Breast Cancer Screening and BI-RADS Scoring Trends Before and During the COVID-19 Pandemic in an Academic Safety-Net Hospital.

BACKGROUND: Little is known about how the COVID-19 pandemic affected screening mammography rates and Breast Imaging Reporting and Data Systems (BI-RADS) categorizations within populations facing social and economic inequities. Our study seeks to compare trends in breast cancer screening and BI-RADS assessments in an academic safety-net patient population before and during the COVID-19 pandemic. PATIENTS AND METHODS: Our single-center retrospective study evaluated women ≥ 18 years old with no known breast cancer diagnosis who received breast cancer screening from March 2019-September 2020. The screening BI-RADS score, completion of recommended diagnostic imaging, and diagnostic BI-RADS scores were compared between the pre-COVID-19 era (from 1 March 2019 to 19 March 2020) and COVID-19 era (from 20 March 2020 to 30 September 2020). RESULTS: Among the 11,798 patients identified, screened patients were younger (median age 57 versus 59 years, p < 0.001) and more likely covered by private insurance (35.9% versus 32.3%, p < 0.001) during the COVID-19 era compared with the pre-COVID-19 era. During the pandemic, there was an increase in screening mammograms categorized as BI-RADS 0 compared with the pre-COVID-19 era (20% versus 14.5%, p < 0.0001). There was no statistically significant difference in rates of completion of diagnostic imaging (81.6% versus 85.4%, p = 0.764) or assignment of suspicious BI-RADS scores (BI-RADS 4-5; 79.9% versus 80.8%, p = 0.762) between the two eras. CONCLUSIONS: Although more patients were recommended to undergo diagnostic imaging during the pandemic, there were no significant differences in race, completion of diagnostic imaging, or proportions of mammograms categorized as suspicious between the two time periods. These findings likely reflect efforts to maintain equitable care among diverse racial groups served by our safety-net hospital.

Association of Race, Ethnicity, Language, and Insurance with Time to Treatment Initiation Among Women with Breast Cancer at an Urban, Academic, Safety-Net Hospital.

INTRODUCTION: Initial treatment for nonmetastatic breast cancer is resection or neoadjuvant systemic therapy, depending on tumor biology and patient factors. Delays in treatment have been shown to impact survival and quality of life. Little has been published on the performance of safety-net hospitals in delivering timely care for all patients. METHODS: We conducted a retrospective study of patients with invasive ductal or lobular breast cancer, diagnosed and treated between 2009 and 2019 at an academic, safety-net hospital. Time to treatment initiation was calculated for all patients. Consistent with a recently published Committee on Cancer timeliness metric, a treatment delay was defined as time from tissue diagnosis to treatment of greater than 60 days. RESULTS: A total of 799 eligible women with stage 1-3 breast cancer met study criteria. Median age was 60 years, 55.7% were non-white, 35.5% were non-English-speaking, 18.9% were Hispanic, and 49.4% were Medicaid/uninsured. Median time to treatment was 41 days (IQR 27-56 days), while 81.1% of patients initiated treatment within 60 days. The frequency of treatment delays did not vary by race, ethnicity, insurance, or language. Diagnosis year was inversely associated with the occurrence of a treatment delay (OR: 0.944, 95% CI 0.893-0.997, p value: 0.039). CONCLUSION: At our institution, race, ethnicity, insurance, and language were not associated with treatment delay. Additional research is needed to determine how our safety-net hospital delivered timely care to all patients with breast cancer, as reducing delays in care may be one mechanism by which health systems can mitigate disparities in the treatment of breast cancer.

Mitigating disparities in breast cancer treatment at an academic safety-net hospital.

PURPOSE: Among women with non-metastatic breast cancer, marked disparities in stage at presentation, receipt of guideline-concordant treatment and stage-specific survival have been shown in national cohorts based on race, ethnicity, insurance and language. Little is published on the performance of safety-net hospitals to achieve equitable care. We evaluate differences in treatment and survival by race, ethnicity, language and insurance status among women with non-metastatic invasive breast cancer at a single, urban academic safety-net hospital. METHODS: We conducted a retrospective study of patients with invasive ductal or lobular breast cancer, diagnosed and treated between 2009 and 2014 at an urban, academic safety-net hospital. Demographic, tumor and treatment characteristics were obtained. Stage at presentation, stage-specific overall survival, and receipt of guideline-concordant surgical and adjuvant therapies were analyzed. Chi-square analysis and ANOVA were used for statistical analysis. Unadjusted survival analysis was conducted by Kaplan-Meier method using log-rank test; adjusted 5 year survival analysis was completed stratified by early and late stage, using flexible parametric survival models incorporating age, race, primary language and insurance status. RESULTS: 520 women with stage 1-3 invasive breast cancer were identified. Median age was 58.5 years, 56.1% were non-white, 31.7% were non-English-speaking, 16.4% were Hispanic, and 50.1% were Medicaid/uninsured patients. There were no statistically significant differences in stage at presentation between age group, race, ethnicity, language or insurance. The rate of breast conserving surgery (BCS) among stage 1-2 patients did not vary by race, insurance or language. Among patients indicated for adjuvant therapies, the rates of recommendation and completion of therapy did not vary by race, ethnicity, insurance or language. Unadjusted survival at 5 years was 93.7% for stage 1-2 and 73.5% for stage 3. Adjusting for age, race, insurance status and primary language, overall survival at 5 years was 93.8% (95% CI 86.3-97.2%) for stage 1-2 and 83.4% (95% CI 35.5-96.9%) for stage 3 disease. Independently, for patients with early- and late-stage disease, age, race, language and insurance were not associated with survival at 5-years. CONCLUSION: Among patients diagnosed and treated at an academic safety-net hospital, there were no differences in the stage at presentation or receipt of guideline-concordant treatment by race, ethnicity, insurance or language. Overall survival did not vary by race, insurance or language. Additional research is needed to assess how hospitals and healthcare systems mitigate breast cancer disparities.

Axillary Lymph Node Dissection is Associated with Improved Survival Among Men with Invasive Breast Cancer and Sentinel Node Metastasis.

BACKGROUND: Male breast cancer (MBC) is rare, and management is extrapolated from trials that enroll only women. It is unclear whether contemporary axillary management based on data from landmark trials in women may also apply to men with breast cancer. This study aimed to compare survival in men with positive sentinel lymph nodes after sentinel lymph node biopsy (SLNB) alone versus complete axillary dissection (ALND). PATIENTS AND METHODS: Using the National Cancer Database, men with clinically node-negative, T1 and T2 breast cancer and 1-2 positive sentinel nodes who underwent SLNB or ALND were identified from 2010 to 2020. Both 1:1 propensity score matching and multivariate regression were used to identify patient and disease variables associated with ALND versus SLNB. Survival between ALND and SLNB were compared using Kaplan-Meier methods. RESULTS: A total of 1203 patients were identified: 61.1% underwent SLNB alone and 38.9% underwent ALND. Treatment in academic centers (36.1 vs. 27.7%; p < 0.0001), 2 positive lymph nodes on SLNB (32.9 vs. 17.3%, p < 0.0001) and receipt or recommendation of chemotherapy (66.5 vs. 52.2%, p < 0.0001) were associated with higher likelihood of ALND. After propensity score matching, ALND was associated with superior survival compared with SLNB (5-year overall survival of 83.8 vs. 76.0%; log-rank p = 0.0104). DISCUSSION: The results of this study suggest that among patients with early-stage MBC with limited sentinel lymph node metastasis, ALND is associated with superior survival compared with SLNB alone. These findings indicate that it may be inappropriate to extrapolate the results of the ACOSOG Z0011 and EORTC AMAROS trials to MBC.

Impact of the COVID-19 Pandemic on Delays to Breast Cancer Surgery: Ripples or Waves?

BACKGROUND: Adherence to current recommendations for optimal time from diagnosis to treatment for patients with breast cancer may have been disrupted by the COVID-19 pandemic. This study aimed to evaluate the impact of the pandemic on time to surgery or systemic treatment with chemotherapy or immunotherapy for patients diagnosed with breast cancer. METHODS: Using the National Cancer Database, patients diagnosed with breast cancer in 2020 were compared to those diagnosed from 2018-2019 (Pre-COVID). Sub-analyses were performed for patients who were tested for COVID-19 and those who had a positive result in 2020. Multivariate logistic regression was used assess odds ratios for delayed time to surgery (DTS, defined as > 90 days) or systemic therapy (defined as > 120 days). RESULTS: In total, 230,997 patients were diagnosed with breast cancer in 2018 and 2019 compared to 102,065 in 2020. Of the 2020 cohort, 47,659 (46.7%) received COVID-19 testing; of which, 3,158 (6.6%) resulted positive. A larger proportion of COVID-tested or COVID-positive patients had higher stage at diagnosis. DTS was more likely for patients who were diagnosed in 2020, uninsured or underinsured, non-white, Hispanic, less educated, or age < 70 years. Similar factors were predictive of delay to systemic therapy (less age < 70 years); however, diagnosis in 2020 was not. CONCLUSION: The COVID-19 pandemic was associated with significant DTS for breast cancer but spared time to systemic therapy. Delays disproportionately impacted vulnerable and underserved patient populations. The true clinical effects of these delays may yet be realized for breast cancer patients.

Association of Race, Ethnicity, Insurance, and Language and Rate of Breast-Conserving Therapy Among Women With Nonmetastatic Breast Cancer at an Urban, Safety-Net Hospital.

INTRODUCTION: Breast-conserving therapy (BCT), specifically breast-conserving surgery (BCS) and adjuvant radiation, provides an equivalent alternative to mastectomy for eligible patients. However, previous studies have shown that BCT is underused in the United States, particularly among marginalized demographic groups. In this study, we examine the association between race, ethnicity, insurance, and language and rate of BCS among patients treated at an academic, safety-net hospital. MATERIALS AND METHODS: We conducted a retrospective cohort study of 520 women with nonmetastatic breast cancer diagnosed and treated at an academic, safety-net hospital (2009-2014). We assessed eligibility for BCT and then differences in the rate of BCT among eligible patients by race, ethnicity, insurance, and language. Reasons for not undergoing BCT were documented. RESULTS: Median age was 60 y; 55.9% were non-White, 31.9% were non-English-speaking, 15.6% were Hispanic, and 47.4% were Medicaid/uninsured. Three hundred seventy one (86.3%) underwent BCS; within this group, 324 (87.3%) completed adjuvant radiation. Among patients undergoing mastectomy, 30 patients (36.7%) were eligible for BCT; within this group, reasons for mastectomy included patient preference (n = 28) and to avoid possible re-excision or adjuvant radiation in patients with significant comorbidities (n = 2). Eligibility for BCT varied by ethnicity (Hispanic [100%], Non-Hispanic [92%], P = 0.02), but not race, language, or insurance. Among eligible patients, rate of BCS varied by age (<50 y [84.9%], ≥50 y [92.9%], P = 0.01) and ethnicity (Hispanic [98.5%], Non-Hispanic [91.3%], P = 0.04), but not race, language, or insurance. CONCLUSIONS: At our safety-net hospital, the rate of BCS among eligible patients did not vary by race, language, or insurance. Excluding two highly comorbid patients, all patients who underwent mastectomy despite being eligible for BCT were counseled regarding BCS and expressed a preference for mastectomy. Further research is needed to understand the value of BCT in the treatment of breast cancer, to ensure informed decision-making, address potential misconceptions regarding BCT, and advance equitable care for all patients.

Impact of Patient Primary Language upon Immediate Breast Reconstruction After Mastectomy.

BACKGROUND: Preoperative decision-making in patients who speak a primary language other than English is understudied. We investigated whether patient primary language is associated with differences in immediate breast reconstruction (IBR) after mastectomy. PATIENTS AND METHODS: This retrospective observational study analyzed female patients undergoing mastectomy in the New Jersey State Inpatient Database (2009-2014). The primary outcome was the odds of IBR with a prespecified subanalysis of autologous tissue-based IBR. We used multivariable logistic regression and hierarchical generalized linear mixed models to control for patient characteristics and nesting within hospitals. RESULTS: Of 13,846 discharges, 12,924 (93.3%) specified English as the patient's primary language, while 922 (6.7%) specified a language other than English. Among English-speaking patients, 6178 (47.8%) underwent IBR, including 2310 (17.9%) autologous reconstructions. Among patients with a primary language other than English, 339 (36.8%) underwent IBR, including 93 (10.1%) autologous reconstructions. Unadjusted results showed reduced odds of IBR overall [odds ratio (OR) 0.64, 95% CI 0.55-0.73], and autologous reconstruction specifically (OR 0.52, 95% CI 0.41-0.64) among patients with a primary language other than English. After adjustment for patient factors, this difference persisted among the autologous subgroup (OR 0.64, 95% CI 0.51-0.80) but not for IBR overall. A hierarchical model incorporating both patient characteristics and hospital-level effects continued to show a difference among the autologous subgroup (OR 0.75, 95% CI 0.58-0.97). CONCLUSIONS: Primary language other than English was an independent risk factor for lower odds of autologous IBR after adjustments for patient and hospital effects. Focused efforts should be made to ensure that patients who speak a primary language other than English have access to high-quality shared decision-making for postmastectomy IBR.

Residential Racial Segregation and Disparities in Breast Cancer Presentation, Treatment, and Survival.

OBJECTIVE: To understand the role of racial residential segregation on Black-White disparities in breast cancer presentation, treatment, and outcomes. SUMMARY OF BACKGROUND DATA: Racial disparities in breast cancer treatment and outcomes are well documented. Black individuals present at advanced stage, are less likely to receive appropriate surgical and adjuvant treatment, and have lower overall and stage-specific survival relative to White individuals. METHODS: Using data from the Surveillance, Epidemiology, and End Results program, we performed a retrospective cohort study of Black and White patients diagnosed with invasive breast cancer from 2005 to 2015 within the 100 most populous participating counties. The racial index of dissimilarity was used as a validated measure of residential segregation. Multivariable regression was performed, predicting advanced stage at diagnosis (stage III/IV), surgery for localized disease (stage I/II), and overall stage-specific survival. RESULTS: After adjusting for age at diagnosis, estrogen/progesterone receptor status, and region, Black patients have a 49% greater risk (relative risk [RR] 1.49 95% confidence interval [CI] 1.27, 1.74) of presenting at advanced stage with increasing segregation, while there was no observed difference in Whites (RR 1.04, 95% CI 0.93, 1.16). Black patients were 3% less likely to undergo surgical resection for localized disease (RR 0.97, 95% CI 0.95, 0.99) with increasing segregation, while Whites saw no significant difference. Black patients had a 29% increased hazard of death (RR 1.29, 95% CI 1.04, 1.60) with increasing segregation; there was no significant difference among White patients. CONCLUSIONS: Our data suggest that residential racial segregation has a significant association with Black-White racial disparities in breast cancer. These findings illustrate the importance of addressing structural racism and residential segregation in efforts to reduce Black-White breast cancer disparities.

Undertreatment of Gallbladder Cancer: A Nationwide Analysis.

BACKGROUND: Gallbladder cancer has a high mortality rate and an increasing incidence. The current National Comprehensive Cancer Network (NCCN) guidelines recommend resection for all T1b and higher-stage cancers. This study aimed to evaluate re-resection rates and the associated survival impact for patients with gallbladder cancer. METHODS: Patients with gallbladder adenocarcinoma who underwent resection were identified from the National Cancer Database (2004-2015). Re-resection was defined as definitive surgery within 180 days after the first operation. Propensity scores were created for the odds of a patient having a re-resection. Patients were matched 1:2. Survival analyses were performed using the Kaplan-Meier and Cox proportional hazard methods. RESULTS: The study identified 6175 patients, and 466 of these patients (7.6%) underwent re-resection. Re-resection was associated with younger median age (65 vs 72 years; p < 0.0001), private insurance (41.6% vs 27.1%; p < 0.0001), academic centers (50.4% vs 29.7%; p < 0.0001), and treatment location in the Northeast (22.8% vs 20.4%; p = 0.0011). Compared with no re-resection, re-resection was associated with pT stage (pT2: 47.6% vs 42.8%; p = 0.0139) and pN stage (pN1-2: 28.1% vs 20.7%; p < 0.0001), negative margins on final pathology (90.1% vs 72.6%; p < 0.0001), and receipt of chemotherapy (53.7% vs 35.8%; p < 0.0001). The patients who underwent re-resection demonstrated significantly longer overall survival (OS) than the patients who did not undergo re-resection (median OS, 44.0 vs 23.0 months; p < 0.0001). After propensity score-matching, re-resection remained associated with superior survival (median OS, 44.0 vs 31.0 months; p = 0.0004). CONCLUSIONS: Re-resection for gallbladder cancer is associated with improved survival but remains underused, particularly for early-stage disease.

Association of MRI T2 Signal Intensity With Desmoid Tumor Progression During Active Observation: A Retrospective Cohort Study.

OBJECTIVE: The aim of this study was to identify predictors of desmoid progression during observation. SUMMARY OF BACKGROUND DATA: Untreated desmoids can grow, remain stable, or regress, but reliable predictors of behavior have not been identified. METHODS: Primary or recurrent desmoid patients were identified retrospectively from an institutional database. In those managed with active observation who underwent serial magnetic resonance imaging (MRIs) with T2-weighted sequences, baseline tumor size was recorded, and 2 radiologists independently estimated the percentage of tumor volume showing hyperintense T2 signal at baseline. Associations of clinical or radiographic characteristics with progression-free survival (PFS; by RECIST) were evaluated by Cox regression and Kaplan-Meier statistics. RESULTS: Among 160 patients with desmoids, 72 were managed with observation, and 37 of these had serial MRI available for review. Among these 37 patients, median age was 35 years and median tumor size was 4.7 cm; all tumors were extra-abdominal (41% in abdominal wall). Although PFS was not associated with size, site, or age, it was strongly associated with hyperintense T2 signal in ≥90% versus <90% of baseline tumor volume (as defined by the "test" radiologist; hazard ratio = 11.3, P = 0.003). For patients in the ≥90% group (n = 20), 1-year PFS was 55%, compared with 94% in the <90% group (n = 17). The percentage of baseline tumor volume with hyperintense T2 signal defined by a validation radiologist correlated with results of the test radiologist (ρ = 0.75). CONCLUSION: The percent tumor volume characterized by hyperintense T2 signal is associated with desmoid progression during observation and may help distinguish patients who would benefit from early intervention from those who may be reliably observed.

Racial differences in genomic testing and receipt of endocrine therapy in early-stage breast cancer.

PURPOSE: Genomic testing in early-stage hormone-positive breast cancer is the standard of care. However, decisions based on genomic testing results are predicated on the assumption that patients receive endocrine treatment. We sought to investigate racial differences in genomic testing and adjuvant treatment in breast cancer. METHODS: A retrospective, population-based hospital registry study using the National Cancer Database. Participants included women with stages I-II, ER + breast cancer between 2010 and 2014. Sociodemographic factors were analyzed. Primary outcomes were the utilization of genomic testing and receipt of endocrine therapy. Logistic regression modeling was used to compute crude and adjusted odds of genomic testing and receipt of endocrine therapy. RESULTS: Among a total sample size of 387,008 patients, 147,863 (38.2%) underwent genomic testing. Older age (≥ 70 years) was associated with a lower adjusted odd of genomic testing (OR 0.33; 95% CI 0.32-0.34, p = < 0.0001). Black patients had lower odds of receiving genomic testing on multivariate analysis compared to Whites (OR 0.82; 95% CI 0.80-0.85, p = < 0.0001). In patients who underwent a genomic test, compared to Whites, Blacks had a lower odds of receiving endocrine therapy (OR 0.86; 95% CI 0.80-0.93, p = < 0.0001) even if they did not receive adjuvant chemotherapy (OR 0.90; 95% CI 0.82-0.98, p = 0.014). CONCLUSIONS: In a national sample of breast cancer patients, Black women are less likely to get genomic testing and receive hormonal therapy, even when adjuvant chemotherapy is omitted. A priority in addressing breast cancer disparities is to ensure adherence to hormonal therapy among all women, including those who do not receive adjuvant chemotherapy.

Breast Cancer Treatment Delays at an Urban Safety Net Hospital Among Women Experiencing Homelessness.

Disparities in outcomes for vulnerable women is an ongoing problem. Homelessness and breast cancer treatment outcomes is understudied. This is a descriptive study exploring types of homelessness and treatment delays at an urban safety net hospital providing care to a vulnerable patient population.This study is a retrospective chart review of homeless female patients diagnosed with breast cancer between January 1, 2000 and December 31, 2014. Data for this study were acquired from the hospital cancer registry and electronic medical record. All demographic characteristics, time to treatment and factors related to delays to treatment were analyzed descriptively, reporting frequencies and proportions. The total number of individuals analyzed was 24. All except two subjects were delayed to treatment (≥ 30 days from diagnosis to treatment). Most women in this cohort were categorized as chronically homeless (46%) with the rest categorized as transitionally (29%) or episodically (12%) homeless. The majority of subjects (70%) were Black, non-Hispanic. All except one subject were publicly insured (71% Medicaid; 12% Medicare) or uninsured (8%). Regardless of type of homelessness, most subjects were either 30-60 or 60-90 days delayed. Those who were chronically homeless experienced significantly more delays to first treatment (56% of those who were delayed 30-60 days and 57% of those who were delayed 60-90 days; p value 0.006) than those who were episodically or transitionally homeless. Significant delays and barriers to breast cancer treatment exist among women experiencing homelessness. Further studies to improve breast cancer care for homeless women are warranted.

Does response to neo-adjuvant chemotherapy impact breast reconstruction?

Neo-adjuvant chemotherapy (NAC) is administered in breast cancer treatment for downstaging of disease. Here, we determined the impact of response to NAC on breast reconstruction uptake. A prospective NAC and mastectomy database with or without reconstruction were reviewed with IRB approval. Univariable analyses were conducted using Kruskal-Wallis or Fisher's exact tests. Multivariable logistic regression was used to adjust for potential confounders. We identified 271 patients with unilateral breast cancer receiving NAC and either unilateral or bilateral mastectomy from 9/2013 to 5/2016. Seventy patients (25.8%) had a pCR to NAC. One hundred and seventy-five patients (64.6%) had immediate reconstruction (IR), and 96 had no IR. On univariable analysis, younger age (P < .001), lower T-stage at presentation (P < .001), bilateral versus unilateral mastectomy (P<.001) and HR-negative tumor subtype (P = .006) were significantly associated with higher IR rates. On multivariable analysis, pCR (P = .792) and tumor subtype (P = 0.061) were not significantly associated with IR; T-stage was significantly associated with IR (P < .001), such that patients with T4 tumors at presentation had lower odds of IR (OR 0.10, 95% CI 0.02-0.50), even when accounting for response to NAC. One hundred and seventy-three patients (63.8%) received adjuvant radiation therapy; this was associated with lower IR frequency (P = .048) but was not associated with reconstruction type (tissue expander versus autologous, P = 1.0) among 175 patients who had IR. In patients who have mastectomy after NAC, IR is influenced by age, T-stage at presentation, and choice of bilateral mastectomy, but not by response to NAC. A subset of patients who are young, with earlier T-stage and pCR, is more likely to proceed with bilateral mastectomy.

Size and Location are the Most Important Risk Factors for Malignant Behavior in Resected Solitary Fibrous Tumors.

PURPOSE: While previously thought to be clinically indolent, recent data suggest significant late metastatic capacity of solitary fibrous tumors (SFTs). We define prognostic factors for recurrence and disease-specific death (DSD) in resected primary SFTs. METHODS: Resected primary SFTs from 1982 to 2015 were identified from a prospective, single institutional database. Risk factors for local (LR) and distant recurrence (DR), and DSD were assessed using competing risk analysis. RESULTS: A total of 219 patients with median follow-up of 6.1 (0.1-22) years were included. Five- and 10-year cumulative DSD was 9 and 11%, respectively. Size greater than the median 8 cm, gender, location, and complete gross resection were significantly associated with DSD (p < 0.05). Five- and 10-year cumulative risk (CR) of LR was 4 and 7%, whereas 5- and 10-year CR of DR was 13 and 16%, respectively. LR was associated with location (p = 0.02) and tumor size (p = 0.02), and DR was associated with size (p < 0.01). Histopathologic classification did not predict long-term behavior with both malignant and benign tumors demonstrating capacity for DR and associated death. Tumors in the thoracic cavity and abdomen/retroperitoneum presented the greatest risk of DR (16 and 27% 10-year CR). On multivariate analysis, size ≥ 8 cm (hazard ratio 2.89, p = 0.05) and tumor location in chest or abdominal/retroperitoneal cavity (hazard ratio 2.68, p = 0.01) significantly impacted DSD. CONCLUSIONS: Recurrence is highly associated with DSD and events occur as late as 16 years after initial presentation, including in patients with initially considered benign tumors. Patients with large (≥ 8 cm) tumors in the chest or abdominal/retroperitoneal cavity are at greatest risk.

The neurokinin 1 receptor regulates peritoneal fibrinolytic activity and postoperative adhesion formation.

BACKGROUND: Intra-abdominal adhesions are a common source of postoperative morbidity. Previous studies in our laboratory have shown that a neurokinin 1 receptor antagonist (NK-1RA) reduces abdominal adhesion formation and increases peritoneal fibrinolytic activity. However, the cellular pathway by which the antagonist exerts its effects is unclear, as cultured peritoneal mesothelial cells exposed to the NK-1RA show increases in fibrinolytic activity despite having very low expression of neurokinin 1 receptor (NK-1R) messenger RNA and protein. Our aim was to determine whether the NK-1R plays an essential role in the adhesion-reducing effects of the NK-1RA, or if the NK-1RA is acting independently of the receptor. METHODS: Homozygous NK-1R knockout mice and age matched wild-type mice underwent laparotomy with cecal cautery to induce adhesions. At the time of surgery, mice received a single intraperitoneal dose of either NK-1RA (25 mg/kg) or saline alone. Adhesion severity at the site of cecal cautery was assessed on postoperative day 7. In a separate experiment, peritoneal fluid was collected from wild type and NK-1R knockout mice 24 h after laparotomy with cecal cautery and administration of either NK-1RA or saline. Tissue plasminogen activator levels, representative of total fibrinolytic activity, were then measured in peritoneal fluid. RESULTS: In wild-type mice, NK-1RA administration significantly decreased adhesion formation compared with saline controls. Among the NK-1R knockout mice, there was no significant reduction in adhesion formation by the NK-1RA. Fibrinolytic activity increased 244% in wild-type mice administered NK-1RA compared with saline controls; however, the NK-1RA did not raise fibrinolytic activity above saline controls in NK-1R knockout mice. CONCLUSIONS: These data indicate that the NK-1R mediates the adhesion-reducing effects of the NK-1RA, in part, by the upregulation of peritoneal fibrinolysis, and suggest that the NK-1R is a promising therapeutic target for adhesion prevention.