Elisabeth R. Garwood

Total Skin-sparing Mastectomy: Complications and Local Recurrence Rates in 2 Cohorts of Patients

Purpose:Dissemination of the total skin-sparing mastectomy (TSSM) technique is limited by concerns of nipple viability, flap necrosis, local recurrence risk, and the technical challenge of this procedure. We sought to define the impact of surgical and reconstructive variables on complication rates and assess how changes in technique affect outcomes. Patients and Methods:We compared the outcomes of TSSM in 2 cohorts of patients. Cohort 1: the first 64 TSSM procedures performed at our institution, between 2001 and 2005. Cohort 2: 106 TSSM performed between 2005 and 2007. Outcomes of cohort 1 were analyzed in 2005. At that time, potential risk factors for complications were identified, and efforts to minimize these risks by altering operative and reconstructive technique were then applied to patients in cohort 2. The impact of these changes on outcomes was assessed. Logistic regression was used to determine the association between predictor variables and adverse outcomes (Stata 10). Results:The predominant incision type in cohort 2 involved less than a third of the nipple areola complex (NAC), and the most frequent reconstruction technique was tissue expander placement. Between cohort 1 and cohort 2, nipple survival rates rose from 80% to 95% (P = 0.003) and complication rates declined: necrotic complications (30% → 13%; P = 0.01), implant loss (31% → 10%; P = 0.005), skin flap necrosis (16%–11%; not significant), and significant infections (17%–9%, not significant). Incisions involving >30% of the NAC (P < 0.001) and reconstruction with autologous tissue (P < 0.001) were independent risk factors for necrotic complications. The local recurrence rate was 0.6% at a median follow-up of 13 months (range, 1–65), with no recurrences in the NAC. Conclusion:Focused improvement in technique has resulted in the development of TSSM as a successful intervention at our institution that is oncologically safe with high nipple viability and early low rates of recurrence. Identifying factors that contribute to complications and changing surgical and reconstructive techniques to eliminate risk factors has greatly improved outcomes.

The effects of acellular dermal matrix in expander-implant breast reconstruction after total skin-sparing mastectomy: results of a prospective practice improvement study.

Background: Neither outcome after total skin-sparing mastectomy and expander-implant reconstruction using acellular dermal matrix nor a strategy for optimal acellular dermal matrix selection criteria has been well described. Methods: Prospective review of three patient cohorts undergoing total skin-sparing mastectomy with preservation of the nipple-areola complex and immediate expander-implant reconstruction from 2006 to 2010 was performed. Cohort 1 (no acellular dermal matrix) comprised 90 cases in which acellular dermal matrix was not used. Cohort 2 (consecutive acellular dermal matrix) included the next 100 consecutive cases, which all received acellular dermal matrix. Cohort 3 (selective acellular dermal matrix) consisted of the next 260 cases, in which acellular dermal matrix was selectively used based on mastectomy skin flap thickness. Complication rates were compared using chi-square analysis. Results: The study included 450 cases in 288 patients. Mean follow-up was 25.5 months. Infection occurred in 27.8 percent of the no–acellular dermal matrix cases, 20 percent of the consecutive cases, and 15.8 percent of the selective cases (p = 0.04). Unplanned return to the operating room was required in 23.3, 11, and 10 percent of cases, respectively (p = 0.004). Expander-implant loss occurred in 17.8, 7, and 5 percent of cases, respectively (p = 0.001). Additional analysis of the odds ratios of developing complications after postmastectomy radiation therapy demonstrated a specific protective benefit of acellular dermal matrix in irradiated patients. Conclusions: Acellular dermal matrix use in expander-implant reconstruction after total skin-sparing mastectomy reduced major postoperative complications in this study. Maximal benefit is achieved with selected use in patients with thin mastectomy skin flaps and those receiving radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Parkinsonism in patients with a history of amphetamine exposure

We recently found a higher rate of prolonged amphetamine exposure in patients diagnosed with Parkinsons disease (PD) than in spouse/caregiver controls. Since distinguishing features have been described in some patients with parkinsonism due to environment exposures (e.g., manganese), we sought to compare the clinical features of patients with PD with prolonged amphetamine exposure with unexposed patients with PD. Prolonged exposure was defined as a minimum of twice a week for ≥3 months, or weekly use ≥1 year. We reviewed the clinical records of patients with PD who had participated in a telephone survey of drug and environmental exposures and compared the clinical features of patients with a history of prolonged amphetamine exposure to patients who had no such exposure. Records were available for 16 of 17 (94%) patients with prior amphetamine exposure and 127 of 137 (92%) of those unexposed. Age at diagnosis was younger in the amphetamine‐exposed group (49.8 ± 8.2 years vs. 53.1 ± 7.4 years; P < 0.05), but other features, including presenting symptoms, initial and later treatments, development of motor fluctuations, and MRI findings were similar between these groups. Because we did not detect clinical features that differentiate parkinsonism in patients with prolonged amphetamine exposure, research to determine whether amphetamine exposure is a risk factor for parkinsonism will require detailed histories of medication and recreational drug use.

Spontaneous hemoperitoneum from a ruptured mesenteric branch arterial aneurysm: Report of a case

We report a case of spontaneous intraperitoneal hemorrhage from a ruptured mesenteric branch artery aneurysm in a patient presenting with syncope. A 54-year-old woman was brought to our emergency department as a medical code, following two syncopal episodes. Computed tomography, carried out to rule out aortic aneurysmal disease, revealed hemoperitoneum without evidence of solid organ injury. Emergency exploratory laparotomy revealed a large jejunal mesenteric hematoma accompanying a ruptured mesenteric branch artery aneurysm with active extravasation. We ligated and excised the lesion and diagnosis was confirmed on final pathologic examination. We report this case because general surgeons should be aware of these vascular lesions and the basic guidelines for treatment.

Fluvastatin has biologic effects on stage 0 and 1 breast cancer.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #4122 Introduction: Statins are safe, reduce cardiovascular risk, and impact pathways critical to cancer progression. We and others have shown lipophilic statins cause apoptosis and growth suppression in vitro and in vivo, and though epidemiologic data are mixed, statin effect appears most evident in estrogen receptor (ER) negative or grade 3 disease. To look for a direct biologic effect of lipophilic statins, we conducted a perioperative pilot window trial in women with breast cancer (BC). Methods: 40 subjects with stage 0,1 BC were randomized to high dose (80mg/day) or low dose (20mg/day) fluvastatin for 3-6 weeks prior to surgery. Paired tissue (core biopsy and surgical specimen), peripheral blood and MRI were obtained. Primary endpoint was Ki-67 (proliferation) change. Secondary endpoints included cleaved caspase-3 (CC3, apoptosis), longest diameter (LD) by MRI, and C-reactive protein (CRP) change. Subgroup analyses was planned by grade (3 vs. 1,2), statin dose; and ER status. Immunohistochemistry (IHC) on paraffin tissue used standard streptavidin biotin methods. A single breast pathologist reviewed all slides; a single radiologist read all MRIs, both blinded to timepoint. Results: Median serum cholesterol decreased by 16% (-23% and -12% for high and low dose, respectively p=0.012), indicating drug effect and compliance. 29 patients had sufficient tumor for paired IHC, 14 and 15 were grade 3 and 1,2, and 10 and 19 were ER - and +, respectively. In grade 3 (73% of which were ER-) vs. 1,2 tumors, there was a significant decrease in Ki-67, -7.2% (interquartile range (IQR) -13.4%, 0% ) vs. -0.3% (IQR -3%, .8%), respectively, p=0.04. CC3 (apoptosis) increased, 60% vs. 13% for grade 3 vs. 1,2 tumors, respectively, p=0.015. ER- and ER+ cases had a similar reduction in Ki67 with a median drop of 2% (IQR -13.4%, 1%) and 1.2% (IQR -6.6%,0.8%), respectively, p=0.56. While CC3 was increased in ER- vs. + (55% vs. 29%), the difference was not statistically significant. There was no dose dependent effect on Ki-67or CC3.There was no evidence of Ki67 or CC3 change when all grades were analyzed together (median drop 1.2%) and no change in CRP. Of 14 subjects with paired MRIs, 4 grade 3 cases showed a significant decrease in LD, marked ductal dilatation and increased necrosis.with statin exposure. Conclusions: A lipophilic statin, fluvastatin, reduced cholesterol and had measurable biologic changes (reduced proliferation, size and increased apoptosis) in stage 0,1 BC after only 3-6 weeks of exposure, specifically in the grade 3 subset. Results support the study of statins for chemoprevention for women at risk for or with stage 0 grade 3 BC, where new agents are needed. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4122.

M1541 Hybrid Laparoscopic-Open Resection for Rectal Carcinoma Is Oncologically Safe: A Long-Term Follow Up Study

PURPOSE: The hybrid laparoscopic-open procedure was devised as a means of providing benefits of minimally invasive methods to rectal cancer patients in whom a fully laparoscopic operation may not be feasible. Hybrid methods use a small infra-umbilical incision to perform open TME and cancer resection after closed splenic flexure mobilization, proximal devascularization, and division of the proximal bowel. Currently, we perform laparoscopic, hand-assisted and hybrid procedures. The purpose of this study is to assess the pathologic and long-term oncologic results of hybrid resection for rectal carcinoma. METHODS: We retrospectively reviewed pathologic and oncologic data from 75 patients who underwent hybrid rectal cancer resection at Columbia University from 1995 to 2004. Mean follow up was 3.3yrs. Half of our population had follow up for mean of 5.3yrs. RESULTS: Procedures included rectosigmoidectomy=10, LAR=49 and APR=15. Tumors were located in the proximal=28, middle=29 and distal=18 rectum. Anastomoses included EEA=57 and hand-sewn coloanal=3. Diverting stomas were used in 19 patients. Mean results of clinical and pathologic outcome data are: incision length 10cm (SD 4.5); days to flatus 3.8 (SD 2), length of stay 7.4days (SD 4), distal margin 3.2cm (SD 1.5), proximal margin 19.7cm (SD 7.2), lymph node harvest 14 (SD 7.5). 5-year disease-free survival for hybrid rectal resections was 80%; 28 patients (37%) had preop XRT (figure). CONCLUSIONS: Hybrid rectal resections do not compromise LN harvest or margins and are feasible even in the context of neoadjuvant radiation therapy. Our 5-year disease-free survival of 80% is comparable to rates achieved by open surgery (64%, SEER data).

Association of Proliferating Macrophages with High Grade, Hormone Receptor Negative Breast Cancer.

Macrophages, a key cell in the inflammatory cascade, have been associated with poor prognosis in cancers, including breast cancer. Tumor associated macrophages (TAM) have also been shown to play a role in invasion and metastases. In this study, we investigated the role of a subset of macrophages known as proliferating macrophages (promacs) in breast cancer. We examined the relationship between promacs and clinico-pathologic characteristics such as tumor size, grade, lymph node metastasis, hormone receptor status, molecular subtype, and survival. This study was conducted at two independent institutions (University of California, San Francisco and University of Chicago) using two independent cohorts of patients with breast cancer. Formalin-fixed, paraffin-embedded sections and/or tissue microarrays were double-stained with anti-CD68 (a macrophage marker) and anti-PCNA (a proliferation marker) antibodies. The number of total macrophages as well as promacs per high power field were counted. Molecular subtypes were determined from gene expression array analyses. Outcomes were available for a subset of the cases and Kaplan Meier survival curves were generated.Tumor tissue from two different cohorts of patients with breast cancer were stained and analyzed at two independent institutions. In both studies, promac density was significantly correlated with higher grade, hormone-receptor negative tumors, and a basal-like subtype. In contrast there was no correlation between numbers of promacs and tumor size, stage, or number of involved lymph nodes. The presence of increased promacs was a significant predictor of survival in these treated patients. Proliferating macrophages are more abundant in high grade tumors, and predict a worse outcome, independent of stage and grade. These findings, corroborated at two independent institutions, suggest that the presence of promacs is associated with tumor progression and increased promac density may serve as a prognostic indicator for poor outcomes. Novel therapies that are able to target and halt the activity of promacs may be a promising strategy for the treatment of promac rich tumors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3042.

Investigation of colony stimulating factor-1 receptor (CSF-1R) expression in peripheral monocytes of breast cancer patients for tumor associated macrophages (TAM): A pilot study

22221 Background: Colony stimulating factor-1 (CSF-1) mediates macrophage (MO) differentiation, proliferation, and survival through colony stimulating factor-1 receptor (CSF-1R, c-FMS, CD115). Tumo...