Ahva Shahabi

A systematic review and meta-analysis of complications associated with acellular dermal matrix-assisted breast reconstruction

Background:Multiple outcome studies have been published on the use of acellular dermal matrix (ADM) in breast reconstruction with disparate results. The purpose of this study was to conduct a systematic review and meta-analysis to determine an aggregate estimate of risks associated with ADM-assisted breast reconstruction. Methods:The MEDLINE, Web of Science, and Cochrane Library databases were queried, and relevant articles published up to September 2010 were analyzed based on specific inclusion criteria. Seven complications were studied including seroma, cellulitis, infection, hematoma, skin flap necrosis, capsular contracture, and reconstructive failure. A pooled random effects estimate for each complication and 95% confidence intervals (CI) were derived. For comparisons of ADM and non-ADM, the pooled random effects odds ratio (OR) and 95% CI were derived. Heterogeneity was measured using the I2 statistic. Results:Sixteen studies met the inclusion criteria. The pooled complication rates were seroma (6.9%; 95% CI, 5.3%–8.8%), cellulitis (2.0%; 95% CI, 1.2%–3.1%), infection (5.7%; 95% CI, 4.3%–7.3%), skin flap necrosis (10.9%; 95% CI, 8.7%–13.5%), hematoma (1.3%; 95% CI, 0.6%–2.4%), capsular contracture (0.6%; 95% CI, 0.1%–1.7%), and reconstructive failure (5.1%; 95% CI, 3.8%–6.7%). Five studies reported findings for both the ADM and non-ADM patients and were used in the meta-analysis to calculate pooled OR. ADM-assisted breast reconstructions had a higher likelihood of seroma (pooled OR, 3.9; 95% CI, 2.4–6.2), infection (pooled OR, 2.7; 95% CI, 1.1–6.4), and reconstructive failure (pooled OR, 3.0; 95% CI, 1.3–6.8) than breast reconstructions without the use of ADM. The relation of ADM use to hematoma (pooled OR, 2.0; 95% CI, 0.8–5.2), cellulitis (pooled OR, 2.0; 95% CI, 0.9–4.3), and skin flap necrosis (pooled OR, 1.9; 95% CI, 0.6–5.4) was inconclusive. Conclusions:In the studies evaluated, ADM-assisted breast reconstructions exhibited a higher likelihood of seroma, infection, and reconstructive failure than prosthetic-based breast reconstructions using traditional musculofascial flaps. ADM is associated with a lower rate of capsular contracture. A careful risk/benefit analysis should be performed when choosing to use ADM in implant-based breast reconstruction.

ANALYSIS OF RISK FACTORS ASSOCIATED WITH MICROVASCULAR FREE FLAP FAILURE USING A MULTI-INSTITUTIONAL DATABASE

There are numerous factors that may contribute to microvascular free flap failure. Although technical issues are dominant factors, patient and clinical characteristics are also contributory. The aim of this study was to investigate non‐technical variables associated with microsurgical free flap failure using a multi‐institutional dataset.

Effect of immediate reconstruction on postmastectomy surgical site infection.

Introduction:Surgical site infections (SSI) are a source of significant postoperative morbidity and cost. Although immediate breast reconstruction after mastectomy has become routine, the data regarding the incidence of SSI in immediate breast reconstruction is highly variable and series dependent. Methods:Using the National Surgical Quality Improvement Program database, all female patients undergoing mastectomy, with or without immediate reconstruction, from 2005 to 2009 were identified. Only “clean” procedures were included. The primary outcome was incidence of SSI within 30 days of operation. Stepwise logistic regression analysis was used to identify risk factors associated with SSI. Results:A total of 48,393 mastectomies were performed during the study period, of which 9315 (19.2%) had immediate breast reconstruction. The incidence of SSI was 3.5% (330/9315) (95% CI [confidence interval]: 3.2%–4%) in patients undergoing mastectomy with reconstruction and 2.5% (966/39,078) (95% CI: 2.3%–2.6%) in patients undergoing mastectomy without reconstruction (P < 0.001). Independent risk factors for SSI include increased preoperative body mass index (BMI), heavy alcohol use, ASA (American Society of Anesthesiologists) score greater than 2, flap failure, and operative time of 6 hours or longer. Conclusions:Immediate breast reconstruction is associated with a statistically significant increase in risk of SSI in patients undergoing mastectomy (3.5% vs 2.5%). However, this difference was not considered to be clinically significant. In this large series, increased BMI, alcohol use, ASA class greater than 2, flap failure, and prolonged operative time were associated with increased risk of SSI.

Incidence of surgical-site infection is not affected by method of immediate breast reconstruction.

Background: To date, few large-scale studies have reported the incidence of surgical-site infection in women undergoing mastectomy with respect to the various methods of immediate breast reconstruction. This study assessed whether the reconstruction method was associated with the risk of surgical-site infection in these patients. Methods: Using the National Surgical Quality Improvement Program database, 9230 female patients undergoing mastectomy with immediate reconstruction from 2005 to 2009 were identified. Reconstruction was classified as autologous, prosthetic, or hybrid. The primary outcome was the incidence of surgical-site infection within 30 days of operation. Univariate and multivariate analyses were performed to derive the unadjusted and adjusted risk of surgical-site infection according to reconstruction method. Results: The overall rate of surgical-site infection was 3.53 percent (95 percent CI, 3.15 to 3.94 percent), with individual rates of 3.33 percent (95 percent CI, 2.93 to 3.76 percent) for prosthetic reconstruction, 4.88 percent (95 percent CI, 3.48 to 6.11 percent) for autologous reconstruction, and 2.19 percent (95 percent CI, 0.88 to 4.45 percent) for hybrid reconstruction. The adjusted odds ratio of surgical-site infection was 1.14 (95 percent CI, 0.83 to 1.58; p = 0.42) for autologous versus prosthetic methods and 0.59 (95 percent CI, 0.27 to 1.27; p = 0.18) for hybrid versus prosthetic methods. Conclusions: Although the risk of surgical-site infection in patients undergoing immediate reconstruction is highest with autologous and lowest with hybrid methods of reconstruction, the difference in infection risk was not statistically significant after adjustment for confounding factors. Thus, all methods of reconstruction are viable options with regard to risk for surgical-site infection. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study.

The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case–Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0–1.6). Among non‐Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1–2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0–1.9). However, no associations were observed between smoking intensity, duration or pack‐year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African‐Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P‐interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non‐Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk.

Genetic admixture and risk of hypertensive disorders of pregnancy among Latinas in Los Angeles County.

Background: Latinos are a heterogeneous population in terms of demographics, culture, and genetic admixture from three racial groups (white, African, and Native American). This study examines the role of genetic ancestry and environmental risk factors in the risk of hypertensive disorder of pregnancy among Latinas in Los Angeles County. Methods: Gestational hypertension, preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome cases (n = 125), plus unaffected controls (n = 161), were recruited from Los Angeles County + University of Southern California Women’s and Children’s Hospital from 1999 through 2008. Diagnoses were confirmed with extensive chart review. Personal information, demographics, and biospecimens were collected from all participants. Ancestry informative markers were used to estimate genetic ancestry proportions. Results: After adjusting for European ancestry and key risk factors, African ancestry was positively associated with hypertensive disorders of pregnancy risk for the highest vs. the lowest quartiles of African ancestry (odds ratio = 2.6 [95% confidence interval = 1.1–6.1]). This association was stronger among women born in Mexico with parents born in Mexico (4.3 [1.4–13]). The results from generalized additive models showed a positive association between joint European/African ancestry and hypertensive disorders of pregnancy risk and an inverse association between Native American ancestry and risk. These associations were stronger among women of Mexican origin. Conclusion: Our findings suggest that higher Native American ancestry among Latinas may protect against hypertensive disorders of pregnancy. Further studies are needed to determine whether this protective effect is driven by specific alleles present in this population or by other risk factors that correlate with Native American ancestry.

Novel Gene Expression Signature Predictive of Clinical Recurrence After Radical Prostatectomy in Early Stage Prostate Cancer Patients.

Current clinical tools have limited accuracy in differentiating patients with localized prostate cancer who are at risk of recurrence from patients with indolent disease. We aimed to identify a gene expression signature that jointly with clinical variables could improve upon the prediction of clinical recurrence after RP for patients with stage T2 PCa.

Predictors of time to biochemical recurrence in a radical prostatectomy cohort within the PSA-era

INTRODUCTION We sought to determine predictors for early and late biochemical recurrence following radical prostatectomy among localized prostate cancer patients. METHODS The study included localized prostate cancer patients treated with radical prostatectomy (RP) at the University of Southern California from 1988 to 2008. Competing risks regression models were used to determine risk factors associated with earlier or late biochemical recurrence, defined using the median time to biochemical recurrence in this population (2.9 years after radical prostatectomy). RESULTS The cohort for this study included 2262 localized prostate cancer (pT2-3N0M0) patients who did not receive neoadjuvant or adjuvant therapies. Of these patients, 188 experienced biochemical recurrence and a subset continued to clinical recurrence, either within (n=19, 10%) or following (n=13, 7%) 2.9 years after RP. Multivariable stepwise competing risks analysis showed Gleason score ≥7, positive surgical margin status, and ≥pT3a stage to be associated with biochemical recurrence within 2.9 years following surgery. Predictors of biochemical recurrence after 2.9 years were Gleason score 7 (4+3), preoperative prostate-specific antigen (PSA) level, and ≥pT3a stage. CONCLUSIONS Higher stage was associated with biochemical recurrence at any time following radical prostatectomy. Particular attention may need to be made to patients with stage ≥pT3a, higher preoperative PSA, and Gleason 7 prostate cancer with primary high-grade patterns when considering longer followup after RP.

Abstract B59: Predictors of early versus late biochemical recurrence after open radical prostatectomy in a patient cohort with T2/T3N0M0 prostate cancer treated within the PSA-era

Abstract Introduction: Patients treated with radical prostatectomy (RP) differ in their risk of prostate cancer (PCa) recurrence. By determining factors associated with an increased risk of biochemical (PSA) recurrence (BCR), patients can be provided with personalized care to prevent disease progression. Identifying which patients are at risk of earlier versus later BCR after surgery is of interest in order to guide monitoring of disease progression and treatment options. Objectives: We evaluated variables associated with PCa progression among a patient population treated with RP. In particular, we examined factors associated with earlier BCR (≤5 years post-RP) versus later BCR (>5 years post-RP) taking into account potential differences across racial/ethnic groups present in this population. Methods: An IRB approved database was used to obtain data on a patient population at USC/Norris Comprehensive Cancer Center with pathologically confirmed localized PCa (T2/T3) without lymph node involvement who underwent RP in the PSA era (1988-2009). We analyzed data on 2,485 patients after excluding individuals treated with neo-adjuvant hormonal therapy. Kaplan Meier and Cox regression analyses were used to evaluate biochemical recurrence-free survival (BCRFS) and risk of BCR adjusting for clinical variables. Results: Among the 2,485 patients, 268 (11%) experienced BCR. Of these individuals, 212 (79%) had BCR ≤5 years after RP versus 56 (21%) >5 years after surgery. The median (range) of follow-up time among patients without any recurrence is 7.45 (2.0-20.4) years and among patients with BCR is 2.9(0.17-15.12) years. The racial distribution is 2,163 (87%) Non-Hispanic White (NHW), 126 (5%) Hispanic, 95 (4%) African-American, and 78 (3%) Asian/Pacific Islander, with 23 patients excluded due to unknown race. Compared to other racial/ethnic groups, more African-American men were diagnosed when younger than 65 years old (66%) (p 10-20 ng/ml, Gleason score 8-10, 61-65 years of age at diagnosis, and extracapsular extension. Radiation therapy and race/ethnicity were not significantly associated with BCR in the multivariate Cox regression for either BCR group. Conclusions: Certain clinical characteristics of localized prostate cancer patients may be useful in determining who is at risk of earlier or later BCR following RP. These data can improve prognosis by providing guidance in determining the appropriate length of time to monitor disease progression and possible treatment options for patients. Citation Format: Ahva Shahabi, Inderbir S. Gill, Gary Lieskovsky, Eila C. Skinner, Siamak Daneshmand, Jacek Pinski, Mariana C. Stern. Predictors of early versus late biochemical recurrence after open radical prostatectomy in a patient cohort with T2/T3N0M0 prostate cancer treated within the PSA-era [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B59.

Abstract B79: Tobacco smoking, polymorphisms in xenobiotic metabolism enzyme genes, and prostate cancer risk and survival

Introduction: The association between tobacco smoking and prostate cancer (PCa) risk and progression remains unclear. This study examined the association between tobacco smoking and risk of localized and advanced PCa, PCa-specific mortality, and overall mortality in African-American, Hispanic and non-Hispanic White men. Polymorphisms in xenobiotic metabolism enzyme genes were further examined as possible modifiers of associations with smoking. Methods: Using data from the California Collaborative Prostate Cancer Study, a multiethnic population-based case-control study conducted in Los Angeles County (631 advanced and 533 localized cases; 594 controls) and the San Francisco Bay Area (568 advanced and 208 localized cases; 545 controls), we evaluated associations between tobacco smoking and risk of localized and advanced PCa using conditional logistic regression. Cox proportional hazards regression models and Kaplan Meier curves with log-rank tests were used to assess associations with PCa-specific and all-cause mortality. Median follow-up time for cases was 8.8 years (IQR: 6.2-9.9). We also investigated the role of 12 metabolism enzyme single nucleotide polymorphisms from 7 genes as potential modifiers of the relationship between tobacco smoking and PCa risk and progression using interaction models. Results: After adjusting for age, PCa family history, body mass index, alcohol consumption, intake of meat cooked at high temperature, and use of snuffing/chewing tobacco, non-Hispanic Whites who were former smokers had an increased risk of localized PCa when compared to never smokers (OR=1.52, 95%CI: 1.11-2.09, p<0.01). Risk increased with younger age at first tobacco use (p-trend<0.01), duration of tobacco smoking (p-trend=0.01), number of daily cigarettes smoked (p-trend=0.02), and cigarette pack-years (p-trend=0.03). Current smoking was associated with an increased risk of advanced PCa (OR=1.41, 95%CI: 1.02-1.94, p=0.037) among non-Hispanic Whites, but a decreased risk among Hispanics (OR=0.48, 95%CI: 0.23-0.99, p=0.047). No significant trends were seen for any of the smoking variables among Hispanics or African-Americans. A CYP1A2 polymorphism (rs7662551) modified the relationship between smoking status and PCa risk; the addition of each C-allele increased risk for localized (p-interaction=0.01) and advanced (p-interaction=0.03) PCa, particularly among current smokers. Tobacco smoking was not associated with PCa-specific mortality. For all-cause mortality, increased risk was associated with current smoking, duration of smoking, cigarette pack-years, and young age at first smoking. Kaplan Meier survival probabilities for current smokers were 77% from all-cause mortality and 89% from PCa-specific mortality. Conclusions: We observed that tobacco smoking was associated with risk of localized and advanced PCa primarily among Non-Hispanic Whites. Moreover, we observed that tobacco smoking was associated with all-cause mortality, albeit no associations were observed for PCa-specific mortality. Genetic variation in CYP1A2 seems to modify the relationship of tobacco smoking status and PCa risk, but not mortality. Citation Format: Ahva Shahabi, Roman Corral, Chelsea Catsburg, Amit D. Joshi, Jocelyn Koo, Esther M. John, Sue A. Ingles, Mariana C. Stern. Tobacco smoking, polymorphisms in xenobiotic metabolism enzyme genes, and prostate cancer risk and survival. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B79.