overall median survival was 62 months after hepatic resection with a range of 6 to 94 months. Fourteen patients were alive at the time of last follow-up, and 10 had no evidence of disease. No significant prognostic factors for overall survival could be identified on univariate analysis. CONCLUSIONS: In highly selected patients with recurrent ovarian or fallopian tube carcinoma involving the liver, hepatic resection along with resection of other gross disease may lengthen survival and should be considered as a treatment option.     

Breast cancer metastatic to abdomen and pelvis: role of surgical resection

OBJECTIVE: The purpose of this study was to describe the characteristics and outcome of women with metastatic breast cancer to the abdomen and pelvis, and to assess the role of surgical resection of abdominal and pelvic metastasis in this disease. METHODS: We retrospectively reviewed the medical records of 59 women with documented metastatic breast cancer to the abdomen or pelvis who had exploratory surgery by the Gynecology Service between 1986 and 2001. RESULTS: Exploratory surgery was performed a median of 5 years (range, 0-25 years) after initial diagnosis of breast cancer. Median survival from diagnosis of abdominal disease was 23 months, and 5-year survival was 24%. Survival was 36 months for optimally debulked patients (<2 cm of residual disease) and 20 months for suboptimally debulked patients (P = 0.07). Patients diagnosed 5 or more years after initial breast cancer diagnosis had a median survival of 36 months versus 17 months if diagnosed earlier (P < 0.01). On multivariate analysis the time to recurrence of breast cancer in the abdomen and optimal debulking were both significant variables. Hazard ratio for dying of disease if recurring before 5 years was 2.7 (CI 1.45-5.03) [P < 0.01]. Hazard ratio for dying of disease if suboptimal debulking was achieved was 2.14 (CI 1.13-4.02) [P = 0.02]. CONCLUSIONS: The disease pattern of metastatic breast carcinoma to the abdomen and pelvis does not appear to effect survival. Survival in patients where optimal debulking is achieved and in those recurring late is improved. Surgical resection of metachronous metastatic breast cancer to the abdomen and pelvis may be an important component of the management of this disease and should be considered in candidate patients.     

Palliative surgery for bowel obstruction in recurrent ovarian cancer:an updated series

OBJECTIVE: Intestinal obstruction is a frequent sequela of recurrent ovarian cancer. Previous series report median survivals of 3-6 months in patients undergoing surgery for obstruction due to recurrent disease. We analyze a contemporary series of patients to determine if outcomes have changed in patients undergoing palliative surgery. METHODS: We retrospectively reviewed all patients undergoing surgery for intestinal obstruction due to recurrent ovarian cancer from 1994 to 1999. RESULTS: During the study period, 68 operations were performed on 64 patients. Mean age at the time of obstruction was 57.3 years. Mean time from original diagnosis of ovarian cancer to obstruction was 2.8 years. Surgical correction (intestinal surgery performed for relief of obstruction) was attained in 57 of 68 (84%) cases. Successful palliation (the ability to tolerate a regular or low-residue diet at least 60 days postoperatively) was achieved in 71% of cases where surgical correction was possible. The rate of major surgical morbidity was 22%. There was one death from pulmonary embolus and one from peritonitis. Two other deaths occurred due to progression of disease, for an overall perioperative mortality rate of 6%. Postoperative chemotherapy was administered in 45 of 57 (79%) cases where surgical correction was possible. The median survival of the entire cohort was 8 months. If surgery resulted in successful palliation, median survival was 11.6 months, versus 3.9 months for all other patients (P <.01). CONCLUSIONS: The majority of our patients undergoing surgery had successful palliation, and were able to receive further chemotherapy. They were discharged home, and could tolerate solid food.     

GAT-1 and reversible GABA transport in Bergmann glia in slices

Although glial GABA uptake and release have been studied in vitro, GABA transporters (GATs) have not been characterized in glia in slices. Whole cell patch-clamp recordings were obtained from Bergmann glia in rat cerebellar slices to characterize carrier-mediated GABA influx and efflux. GABA induced inward currents at -70 mV that could be pharmacologically separated into GABA(A) receptor and GAT currents. In the presence of GABA(A/B/C) receptor blockers, mean GABA-induced currents measured -48 pA at -70 mV, were inwardly rectifying between -70 and +50 mV, were inhibited by external Na(+) removal, and were diminished by reduction of external Cl(-). Nontransportable blockers of GAT-1 (SKF89976-A and NNC-711) and a transportable blocker of all the GAT subtypes (nipecotic acid) reversibly reduced GABA-induced transport currents by 68 and 100%, respectively. A blocker of BGT-1 (betaine) had no effect. SKF89976-A and NNC-711 also suppressed baseline inward currents that likely result from tonic GAT activation by background GABA. The substrate agonists, nipecotic acid and beta-alanine but not betaine, induced voltage- and Na(+)-dependent currents. With Na(+) and GABA inside the patch pipette or intracellular GABA perfusion during the recording, SKF89976-A blocked baseline outward currents that activated at -60 mV and increased with more depolarized potentials. This carrier-mediated GABA efflux induced a local accumulation of extracellular GABA detected by GABA(A) receptor activation on the recorded cell. Overall, these results indicate that Bergmann glia express GAT-1 that are activated by ambient GABA. In addition, GAT-1 in glia can work in reverse and release sufficient GABA to activate nearby GABA receptors.     

Epithelial ovarian carcinoma and European birthplace of grandparents

OBJECTIVE: The aim of this study was to determine whether the risk of ovarian carcinoma was related to latitude or to genetically based patterns of European geographic origin. PATIENTS AND METHODS: We studied the countries of origin of European-born grandparents of 168 newly diagnosed patients in two hospitals in New York City, compared with 159 controls from similar neighborhoods. We measured the risk of this cancer associated with having one or more white, non-Jewish grandparents born in North Europe versus none or in South Europe versus none. We also classified geographic origins in other ways to reflect the two main trends in genetic variations between Europeans mapped by Cavalli-Sforza et al. (The History and Geography of Human Genes, Princeton University Press, Princeton, 1994). Unconditional logistic regression was used to control for age, parity, years of use of oral contraception, age at menarche, education, Catholic religion, and area of residence and for numbers of Jewish grandparents, siblings, and first-degree relatives with breast or ovarian cancer. RESULTS: Approximately half of the subjects had least one white, non-Jewish grandparent born in Europe. There was no significant effect of ancestral latitude: among women born in the United States the odds ratio (OR) and 95% confidence limits associated with North European ancestry were 0.87 (0.47--1.63) compared with a reference group of women with no such ancestry. The corresponding OR for South Europe was 0.73 (0.39--1.74). Using the genetically based classifications of countries of origin, however, we found significant differences between cases and controls; ancestries from North West Europe and those from countries concentrically near Spain showed lower risks of ovarian carcinoma. CONCLUSIONS: The results support the hypothesis that the previously observed effects of latitude must act through environmental effects or through gene-environment interactions. Other variations in risk related to geographic origins are consistent with known patterns of genetic differences, but require confirmation in larger, population-based studies.     

Risk of endometrial carcinoma associated with BRCA mutation

OBJECTIVE: Inherited mutations in the BRCA1 or BRCA2 genes are associated with a greatly increased lifetime risk of breast and ovarian cancers and a modestly increased risk of several other cancer types. Several case reports of endometrial carcinoma in women with a BRCA mutation have led to speculation regarding the effect of these genes on the risk of endometrial cancer. The purpose of this study was to test the hypothesis that germline mutation of a BRCA gene is associated with an increased risk of endometrial carcinoma. METHODS: A retrospective cohort of 199 consecutive Ashkenazi Jewish patients with endometrial carcinoma was identified from a 12-year period at this institution. All were genotyped for the three BRCA founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2) that exist in this population, and the case frequency was compared to the known population frequency of these mutations. Additionally, endometrial carcinomas occurring in patients with BRCA mutations were assessed for somatic loss of the wild-type BRCA allele. RESULTS: Germline BRCA mutations were identified in 3 (1 in BRCA1 and two in BRCA2) of 199 (1.5%) patients, compared to a frequency of 2.0% in this population generally. A relative risk of endometrial carcinoma associated with BRCA mutation, as estimated by the odds ratio, was calculated as 0.75 (95% CI = 0.24--2.34; P = 0.6). Loss of the wild-type BRCA allele was observed in two of three tumors associated with a BRCA mutation. CONCLUSIONS: For individuals with a germline BRCA mutation, the lifetime risk of endometrial carcinoma is not increased.     

Antenatal diagnosis of renal abnormalities: a review of the state of the art

Antenatal diagnosis of fetal abnormalities is an important component of genetic counseling. This paper reviews the indications and techniques of antenatal diagnosis of renal and urinary tract abnormalities, and outlines their follow-up and modes of treatment.     

An early comparison of clinical and mechanical aspects of hybrid and uncemented hip resurfacing

Hip resurfacing is a popular operation for hip joint arthritis. It has been performed using hybrid and uncemented components. We aim to compare the two techniques functionally and mechanically over a 2 year post-operative period. We studied anteroposterior (AP) radiographs from 30 patients who had undergone hybrid hip resurfacing and 30 patients who had undergone uncemented hip resurfacing using the transgluteal approach to the hip. We measured the acetabular offset, femoral offset, stem/shaft angle, medialization of the cup, head/neck ratio, cup height, leg length and the implant seating pre-operatively, immediately post-operatively, 1 and 2 years post-operatively. Harris Hip Scores were performed pre-operatively and at 1 year post-operatively. There was no significant loss of offset and no femoral neck thinning at 2 years post-operatively with no loss of leg length. We note a smaller femoral offset and a reduction on average of 2.87 mm in seating of the femoral cap in the uncemented group when compared to the hybrid group at the 1 year postoperative review. Thus, we attribute to movement of the femoral component in the first year postoperatively, and as such restoration of the femoral offset to the pre-operative level. Both groups showed an equal significant improvement in the Harris Hip Scores at the 1 year postoperative period when compared to the pre-operative score. We conclude that uncemented hip resurfacing is statistically as good as the hybrid hip resurfacing, with a stable uncemented femoral component relying on biological cancellous fixation rather than cement fixation. We also note that in both groups, no evidence of neck thinning was noted at the 2 year postoperative period.