Prognostic Factors for Metachronous Contralateral Breast Cancer: Implications for Management of the Contralateral Breast.

The absolute number of breast cancer survivors who are at risk for metachronous contralateral breast cancer (mCBC) has dramatically increased. The objectives of this study were to identify factors predictive of survival for patients with mCBC and to determine clinicopathological factors predictive of advanced mCBC. Using the Surveillance, Epidemiology, and End Results data base, we identified women, ages 18-80, diagnosed with invasive breast cancer from 1992 to 2010. We excluded patients with bilateral and stage IV primary breast cancer. Patients who developed mCBC ≥12 months from initial diagnosis were identified. Kaplan-Meier methods and Cox proportional hazards modeling were used to determine survival of patients with mCBC. Multivariate logistic regression was utilized to determine factors associated with advanced mCBC. We identified 6,673 patients who developed mCBC during our study period. The median interval between initial breast cancer and mCBC was 5 years. The strongest predictor of overall survival was the nodal status of the mCBC. Other significant prognostic factors included patient age; race; size, nodal status, estrogen receptor status, grade, and type of surgery of the initial breast cancer; grade of the mCBC; and use of radiation therapy for the mCBC. Overall, 25% of mCBCs were node positive. Younger age, black race, and characteristics of the initial breast cancer (increased size, invasive lobular histology, mastectomy treatment, and node-positivity) were significantly associated with node-positive mCBC (all p < 0.0.05). The most powerful predictor of survival for patients with mCBC is the nodal status of mCBC. Patients with advanced initial breast cancers are more likely to develop node-positive mCBC. Adherence to current surveillance and adjuvant therapy guidelines may minimize the risk and mortality of mCBCs.

Postmastectomy Reconstruction Outcomes After Intraoperative Evaluation with Indocyanine Green Angiography Versus Clinical Assessment.

BACKGROUND: Mastectomy flap necrosis is a major complication in patients undergoing tissue expander-based reconstruction. This study compared the complication rates following mastectomy and immediate reconstruction with intraoperative indocyanine green (ICG) angiography evaluation to those with clinical assessment only. METHODS: We performed a single-institution retrospective study of mastectomy patients who underwent immediate tissue expander-based reconstruction between September 2009 and December 2013. ICG angiography was adopted in March 2012. The rates of complications in the ICG and clinical assessment only groups were compared. Factors associated with complications were identified with the Fischer exact test and univariate analysis. RESULTS: A total of 114 patients were identified; clinical assessment only, 53 patients; ICG angiography, 61 patients. The overall complication rates were not significantly different between the two groups (ICG angiography, 50.8 %; clinical assessment, 43.4 %; p = 0.46). There was no significant difference in the rates of unexpected return to the operating room, cellulitis, hematomas, and seromas. The overall rates of flap necrosis were not significantly different (ICG angiography, 27.9 %; clinical assessment, 18.9 %; p = 0.28). However, the rates of severe flap necrosis were significantly lower with intraoperative ICG angiography (4.9 %) than with clinical assessment only (18.9 %, p = 0.02). On univariate analysis, breast weight (≥500 g) was significantly associated with increased rates of severe flap necrosis (p = 0.04), whereas body mass index, age, smoking status, prior breast surgery, history of radiation therapy, and receipt of nipple-sparing mastectomy were not. CONCLUSIONS: We observed that the implementation of intraoperative ICG angiography was associated with a significant decrease in the rate of severe flap necrosis.

Completion Lymph Node Dissection or Observation for Melanoma Sentinel Lymph Node Metastases: A Decision Analysis.

BACKGROUND: Long-term, randomized trial results comparing completion lymph node dissection (CLND) with observation for patients with sentinel lymph node (SLN) metastases are not available. Our goal was to determine whether melanoma patients with SLN metastases should undergo CLND. METHODS: We developed a Markov model to simulate the prognosis of hypothetical cohorts of patients with SLN metastases who underwent either immediate CLND or observation with delayed CLND if macroscopic disease developed. Model parameters were derived from published studies and included the likelihood of non-SLN metastases, risk of dying from melanoma, CLND complication rates, and health-related quality-of-life weights. Outcomes included 5-year overall survival (OS), life expectancy (LE), and quality-adjusted life expectancy (QALE). RESULTS: The projected 5-year OS for 50-year-old patients with SLN metastases who underwent immediate CLND was 67.2 % compared with 63.1 % for the observation group. The LE gained by undergoing immediate CLND ranged from 2.19 years for patients aged 30 to 0.64 years for patients aged 70 years. The QALE gained by undergoing immediate CLND ranged from 1.39 quality-adjusted life years for patients aged 30 to 0.36 for patients aged 70 years. In sensitivity analysis over a clinically plausible range of values for each input parameter, immediate CLND was no longer beneficial when the rate of long-term complications increased and the quality-of-life weight for long-term complications decreased. CONCLUSIONS: Immediate CLND following positive SLN biopsy was associated with OS and QALE gains compared with observation and delayed CLND for those who develop clinically apparent LN metastases.

Lymph node evaluation for treatment of adenocarcinoma of the pancreas.

BACKGROUND: Increased lymph node evaluation has been associated with improved survival rates in patients with pancreatic cancer. We sought to evaluate the trends and factors associated with lymph node examination over time and the effects on survival. METHODS: Using the Surveillance, Epidemiology and End Results database, we conducted an analysis of adults with adenocarcinoma of the pancreas who underwent surgical resection. Using the Cochrane Armitage test for trend and logistic regression we identified factors associated with lymph node evaluation. Kaplan-Meier and Cox proportional hazards modeling were used to examine survival. RESULTS: We identified 4831 patients who underwent surgical resection from 1990 to 2010. The proportion of patients with 15 or more lymph nodes evaluated increased from 16% to 42% (p < 0.05) and the median number of lymph nodes examined increased from 7 to 15 nodes (p < 0.05) during the study period. Overall, 56% of patients had lymph node metastases; this proportion significantly increased during the study period. Factors that were independently associated with less than 15 lymph nodes evaluated included male gender, receipt of pre-operative radiation therapy, early year of diagnosis, older age, and missing information on tumor grade and size (p < 0.05). Survival rates significantly improved when 15 or more lymph nodes were examined. CONCLUSION: We observed a significant increase in the number of lymph nodes evaluated with pancreas cancer resection over time. Lymph node evaluation was significantly associated with patient, tumor, and treatment characteristics. Our results suggest that adequate lymph node evaluation is associated with improved survival.

Trends in the use of pre-operative radiation for adenocarcinoma of the pancreas in the United States.

BACKGROUND: The benefit and timing of radiation therapy (RT) for patients undergoing a resection for pancreatic adenocarcinoma remains unclear. This study identifies trends in the use of radiation over a 10-year period and factors associated with the use of pre-operative radiation, in particular. METHODS: The Surveillance, Epidemiology and End Results registry was used to identify patients aged ≥18 years with pancreatic adenocarcinoma who underwent a surgical resection between 2000 and 2010. Logistic regression was used to identify time trends and factors associated with the use of pre-operative radiation. RESULTS: The overall use of radiation decreased with time among the 8474 patients who met the inclusion criteria. However, the use of pre-operative radiation increased from 1.8% to 3.9% (P ≤ 0.05). Factors significantly associated with receipt of pre-operative radiation were younger age, treatment in more recent years and having an advanced T-stage tumour. The 5-year hazard of death was significantly less for those who received pre-operative radiation versus surgery alone [hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.55-0.74] and for those who received post-operative radiation versus surgery alone (HR 0.69, 95% CI 0.65-0.73). DISCUSSION: The use of pre-operative radiation significantly increased during the study period. However, the overall use of pre-operative radiation therapy remains low in spite of the potential benefits.

Perceptions of Contralateral Breast Cancer Risk: A Prospective, Longitudinal Study.

PURPOSE: An increasing proportion of breast cancer patients undergo contralateral prophylactic mastectomy (CPM) to reduce their risk of contralateral breast cancer (CBC). Our goal was to evaluate CBC risk perception changes over time among breast cancer patients. METHODS: We conducted a prospective, longitudinal study of women with newly diagnosed unilateral breast cancer. Patients completed a survey before and approximately 2 years after treatment. Survey questions used open-ended responses or 5-point Likert scale scoring (e.g., 5 = very likely, 1 = not at all likely). RESULTS: A total of 74 women completed the presurgical treatment survey, and 43 completed the postsurgical treatment survey. Baseline characteristics were not significantly different between responders and nonresponders of the follow-up survey. The mean estimated 10-year risk of CBC was 35.7 % on the presurgical treatment survey and 13.8 % on the postsurgical treatment survey (p < 0.001). The perceived risks of developing cancer in the same breast and elsewhere in the body significantly decreased between surveys. Both CPM and non-CPM (breast-conserving surgery or unilateral mastectomy) patients' perceived risk of CBC significantly decreased from pre- to postsurgical treatment surveys. Compared with non-CPM patients, CPM patients had a significantly lower perceived 10-year risk of CBC (5.8 vs. 17.3 %, p = 0.046) on postsurgical treatment surveys. CONCLUSIONS: The perceived risk of CBC significantly attenuated over time for both CPM and non-CPM patients. These data emphasize the importance of early physician counseling and improvement in patient education to provide women with accurate risk information before they make surgical treatment decisions.

The rise in appendiceal cancer incidence: 2000-2009.

PURPOSE: Appendiceal cancer is a rare and potentially aggressive malignancy. The objectives of this study were to characterize secular demographic patterns of disease and to determine survival by using a population-based data source. METHODS: Using the Surveillance, Epidemiology, and End Results database, we conducted a retrospective cohort analysis of patients treated from 2000-2009. RESULTS: We identified 4765 patients with appendiceal cancer. The incidence of appendiceal cancer increased by 54% from 2000 (0.63 per 100,000) to 2009 (0.97 per 100,000 population). Incidence rates increased across all tumor types, stages, age groups, and gender. The most common malignancies were mucinous adenocarcinoma (38%), followed by carcinoids (28%), adenocarcinoma-not otherwise specified (NOS) (27%), and signet ring cell adenocarcinoma (7%). Larger tumor size and older patient age were significantly associated with higher relative odds of distant disease at diagnosis (P < 0.0001). Patient and demographic characteristics were significantly associated with higher relative hazard of death (P < 0.0001). CONCLUSIONS: Although appendiceal cancer is rare, the incidence increased significantly in the USA from 2000 to 2009. The cause of this trend is not obvious. We did not observe increases differentially associated with stage, histology, or demographic characteristics. Further investigation is needed to examine factors underlying this increase.

Prophylactic mastectomy: who needs it, when and why.

Prophylactic mastectomy generally occurs in two different patient populations: (1) high-risk women without breast cancer who undergo bilateral prophylactic mastectomy (BPM) to reduce their risk of developing breast cancer and (2) women with unilateral breast cancer who choose contralateral prophylactic mastectomy (CPM) to prevent cancer in the contralateral breast. The purpose of this article is to review the indications, outcomes, and trends in the use of BPM and CPM.

Survival outcomes after contralateral prophylactic mastectomy: a decision analysis.

BACKGROUND: Contralateral prophylactic mastectomy (CPM) rates have substantially increased in recent years and may reflect an exaggerated perceived benefit from the procedure. The objective of this study was to evaluate the magnitude of the survival benefit of CPM for women with unilateral breast cancer. METHODS: We developed a Markov model to simulate survival outcomes after CPM and no CPM among women with stage I or II breast cancer without a BRCA mutation. Probabilities for developing contralateral breast cancer (CBC), dying from CBC, dying from primary breast cancer, and age-specific mortality rates were estimated from published studies. We estimated life expectancy (LE) gain, 20-year overall survival, and disease-free survival with each intervention strategy among cohorts of women defined by age, estrogen receptor (ER) status, and stage of cancer. RESULTS: Predicted LE gain from CPM ranged from 0.13 to 0.59 years for women with stage I breast cancer and 0.08 to 0.29 years for those with stage II breast cancer. Absolute 20-year survival differences ranged from 0.56% to 0.94% for women with stage I breast cancer and 0.36% to 0.61% for women with stage II breast cancer. CPM was more beneficial among younger women, stage I, and ER-negative breast cancer. Sensitivity analyses yielded a maximum 20-year survival difference with CPM of only 1.45%. CONCLUSIONS: The absolute 20-year survival benefit from CPM was less than 1% among all age, ER status, and cancer stage groups. Estimates of LE gains and survival differences derived from decision models may provide more realistic expectations of CPM.

Contralateral prophylactic mastectomy: are we overtreating patients?

Patients with unilateral breast cancer are at increased risk for developing cancer in the contralateral breast. As a result, some patients choose contralateral prophylactic mastectomy (CPM) to prevent cancer in the contralateral breast. Several studies have reported that the CPM rates have markedly increased in recent years in the United States. In this article, we will discuss recent CPM trends, potential reasons patients choose CPM, outcomes after CPM, and alternative strategies for managing the increased risk of contralateral breast cancer among survivors of unilateral breast cancer. In addition, we will try to determine if women undergoing CPM are adequately informed about their decision.

Prospective multicenter trial evaluating balloon-catheter partial-breast irradiation for ductal carcinoma in situ.

PURPOSE: To determine outcomes of accelerated partial-breast irradiation (APBI) with MammoSite in the treatment of ductal carcinoma in situ (DCIS) after breast-conserving surgery. METHODS AND MATERIALS: We conducted a prospective, multicenter trial between 2003 and 2009. Inclusion criteria included age >18 years, core needle biopsy diagnosis of DCIS, and no prior breast cancer history. Patients underwent breast-conserving surgery plus MammoSite placement. Radiation was given twice daily for 5 days for a total of 34 Gy. Patients were evaluated for development of toxicities, cosmetic outcome, and ipsilateral breast tumor recurrence (IBTR). RESULTS: A total of 41 patients (42 breasts) completed treatment in the study, with a median follow up of 5.3 years. Overall, 28 patients (68.3%) experienced an adverse event. Skin changes and pain were the most common adverse events. Cosmetic outcome at 6 months was judged excellent/good by 100% of physicians and by 96.8% of patients. At 12 months, 86.7% of physicians and 92.3% of patients rated the cosmetic outcome as excellent/good. Overall, 4 patients (9.8%) developed an IBTR (all DCIS), with a 5-year actuarial rate of 11.3%. All IBTRs were outside the treatment field. Among patients with IBTRs, the mean time to recurrence was 3.2 years. CONCLUSIONS: Accelerated partial-breast irradiation using MammoSite seems to provide a safe and cosmetically acceptable outcome; however, the 9.8% IBTR rate with median follow-up of 5.3 years is concerning. Prospective randomized trials are necessary before routine use of APBI for DCIS can be recommended.

Trends in incidence and management of lobular carcinoma in situ: a population-based analysis.

PURPOSE: Lobular carcinoma in situ (LCIS) is a marker of increased risk of breast cancer. Current guidelines do not recommend mastectomy as a strategy for risk reduction for most patients with LCIS. We conducted a population-based study to evaluate national trends in incidence and management of LCIS. METHODS: Using the Surveillance, Epidemiology, and End Results database, we conducted a retrospective cohort analysis of women diagnosed with microscopically confirmed LCIS from 2000 through 2009. We excluded patients with invasive breast cancer or ductal carcinoma in situ. We evaluated variation in treatment, including biopsy alone, excision, excision with radiation therapy, and mastectomy. We utilized logistic regression to identify time trends, demographics, and patient factors associated with mastectomy. RESULTS: We identified 14,048 patients diagnosed with LCIS from 2000 to 2009. The rate of LCIS incidence increased from 2.0 per 100,000 in 2000 to 2.75 per 100,000 in 2009 (38 % increase). Of these patients, 10 % underwent biopsy only, 73 % underwent excision alone, 1 % underwent excision with radiation, and 16 % underwent mastectomy. Mastectomy rates were significantly higher among white and younger women. The proportion of women with LCIS to receive mastectomy increased by 50 % from 2000 to 2009 (p < 0.01). Mastectomy rates varied significantly based on geographic region ranging from 12 to 24 %. CONCLUSIONS: This is the first population-based analysis evaluating patterns and trends in surgical management of LCIS. Despite current recommendations, risk-reduction surgery is increasingly performed in the United States for women with LCIS.

Meta-analysis of bioabsorbable staple line reinforcement and risk of fistula following pancreatic resection.

BACKGROUND: Stapled pancreatic transection is widely used although pancreatic fistula remains a common post-surgical complication. METHODS: We performed a meta-analysis of existing data regarding pancreatic fistula following stapled pancreatic transection, comparing bare metal staples to reinforced staple loads. RESULTS: We identified ten manuscripts between 2007 and 2009 reporting outcomes following stapled division of the pancreas (five retrospective reviews, five prospective case series). A total of 483 stapled pancreatic resections are included in this meta-analysis. Of these, 234(48 %) were reinforced (REINF) and 249 (52 %) were bare staples (STPL). Out of 483 cases, there were a total of 100 documented pancreatic leaks (21 %). Sixty-one leaks were reported out of 249 STPL divisions (24 %), while 39 leaks were reported following REINF division (17 %). The overall relative risk of developing a pancreatic fistula following distal pancreatectomy was not significantly different comparing STPL to REINF when all studies were combined (RR 1.00, 95% CI 0.65-1.53). We further evaluated the data stratifying by study design (prospective or retrospective) and found that prospective studies reported a significantly higher risk of pancreatic fistula with STPL compared to REINF technique (RR 14.45, 95 % CI 3.15-66.21). CONCLUSION: Reinforced staples may be a preferred method of pancreatic stump closure following distal pancreatectomy.

Assessment of postoperative venous thromboembolism risk in plastic surgery patients using the 2005 and 2010 Caprini Risk score.

BACKGROUND: Venous thromboembolism is an important patient safety issue. The authors sought to compare the predictive capacity of the 2005 and 2010 Caprini Risk Assessment Models for perioperative venous thromboembolism risk. METHODS: The authors performed a retrospective, observational, crossover study using an established surgical outcomes database. A total of 3334 adult plastic surgery patients were identified. Patients were risk-stratified using both the 2005 and 2010 Caprini Risk Assessment Models. Each patient served as his or her own control, resulting in precise matching for identified and unidentified confounders. The outcome of interest was 60-day, symptomatic venous thromboembolism. The predictive capacities of the 2005 and 2010 Caprini risk scores were compared. RESULTS: Use of the 2010 Caprini Risk Assessment Model resulted in a systematic increase in the aggregate risk score. The median 2010 Caprini score was significantly higher than the median 2005 Caprini score (6 versus 5, p<0.001). When compared with the 2010 model, the 2005 Caprini Risk Assessment Model was able to better separate the lowest and highest risk patients from one another. Patients classified as "super-high" risk (Caprini score>8) using the 2005 Caprini Risk Assessment Model were significantly more likely to have a 60-day venous thromboembolism event when compared with patients classified as super-high risk using the 2010 guidelines (5.85 percent versus 2.52 percent, p=0.021). CONCLUSIONS: When compared with the 2010 Caprini Risk Assessment Model, the 2005 Caprini Risk Assessment Model provides superior risk stratification. The 2005 Caprini Risk Assessment Model is the more appropriate method to risk-stratify plastic surgery patients for perioperative venous thromboembolism risk. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

The effect of postoperative enoxaparin on risk for reoperative hematoma.

BACKGROUND: The risk of postoperative bleeding is the chief concern expressed by plastic surgeons who do not use pharmacologic prophylaxis against venous thromboembolism. The Plastic Surgery Foundation-funded Venous Thromboembolism Prevention Study examined whether receipt of postoperative enoxaparin prophylaxis changed 60-day reoperative hematoma rates. METHODS: In 2009, the study's network sites uniformly adopted a "best practice" clinical protocol to provide postoperative enoxaparin to adult plastic surgery patients at risk for perioperative venous thromboembolism. Historical control patients (2006 to 2008) received no chemoprophylaxis for 60 days after surgery. Retrospective chart review identified demographic and surgery-specific risk factors that potentially contributed to bleeding risk. The primary study outcome was 60-day reoperative hematoma. Stratified analyses examined reoperative hematoma in the overall population and among high-risk patients. Multivariable logistic regression controlled for identified confounders. RESULTS: Complete data were available for 3681 patients (2114 controls and 1567 enoxaparin patients). Overall, postoperative enoxaparin did not change the reoperative hematoma rate when compared with controls (3.38 percent versus 2.65 percent, p = 0.169). Similar results were seen in subgroup analyses for breast reconstruction (5.25 percent versus 4.21 percent, p = 0.737), breast reduction (7.04 percent versus 8.29 percent, p = 0.194), and nonbreast plastic surgery (2.20 percent versus 1.46 percent, p = 0.465). In the regression model, independent predictors of reoperative hematoma included breast surgery, microsurgical procedure, and post-bariatric surgery body contouring. Receipt of postoperative enoxaparin was not an independent predictor (odds ratio, 1.16; 95 percent CI, 0.77 to 1.76). CONCLUSION: Postoperative enoxaparin does not produce a clinically relevant or statistically significant increase in observed rates of reoperative hematoma. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk: II.

Postoperative enoxaparin prevents symptomatic venous thromboembolism in high-risk plastic surgery patients.

BACKGROUND: Venous thromboembolism is a major patient safety issue. The Plastic Surgery Foundation-sponsored Venous Thromboembolism Prevention Study examined whether postoperative enoxaparin prevents symptomatic venous thromboembolism in adult plastic surgery patients. METHODS: In 2009, four sites uniformly adopted a clinical protocol. Patients with a Caprini score of 3 or higher received postoperative enoxaparin prophylaxis for the duration of inpatient stay. Venous Thromboembolism Prevention Study historical control patients had an operation between 2006 and 2008 but received no chemoprophylaxis for 60 days after surgery. The primary study outcome was symptomatic 60-day venous thromboembolism. RESULTS: Three thousand three hundred thirty-four patients (1876 controls and 1458 enoxaparin patients) were included. Notable risk reduction was present in patients with a Caprini score greater than 8 (8.54 percent versus 4.07 percent; p=0.182) and a Caprini score of 7 to 8 (2.55 percent versus 1.15 percent; p=0.230) who received postoperative enoxaparin. Logistic regression was limited to highest risk patients (Caprini score≥7) and demonstrated that length of stay greater than or equal to 4 days (adjusted odds ratio, 4.63; p=0.007) and Caprini score greater than 8 (odds ratio, 2.71; p=0.027) were independent predictors of venous thromboembolism. When controlling for length of stay and Caprini score, receipt of postoperative enoxaparin was protective against venous thromboembolism (odds ratio, 0.39; p=0.042). CONCLUSIONS: In high-risk plastic surgery patients, postoperative enoxaparin prophylaxis is protective against 60-day venous thromboembolism when controlling for baseline risk and length of stay. Hospitalization for 4 or more days is an independent risk factor for venous thromboembolism. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.