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Breast augmentation with implants is a popular cosmetic procedure which has been performed for nearly six decades. As the number of breast augmentation procedures continually rises, we increasingly encounter breast cancer patients who have silicone implants. A significant portion of these patients includes candidates suited for lumpectomy. In these cases, a major concern is the potential exposure of the implant during lumpectomy while an additional consideration is the need to replace the implants due to their age or condition. The purpose of this study is to present an original surgical approach to patients with breast implants requiring breast conservative resection due to breast carcinoma. Over the course of 10 years, breast-augmented candidates for a lumpectomy who underwent a technique that combines lumpectomy with the replacement of the old implant through an incision from the previous scar in the inframammary fold (IMF) were reviewed. With this approach, after removal of the implant through the IMF incision, the tumor is resected with appropriate surgical margins from inside the implant pocket, leaving the overlying skin intact. Data on demographic characteristics, implants, oncologic information, intraoperative surgical findings, and complication were collected. The implant information included brand, size, age, plan of dissection, and condition of the implant as assessed preoperatively. Oncologic information included tumor type, number of tumors, size, and location. Surgical information included the size of the tissue excised, condition of the implant removed, as well as characteristics of the new implants, plane of augmentation, and intraoperative and postoperative complications. All breast specimens were marked and weighed, and the patients were followed-up postoperatively for at least 6 months by the plastic and breast surgeons and by the oncologists. This technique has been employed in 21 patients with previous breast augmentation and a recent diagnosis of breast carcinoma. The average implant age was 13.3 years. The average tumor size was 2.1 cm × 2.8 cm. All patients had clear surgical margins. No significant complications were reported. This technique enables the performing of a lumpectomy procedure without adding additional scars to the breast, the exchange of the implant in a simultaneous procedure, and the decrease of the risk of implant exposure due to additional scars on the breast parenchyma. It minimizes postoperative complications and provides excellent results both therapeutically and aesthetically.

Background Low back pain (LBP) is one of the most common health complaints, with lifetime prevalence rates as high as 84%. The Oswestry Disability Index (ODI) is often the measure of choice for LBP in both research and clinical settings and, as such, has been translated into 29 languages and dialects. Currently, however, there is no validated version of Hebrew-translated ODI (ODI-H). Objective To examine the psychometric properties of the ODI-H. Methods Cross-culturally appropriate translation into Hebrew was conducted. A convenience sample of 115 participants (Case Group) with LBP and 68 without LBP (Control Group) completed the ODI-H, SF-36 Health Survey, and two Visual Analog Scales (VAS). Results Internal consistency was α = 0.94 and test-retest reliability for 18 participants repeating the ODI-H was 0.97. No floor or ceiling effects were noted for Cases, although there was a floor effect for the Control Group. Scores were significantly different for the two groups, indicating discriminant validity. Concurrent validity was reflected by significant correlations with SF-36 scores, particularly the Physical Functioning and Bodily Pain subscales (-0.83 and -0.79, respectively) and with the VAS (0.84 and 0.79). Conclusions The ODI-H is a valid and reliable measure of low back pain-related disability for the Hebrew-speaking public.

The purpose of this study was to assess pathological complete response and whether it serves a surrogate for survival among patients receiving neo-adjuvant doxorubicin–cyclophosphamide followed by paclitaxel for triple-negative breast cancer with respect to BRCA1 mutation status. From a neo-adjuvant systemic therapy database of 588 breast cancer cases, 80 triple-negative cases who had undergone BRCA genotyping were identified. Logistic regression model was fitted to examine the association between BRCA1 status and pathological complete response. Survival outcomes were evaluated using Kaplan–Meier method, differences between study groups calculated by log-rank test. Thirty-four BRCA1 carriers and 43 non-carriers were identified. The BRCA1 carriers had pathological complete response rate of 68 % compared with 37 % among non-carriers, p = 0.01. Yet this did not translate into superior survival for BRCA1 carriers compared with non-carriers. No difference in relapse-free survival were noted among those with or without pathological complete response in BRCA1 carriers regardless of pathological complete response status (Log-rank p = 0.25), whereas in the non-carrier cohort, relapse-free survival was superior for those achieving pathological complete response (Log-rank p < 0.0001). Response to neo-adjuvant systemic therapy differed in BRCA1-associated triple-negative breast cancer compared with triple-negative non-carriers, with a higher rate of pathological complete response. However, compared with non-carrier triple-negative breast cancer, pathological complete response was not a surrogate for superior relapse-free survival in BRCA1 patients. Future studies using specific chemotherapy regimens may provide further improvements in outcomes.

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

Laparoscopic sleeve gastrectomy (LSG) is an accepted bariatric procedure. Swallow studies (SS) after LSG are not uniform and display different patterns with regard to contrast passage through the gastric sleeve. The impact of immediate postoperative contrast transit time on weight loss has not been studied. The influence of immediate fluid tolerance on weight loss after LSG is herein reported.Ninety-nine patients after LSG were included. There were 67 females, mean age 41 (range 17-67), mean BMI 44.4 (range 37-75). A routine SS was performed on postoperative day (POD) 1. Pattern of contrast transit was noted. Patients were followed-up in our bariatric clinic.Percent excess weight loss was significantly lower in the patients with rapid contrast passage (Group 1, n = 50) than those with delayed passage (Group 2, n = 49). Group 1 achieved 62, 58, and 53 % at 1, 2, and 3 years, respectively, while Group 2 attained 69, 74, and 75 % at the same time points (p = 0.05, 0.001, and 0.04, respectively). Group 1 patients displayed a negative weight loss trend after 1 year whereas Group 2 patients plateaued after 2 years.Tolerance of fluid intake after LSG is crucial for patient recovery and discharge. Distinct radiologic appearance on POD 1 helps predict this behavior. Mid-term weight loss after LSG appears to be dependent on immediate postoperative contrast transit time, whereas patients with slow contrast passage tend to lose more weight. Long-term follow-up will reveal whether this finding will hold true.

Up to 4% of breast cancer cases occur in women younger than 35 years. Studies have suggested an association between breast cancer at a young age, poorer outcome, and adverse clinical and pathologic characteristics. It is unclear whether age is an independent prognostic factor.To characterize the prognostic significance of young age at diagnosis through comparison of disease characteristics of "less-young" (born between 1958-1962 and aged 37-44 years) and "very-young" (born after 1967 and aged ≤35 years) premenopausal patients.Consecutive patients with breast cancer born after 1967 treated at Sheba Medical Centre between January, 1999 and October, 2002 were identified and their files reviewed. This cohort was identified as "very-young" and was compared with a group of "less-young" patients. The clinico-pathologic characteristics and survival data were compared.Sixty-one very young and 94 less-young patients were identified. The mean age at diagnosis was 29.9 (range, 23-34 years) and 40.5 years (range, 37-44 years) for the very young and less young patients, respectively (P0.0001). Significantly more very young patients had metastatic disease at presentation (20% vs. 3%, respectively, P = 0.0007). The very young patients were more likely to have high grade, endocrine nonresponsive tumors than the less young patients. After controlling for stage and tumor grade, very-young age was not shown to be an independent risk factor for reduced survival.Very young age among Israeli women with breast cancer is associated with higher stage at diagnosis, adverse pathologic characteristics and adverse outcome but is not an independent prognostic factor for survival.

Background Appendiceal carcinoid tumor is the most common type of primary appendiceal malignant lesion. Nonetheless; it is an exceedingly rare diagnosis; found in only about .3% to .9% of appendectomy specimens. We report the clinical and pathologic characteristics of carcinoids found with long-term follow-up evaluation. Methods Data of patients who were histologically reported to have carcinoid tumor of the appendix; in a single center; during a 16-year period were collected retrospectively. In addition; patients were contacted for current follow-up information. Results A total of 44 patients were diagnosed with appendiceal carcinoid during the study period. The median follow-up period for the cohort was 7 years. No evidence of any recurrent disease or other noncarcinoid neoplasm was found. Conclusions Our data confirm the good prognosis as seen in earlier reports. The long-term significance of having a carcinoid; and whether this poses a risk for future neoplasms; need even longer-term studies.

Prevention of blood loss in liver resections is essential for reducing postoperative morbidity. The main method to control bleeding during surgery of the left hemiliver is occlusion of the left portal pedicle. This may be accomplished by hilar, fissural or posterior intrahepatic techniques. However, these techniques may injure transposed vessels or bile ducts from the right portal pedicle to the left. The purpose of this study was to describe the anatomical aspects of the posterior intrahepatic ligamentum venosum approach to the left portal pedicle. Anatomical study was carried out on 215 isolated adult livers. In 57 specimens, sections of the extra- and intrahepatic portions of the left portal pedicle were prepared under stereoscopic microscopy. The ligamentum venosum is the anatomical landmark between the medial and lateral portions of the left portal vein. The convergence of the ligamentum venosum along the left portal pedicle is where the left portal sheath reaches its maximal thickness and these connections are tight. In 8–12%, the medial portion of the left portal pedicle includes a transposed right paramedian vein or right-sided bile ducts. According to our anatomical study, we believe that it is possible to use the ligamentum venosum as an anatomical guide to achieve a controlled approach of the left portal pedicle during left-sided hepatectomies. Moreover, ligation of the left portal pedicle at its convergence with the ligamentum venosum may prevent erroneous injury of transposed right paramedian vessels or bile ducts.

Trastuzumab in combination with adjuvant chemotherapy improves disease free survival and overall survival in HER2 over-expressing breast cancer patients. Data concerning the use of trastuzumab in the neo-adjuvant setting is limited. We aimed to compare outcome of HER2 over-expressing breast cancer patients treated with either standard chemotherapy, consisting of doxorubicin, cyclophosphamide and a taxane to outcome of patients treated with the same chemotherapy regimen with the addition of trastuzumab in concurrence with paclitaxel.We conducted a retrospective review of all consecutive HER2 over-expressing breast cancer patients treated at the participating institutions during the study period and received neo-adjuvant therapy. Allocation to trastuzumab was not based on clinical parameters and was approved only by part of the insurers. Clinical and pathological characteristics, as well as response rate and type of surgery were analyzed.Thirty seven patients received chemotherapy alone and 24 patients received chemotherapy and trastuzumab. A similar distribution of age, clinical stage and histology was noted in both groups. The rate of pathological complete response (pCR) was significantly higher among the trastuzumab-treated group compared to chemotherapy-alone group (75 vs. 24% respectively, p=0.0002). pCR in the breast was noted in 18 of 24 (75%) compared to 10 of 36 (28%, p=0.0005) and pCR in the axillary lymph nodes was noted in 19 of 20 (95%) compared to 8 of 28 (29%, p=0.0001), in the trastuzumab group compared to the chemotherapy-alone group respectively. The safety profile was similar between both groups and no clinical cardiotoxicity were noted.The addition of trastuzumab to standard chemotherapy in the neo-adjuvant setting improves pathological complete response rates in HER2 over-expressing breast cancer patients.

This article reviews and discusses the up-to-date data on and feasibility of focused ultrasound surgery. This technique uses high-energy ultrasound beams that can be directed to penetrate through the skin and various soft tissues, focus on the target, and destroy tumors by increasing the temperature at the targeted tissue volume. The boundaries of the treatment area are sharply demarcated (focused) without causing damage to the surrounding organs. Although the idea of using sound waves to ablate tumors was first demonstrated in the 1940 s, only recent developments have enabled this technology to become more controlled and, hence, more feasible. The major breakthrough toward its clinical use came with coupling the thermal ablative process to advanced imaging. The development of magnetic resonance as the foundation to guide and evaluate the end results of focused ultrasound surgery treatment, the image guidance of the ultrasound beam, and the development of a reliable method for tissue temperature measurement and real-time feedback of the extent of tissue destruction have pushed this novel technology forward in oncological practice.

Liver surgery is technically demanding and is considered a major procedure with relatively high morbidity rates. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) uses focused ultrasonic energy to create a heat coagulation lesion, which can be achieved in a totally controlled, very accurate manner (1 mm). The aim of this study was to evaluate the safety and accuracy of non-invasive focal ablation of liver tissue achieved by consecutive MRgFUS sonications.Six MRgFUS procedures were performed in five pigs under general anesthesia, with the ExAblate 2000 system (InSightec, Israel). Real-time imaging and temperature mapping (Signa Twinspeed 1.5T, GEHC, USA) enabled the immediate evaluation of the results of each sonication. Different foci were chosen within the liver. These mock lesions were ablated by several sonications, each of them performed during 20-30 s of apnea. Between sonications, the pigs were normally ventilated. The pigs were sacrificed 3-21 days after the procedure and their livers were examined.The MRgFUS created complete tissue destruction of mock lesions in different areas of the pig's liver. The lesion sizes in each animal varied according to the number of sonications used and the extent of overlap between adjacent sonications. The lesion ranged in size from 1.5 cm x 1.5 cm x 2.0 cm to 5.5 cm x 4.5 cm x 2.0 cm. There was no morbidity.MRgFUS under general anesthesia is a safe, completely non-invasive technology for the ablation of liver tissue. Liver tissue can be ablated in a very accurate manner, based on the pre-treatment planning on the MR images. The MR imaging characteristics, including real-time temperature mapping, enable real-time control of every step of the ablation process. Mechanical ventilation with intermittent periods of apnea is a technique that overcomes the problem of the respiratory movements of the liver.

Background. Canine hepatocellular adenomas are benign, well-differentiated, primary hepatic tumors. Surgical resection is technically demanding and is considered a major procedure with relatively high morbidity rates. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) uses focused ultrasonic energy to non-invasively create a heat-coagulated lesion deep within the body. This effect can be achieved in a controlled, accurate manner. The aim of this study was to evaluate the safety, accuracy and efficacy of non-invasive focal ablation of tissue volumes of a canine benign liver tumour by consecutive MRgFUS sonications. Materials and methods. Four MRgFUS procedures were performed in a 10-year-old, male, mixed large breed dog (45 kg) under general anaesthesia. The exact location and volume of the ablated areas were planned on the MR images. Real-time MR imaging and temperature mapping enabled the immediate evaluation of the effect of each sonication. Different areas were chosen within the tumour. These volumes of tumoral tissue were ablated by multiple sonications. To allow accurate targeting and quality imaging, sonications were performed during 20–30s of apnoea. Between the sonications the dog was normally ventilated. The dog was operated 21 days after the fourth ablative procedure. The tumour was resected and histopathologically examined. Results. The MRgFUS created necrosis with contiguous areas of complete tissue destruction within the liver tumour, in full accordance with the planning. A focal thermal injury to the cartilage of the right lower ribs was noted after the fourth treatment. This lesion became infected and was treated surgically. Ten months after the last treatment the dog is well and healthy. Conclusions. Focused ultrasound ablation of liver tumoral tissue with MR guidance under general anaesthesia and controlled apnoea is a safe and accurate treatment modality. Its main advantage is that it is a completely non-invasive image-guided treatment. The ablation of significant volumes of a highly vascular liver tumoral tissue was achieved. Such tissue can be ablated in a very accurate manner, exactly according to the pretreatment planning on the MR images. The MR imaging characteristics, including real-time temperature mapping, enable real-time control of every step of the ablation process. Mechanical ventilation with intermittent apnoea periods overcomes the problem of the respiratory movements of the liver. Care must be taken to avoid the passage of the ultrasound beam through energy-absorbing calcified tissue.

BRCA1/BRCA2 germline mutations are associated with an increased breast/ovarian cancer risk. Offspring gender ratios may be skewed against male births in BRCA1 mutation carriers. In addition, the lack of viable homozygous BRCA1/BRCA2-mutation carriers implies that recurrent miscarriages may be associated with homozygous fetuses. Jewish Israeli high-risk women who were tested for being carriers of the predominant BRCA1/BRCA2 mutations in Jewish high-risk families were analyzed for the sex of offspring and the rate of spontaneous miscarriages. Overall, 817 women participated: 393 BRCA1/BRCA2-mutation carriers (229 with breast/ovarian cancer) and 424 high-risk noncarriers (208 with breast/ovarian cancer). No differences between the male-to-female offspring ratios of all study groups were noted. Among mutation carriers, the offspring male-to-female ratio was 0.97 (444 : 460), and among mutation carriers with cancer it was 0.92 (262 : 284). Similarly, no offspring gender skewing was noted among high-risk noncarriers, regardless of health status. The rates of three or more spontaneous miscarriages among participants with at least one live birth were 4.37% (15/343) among mutation carriers and 3% (12/401) among high-risk women (P = not significant). In conclusion, the offspring gender ratio is similar in high-risk Jewish families and in the general population. The issue of the rate of recurrent miscarriages in high-risk Jewish women is unresolved.

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.

Objective: To evaluate the risk for developing second primary thyroid cancer (TC) following breast cancer (BC) and second primary BC following TC on a nationwide basis. Methods: All BC and TC Jewish females diagnosed in Israel during 1960–1998 were identified through the Israel Cancer Registry. The expected second primaries were calculated using cancer incidence rates stratified by age, country of birth and period of diagnosis among the Jewish population in Israel. Standardized incidence ratios (SIRs) were estimated using Poisson regression. Results: A total of 49,207 breast and 4911 thyroid neoplasms were identified. After the exclusion of concomitant disease (diagnosed within 1 year), 59 and 70 second primaries TC and BC yielded SIRs of 1.34 (95% CI: 1.03, 1.72) and 1.07 (95% CI: 0.84, 1.34), respectively. Younger age and earlier calendar year of first primary diagnosis and shorter follow-up period were associated with increased risk for developing second primary neoplasm. Conclusions: Considering the long latency required for carcinogenesis, excess risk of second primary diagnoses soon after the first cancer, argues against the hypothesis of first primary treatment as an initiator for the second cancer. A detection bias of meticulously followed cancer patients, early exposure to common risk factors or genetic susceptibility of certain subpopulations for both malignancies seem plausible.

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.

INTRODUCTION In patients receiving pre-operative anthracyclines for locally advanced breast cancer, early cardiotoxicity is a well-recognised complication that may interfere with surgery. The aim of this study was to assess the safety of breast surgery after neoadjuvant treatment with Doxorubicin. PATIENTS AND METHODS A retrospective study of breast cancer patients treated with Doxorubicin as part of their neoadjuvant protocol. All patients were subsequently operated in our institution. Intra-operative and postoperative haemodynamic, cardiac or respiratory events were collected. RESULTS A total of 83 patients were included. All patients had a normal left ventricular ejection fraction before starting on chemotherapy. Doxorubicin was given in conjunction with Cyclophosphamide and Paclitaxel. The cumulative dose of Doxorubicin was 240 mg/m2. All patients completed their chemotherapy less than a year before surgery and were clinically asymptomatic. Of the patients, 2.3% displayed a significant reduction in cardiac function to meet cardiotoxicity criteria, although not clinically apparent. No complications occurred intra-operatively or postoperatively. CONCLUSIONS Breast surgery can be safely performed after breast neoadjuvant chemotherapy with Doxorubicin. The risk of early cardiotoxicity does not mandate a cardiac function assessment after completion of treatment. Work-up should be individualised according to the anthracycline regimen, patient's cardiac risk factors and functional status before surgery.

We present data acquired in our institution about the incidence of incidental appendiceal carcinoids over a period of 16 years. The possibility of occult carcinoids raises the question of appendectomy of a noninflamed appendix during diagnostic laparoscopy for suspected appendicitis. We performed a retrospective chart analysis of the surgical registry of a university-affiliated tertiary care center of a major population area for the past 16 years. Data were collected on all patients (n = 7592) who underwent appendectomy for the presumed diagnosis of acute appendicitis. Outcome measures were the incidence of incidental carcinoids of the appendix found during appendectomies and whether the introduction of laparoscopic appendectomy should alter the surgical management of a normal-appearing appendix. A total of 20 carcinoid appendices were resected by open surgery and 17 by laparoscopy. The diagnosis of a carcinoid tumor was not suspected in any patient before the operation, nor was a tumor identified at the time of the operation. In 6 (16%) patients the appendix appeared normal at the time of the operation. It has long been the standard of care to remove any appendix found in laparotomy for suspected appendicitis, but it is not clear what should be done during laparoscopy for suspected appendicitis when the appendix appears normal. Our data confirm the presence of occult carcinoids in normal-appearing appendices. Further studies are needed to determine the clinical significance of this finding.

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.

Recent data from animal studies suggest thatinduced hypothyroidism inhibits the development of liverinjury in several animal models, including livercirrhosis and fulminant hepatic failure in rats, and immune-mediated acute liver injury in mice. Theaim of the present study was to determine whetherhypothyroidism would likewise preventacetaminophen-induced hepatic damage in rats. Liverdamage was induced by acetaminophen (2 g/kg) administered bygavage to fasting rats as a single dose. Hypothyroidismwas induced by methimazole, propylthiouracil, orsurgical thyroidectomy and confirmed by elevated serum levels of TSH. Hypothyroidism significantlyinhibited acetaminophen-induced liver damage asmanifested by the decreased serum levels of liverenzymes, malondialdehyde and blood ammonia, as well asby the higher hepatic glutathione content, in allthree groups of hypothyroid rats compared to euthyroidcontrols (P < 0.01). Histopathologic analysis showedsignificantly less liver necrosis and inflammation in the acetaminophen-treated hypothyroid rats.Oxygen extraction, measured in isolated perfused ratliver preparation, was also reduced in the hypothyroidlivers to 42 ± 8% compared to 81 ± 14% ofcontrols (P < 0.01). However, the expression ofCYP2E1 in the livers of hypothyroid rats, as measured bywestern blot analysis, was not decreased compared tocontrol rats. These results suggest that inducedhypothyroidism, regardless of the mode of induction, protectsrat liver from acetaminophen hepatotoxicity. This effectmay be related to hypometabolism of liver cells, but theexact mechanism needs further clarification.

Recent data from animal studies suggest that induced hypothyroidism prevents the hyperdynamic circulation in portal vein ligated rats, liver cirrhosis in rats chronically treated with thioacetamide (TAA), and immune-mediated acute liver injury induced in mice by concanavalin A. Therefore, the aim of this present study is to determine whether hypothyroidism would likewise prevent fulminant hepatic failure (FHF) in rats. FHF was induced by 3 consecutive ip injections of TAA (400 mg/kg) at 24-hour intervals. Hypothyroidism was induced in rats by either methimazole (MMI) or propylthiouracil (PTU) and surgical thyroidectomy and was confirmed by elevated serum thyroid stimulating hormone levels. Serum levels of liver enzymes, blood ammonia, and prothrombin time were significantly lower in all 3 groups of hypothyroid rats. The stage of hepatic encephalopathy (HE) and the survival rates were significantly improved in the hypothyroid rats (P < .01); the histologic examination of their livers showed less necrosis and inflammation (P < .01). In the hypothyroid rats, the serum levels of malondialdehyde 48 hours after thioacetamide (TAA) administration were lower than in control rats (P < .01). Exogenous supplementation of hypothyroid rats with L-thyroxine started 48 hours before TAA administration abrogated the protective effects of hypothyroidism. The serum levels of tumor necrosis factor alfa (TNF-alpha), interleukin (IL) 2 and IL-6 after 24 hours were slightly lower in the hypothyroid rats, but the administration of soluble receptor of TNF (10-1,000 microg/rat) did not prevent the induction of fulminant liver failure by TAA. Oxygen extraction, studied in isolated perfused liver preparation, was significantly lower in livers of hypothyroid rats (P < .01). These results suggest that induced hypothyroidism decreases the development of liver injury in a rat model of FHF. The mechanism may involve diminished oxidative cell injury caused by decreased oxygen utilization and hypometabolism associated with hypothyroidism.

The coexistence of hyperkinetic circulation, hypermetabolism, and hyperactivity of the sympathetic nervous system is encountered in both cirrhosis and hyperthyroidism. Several drugs, such as propylthiouracil and propranolol, that are beneficial for treating some patients with chronic liver diseases are also prescribed for the treatment of thyrotoxicosis. We investigated the effects of experimentally induced hypo- and hyperthyroidism on the development of cirrhosis induced in rats by thioacetamide (TAA). We specifically examined whether hypothyroidism could prevent and hyperthyroidism could aggravate liver damage. Hypothyroidism induced by methimazole (MMI, 0.04%), propylthiouracil (PTU 0.05%), and by thyroidectomy was confirmed by a significant elevation of thyroid-stimulating hormone (TSH) levels. Hyperthyroidism (decreased TSH levels) was induced by eltroxin (ELT:50 micrograms/kg). Thirteen groups of 10 rats each were studied: euthyroid controls (3 groups: water, TAA 1.5 months, and TAA 3 months), hypothyroid (6 groups: MMI, PTU, surgical, MMI-TAA, PTU-TAA, surgical-TAA), and hyperthyroid (4 groups:ELT 1.5 months and 3 months, and ELT-TAA for 1.5 months and 3 months). Hepatic fibrosis (scored from 0 to 3) was significantly reduced (P < .0001) in hypothyroid rats as compared with euthyroid controls, and was aggravated in TAA-treated hyperthyroid rats (P < .0001). Quantitative microscopic analysis of liver biopsy specimens from all groups confirmed the semiquantitative histopathological scores (P < .001). Direct intrasplenic pressure measurement revealed a significant portal pressure elevation in the TAA and the ELT-treated rats (from 4.7 +/- 0.1 in the euthyroid group to 8.1 +/- 2.3 and 10.2 +/- 2.1 and 12.5 +/- 1.6 in the TAA, ELT and ELT-TAA groups, respectively). However, in the hypothyroid-TAA groups, the portal pressure was found to be within the euthyroid normal range (4.6 +/- 1.2 and 5.8 +/- 0.6 in the PTU-TAA and surgical-TAA, respectively). After 12 weeks, the mean spleen weight of rats receiving only TAA was significantly higher than the TAA-treated hypothyroid rats (P < .0001), indicating that the hypothyroid TAA-treated rats were less portal hypertensive. These results suggest that induced hypothyroidism can inhibit, whereas hyperthyroidism can aggravate, the development of cirrhosis in a rat model.

OBJECTIVES: To investigate the ability of parametric diffusion tensor imaging (DTI), applied at 3 Tesla, to dissect breast tissue architecture and evaluate breast lesions. MATERIALS AND METHODS: All protocols were approved and a signed informed consent was obtained from all subjects. The study included 21 healthy women, 26 women with 33 malignant lesions, and 14 women with 20 benign lesions. Images were recorded at 3 Tesla with a protocol optimized for breast DTI at a spatial resolution of 1.9 × 1.9 × (2-2.5) mm3. Image processing algorithms and software, applied at pixel resolution, yielded vector maps of prime diffusion direction and parametric maps of the 3 orthogonal diffusion coefficients and of the fractional anisotropy and maximal anisotropy. RESULTS: The DTI-derived vector maps and parametric maps revealed the architecture of the entire mammary fibroglandular tissue and allowed a reliable detection of malignant lesions. Cancer lesions exhibited significantly lower values of the orthogonal diffusion coefficients, λ1, λ2, λ3, and of the maximal anisotropy index λ1-λ3 as compared with normal breast tissue (P < 0.0001) and to benign breast lesions (P < 0.0009 and 0.004, respectively). Maps of λ1 exhibited the highest contrast-to-noise ratio enabling delineation of the cancer lesions. These maps also provided high sensitivity/specificity of 95.6%/97.7% for differentiating cancers from benign lesions, which were similar to the sensitivity/specificity of dynamic contrast-enhanced magnetic resonance imaging of 94.8%/92.9%. Maps of λ1-λ3 provided a secondary independent diagnostic parameter with high sensitivity of 92.3%, but low specificity of 69.5% for differentiating cancers from benign lesions. CONCLUSION: Mapping the diffusion tensor parameters at high spatial resolution provides a potential novel means for dissecting breast architecture. Parametric maps of λ1 and λ1-λ3 facilitate the detection and diagnosis of breast cancer.

Tumor-infiltrating lymphocytes (TILs) are produced by resecting tumor tissue and growing and expanding ex vivo large quantities of autologous T cells. Once the TILs are ready for infusion, the patient undergoes a non-myeloablative lympho-depleting course of chemotherapy and subsequent TIL infusion with high-dose bolus IL-2. This study reviews the surgical experience of the TIL program at the Chaim Sheba Cancer Research Center in Israel. Eligible patients underwent surgical consultation to determine what tumorectomy would be beneficial for harvesting appropriate tissue. Factors involved in the decision included tumor mass size, location and morbidity of the procedure. Between January 2006 and May 2010, 44 patients underwent 47 procedures of adoptive transfer of TILs. Three patients underwent the procedure twice for recurrence after initial good responses, including an additional surgical procedure to produce fresh tumor. Thirty-seven excisions were with general anesthesia and 10 were with local anesthesia. Of the 37 general anesthesia procedures, 27 were open procedures involving a thoracotomy, a laparotomy or dissection of a major lymph node basin. Ten used minimally invasive techniques such as thorascopy or laparoscopy. Tumorectomy sites included 18 lymph node metastasis, 13 subcutaneous nodules, 11 lung specimens and 5 abdominal visceral metastasis including 2 liver lesions. Surgical mortality and major morbidity was 0%. Minor morbidity included only wound complications. Maximal number of TILs were derived from lymph node specimens, while liver metastasis procured the fewest TILs. Adoptive cell transfer technology affords a maximal tumor response with minimal surgical morbidity in metastatic patients.

Laparoscopic adjustable gastric banding (LAGB) is an effective bariatric procedure with low morbidity and mortality. Unfortunately, it is fraught with high failure rates in long-term follow-up. Laparoscopic sleeve gastrectomy (LSG) is an emerging procedure, quickly gaining momentum in the arsenal of bariatric practice as a first step toward gastric bypass/biliopancreatic diversion or as a stand-alone operation. Recently, it has been described as a revisional option for previous bariatric surgery failures. We report our early experience with LSG as a revisional procedure for failed LAGB.From January 2007 to April 2010, 46 patients, who had undergone LAGB, underwent LSG. Patient demographics, reason for band removal, interval between removal and LSG, operative times, estimated blood loss, complications, length of hospital stay, and percent of excess weight loss were collected.Of the 46 patients, 20 (43%) had their bands removed before LSG (median time interval, 2 years; range, 2 months to 9 years); the rest had concomitant band removal and LSG. Twelve patients were men (26%). Mean age and BMI were 40 (range, 20-60) years and 43.1 kg/m(2) (range, 33-57), respectively. In two cases, surgery was converted to an open procedure due to extensive adhesions related to previous surgeries. Median operative time, estimated blood loss, and length of hospital stay were 118 (range, 70-250) minutes, 41 (range, 5-600) ml, and 3 (range, 1-100) days, respectively. Major morbidity was encountered in three patients (6%; leak in 2 and bleeding in 1). There were no mortalities. Mean follow-up time for our cohort is 17 (range, 1-39) months. Percent of excess weight loss at 2, 6, 12, 24, and 36 months was 24, 37, 53, 51, and 48%, respectively.Our results suggest that LSG is safe, feasible, and effective as a revisional procedure for failed LAGB and can be considered as an appealing option in these cases. Larger series and longer follow-up are needed to confirm this.

Laparoscopic sleeve gastrectomy (LSG) is gaining popularity as an additional bariatric procedure, either as a first step for biliopancreatic diversion or gastric bypass or as a stand-alone option for selected patients. Early postoperative fluid tolerance varies between patients and influences the length of hospital stay. Swallow studies after LSG are not uniform and display different patterns with regard to contrast passage through the gastric sleeve. The 55 patients (40 women) in this study underwent LSG during 18 months. These patients had a mean age of 38.2 years (range: 17–61 years) and a mean body mass index (BMI) of 44.8 kg/m2 (range: 39–75 kg/m2). The LSG procedure was performed using a four-port technique to resect the greater curvature of the stomach around a bougie. The mean operative time was 120 min (range: 45–240 min). A routine swallow study was performed on postoperative day 1, and clear fluids were initiated if no leak was detected. Patients were discharged when they could tolerate a daily fluid intake of 2 l. No mortalities, obstructions, or leaks occurred in the study cohort. Two main patterns of contrast passage were identified: type 1 (immediate unhindered flow through the sleeve to the antrum with a slight delay before continuation of the contrast to the duodenum) and type 2 (contrast filling of the proximal sleeve with delay of flow distally toward the duodenum). Patients with rapid contrast passage (group 1, n = 24) tolerated clear fluids better than those with delayed flow (group 2, n = 31) and were discharged earlier than their counterparts (mean length of hospital stay, 2.5 vs. 3.4 days; p

Objective To address optimal timing of sentinel lymph node biopsy (SLNB) in breast cancer patients undergoing neoadjuvant treatment. Methods The study population included 117 patients with locally advanced cancer with clinically negative nodes treated with primary chemotherapy. Group 1 underwent SLNB and completion axillary lymph node dissection (ALND) in conjunction with lumpectomy/mastectomy, after neoadjuvant treatment (n = 31). Group 2 underwent SLNB followed by neoadjuvant therapy and subsequently surgery and completion of ALNDs (n = 58). Group 3 was treated using the same sequence as group 2, however, completion ALND was performed only for patients with positive sentinel lymph nodes (SLNs) (n = 28). Results SLN identification was lowest in group 1 compared to groups 2 and 3 (87% and 98.8% respectively; P =

Advances in technology and the increase in screening for breast cancer that identifies tumors at earlier stages have made it possible to destroy tumors in situ without surgery. This can also be used to treat locally advanced tumors. These locoregional ablative techniques include minimally invasive surgical as well as noninvasive ablative modalities, new radiation technologies, and regional chemotherapy. New developments in imaging modalities such as MR make these treatment opportunities more precise and reliable. The regional minimally invasive technologies provide treatment options that are physiologically, cosmetically, and psychologically more acceptable to the patient. Many of these need further investigation before they become an accepted sound practice. This paper reviews and discusses the up-to-date data and feasibility of technologies for locoregional treatment of breast cancer

Type 2 diabetes mellitus is associated with increased incidence and inferior outcome of various malignancies. The aim of this study was to explore the impact of type 2 diabetes on breast cancer characteristics at presentation. The study population included 79 diabetic and 158 age-matched non-diabetic patients. Parity, country of birth, co-morbidity other than diabetes, and mode of diagnosis were similar in both groups. Mean body mass index (BMI) was higher among diabetic patients. Tumour stage and size were higher among diabetic patients and the differences remained significant after adjustment for BMI. Moreover, after adjustment for BMI, breast cancer among diabetic patients was more often hormone receptor negative. Our results show that diabetes mellitus is associated with negative prognostic factors at breast cancer presentation.

While the precise genes involved in determining familial breast cancer risk in addition to BRCA1/2 are mostly unknown, one strong candidate is RAD51 . Jewish non-Ashkenazi women at high-risk for breast/ovarian cancer and ethnically matched controls were genotyped using four single nucleotide polymorphisms spanning the RAD51 genomic region, and the resulting haplotypes were constructed using the GERBIL algorithm. A total of 314 individuals were genotyped: 184 non-Ashkenazi high-risk women (119 with breast cancer), and 130 unaffected, average-risk ethnically matched controls. Using GEBRIL, three frequent haplotypes were constructed. One of the haplotypes (TGTA – coined haplotype 3) was present in 7.3% (19/260 haplotypes) of controls ( n = 130) and in 16.8% (40/238 haplotypes) of high-risk breast cancer patients ( n = 119, P = 0.001). A specific RAD51 haplotype is more prevalent among non-Ashkenazi Jewish high-risk women than in average-risk population.

The use of high energy focused ultrasound (FUS) waves to destroy tumor tissue in breast cancer is explored. High energy FUS destroys cells by raising the temperature of the treated volume high enough to denature cell proteins and bring about cellular death. The absorbed energy results in extremely high tissue gradients between target cells and surrounding tissue, so the effect of the focused energy is concentrated only at the target, leaving the healthy tissue unscathed. This phase one trial has examined the possibility of ablating breast carcinoma using MRI Guided FUS (MRIgFUS) in place of lumpectomy. Ten female patients underwent the procedure at the Chaim Sheba Medical Center between September 2002 and August 2004, using the ExAblate 2000 (InSightec, Haifa Israel Ltd.). Seven to 10 days after the procedure, all patients underwent standard lumpectomy and axillary sampling to complete standard treatment and to allow pathological evaluation of the procedure. Two patients had a complete pathological response. The remaining 8 patients had varying amounts of residual tumor; 2 had microscopic foci of residual carcinoma, 3 had 10% residual tumor, and 3 had 10-30% of residual tumor. Although still in its infancy, the future role of this type of ablation in breast cancer and other tumors is discussed.

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.

Tumor downstaging by preoperative neoadjuvant chemotherapy in patients with locally advanced breast tumors allows breast conservation in women who were previously candidates for mastectomy. Nevertheless, lumpectomy success in such cases cannot be fully achieved. The aim of this study was to create a quantitative tool for preoperative evaluation of the success of breast conservation in such patients.The study population included 100 consecutive patients with stage II and III breast cancer who were designated for lumpectomy and 19 patients who were designated for mastectomy. All patients received neoadjuvant therapy. Breast-conserving surgery was offered in accordance with clinical and esthetic criteria. Demographic details and clinical, imaging, and pathologic information were collected from medical files. A decision protocol for classifying patients to lumpectomy or mastectomy was built by using the Classification and Regression Trees procedure based on preoperative characteristics.Three factors were found to be the main predictors for successful breast conservation: absence of diffuse microcalcifications as seen in the pretreatment mammogram, a postchemotherapy tumor size of25 mm, and the existence of a circumscribed lesion on mammography.The use of these criteria as a basis for decision on the type of surgery may decrease the performance of unnecessary procedures.

Background: Fertility drug therapy (FDT) induces supraphysiologic endogenous estrogen production and might transiently increase breast cancer risk. Tumors developing following FDT exposure have not been extensively studied. Methods: Thirty-eight breast cancer patients with 40 primary tumors and with history of FDT exposure were identified and compared with two other breast cancer groups: women with pregnancy-associated breast cancer (PABC, 22 patients with 23 tumors) and premenopausal women born during same calendar years and not exposed to hormonal manipulations or recent pregnancy (controls, 192 patients with 201 tumors). Patients were diagnosed and treated mostly during the last decade. Results: Compared with controls, tumors of patients with FDT exposure presented at advanced stages (P < .005), were more likely to be estrogen or progesterone receptor negative (P < .03) and of poor histology grade (P

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.

Hemorrhoidal disease is a common pathology in patients with chronic spinal cord injury (SCI). We describe our experience with the primary approach to this problem at the Proctology Division of the Sheba Medical Center. We treated 29 patients (26 men) with paraplegia due to SCI between 1995 and 1999. The mean age was 49 years (range, 22–74 years). All patients had hemorrhoids in stages ranging between II and IV. Main complaints were rectal bleeding (83%), difficulties in evacuation (38%) and discomfort or pain (28%). Eleven patients (38%) were treated conservatively (e. g. diet, hygiene and laxatives), while 18 patients (62%) underwent either banding or sclerotherapy of hemorrhoids or both. No major complication were observed. In 28 of 29 patients (96%), there was a significant reduction or cessation of bleeding and/or relief of symptoms; one patient (3%) required hemorrhoidectomy. Of the 28 successful treatments, 16 (57%) had partial reduction of bleeding or relief of symptoms, while in 12 (43%) response was complete. Of those who were treated conservatively, 9 (82%) had partial and 2 (18%) had complete relief of symptoms. Of those who had banding/sclerotherapy, 7 (41%) had partial and 10 (59%) had complete relief. We also examined the effect of perianal sensation on the treatment outcome. Of 16 patients with complete anesthesia, 11 (69%) had partial and 5 (31%) had complete relief, whereas of the 12 patients with preserved sensation, 5 (42%) had partial and 7 (58%) had complete relief. In conclusion, the approach of banding or sclerotherapy of hemorrhoids in SCI patients is safe and effective. When sensation of the perianal region is preserved, the outcome seems to be better. The cause of SCI has no impact on the treatment results. There was no difference in the outcome of treatment between patients with stage II and stage III hemorrhoids; patients with stage IV hemorrhoids seem to do worse than those with stages II and III.

1023 Background: Pathological complete response (pCR) has been demonstrated to serve as a surrogate for outcome in patients receiving neo-adjuvant systemic therapy (NAT) for triple negative (TN) br...

Background and Objectives Breast-conserving surgery requires excision of all gross tumor and subsequent radiation therapy. It is generally accepted that the presence of microscopically positive margins requires reexcision. The goal of this study was to identify characteristics that distinguish breast biopsy specimens with positive margins that when reexcised are free from residual tumor. This population of patients may benefit from breast irradiation only, without the need for another surgical procedure. Methods One hundred and fifteen of 395 cancer-proven biopsies had positive surgical margins and were treated with reexcision or mastectomy. Sixty-seven of these were negative for residual tumor and 48 were positive for residual tumor. Evaluation for tumor type, tumor size, grade, presence of vascular invasion, volume of the biopsy specimen, true positivity and the number of positive margins, multifocality of the tumor, and type of anesthesia was done by univariate and multivariate analysis. Results Univariate and multivariate analysis revealed that factors associated with a positive reexcision included margin status, method of detection, histologic appearance, and type of anesthesia used. Conclusion These results suggest that small, clinically detectable unifocal tumors could be treated without the need for a further excision. Eradication of microscopic residual tumor could be done by irradiation only, sparing the patient an additional surgical procedure. J. Surg. Oncol. 1999;70:167–171. © 1999 Wiley-Liss, Inc.

The purpose of this chapter will be to discuss the role of prophylactic oophorectomy and prophylactic mastectomy in the management of patients with hereditary breast and ovarian cancer syndrome. The approach described here can serve as a template in reviewing the efficacy of prophylactic surgery for other hereditary cancer syndromes.

Cyclic neutropenia is an hereditary disorder of white blood cells, characterized by profound neutropenic episodes approximately every three weeks. Septic complications are usually limited to cutaneous and oropharyngeal infections. A 4-year-old boy with known cyclic neutropenia was in shock with neutropenia, clostridial septicemia, and right lower quadrant peritonitis when he was admitted. At the time of laparotomy, inflammation of the cecum, with no gross perforation, was found; no resection or appendectomy was done. He subsequently developed a right lower quadrant abscess that was drained, resulting in a colocutaneous fistula. For the next 8 months his fistula persisted, with intermittent episodes of fever, increased fistula output, and abdominal pain during his neutropenic periods. Standard nonoperative approaches to healing the fistula failed (ie, elemental feeds, total parenteral nutrition, irrigations, antibiotics, and drains). Attempts to medically abolish his neutropenic episodes using lithium, gammaglobulin, and steroids also failed. Ultimately, he underwent an ileocecal resection with primary anastamosis; the operation was done immediately following a neutropenic episode, in order to allow adequate healing of his anastamosis before his next period of neutropenia. Postoperative course was satisfactory, and he remains well after 8 months follow-up. This case, and several similar previously reported cases, illustrate that cyclic neutropenia may present with serious surgical complications. They also underlines the important role that neutrophils play in the healing of enteric fistulae.

Background and Objectives: Implanted central venous access ports are frequently used. Spontaneous break and catheter transection are serious but rare complications of permanent subclavian catheters. We report our experience with this serious complication and identify possible warning signs. Materials and Methods Between 1990 and 1996, 285 permanent subclavian catheters were placed at the Sheba Medical Center, Tel Hashomer, Israel. Results We evaluated the patient population for this complication and searched for possible warning signs. A total of 12 patients (4.2%) with this complication were identified, 8 with transection and distal embolization and 4 with a partial tear only. The pinch-off sign was noted as an early warning in only 5 patients. All other patients developed symptoms only immediately before the diagnosis of this complication. The mean duration from insertion to identification of tear or transection was 9.6 months (range 1–24 months). Conclusion Awareness and clinical suspicion are most important in identification and prevention of this serious complication. Catheters should be taken out when treatment is completed or after 12 months in order to prevent catheter breaks. J. Surg. Oncol. 1998;68:166–168. © 1998 Wiley-Liss, Inc.

Aims Axillary node dissection for breast cancer is important for staging and its prognostic value. Sentinel nodes are defined as the first nodes into which the primary cancer drains. This study investigates whether identification, removal and pathological examination of these nodes indicates whether the completion of axillary lymphadenectomy is required. Methods Using a vital dye injected at the primary tumour site, we were able to identify sentinel nodes in 96 out of 98 women examined. Results An average number of 2.7±1.2 nodes per patient were identified as sentinel nodes. In 83% of cases there was a correlation between the involvement of the sentinel nodes and the rest of the axillary nodes. In 14% of patients the sentinel nodes were the only nodes involved with tumour. In three cases the sentinel nodes were negative, but other axillary nodes were tumour-positive. Conclusion The major problem in routine application of this method to the decision to perform axillary lymph node dissection (ALND) is the time needed for pathological identification of lymph node involvement by tumour.

Efforts directed at early detection of breast cancer have resulted in an increased incidence of nonpalpable mammographic lesions that warrant excisional biopsy. The most common localization method is by use of the hook wire technique, or needle localization biopsy. Although much has been written about the localization technique, the impact of the method of anesthesia on the accuracy of the biopsy and especially on the completeness of the excision has not been clarified.We studied 450 needle localization breast biopsies to determine whether the type of anesthesia (local versus general) influenced the accuracy and completeness of the biopsy. We compared 153 biopsies performed under local anesthesia to 297 done under general anesthesia.The use of local versus general anesthesia did not affect accuracy; however, it did determine the inability to achieve clean margins (27.6% versus 7.3%, respectively, P0.02). It was more difficult to excise completely specimens located deeper than 3 cm in the breast, when the localizing needle travelled more than 3 cm, and when the lesions were of the microcalcification mammographic pattern.For lesions mammographically suspicious for malignancy, mainly those located deeper than 3 cm, general anesthesia is preferred.

Insulin-like growth factors (IGFs) are potent mitogens that stimulate the growth of prostate cells. In serum, IGFs circulate bound to IGF-binding proteins (IGFBPs), which modulate their proliferative action. We studied the electrophoretic pattern of IGFBPs in the serum of patients with prostate cancer and in individuals with increased serum levels of prostate-specific antigen (PSA) in the absence of prostate malignancy. Serum IGFBP-2 was dramatically increased in patients with metastatic prostate cancer compared with healthy controls (23.83 +/- 6.93% vs. 2.95 +/- 0.52% of total serum IGFBPs; P0.02). A moderate rise in IGFBP-2 was also observed among patients with increased PSA without malignancy. In contrast, a decrease in serum IGFBP-3 was detected in most patients with metastatic prostate cancer (68.2 +/- 9.1% vs. 95.4 +/- 0.9% of total serum IGFBPs; P0.02) and was more pronounced in advanced cases. A highly significant correlation between serum IGFBP-2 and PSA levels was found (r = 0.62; P0.002), with a significant negative correlation between serum PSA and IGFBP-3 (r = -0.63; P0.002). We suggest that IGFBPs may be involved in growth modulation of prostate malignancy and that alterations in their serum levels may serve as a marker for prostate cancer.

Abstract #5104 Background: Germline mutations in BRCA1 and BRCA2 occur in ∼ 11% of Jewish Ashkenazi women with breast cancer. BRCA1 and BRCA2 proteins are key players in the repair mechanisms of double-strand DNA breaks induced by DNA-damaging agents such as anthracyclines. Hence, inactivating mutations in BRCA1/2 genes have been postulated to result in increased chemo-sensitivity in women with breast cancer who carry these germline mutations. Neo-adjuvant therapy provides the opportunity for a rough, in vivo assessment of this notion by assessing chemotherapy (CT) sensitivity via pathological complete response (pCR) rates, in breast cancer patients, both carriers and non-carriers of deleterious BRCA1 BRCA2 mutations. In particular, response in the axillary lymph nodes to neo-adjuvant therapy is significant, as it is a surrogate marker for long-term outcome. This study assessed the pCR amongst women with BRCA1/2 mutations compared to those who are BRCA1/2 mutation negative. Methods: Retrospective evaluation of response to neo-adjuvant CT amongst consecutive women diagnosed with breast cancer who had received neo-adjuvant CT and who have all undergone genetic testing at the Oncogenetics unit, Sheba Medical Centre to define their BRCA1 BRCA2 mutational status. pCR was defined as the absence of residual invasive carcinoma in the breast and axillary lymph nodes. Only women who received anthracycline based therapy were included. Women who had received concurrent trastuzumab in the neo-adjuvant setting were excluded. Statistical analysis included Fisher's exact test for categorical variables, and student t-test for continuous variables. Results: A total of 75 women were identified who had received neo-adjuvant chemotherapy and who had undergone genetic testing. Overall, 61 were BRCA non-carriers and 14 harbored BRCA1/2 mutations (5 BRCA1 mutation carriers and 9 BRCA2 mutation carriers). There were no statistically significant differences between the BRCA1/2 positive and BRCA1/2 negative groups with regard to mean age, grade 3 histology, hormone receptor status or HER2/neu over-expression, and clinical T and N staging. Seven women received anthracycline based CT and 68 received an anthracycline and taxane regimen. No statistically significant differences existed between the two groups with regards to chemotherapy treatment protocol. Amongst women with a BRCA1/2 mutation 50% had a pCR compared with only 21% in BRCA-negative women, p=0.035. Conclusions: Women with BRCA1/2 mutations demonstrated a higher pCR compared with women who were BRCA negative. Further studies that encompass more mutation carriers with a prospective design are needed to optimize choice of chemotherapy agents in BRCA1/2 positive breast cancer patients in order to exploit the putative biological mechanisms underlying the seemingly unique chemo-sensitivity in this subset of patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5104.