Does Axillary Reverse Mapping Prevent Lymphedema After Lymphadenectomy?

BACKGROUND: We hypothesized that disconcerting lymphedema rates in both sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) may be because of unrecognized vunerable variations in arm lymphatic drainage within the axilla. Axillary reverse mapping (ARM) facilitates identification and avoidance of arm lymphatics within the axilla and its use may reduce lymphedema. METHODS: This institutional review board-approved study from June 2007 to December 2013 involved patients undergoing SLNB with or without ALND, or ALND alone. Technetium is injected subareolarly for localization of the breast SLN and isosulfan blue dye (5 mL) is injected in the ipsilateral upper arm for localization of nonbreast lymphatics. Data were collected on identification and preservation of arm lymphatics, crossover rates, blue node metastases, axillary recurrence, and lymphedema as measured by volume displacement. RESULTS: A total of 654 patients prospectively underwent 685 ARM procedures with a SLNB and/or ALND. Objective lymphedema rates for SLNB and ALND were 0.8% and 6.5% respectively, with 26-month median follow up. Blue lymphatics were identified in 29.2% (138/472) of SLNB and 71.8% (153/213) of ALND. Crossover was seen in 3.8% (18/472) of SLNB and 5.6% (12/213) of ALND. Blue node metastases rate was 4.5% (2/44). Axillary recurrence rate was 0.2% and 1.4% for SLNB and ALND, respectively. CONCLUSIONS: ARM allows frequent identification of arm lymphatics in the axilla, which would have been transected during routine surgery. Rates of metastases in noncrossover nodes and axillary recurrences are low. Lymphedema rates are dramatically reduced using ARM when compared with accepted standards.

Whey Protein Hydrolysate but not Whole Whey Protein Protects Against 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumors in Rats.

Effects of intact and processed bovine milk proteins on development of chemically induced mammary tumors in female rats were compared. AIN-93G diets were made with 20% casein (CAS), casein hydrolysate (CASH), intact whey protein (IWP), or whey protein hydrolysate (WPH). Pregnant Sprague-Dawley rats were fed the diets starting at Gestational Day 4. Offspring were fed the same diet. At 50 days, female offspring (44-49/group) were gavaged with sesame oil containing 80 mg/kg of the mammary carcinogen dimethylbenzanthracene (DMBA) and euthanized 62 days posttreatment. Rats fed WPH had an adenocarcinoma incidence of 17% compared to the rats fed CAS, CASH, and IWP diets (34%, 33%, and 36% respectively) (P < 0.001). Median palpable tumor latency for rats fed WPH was greater (61 days, P < 0.001) compared to CAS (44 days), CASH (42 days) and IWP (45 days). Tumor multiplicity was also lower (1.5 vs. 3.0, P < 0.05) in rats fed WPH than in CAS and CASH fed groups. Results demonstrate that hydrolytic processing of whey protein is required for this diet to be effective in reducing DMBA-induced mammary tumors. The bioactive compounds produced during whey protein processing and mechanisms underlying the anticancer effects of WPH are yet to be identified.

Surgeon-performed touch preparation of breast core needle biopsies may provide accurate same-day diagnosis and expedite treatment planning.

BACKGROUND: We aimed to determine the accuracy of surgeon-performed touch-preparation cytology (TPC) of breast core-needle biopsies (CNB) and the ability to use TPC results to initiate treatment planning at the same patient visit. METHODS: A single-institution retrospective review of TPC results of ultrasound-guided breast CNB was performed. All TPC slides were prepared by surgeons performing the biopsy and interpreted by the pathologist. TPC results were reported as positive/suspicious, atypical, negative/benign, or deferred; these were compared with final pathology of cores to calculate accuracy. Treatment planning was noted as having taken place if the patient had requisition of advanced imaging, referrals, or surgical planning undertaken during the same visit. RESULTS: Four hundred forty-seven CNB specimens with corresponding TPC were evaluated from 434 patient visits, and 203 samples (45.4 %) were malignant on final pathology. When the deferred, atypical, and benign results were considered negative and positive/suspicious results were considered positive, sensitivity and specificity were 83.7 % (77.9-88.5 %) and 98.4 % (95.9-99.6 %), respectively; positive and negative predictive values were 97.7 % (94.2-99.4 %) and 87.9 % (83.4-91.5 %), respectively. In practice, patients with atypical or deferred results were asked to await final pathology. An accurate same-day diagnosis (TPC positive/suspicious) was hence feasible in 83.7 % (170 of 203) of malignant and 79.5 % (194 of 244) of benign cases (TPC negative). Of patients who had a same-day diagnosis of a new malignancy, 77.3 % had treatment planning initiated at the same visit. CONCLUSIONS: Surgeon-performed TPC of breast CNB is an accurate method of same-day diagnosis that allows treatment planning to be initiated at the same visit and may serve to expedite patient care.

Rare breast cancer: 933 adenoid cystic carcinomas from the National Cancer Data Base.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare subtype of breast malignancy. METHODS: Patients with ACC and infiltrating ductal carcinoma (IDC) reported to the National Cancer Data Base from 1998 to 2008 were reviewed for patient age, ethnicity, tumor size, nodal status, American Joint Committee on Cancer TNM Stage, tumor grade, initial treatment, hormone receptor status (for patients from 2004 to 2008), and survival (for patients from 1998 to 2003). RESULTS: A total of 933 patients with ACC and 729,938 with IDC were identified. No differences were found for incidence by race/ethnicity (p = 0.97). The group with ACC was older (median 60 vs. 58 years), had larger tumors (median 18 vs. 16 mm), had more grade 1 tumors (46 vs. 18 %), was less likely to undergo axillary lymph node evaluation (75.9 vs. 96.3 %), had fewer node-positive patients (5.1 vs. 35.5 %), had fewer estrogen receptor-positive tumors (15.4 vs. 75.6 %), had fewer progesterone receptor-positive tumors (13.3 vs. 65.2 %), and underwent breast-conserving surgery more often (69.8 vs. 59.8 %). Chemotherapy was provided less often for ACC (11.3 vs. 46.4 %), as was hormone therapy (9.1 vs. 42.3 %). All of these differences were statistically significant (p < 0.0001). With a median follow-up of 65.7 months (ACC) and 64.9 months (IDC), 5-year overall survival (OS) was 88 % for ACC vs. 84 % for IDC (p = 0.02). Grade 1 OS (ACC, 91 % vs. IDC, 92 %; p = 0.50) and stage I OS (ACC, 90 % vs. IDC, 91 %; p = 0.93) were equal. CONCLUSIONS: Compared with IDC, ACC has different characteristics (lower grade, hormone receptor negative, node negative), is treated differently (less axillary surgery, fewer mastectomies, less chemotherapy, less hormone therapy), and has an improved prognosis, with 88 % 5-year survival.

Nipple skin-sparing mastectomy is feasible for advanced disease.

BACKGROUND: Skin-sparing mastectomy (SSM) or nipple skin-sparing mastectomy (NSSM) are procedures commonly offered as part of the surgical treatment for breast cancer. Each involves a mastectomy with preservation of the skin overlying the breast (in SSM) and often also the skin overlying the nipple-areolar complex (NSSM). At the time of mastectomy, immediate reconstruction with a tissue expander or implant is performed for a more favorable cosmetic outcome. Until now, these procedures have been reserved for low-risk patients and are rarely offered to patients with advanced disease where neoadjuvant chemotherapy and postmastectomy radiation are a planned part of the treatment. We report our experience of SSM and NSSM in such high-risk patients. METHODS: This retrospective study from 2001 to 2012 evaluates the outcomes of 527 patients who underwent SSM or NSSM. Sixty patients with advanced disease who underwent neoadjuvant chemotherapy followed by SSM or NSSM with immediate reconstruction and subsequent radiotherapy (RT) were identified. The cosmetic and oncologic outcomes of this patient group were noted. RESULTS: A total of 527 patients in our study group had a total of 1,035 skin-sparing mastectomies (558 NSSM and 477 SSM; 444 patients with bilateral and 83 with unilateral procedures). Of the 60 patients with locally advanced disease, 39 underwent NSSM and 21 underwent SSM. All patients received RT to the diseased side. Mean age of the group was 50.2 ± 10.8 years, with a range of 27-75 years for NSSM and 29-73 years for SSM. The lymph node status was positive in 71.8 % with an average tumor size of 3.8 ± 2.5 cm. The overall radiation-induced complication rate was 38.1 % (8 of 21) in the SSM group and 30.8 % (12 of 39) in the NSSM group. Wound infections and tissue necrosis occurred at a rate of 16.7 %. The implant was removed in 5 % of these cases. Capsular contracture occurred at a rate of 10.2 %. Radiation-related nonbreast complications occurred in 6.7 % of the cases. Examples of these radiation-related nonbreast complications included radiation pneumonitis, stenosis of the superior vena cava requiring venoplasty and severe atypical chest pain thought to be consistent with osteochondritis. The locoregional recurrence rate (median follow-up of 18 months) was 14.3 % (3 of 21) in the SSM group and 10.3 % (4 of 39) in the NSSM group. CONCLUSIONS: SSM and NSSM have been offered to patients with relatively low-risk breast cancer as oncologically safe while affording superior cosmesis with one-step immediate reconstruction. Our series demonstrates that either procedure can be offered to patients with more advanced cancers requiring postoperative RT. The complication rates are comparable to those reported for patients undergoing RT after traditional mastectomies.

Long-Term Feeding Soy Protein Concentrates Protect Against Hepatic Steatosis Independent of Isoflavone Levels.

The health benefits of soy foods are attributed to the high-quality protein and the bioactive compounds such as isoflavones. We previously reported that feeding obese (fa/fa) Zucker rats soy protein concentrates (SPCs) with low isoflavone (LIF) and high isoflavone (HIF) for 9 weeks significantly reduced liver steatosis compared to a casein control (C) diet. The current study extended the dietary treatments to 18 weeks to investigate the long-term effect of LIF and HIF SPC diets. 6-week-old male lean (L, n = 21) and obese (O, n = 21) Zucker rats were fed a casein C diet, LIF and HIF SPC diets for 18 weeks and body weight (BW) was recorded twice weekly. Rats were killed after 18 weeks to measure liver steatosis and serum aspartate aminotransferase and alanine aminotransferase. Obese rats had significantly greater final BW, liver weight, liver weight as the percentage of BW, and steatosis score compared to lean rats in all three dietary groups. The obese high-isoflavones (OHIF) group had significantly higher BW compared to obese control (OC) group (P < .0001) and obese low-isoflavones (OLIF) group (P = .01). OC group had significantly greater liver weight, liver weight as the percentage of BW, and liver steatosis score compared to OLIF (P = .0077, P < .0001 and P < .0001, respectively) and OHIF (P = .0094, P < .0001, and P < .0001, respectively) groups. Taken together, long-term feeding of SPC diets protected against liver steatosis regardless of isoflavone levels.

Long-term results of excision followed by radiofrequency ablation as the sole means of local therapy for breast cancer.

INTRODUCTION: Clinical trials have yet to find a size or grade of invasive cancer which can be treated with lumpectomy alone due to the higher local recurrence (LR) rate without radiation (XRT). Excision followed by radiofrequency ablation (eRFA) is an intraoperative method which utilizes heat to create an additional tumor-free zone around the lumpectomy cavity. We hypothesized that eRFA after lumpectomy for invasive breast cancer could reduce the need for re-excision in close margins and potentially maintain local control without the need for XRT. METHODS: This institutional review board-approved study from July 2002 to December 2010 involved patients undergoing eRFA. A standard lumpectomy was performed and then the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 °C for 15 min. Validated doppler sonography was used to determine final ablation size. RESULTS: Seventy-three patients (mean age of 68.8 ± 10.9 years) with invasive cancer who had an average tumor size of 1.0 ± 0.54 cm (range of 0.2-2.6 cm) underwent eRFA. Margins were negative in 54, close in 10, focally positive in 6, and grossly positive in 3 patients. Sixteen out of 19 (84 %) of patients with close or positive margins were spared of re-excision. Median follow-up was 55 ± 21 months. Only one patient (1.3 %) developed an in site recurrence. There were three recurrences, elsewhere. CONCLUSIONS: Long-term follow-up suggests that eRFA may reduce the need for re- excision as well as reduce LR for invasive breast cancer treated without XRT.

Diet Containing Soy Protein Concentrate With Low and High Isoflavones for 9 Weeks Protects Against Non-alcoholic Fatty Liver Steatosis Using Obese Zucker Rats.

Non-alcoholic fatty liver disease (NAFLD), is one of the main liver diseases in the US and the world which often is related to obesity. Previously, we reported short- and long-term consumption of soy protein isolate diet with high isoflavones can reduce liver steatosis in the male and female obese Zucker rat model. However, the effects of high vs. low soy isoflavones on NAFLD is less known. The objectives of the present study were to examine the role of isoflavones levels in soy protein concentrate diets on protection against NAFLD in an obese rat model. Forty-two 6-week old lean (L, n = 21) and obese (O, n = 21) Zucker rats were randomly assigned to 1 of 3 dietary groups: casein diet (C = control), soy protein concentrate with low isoflavones (LIF), or soy protein concentrate with high isoflavones (HIF) for 9 weeks. Rats were weighed twice weekly. After 9 weeks, rats were sacrificed and samples of livers were taken for histopathological analysis. Serums were collected to measure ALT and AST levels. Results indicate that obese rats gained significantly more weight than lean rats for all three diet groups (P < 0.001). No significant difference in body weight between LC, LLIF and LHIF was noted. However, the OLIF and OHIF rats gained significantly more weight than OC rats (P < 0.001). Liver steatosis scores were significantly greater in obese rats compared to lean rats (P < 0.001). The OLIF and OHIF-fed rats had significantly reduced steatosis scores than OC rats (P = 0.013 and P < 0.001, respectively). The serum ALT levels were significantly greater in OC, OLIF and OHIF compared to LC, LLIF and LHIF, respectively (P < 0.001, P < 0.001, and P = 0.011). AST serum levels were greater in OC and OLIF compared to LC and LLIF, respectively (P = 0.001 and P = 0.022). In summary, we found that soy protein concentrate with isoflavones protects against liver steatosis and the protection is greater with a higher concentration of isoflavones.

Intraoperative injection of subareolar or dermal radioisotope results in predictable identification of sentinel lymph nodes in breast cancer.

OBJECTIVE: Our objective is to prove that injection of technetium-99m (Tc99) sulfur colloid in a subareolar manner, after induction of anesthesia, is a safe and effective technique for sentinel lymph node identification in breast cancer patients. INTRODUCTION: Preoperative injection of Tc99 and lymphoscintigraphy is standardly performed before sentinel lymph node biopsy (SLNB) for breast cancer. Blue dye is often used to help guide and confirm the localization but tattoos the breast. This method is limited because of painful injections, variable identification rates, added costs and unnecessary scheduling delays. We hypothesized that intraoperative injection alone by the surgeon of dermal or subareolar Tc99 is practical for the identification of sentinel lymph node in breast cancer. METHODS: This is a prospective single institution study that was approved by our institutional review board. All patients with operable breast cancer that were eligible for a SLNB from October 2002 to October 2010 were included in our study population. After induction and before sterile preparation of the operative field 1 mCi of Tc-99 unfiltered was administered by a subareolar injection. In patients where the scar was in the periareolar region or in the upper outer quadrant a dermal injection using 0.25mCi was used. Confirmatory Lymphazurin was also injected early on in this series but became unnecessary later in the study. Site and type of injection, injection time, incision time, and extraction time along with other factors for the purposes of the study were recorded. Data comparing injection preoperative and intraoperative were collected. RESULTS: Six hundred ninty-nine patients were accrued for a SLNB with an average age 57.1 ± 12.8 (range 24-92). Seventy-six patients underwent 2 SLNB procedures for a total of 775 intraoperative Tc-99 injections. Six patients underwent intraoperative dermal injection with Tc-99. The average dose of Tc-99 administered was 1.157 ± 0.230 mCi. The sentinel node was localized in 98.6% of the cases (419/425) of subareolar radiotracer alone, 94.8% (326/344) in dual injection and 100% (6/6) in dermal injection. Average time from injection to incision was 41.20 ± 29.56 minutes for radiotracer injection in subareolar region only. For dermal injections it was 40.83 ± 39.64 minutes. For patients with dual injection of Lymphazurin and radiotracer it was 31.74 ± 24.86 minutes. The average ex vivo count was 6474 ± 8395 for dermal injection, 28,250 ± 69,932 for Tc-99 subareolar injection, and 35,501 ± 97,753 for dual subareolar injection. Intraoperative radiotracer alone incurred a charge of $189.00; Lymphazurin blue dye added $591.40, whereas preoperative injection had a charge of $1257.06 associated with imaging, injection, and interpretation of images. CONCLUSION: Intraoperative injection of Tc99 alone with a subareolar or dermal injection technique rapidly localizes the sentinel node in breast cancer, is an oncologically sound procedure, is cost effective and facilitates operative room time management.

Sensitivity of axillary specimen x-ray to predict nodal count and positivity.

BACKGROUND: The number of examined axillary lymph nodes (ALN) has been proposed as an indicator of prognosis along with quality and adequacy in breast cancer surgery. The purpose of this study was to examine the utility of imaging axillary specimens with x-ray (lymphogram) to determine the number of lymph nodes. We sought to determine the sensitivity and specificity of a lymphogram in identifying nodal positivity. METHODS: Patients who underwent sentinel lymph node (SLN) and axillary lymph node dissections (ALND) were prospectively accrued to this double-blinded, single-institution trial from December 2009 to January 2011. A single physician interpreted all lymphograms for the number of ALNs and positivity determined by size, spiculations, irregularities, and calcifications. RESULTS: Twenty female (age 50.8 ± 14.3 years) patients were accrued to the study. The lymphogram located more lymph nodes compared with pathology in 11 of 16 cases (68.8%). In these 11 cases, lymphogram identified 170 nodes and the pathologist located 132 (77.6%). Of the 16 ALND specimens, 6 were from patients naive to chemotherapy and averaged 13.8 ± 6.6 nodes; 10 were from neoadjuvant chemotherapy patients and had an average number of 14.9 ± 7.4 nodes. In neoadjuvant chemotherapy patients, sensitivity of the lymphogram to detect nodal positivity was 91.7% and specificity was 33.3%. CONCLUSIONS: This study demonstrated that lymphogram accurately identifies nodal count. This can be used for documentation of an adequate ALND for reimbursement. Furthermore, there may be potential value of lymphogram in intraoperative determination of nodal positivity.

Feasibility of percutaneous excision followed by ablation for local control in breast cancer.

PURPOSE: Percutaneous ablation of breast cancer has shown promise as a treatment alternative to open lumpectomy. We hypothesized that percutaneous removal of breast cancer followed by percutaneous ablation to sterilize and widen the margins would not only provide fresh naive tissue for tumor marker and research investigation, but also better achieve negative margins after ablation. METHODS: Patients diagnosed by percutaneous biopsy (ultrasound or stereotactic-guided) with breast cancer ≤1.5 cm, >1 cm from the skin, and ≤1 cm residual disease and no multicentric disease by magnetic resonance imaging were accrued to this institutional review board-approved study. Patients were randomized to laser versus radiofrequency ablation. The ultrasound-guided ablation was performed in the operating room and followed by immediate excision, whole-mount pathology with proliferating cell nuclear antigen staining, and reconstruction. RESULTS: Twenty-one patients were enrolled onto the study. Fifteen patients received radiofrequency ablation, and all showed 100% ablation and negative margins. Magnetic resonance imaging was helpful in excluding multicentric disease but less so in predicting presence or absence of residual disease. Seven of these patients showed no residual tumor and eight showed residual dead tumor (0.5 ± 0.7 cm, range 0.1-2.5 cm) at the biopsy site with clear margins. The laser arm (3 patients) pathology demonstrated unpredictability of the ablation zone and residual live tumor. CONCLUSIONS: This pilot study demonstrates the feasibility of a novel approach to minimally invasive therapy: percutaneous excision and effective cytoreduction, followed by radiofrequency ablation of margins for the treatment of breast cancer. Laser treatment requires further improvement.

Intraoperative sentinel lymph node analysis in melanoma.

BACKGROUND: The objective of this retrospective cohort study was to evaluate the sensitivity and specificity of touch preparation cytology (TPC) and frozen section (FS) histology in the intraoperative staging of melanoma. METHODS: The cohort was identified from all patients with clinically node negative melanoma undergoing a SLN biopsy using Technetium and/or blue dye mapping from 1/1998 to 10/2008. TPC and FS analysis was performed utilizing Diff-quick and compared to permanent section interpretation with H&E. RESULTS: Of 271 patients undergoing SLN biopsy, 163 underwent intraoperative analysis of the sentinel node (125 underwent TPC alone, 15 underwent FS alone, 23 underwent both TPC and FS), and 108 underwent no intraoperative analysis. Thirty-three patients undergoing intraoperative analysis of the SLN were found to have positive nodes (20%) on permanent histology. There were no false positives identified (specificity = 100%). The overall sensitivity for all methods of intraoperative analysis was 61% (20/33). On a per patient basis, the sensitivity was 47% (9/19) for TPC alone, 75% (3/4) for FS alone, and 80% (8/10) for both TPC and FS. CONCLUSIONS: There were no false positives identified suggesting TPC and FS can be used safely to identify the majority of SLN that harbor metastases from melanoma.

Effects of obesity and 10 weeks metformin treatment on liver steatosis.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in adolescents and adults, and the risk of developing NAFLD increases with obesity. In the present study, it was shown that obesity increased fatty liver (steatosis) using an obese Zucker rat model. Metformin is an oral anti-hyperglycemic agent approved by the FDA for treatment of type 2 diabetes in adults and children >10 years of age. There is insufficient evidence regarding the effects of metformin on pediatric liver steatosis. Thus, in the present study, the effects of 10 weeks metformin treatment on liver steatosis and related serum markers for liver damage was assessed. Lean and obese (n=16 per group) 5-week old female Zucker rats were provided an AIN-93 G diet for 8 weeks to induce NAFLD, and then rats were randomly assigned to 4 groups (8 rats/group): i) lean without metformin (LC), ii) lean + metformin (LM), iii) obese without metformin (OC), and iv) obese + metformin (OM). Rats were provided ad libitum access to the diet containing metformin (1 g metformin per kg of food). Rats were weighed twice weekly and were sacrificed 10 weeks later. Serum was collected to measure the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), leptin and adiponectin. Livers were collected for histological analysis. The results showed that obese rats gained significantly more weight than lean rats in both the control and metformin treatment groups (P<0.001). OM treated rats exhibited a lower degree of liver steatosis compared with the OC rats (P<0.04). There were no significant differences in serum ALT levels between the groups. However, obesity significantly increased serum AST levels in both the control and metformin treatment groups (P=0.01). The ratio of leptin to adiponectin was increased in obese compared with the lean rats in both the control and metformin treatment groups (P<0.0001). There was no effect of metformin on serum biomarkers. In summary, short-term metformin treatment decreased liver steatosis but did not affect the serum markers of liver steatosis.

Ten-year experience with hematoma-directed ultrasound-guided (HUG) breast lumpectomy.

BACKGROUND: Pain, patient inconvenience, vasovagal symptoms, scheduling problems, wire malposition, and a positive margin rate of 40-75% are problems commonly associated with needle localized biopsy (NLBB). Despite these issues, NLBB is still the primary means of identifying nonpalpable lesions in the breast. We hypothesized that the hematoma-directed ultrasound-guided (HUG) procedure for intraoperative localization of nonpalpable lesions would allow for lumpectomy without the downfalls of needle localization and decrease the high positive-margin rate with NLBB. METHODS: This is a retrospective study from January 2000 to October 2009. Electronic chart review identified lumpectomy procedures performed in the clinic and operating room. These patients underwent preoperative core-biopsy diagnosis by ultrasound (US) or stereotactic means. When excision was necessary needle localization or HUG was planned. A multifrequency linear array transducer was used intraoperatively for the HUG procedures, and a block of tissue surrounding the hematoma was removed. RESULTS: Localization procedures were performed in 455 patients: 126 (28%) via needle localization and 329 (72%) via HUG. The previous core-biopsy site in 100% of patients was successfully excised using HUG: 152 of 329 (46%) were benign and 177 of 329 (54%) were malignant. Margins were positive in 42 of these 177 cases (24%). was successful in 100% of patients: 88 of 126 (70%) were benign and NLBB 38 of 126 (30%) were malignant; margins were positive in 18 of these 38 (47%). Margin positivity was significantly higher for NLBB than HUG (P = 0.045, Fisher exact). CONCLUSIONS: This 10-year experience, representing the largest to date, suggests that HUG is more accurate in localizing nonpalpable lesions than NLBB. Compared with the additional painful procedure of NLBB, HUG is more time and cost-efficient. Preoperative needle core biopsy is not only the minimally invasive diagnostic procedure of choice, but also becomes the localization procedure when excisional biopsy is necessary.

Enhanced mammary progesterone receptor-A isoform activity in the promotion of mammary tumor progression by dietary soy in rats.

Dietary contribution to breast cancer risk, recurrence, and progression remains incompletely understood. Increased consumption of soy and soy isoflavones is associated with reduced mammary cancer susceptibility in women and in rodent models of carcinogenesis. In rats treated with N-methyl-N-nitrosourea, dietary intake of soy protein isolate (SPI) reduced mammary tumor occurrence but increased incidence of more invasive tumors in tumored rats, relative to the control diet casein. Here we evaluated whether mammary tumor progression in tumor-bearing rats lifetime exposed to SPI is associated with deregulated progesterone receptor (PR) isoform expression. In histologically normal mammary glands of rats with invasive ductal carcinoma lesions, PR-A protein levels were higher for SPI- than casein-fed rats, whereas PR-B was undetectable for both groups. Increased mammary PR-A expression was associated with higher transforming growth factor-beta1, stanniocalcin-1, and CD44 transcript levels; lower E-cadherin and estrogen receptor-alpha expression; and reduced apoptotic status in ductal epithelium. Serum progesterone (ng/ml) (CAS: 25.94 +/- 3.81; SPI: 13.19 +/- 2.32) and estradiol (pg/ml) (CAS: 27.9 +/- 4.49; SPI: 68.48 +/- 23.87) levels differed with diet. However, sera from rats of both diet groups displayed comparable mammosphere-forming efficiency in human MCF-7 cells. Thus, soy-rich diets may influence the development of more aggressive tumors by enhancing PR-A-dependent signaling in premalignant breast tissues.

Short-Duration Rapid Chilling of Mastectomy Specimens Does Not Interfere With Breast Cancer Biomarker and Molecular Testing.

CONTEXT.­: A thorough gross examination of specimens for breast cancer requires the tissue to be very thinly sectioned, which is often difficult in large mastectomy samples. We have implemented rapid chilling of mastectomy specimens before formalin fixation. OBJECTIVE.­: To evaluate the effects of rapid chilling of breast tissue on subsequent biomarker and molecular testing. DESIGN.­: Mastectomy specimens were chilled at -80°C for 20 minutes to facilitate uniform sectioning of tissue at 4-mm intervals and enhance proper fixation and identification of small lesions. The integrity of chilled tissue for ancillary and molecular testing was assessed. We identified patients who were diagnosed with breast cancer on biopsy at outside institutions and subsequently underwent mastectomy at our institution during 2010-2014. We compared the results of biomarker testing performed on biopsy tissue with those performed on mastectomy tissue. The quantity and quality of DNA extracted from formalin-fixed, paraffin-embedded (FFPE) mastectomy tissue with invasive carcinoma were assessed by using spectrophotometry and polymerase chain reaction. All Oncotype DX reports from 2011-2014 were reviewed to identify any documented evidence of assay interference caused by rapid chilling of tissue. RESULTS.­: We found essentially 100% concordances in estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 gene ERBB2 (HER2/neu) studies. Extracted tumor DNA showed suitable purity and concentration that produced amplified fragments of 300 to 400 base pair lengths by polymerase chain reaction of FFPE tissue. No documented assay interferences were found in the Oncotype DX reports. CONCLUSIONS.­: Short-duration rapid chilling of mastectomy tissue improves gross examination, optimally preserves DNA, allows for molecular testing, and does not interfere with biomarker assessment.

Comparison of liver gene expression by RNAseq and PCR analysis after 8 weeks of feeding soy protein isolate- or casein-based diets in an obese liver steatosis rat model.

Previously, we reported that feeding soy protein isolate (SPI) reduced liver steatosis in obese rats compared to those fed a casein (CAS)-based diet; however, the mechanism for this protection is unknown. To gain insight into the ability of SPI to ameliorate liver steatosis, we conducted transcriptomic (RNAseq) analysis on liver samples from obese rats fed either the SPI- or CAS-based diets (n = 8 per group) for 8 weeks using an Ilumina HiSeq with 100 base paired end reads for sequencing. Data were analyzed by Ingenuity Pathway Analysis (IPA) software using a P < 0.05 and 1.3-fold differential expression cutoff values between the SPI- and CAS-based groups. To independently validate the RNAseq data, we conducted targeted mRNA expression analysis using quantitative PCR (qPCR) on a subset of differently expressed genes. The results indicate that mRNA expression by qPCR concurred with RNAseq for NPTX2, GPT, INMT, and HAL that were up-regulated in SPI-fed rats (P < 0.05) and PRSS8, AJUBA, CSF2RB, and Cyp2c12 that were down-regulated (P < 0.05) in SPI-fed rats compared to CAS-fed rats. Our findings may shed light on understanding mechanisms enabling SPI diet to reduce liver steatosis in this obese Zucker rat model.

Intraoperative radioisotope injection for sentinel lymph node biopsy.

BACKGROUND: Preoperative injection of technetium-99 m sulfur colloid (Tc-99) in the Nuclear Medicine Department for localizing sentinel lymph nodes (SLNs) can be extremely painful for the patient. The difficulties in scheduling and the delay in starting surgery can be frustrating for the patient and the surgeon. We hypothesized that intraoperative injection facilitated by the subareolar technique would obviate the problems associated with preoperative injection. METHODS: We performed an institutional review board-approved prospective study of patients with operable breast cancer who were candidates for an SLN biopsy from October 2002 to January 2006 at our institution. After induction of general anesthesia, patients underwent a subareolar injection of 1 mCi Tc-99 unfiltered and blue dye. Data comparing preoperative cost were collected. RESULTS: A total of 236 patients had 252 intraoperative SLN procedures. The mean patient age was 57.3 (range, 24-88) years. The mean +/- standard deviation time from injection to incision was 25.5 +/- 16.2 minutes. Identification rate was 96%, and the number of SLNs identified per patient was 1.6 +/- .8. The count of SLN was 60,313 +/- 134,692 with 20% SLN positivity. Tumor staging distribution was standard staging terminology for an in situ cancer (Tis) = 17 with 0% (+) SLN, T1 = 115 with 11% (+) SLN, T2 = 56 with 29% (+) SLN, T3 = 19 with 37% (+) SLN, and T4 = 4 with 50% (+) SLN. Maximum exposure to the surgeon was well below maximum, at 100 microSV/mo. Preoperative injection had an additive charge of $1325 associated with it for imaging, injection, and interpretation of images by physician. CONCLUSION: Intraoperative subareolar injection of Tc-99 localizes the SLN and avoids the pain, vasovagal events, delays, and cost associated with preoperative procedure.

Expression analysis of carbohydrate antigens in ductal carcinoma in situ of the breast by lectin histochemistry.

BACKGROUND: The number of breast cancer patients diagnosed with ductal carcinoma in situ (DCIS) continues to grow. Laboratory and clinical data indicate that DCIS can progress to invasive disease. Carbohydrate-mediated cell-cell adhesion and tumor-stroma interaction play crucial roles in tumorigenesis and tumor aggressive behavior. Breast carcinogenesis may reflect quantitative as well as qualitative changes in oligosaccharide expression, which may provide a useful tool for early detection of breast cancer. Because tumor-associated carbohydrate antigens (TACA) are implicated in tumor invasion and metastasis, the purpose of this study was to assess the expression of selected TACA by lectin histochemistry on DCIS specimens from the archival breast cancer tissue array bank of the University of Arkansas for Medical Sciences. METHODS: For detection of TACA expression, specimens were stained with Griffonia simplicifolia lectin-I (GS-I) and Vicia vilosa agglutinin (VVA). We studied associations of lectin reactivity with established prognostic factors, such as tumor size, tumor nuclear grade, and expression of Her-2/neu, p53 mutant and estrogen and progesterone receptors. RESULTS: We observed that both lectins showed significant associations with nuclear grade of DCIS. DCIS specimens with nuclear grades II and III showed significantly more intense reactivity than DCIS cases with nuclear grade I to GS-1 (Mean-score chi-square = 17.60, DF = 2; P = 0.0002) and VVA (Mean-score chi-square = 15.72, DF = 2; P = 0.0004). CONCLUSION: The results suggest that the expression of VVA- and GS-I-reactive carbohydrate antigens may contribute to forming higher grade DCIS and increase the recurrence risk.

Cytokine and chemokine expression associated with steatohepatitis and hepatocyte proliferation in rats fed ethanol via total enteral nutrition.

To determine the temporal relationship between alcohol-induced changes in cytokines and chemokines, development of liver pathology and stimulation of hepatocyte proliferation, male Sprague-Dawley rats were intragastrically fed low carbohydrate-containing ethanol (EtOH) diets via total enteral nutrition (TEN) for up to 49 d. Induction of EtOH metabolism and appearance of steatosis preceded development of oxidative stress, inflammation, and cell death. A transitory peak of tumor necrosis factor (TNFalpha) and interferon gamma (IFN gamma) was observed at 14 d followed by reduced expression of TNFalpha, IFN gamma and another Th1 cytokine IL-12 accompanied by reduced expression of the Th1 regulators T-bet and STAT4. After 35-49 d of EtOH, at a time when hepatocyte proliferation was stimulated, IL-12 returned to control values and a second peak of TNFalpha occurred. The Th2 cytokine IL-4 remained suppressed throughout the study and was accompanied by reductions in the Th2 regulator GATA3. There was no temporal effect of EtOH on expression of IL-6 or TGFbeta. IL-5 and IL-13 mRNA were undetectable. Chemokine CXCL-2 expression increased progressively up to 35 d and preceded the appearance of inflammatory infiltrates. These data suggest that steatosis, increased ethanol metabolism, a transient induction of the innate immune response and suppression of Th2 responses were acute consequences of ethanol treatment and were followed by suppression of Th1 responses. However, the majority of necrosis, apoptosis and a late peak of TNFalpha only occurred after 6-7 weeks of ethanol, coincided with the appearance of inflammatory infiltrates and were associated with stimulation of hepatocyte proliferation.