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Background and Objectives One of the major unmet needs in Breast Conserving Surgery (BCS) is a rapid and accurate margin assessment of the lumpectomy specimen. This study evaluates the ability of a novel MRI system (prototype of the ClearSight™ system; Clear-Cut Medical Ltd., Rehovot, Israel) to distinguish malignant and non-malignant tissues in freshly excised breast specimen by comparing MR measurements to histopathology results. Methods Seventy-seven samples were obtained from 22 patients undergoing BCS enrolled in the study. A T2* (T2 Star) value in milliseconds (ms) was calculated for each sample and correlated with histopathology results. Results Of the 77 samples, 35 samples were classified by histopathology as malignant and 42 as non-malignant. T2* values were significantly higher in malignant samples compared to non-malignant samples (15.3 ± 2.72 ms and 10.6 ± 1.47 ms, respectively [P

Germline mutations in the BRCA1 and BRCA2 genes are associated with a significantly increased lifetime risk for developing breast and/or ovarian cancer. However, incomplete penetrance and substantial variability in age of disease onset among carriers of the same mutation suggests the involvement of additional modifier genes and/or environmental factors. Somatic inactivating mutations in the p53 gene and genes of the p53 pathway often accompany BRCA1/2-associated tumors. Therefore, we assessed whether these genes are modifiers of penetrance. We genotyped Jewish-Ashkenazi women for functional single-nucleotide polymorphisms (SNPs) in the AKT1 (C>T rs3730358) and the PERP (C>T rs2484067) genes that affect p53-mediated apoptosis, as well as two tag-SNPs in the CHEK2 (C>T rs743184) and the ZBRK1/ZNF350 (G>A rs2278414) genes that encode for proteins involved in growth arrest following DNA damage. The study population included 138 healthy women, 148 breast/ovarian cancer BRCA1/2 mutation carriers, 121 asymptomatic BRCA1/2 mutation carriers, and 210 sporadic noncarrier breast cancer patients. Utilizing lambda(2) and Kaplan-Meier analysis revealed a hazard ratio (HR) of 3.23 (95% CI: 1.44-54, P = 0.0184) for the TT genotype of AKT (rs3730358), HR = 2.105 (95% CI: 1.049-7.434, P = 0.039) for CHEK2 CC genotype (rs743184), and HR = 2.4743 (95% CI: 1.205-11.53, P = 0.022) for the AG genotype of ZBRK1/ZNF350 (rs2278414). No significant association between PERP variants and cancer was identified HR = 0.662 (95% CI: 0.289-1.324, P = 0.261). Our results suggest that genes that act upstream of p53, or participate in the DNA damage response, may modify the risk of cancer in women with mutant BRCA1/2 alleles.

Background Operative blood loss is among the most important factors determining the prognosis of patients undergoing hepatic resection. The best method for preventing bleeding is preliminary selective vascular occlusion of lobar, sectoral, or segmental portal triads, although not always technically feasible. Method Transportal occlusion of the portal triad with a balloon catheter was used in 35 hepatectomies for various tumors. Results In 27 out of 35 resections, there was absence or minimal bleeding from afferent vessels (portal vein, hepatic artery). In the remaining eight cases, there was significant bleeding from the hepatic artery. In these cases, transportal occlusion of portal triad was combined with a temporary interruption of the hepatic artery after the dissection of the hepatoduodenal ligament. The average intraoperative blood loss was 350–1,500 ml. Conclusion The use of a balloon catheter occlusion of the portal triad during liver resection is often technically feasible. It facilitates temporary occlusion of hardly accessible portal veins in the hepatic hilus without their prior exposure and minimizes bleeding. J. Surg. Oncol. 2005;89:39–42. © 2004 Wiley-Liss, Inc.

Germline mutations in BRCA1 or BRCA2 account for the majority of inherited breast cancer cases. Yet, in up to 40% of familial breast cancer cases, no mutations can be detected in either gene. Germline mutations in PTEN underlie two inherited syndromes: Cowden disease (CD) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). The known association of CD with breast cancer risk made it plausible that germline mutations within PTEN may play a role in inherited predisposition to breast cancer. The nine coding exons of the PTEN gene were screened for harboring germline mutations using denaturing gradient gel electrophoresis (DGGE) complemented by sequencing, in two subsets of Israeli patients: 12 patients clinically diagnosed with BRRS, and 89 women with an apparent inherited predisposition to breast cancer, some with salient features of CD. Two of three familial BRRS patients exhibited novel germline mutations in PTEN: a missense mutation changing methionine to arginine at codon 134, and insertion of two nucleotides (CA) at cDNA position 1215 resulting in a frameshift at codon 61 and a premature stop at codon 99. Among 89 high-risk women, two missense mutations were detected in exon 4: A to C change at cDNA position 1279 resulting in a change of aspargine to threonine at codon 82 (N82T), and a G to an A alteration in 1269 which alters threonine to alanine at codon 78 (T78A), a non-conservative missense mutation. This study suggests that PTEN does not play a major role in predisposing to hereditary breast cancer in Israeli women, and that detection of PTEN mutations in BRRS patients is more likely in familial cases.

Genetic counseling for individuals at high risk for developing breast and ovarian cancer (oncogenetic counseling) involves evaluation of cancer risk, psychological assessment, and genetic testing for germline mutations in BRCA1/BRCA2 genes. The long-term psychosocial impact of oncogenetic counseling on consultees and the retention of oncogenetic information are uncertain. We retrospectively interviewed 155 women who underwent oncogenetic counseling in a single medical center in Israel in 1996 (N = 50) and 1998 (N = 105). There were 29 (18.7%) BRCA1/BRCA2 mutation carriers and 126 non-carriers; 58 (37.4%) had a past or present history of cancer, and 97 (62.6%) were first-degree relatives within breast/ovarian cancer families. A questionnaire evaluating self-reported distress and anxiety symptoms before and after counseling, as well as the retention of relevant information (e.g., individual and offspring cancer risk, early detection schemes), one and three years after the initial consultation was administered. Overall, oncogenetic counseling had a minimal effect on anxiety-related symptoms. Mutation carriers reported anxiety-associated symptoms, such as sleeplessness and “bad mood”, more frequently than non-carriers following oncogenetic counseling. As expected, 61.8% of carriers and only 30% of non-carriers accurately remembered the personal and offspring cancer risk and preventive and early detection schemes. We conclude that although there seemed to be slight worsening of anxiety-related symptoms following oncogenetic counseling in BRCA1/BRCA2 mutation carriers, these symptoms were minimal and did not affect everyday life activities. In addition, there is an ongoing need to emphasize oncogenetic information to high-risk individuals. © 2002 Wiley-Liss, Inc.

We investigated the effect of hepatocyte-derived extracellular matrix (ECM) on the expression of erb-B2 and erb-B3 in colon cancer cell lines, as well as the role of erb-B2 and erb-B3 in colon cancer cell proliferation. Colon cancer cell lines plated on hepatocyte-derived ECM had increased protein levels of both erb-B2 and erb-B3. The addition of soluble recombinant proteoglycan syndecan-4 also resulted in higher expression of erb-B2 and erb-B3. We prepared hepatocyte-derived ECM from 1 to 7 days' cultures of hepatocytes, which contained different amounts of sulfated glycosaminoglycans. There was a direct correlation between the amounts of sulfated glycosaminoglycans in the ECM and the levels of erb-B2 and erb-B3 in the colon cell line KM12. The stimulatory effect of hepatocyte-derived ECM was abolished when the colon cancer cells were cultured in the presence of antibodies to erb-B2. These studies show that hepatocyte-derived ECM and the heparan sulfate proteoglycans present in it are responsible for inducing erb-B2 and erb-B3 in colon cancer cells. The growth stimulatory effect of extracellular matrix is mediated, at least in part, by increased expression of erb-B2 and erb-B3. © 2001 Wiley-Liss, Inc.

Relative to her risk of breast carcinoma, the woman with a BRCA1 or BRCA2 gene mutation can be managed either by intensive screening (with or without chemoprevention) or by prophylactic mastectomy. Although it would be preferable to avoid prophylactic surgery, the current level of screening technology and the rudimentary state of chemoprevention do not guarantee a good outcome with intensive surveillance. A review of the currently available data was undertaken to determine the efficacy of prophylactic surgery, intensive screening, and chemoprevention. An attempt then was made to extrapolate the efficacy of the various approaches to the management of women who carry BRCA1 or BRCA2 gene mutations. Intensive surveillance may not detect breast carcinoma at an early, curable stage in young women with BRCA1 or BRCA2 gene mutations because the growth rate of the tumors in these women most likely will be rapid and the density of the breast tissue may compromise detection. Chemoprevention is in its infancy, and its efficacy in this population is unknown. Conversely, prophylactic surgery may not be completely effective in preventing breast carcinoma. The authors are hopeful that sometime in the next decade advances in chemoprevention, screening technology, or breast carcinoma treatment will make mastectomy obsolete. However, for the time being prophylactic mastectomy has attributes that make it an alternative for this population that must be considered. Careful discussion of all options is essential in the management of these women.

During a 2 year period (1992–1993), 149 patients with advanced abdominal cancer underwent total abdominal ischemic perfusion (TAP) and stop-flow infusion (SFI) 159 times in an attempt to achieve palliation. These procedures and aortic stop-flow infusion require insertion of balloon catheters into the abdominal aorta and inferior vena cava by a transfemoral approach. Flow is arrested for 15 minutes, during which time chemotherapeutic agents are infused into the aorta, distal to the balloon occlusion. Femoral access is by a surgical incision. The passage of the catheters is guided by fluoroscopy. Some tumor response was observed in 35% of the patients. Ten patients had major vascular complications; two iliac artery aneurysms were lacerated and required emergency repair. There were two femoral artery false aneurysms that required surgical correction, one early and one late. Aortic dissection was detected in four patients, but these did not require surgical intervention. Two patients had thrombosis distal to the occluded vessel, both required surgical intervention. To reduce the incidence of these vascular complications we recommend: (1) a clinical and vascular laboratory evaluation before the procedure, and (2) angiography of normal flow in patients with underlying vascular disease. © 1996 Wiley-Liss, Inc.

The authors describe a retroperitoneal liposarcoma with secondary involvement of the left ventricle. Therapy has been disappointing, and is guided by the nature of the primary tumor, previous therapy, extent of metastatic spread, and feasibility of cardiac resection. In selected patients whose primary tumor is well-controlled and progressing slowly, with no evidence of widespread disease, resection of the cardiac metastases can be performed when technically feasible.