Refining breast cancer prognosis by incorporating age at diagnosis into clinical prognostic staging: introduction of a novel online calculator.

PURPOSE: American Joint Committee on Cancer (AJCC) clinical staging is used to estimate breast cancer prognosis, but individual patient survival within each stage varies considerably by age at diagnosis. We hypothesized that the addition of age at diagnosis to the staging schema will enable more refined risk stratification. METHODS: We performed a retrospective population analysis of adult women diagnosed with invasive breast cancer between 2010 and 2015 registered in SEER. Multivariable Cox hazards models were used to evaluate the association of AJCC 8th edition clinical prognostic stage (CPS) and age with risk of overall mortality. Separate hierarchical models were fit to the data: Model 1: CPS alone; Model 2: CPS + age + age2; and Model 3: CPS + age + age2 + CPS x age + CPS x age2. Models were compared by the Akaike information criterion (AIC), the c-statistic for time-dependent receiver operator characteristic curves, and category-free net reclassification improvement (NRI). Internal validation was performed using bootstrapping samples. RESULTS: Among 86,637 women, the median follow-up was 36 months and 3-year overall survival was 91.9% ± 0.1%. Age significantly modified the effect of CPS on survival (p < 0.0001). Model 3 was the most precise, with the lowest AIC (126,619.63), the highest c-statistic (0.8212, standard error 0.0187), and superior NRI indices. CONCLUSION: Age at diagnosis is a highly prognostic variable that warrants consideration for inclusion in future editions of the AJCC Breast Cancer Staging Manual.

The effect of local therapy on breast cancer-specific mortality of women with occult breast cancer and advanced nodal disease (N2/N3): a population analysis.

PURPOSE: Current NCCN guidelines for occult breast cancer (OBC) recommend modified radical mastectomy, with the option for breast preservation with radiation instead of mastectomy for N1 patients. Our aim was to compare the effect of local therapy-mastectomy versus breast radiation-on breast cancer-specific mortality (BCSM) in a contemporary cohort of OBC patients of all nodal stages. METHODS: Competing risk analyses were performed to evaluate the effect of local therapy, nodal stage, and other demographic and clinical prognostic variables on risk of BCSM for women registered in the SEER database with T0N+M0 breast cancer from 2004 to 2015. RESULTS: Of the 353 women with OBC who underwent axillary nodal dissection, 152 received breast radiation and 201 underwent mastectomy. Overall, 57.5% had N1 disease, 54.4% had estrogen receptor (ER) positive tumors, 80.7% were white, and 88.1% received chemotherapy. Women treated with radiation were older (p < 0.001). The two groups were comparable with respect to all other variables analyzed. During a median follow-up of 66 months, 32 women died from breast cancer (radiation: 11, mastectomy: 21). Five-year cumulative incidence of BCSM was 8.0% ± 2.6% with radiation versus 10.9% ± 2.6% with mastectomy (p = 0.309). On multivariate analysis, independent predictors of BCSM included older age, higher N stage, and ER negativity, but the type of local therapy was not significantly associated with outcome. CONCLUSIONS: These results suggest that breast preservation is a reasonable alternative to mastectomy for OBC patients, regardless of nodal stage.

Quantifying the relationship between age at diagnosis and breast cancer-specific mortality.

PURPOSE: The relationship between age at diagnosis and breast cancer-specific mortality (BCSM) is unclear. The aim of this study was to examine the nature of this relationship using rigorous statistical methodology. METHODS: A historical cohort study of adult women with invasive breast cancer in the SEER database from 2000 to 2015 was conducted. Multivariable Cox's cause-specific hazards model was used to evaluate the association of age at diagnosis with risk of BCSM. Functional relationship of age was assessed using cumulative sums of Martingale residuals and the Kolmogorov-type supremum test. RESULTS: A total of 206,332 women were eligible for study. Mean age at diagnosis was 59.7 ± 13.8 years. Median follow-up was 80 months. During the study period, 21,771 women (10.6%) died from breast cancer and 18,566 (9.0%) died from other causes. Cumulative incidence of BCSM at 120 months post-diagnosis was 14.4% (95% CI 14.2-14.6%). Age was found to be quadratically related to the risk of BCSM (p < 0.001), with a nadir at 45 years of age. The final Cox model suggests that a 30-year-old woman has approximately the same adjusted BCSM risk (HR 1.187, 95% CI 1.187-1.188) as a 60-year-old woman (HR 1.174, 95% CI 1.174-1.175). CONCLUSIONS: Women diagnosed with breast cancer at the extremes of age suffer disproportionate rates of cancer-specific mortality. The relationship between age at diagnosis and adjusted risk of BCSM is complex, consistent with a quadratic function. With the growing appreciation for breast cancer as a heterogeneous disease, it is essential to accurately address age as a prognostic risk factor in predictive models.

Post-Treatment Symptoms of Pain, Anxiety, Sleep Disturbance, and Fatigue in Breast Cancer Survivors.

BACKGROUND: In part because of improvements in early detection and treatment, the number of breast cancer survivors is increasing. After treatment, however, breast cancer survivors often experience distressing symptoms, including pain, sleep disturbance, anxiety, and fatigue; at the same time, they have less frequent contact with health care providers. Pain commonly co-occurs with other symptoms and the combination of symptoms contribute to the amount of distress experienced by survivors. Previous studies of post-treatment symptoms include primarily urban and white women. AIMS: The purpose of this study was to describe the post-treatment cluster of symptoms, to examine the correlations among these symptoms, and to examine the role pain intensity may play in understanding the variation in sleep disturbance, fatigue, and anxiety in a racially diverse sample of rural breast cancer survivors. DESIGN: The theoretical framework for this descriptive correlational study was the theory of unpleasant symptoms. SETTINGS: Outpatient university-affiliated cancer clinic. PARTICIPANTS/SUBJECTS: Forty women who were between 6 months and 5 years post breast cancer diagnosis. METHODS: Participants completed the following self-report instruments: Patient Reported Outcomes Measurement Information System of pain intensity, pain interference, anxiety, and sleep disturbance and the Piper Fatigue Short Form 12. RESULTS: The average age of participants was 58 years, and 57.5% were black. Most women reported sleep disturbance (78%), pain interference (68%), and pain intensity (63%) above the national average for an American adult. Black women reported higher pain intensity than whites. There were moderate to strong correlations among the symptoms (range r = 0.35-0.89). CONCLUSIONS: Nurses and health care providers in primary care settings need to screen for symptoms, and nursing interventions are needed to assist breast cancer survivors to manage distressing symptoms.

Primary tumor resection in metastatic breast cancer: A propensity-matched analysis, 1988-2011 SEER data base.

Primary tumor resection (PTR) in metastatic breast cancer is not a standard treatment modality, and its impact on survival is conflicting. The primary objective of this study was to analyze impact of PTR on survival in metastatic patients with breast cancer. A retrospective study of metastatic patients with breast cancer was conducted using the 1988-2011 Surveillance, Epidemiology, and End Results (SEER) data base. Cox proportional hazards regression models were used to evaluate the relationship between PTR and survival and to adjust for the heterogeneity between the groups, and a propensity score-matched analysis was also performed. A total of 29 916 patients with metastatic breast cancer were included in the study, and 15 129 (51%) of patients underwent primary tumor resection, and 14 787 (49%) patients did not undergo surgery. Overall, decreasing trend in PTR for metastatic breast cancer in last decades was noted. Primary tumor resection was associated with a longer median OS (34 vs 18 months). In a propensity score-matched analysis, prognosis was also more favorable in the resected group (P = .0017). Primary tumor resection in metastatic breast cancer was associated with survival improvement, and the improvement persisted in propensity-matched analysis.

Impact of malnutrition on gastrointestinal surgical patients.

BACKGROUND: The accurate diagnosis of malnutrition is imperative if we are to impact outcomes in the malnourished. The American Society of Parenteral and Enteral Nutrition (ASPEN) and Academy of Nutrition and Dietetics (AND), in an attempt to address this issue, have provided evidence-based criteria to diagnose malnutrition. The purpose of this study was to validate the ASPEN/AND criteria in a cohort of patients from a single high-volume surgical oncology unit. METHODS: Patients undergoing major abdominal surgery from June 2013 to March 2015 were classified by their nutritional status using the ASPEN/AND criteria. RESULTS: A total of 490 patients were included. Median age was 64 y, a majority were female (50.6%), white (60.2%), underwent elective procedures (77.6%), had a Charlson comorbidity score (CCS) of 3-5 (40.0%), and a Clavien-Dindo complication (CDC) grade of 0-II (81.2%). A total of 93 (19.0%) patients were classified as moderately/severely malnourished. On univariate analysis, malnourished patients were more likely to be older, undergo emergent procedures, and have a CCS >5 (P < 0.05). Malnutrition was also associated with a longer postoperative length of stay (LOS), higher cost, higher in-hospital mortality, more severe complications, and higher readmission rates (P < 0.05). Multivariate analysis reaffirmed the association between malnutrition, LOS (odds ratio [OR] = 1.67), and cost (OR = 2.49), P < 0.05. Complications (OR = 1.35), mortality rates (OR = 3.05), and readmission rates (OR = 1.34) P > 0.05 failed to reach significance. CONCLUSIONS: Malnutrition worsens LOS and cost. Utilization of standardized criteria consistently identifies patients at risk of negative outcomes who may benefit from perioperative nutritional support.

Radiotherapy associated with improved survival for high-grade sarcoma of the extremity.

BACKGROUND: The impact of radiotherapy on local control in limb-preserving surgery for high-risk sarcoma has been well studied. However, the impact of the use and timing of radiation therapy on survival is unclear. METHODS: From 1988 to 2010, patients with Stage III extremity sarcoma were identified within the SEER registry and cohorts were created using propensity score matching between irradiated and non-irradiated groups. RESULTS: A total of 2,606 patients were identified, with a median age of 59 years a majority were white (81%), male (54%), received radiotherapy (78%), and had lower extremity (80%) sarcomas. The most common subtype was fibrohistiocytic (29.8%). Patients treated with radiotherapy were younger (57.2 vs. 60.3 years) and differed in subtype compared to those untreated. The matched cohorts were better balanced for all factors. Radiation therapy was associated with a 5% 5-year survival advantage on univariate analysis for both the unmatched (P = 0.002) and matched cohorts (P = 0.01). On multivariate analysis radiotherapy was associated with a 20% and 30% survival advantage for the matched and unmatched cohorts, respectively (P ≤ 0.02). The timing of radiotherapy did not affect survival. CONCLUSIONS: Radiotherapy, regardless of the timing, is associated with improved survival in high-risk sarcoma.

Assessment of health care cost for complex surgical patients: review of cost, re-imbursement and revenue involved in pancreatic surgery at a high-volume academic medical centre.

BACKGROUND: Pancreatic surgery is complex with the potential for costly hospitalization. METHODS: A retrospective review of patients undergoing a pancreatic resection was performed. RESULTS: The median age of the study population was 64 years. Half of the cohort was female (51%), and the majority were white (62%). Most patients underwent a pancreaticoduodenectomy (PD) (69%). The pre-operative age-adjusted Charlson comorbidity index was zero for 36% (n = 50), 1 for 31% (n = 43) and ≥2 for 33% (n = 45). The Clavien-Dindo grading system for post-operative complication was grade I in 17% (n = 24), whereas 45% (n = 62) were higher grades. The medians direct fixed, direct variable, fixed indirect and total costs were $2476, $15,397, $13,207 and $31,631, respectively. There was a positive contribution margin of $7108, whereas the net margin was a loss of $6790. On univariate analyses, age, type of operation and complication grade were associated with total cost (P ≤ 0.05), whereas operation type and complication grade were associated with a net margin (P = 0.01). These findings remained significant on multivariate analysis (P < 0.05). CONCLUSIONS: Increased cost, reimbursement and revenue were associated with type of operation and post-operative complications.

The influence of sentinel lymph node biopsy on survival for intermediate-thickness melanoma.

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1) failed to demonstrate a survival advantage for sentinel lymph node biopsy (SNB) in melanoma. This may have been secondary to inadequate statistical power. This study was designed to determine the impact of SNB on melanoma-specific survival (MSS) in a larger patient cohort. METHODS: From 2003-2008, patients with tumors 1-4 mm in thickness and clinically negative nodes were identified within the SEER registry. Propensity score was used to create two matched cohorts: those who underwent a wide excision with SNB or wide excision alone. RESULT: A total of 15,274 met inclusion criteria and 7,910 comprised the match cohort. Average age was 67.4 years. The majority were male (62.3 %) and white (97.2 %). Primary tumors were most frequently nonulcerated (77.1 %), located on the extremity (42.3 %), and T2 (64.1 %). There were 3,955 patients in both the SNB and observation groups. There was no significant difference in gender, ethnicity, ulceration status, primary site, or T-classification between the groups. Improved 5-year MSS was associated with SNB (85.7 vs. 84.0 %), female gender (88.3 vs. 82.7 %), absence of ulceration (87.5 vs. 75.7 %), extremity location (87.4 %), T2 disease (88.6 vs. 77.9 %), and a negative SNB (88.9 vs. 64.8 %). The relationships between observation [hazard ratio (HR) 1.18], male gender (HR 1.33), ulceration (HR 1.77), head-and-neck location (HR 1.34), and T3 disease (HR 1.82) persisted on multivariate analysis. CONCLUSIONS: Status of the sentinel node is the strongest predictor of survival in patients with intermediate thickness melanoma. SNB compared with observation was associated with a modest survival advantage.

Sentinel lymph node biopsy is associated with improved survival in Merkel cell carcinoma.

BACKGROUND: Although sentinel lymph node biopsy (SNB) has become a standard for Merkel cell carcinoma (MCC), the impact on survival is unclear. To better define the staging and therapeutic value of SNB, we compared SNB with nodal observation. METHODS: Patients with clinical stage I and II MCC in the Surveillance, Epidemiology, and End Results (SEER) registry undergoing surgery between 2003 and 2009 were identified and divided into two groups-SNB and observation. RESULTS: A total of 1,193 patients met the inclusion criteria (SNB 474 and Observation 719). The median age was 78 years, and the majority were White (95.3 %), male (58.8 %), received radiation therapy (52.9 %) and had T1 tumors (65.3 %). Twenty-four percent had a positive SNB. SNB patients were younger (73 vs. 81 years; p < 0.0001), had T1 tumors (69.6 vs. 62.5 %; p = 0.04) and received radiotherapy (57.8 vs. 40 %; p < 0.0001). Among biopsy patients, a negative SNB was associated with improved 5-year MCC-specific survival (84.5 vs. 64.6 %; p < 0.0001). Univariate analysis demonstrated an increased 5-year MCC-specific survival for the SNB group versus the Observation group (79.2 vs. 73.8 %; p = 0.004), female gender (83.2 vs. 70.4 %; p = 0.0004), and lower T stage (p < 0.0001). On Cox regression, diminished survival was noted for the Observation group (risk ratio [RR] 1.43; p = 0.04), male gender (RR 2.06; p < 0.0001), and a higher T stage. CONCLUSION: SNB for MCC provides prognostic information and is associated with a significant survival advantage.

Immunotherapy for gastrointestinal malignancies.

BACKGROUND: Gastrointestinal (GI) cancers are the most common human tumors encountered worldwide. The majority of GI cancers are unresectable at the time of diagnosis, and in the subset of patients undergoing resection, few are cured. There is only a modest improvement in survival with the addition of modalities such as chemotherapy and radiation therapy. Due to an increasing global cancer burden, it is imperative to integrate alternative strategies to improve outcomes. It is well known that cancers possess diverse strategies to evade immune detection and destruction. This has led to the incorporation of various immunotherapeutic strategies, which enable reprogramming of the immune system to allow effective recognition and killing of GI tumors. METHODS: A review was conducted of the results of published clinical trials employing immunotherapy for esophageal, gastroesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers. RESULTS: Monoclonal antibody therapy has come to the forefront in the past decade for the treatment of colorectal cancer. Immunotherapeutic successes in solid cancers such as melanoma and prostate cancer have led to the active investigation of immunotherapy for GI malignancies, with some promising results. CONCLUSIONS: To date, monoclonal antibody therapy is the only immunotherapy approved by the US Food and Drug Administration for GI cancers. Initial trials validating new immunotherapeutic approaches, including vaccination-based and adoptive cell therapy strategies, for GI malignancies have demonstrated safety and the induction of antitumor immune responses. Therefore, immunotherapy is at the forefront of neoadjuvant as well as adjuvant therapies for the treatment and eradication of GI malignancies.

The use of isolated limb infusion in limb threatening extremity sarcomas.

UNLABELLED: This paper reports a single-institution experience with the use of isolated limb infusion for limb salvage in locally advanced, unresectable, recurrent limb threatening soft tissue sarcomas. BACKGROUND: Locally advanced, limb threatening soft tissue sarcomas (STS) pose a significant treatment challenge. We report our experience using isolated limb infusion (ILI) in patients with unresectable extremity STS. METHODS: A total of 22 patients with extremity STS underwent 26 ILIs with melphalan and dactinomycin. Patient characteristics, intra-operative parameters and toxicity were recorded. Outcome measures included limb-salvage and in-field response rates. RESULTS: Of the 19 lower and 7 upper extremity ILIs, Wieberdink grade III toxicity or less was observed in all. Median followup was 11 months. A total of 17 patients were evaluable at 3 months post-ILI with an overall response rate of 42%. Four (24%) had complete response (CR), three (18%) partial response (PR), three (18%) stable disease (SD) and seven (41%) progressive disease (PD). Twelve of 17 (71%) underwent successful limb preservation at a median of 9 months post-ILI. Two (12%) were downstaged to resectable disease and remain showing no evidence of disease (NED) after surgery at 30 and 22 months post-ILI. CONCLUSIONS: ILI is an attractive modality that provides regional disease control and limb preservation in patients with limb threatening sarcoma. Although short-term results appear encouraging, long-term follow-up is needed to fully assess the role of ILI in unresectable extremity STS.

Race-Related Differences in the Clinical Presentation and Histopathologic Features of Phyllodes Tumor.

BACKGROUND: Phyllodes tumor (PT) is a rare fibroepithelial lesion of the breast with variable malignant potential. Black women have a higher incidence of a related benign tumor, fibroadenoma, but there are limited epidemiological data on PT. The aim of our study was to evaluate race-related differences in the clinicopathologic features and outcomes of PT. METHODS: Our institutional pathology database was queried for breast specimen reports from 01/2009 to 10/2019 to identify patients with a pathologic diagnosis of PT. Chart review and detailed slide review were performed to obtain clinical and histopathologic variables, respectively. RESULTS: Among twelve patients, two had malignant PT, three had borderline PT, and seven had benign PT. All patients with malignant and borderline PT were black, compared with 29% of those with benign PT. There were no apparent race-related differences in specific histopathologic features among black vs. non-black women with benign PT. Malignant and borderline PT were relatively larger than benign PT, with mean tumor sizes of 9.0 cm (standard deviation [SD] 4.7 cm), 12.2 cm (SD 9.4 cm), and 5.4 cm (SD 5.8 cm), respectively. Two women had a local recurrence, both of whom were black. DISCUSSION: In this single-institution retrospective study, we observed disproportionate rates of aggressive histopathologic features and disparate outcomes among black women with PT. A multi-institutional PT registry would facilitate improved knowledge about race-related differences in the presentation and outcomes of this rare tumor.

Pan-tissue mitochondrial phenotyping reveals lower OXPHOS expression and function across cancer types.

Targeting mitochondrial oxidative phosphorylation (OXPHOS) to treat cancer has been hampered due to serious side-effects potentially arising from the inability to discriminate between non-cancerous and cancerous mitochondria. Herein, comprehensive mitochondrial phenotyping was leveraged to define both the composition and function of OXPHOS across various murine cancers and compared to both matched normal tissues and other organs. When compared to both matched normal tissues, as well as high OXPHOS reliant organs like heart, intrinsic expression of the OXPHOS complexes, as well as OXPHOS flux were discovered to be consistently lower across distinct cancer types. Assuming intrinsic OXPHOS expression/function predicts OXPHOS reliance in vivo, these data suggest that pharmacologic blockade of mitochondrial OXPHOS likely compromises bioenergetic homeostasis in healthy oxidative organs prior to impacting tumor mitochondrial flux in a clinically meaningful way. Although these data caution against the use of indiscriminate mitochondrial inhibitors for cancer treatment, considerable heterogeneity was observed across cancer types with respect to both mitochondrial proteome composition and substrate-specific flux, highlighting the possibility for targeting discrete mitochondrial proteins or pathways unique to a given cancer type.

Improvement in Surgical Quality Following Pancreaticoduodenectomy With Increasing Case Volume in a Rural Hospital.

BACKGROUND: The literature is replete with studies that define the nexus of quantity and quality in complex surgical operations. These observations have heralded a call for centralization of care to high-volume centers. The purpose of this study was to chronicle improvements in quality associated with pancreaticoduodenectomy (PD) as a rural hospital matures from a low- to very high-volume center. METHODS: A retrospective review of a prospective pancreatic surgery database was undertaken from July 2007 to June 2020. Annual periods were characterized as low (≤12/year), high (13-29/year), and very high volume (≥30/year). Data for the following quality benchmarks were aggregated and compared: length of stay (LOS), 30-day readmissions, 30-day mortality, and 1- and 3-year survival. A subgroup analysis was undertaken in those patients undergoing PD for adenocarcinoma detailing margin status and number of lymph nodes harvested. Outcomes were compared using the Fisher's exact and Student's t-test. RESULTS: 375 PD were completed over the 13-year period; 62.1% were undertaken for ductal adenocarcinoma. There was a significant decrease in LOS and 30-day readmissions as the institution matured toward very high volume. There were no significant differences in 30-day mortality, 1- and 3-year survival, or margin negativity rates associated with volume. Extent of lymph node harvest significantly improved as institutional experience increased. DISCUSSION: Our pancreatic surgery program matured rapidly from low to very high volume with institutional commitment and dedicated resources. As the institution matured, operational efficiencies and surgical quality improved. Not unexpectedly, biology trumped volume as reflected in 1- and 3-year survival rates.

Bioenergetic Phenotyping of DEN-Induced Hepatocellular Carcinoma Reveals a Link Between Adenylate Kinase Isoform Expression and Reduced Complex I-Supported Respiration.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide. Increasing evidence suggests that mitochondria play a central role in malignant metabolic reprogramming in HCC, which may promote disease progression. To comprehensively evaluate the mitochondrial phenotype present in HCC, we applied a recently developed diagnostic workflow that combines high-resolution respirometry, fluorometry, and mitochondrial-targeted nLC-MS/MS proteomics to cell culture (AML12 and Hepa 1-6 cells) and diethylnitrosamine (DEN)-induced mouse models of HCC. Across both model systems, CI-linked respiration was significantly decreased in HCC compared to nontumor, though this did not alter ATP production rates. Interestingly, CI-linked respiration was found to be restored in DEN-induced tumor mitochondria through acute in vitro treatment with P1, P5-di(adenosine-5') pentaphosphate (Ap5A), a broad inhibitor of adenylate kinases. Mass spectrometry-based proteomics revealed that DEN-induced tumor mitochondria had increased expression of adenylate kinase isoform 4 (AK4), which may account for this response to Ap5A. Tumor mitochondria also displayed a reduced ability to retain calcium and generate membrane potential across a physiological span of ATP demand states compared to DEN-treated nontumor or saline-treated liver mitochondria. We validated these findings in flash-frozen human primary HCC samples, which similarly displayed a decrease in mitochondrial respiratory capacity that disproportionately affected CI. Our findings support the utility of mitochondrial phenotyping in identifying novel regulatory mechanisms governing cancer bioenergetics.

Proteomic identification of tumor- and metastasis-associated galectin-1 in claudin-low breast cancer.

BACKGROUND: Metastasis and mortality remain high among breast cancer patients with the claudin-low subtype because these tumors are aggressive, chemoresistant, and lack targeted therapies. Our objective was to utilize discovery-based proteomics to identify proteins associated with claudin-low primary and metastatic tumors to gain insight into pathways and mechanisms of tumor progression. METHODS: We used nano-LC-MS/MS proteomics to analyze orthotopic and metastatic tumors from the syngeneic murine T11 tumor model, which displays gene expression profiles mirroring human claudin-low tumors. Galectin-1 identity, expression and spatial distribution were investigated by biochemical and immunochemical methods and MALDI/IMS. RNA seq data from mouse and human tumors in our study and publicly available microarray data were analyzed for differential galectin-1 expression across breast cancer subtypes. RESULTS: Galectin-1, an N-acetyllactosamine-binding protein, exhibited the highest sequence coverage and high abundance rank order among nano-LC-MS/MS-identified proteins shared by T11 claudin-low tumors but not normal tissue. Label-free quantitation, Western immunoblot and ELISA confirmed galectin-1 identity and significant differential expression. MALDI/IMS spatial mapping and immunohistochemistry detected galectin-1 in T11 metastatic lung foci. Immunohistochemistry of human claudin-low tumors demonstrated intermediate-to-high intensity galectin-1 staining of tumor and stroma. Gene expression analysis of mouse and human tumors found the highest galectin-1 levels in the claudin-low breast cancer subtype. CONCLUSIONS: Proteomics and genomics reveal high expression of galectin-1 protein and RNA in primary and metastatic claudin-low breast cancer. GENERAL SIGNIFICANCE: This work endorses proteomic approaches in cancer research and supports further investigations of the function and significance of galectin-1 overexpression in claudin-low tumor progression.

Development and Assessment of a Systematic Approach for Detecting Disparities in Surgical Access.

Importance: Although optimal access is accepted as the key to quality care, an accepted methodology to ascertain potential disparities in surgical access has not been defined. Objective: To develop a systematic approach to detect surgical access disparities. Design, Setting, and Participants: This cross-sectional study used publicly available data from the Health Cost and Utilization Project State Inpatient Database from 2016. Using the surgical rate observed in the 5 highest-ranked counties (HRCs), the expected surgical rate in the 5 lowest-ranked counties (LRCs) in North Carolina were calculated. Patients 18 years and older who underwent an inpatient general surgery procedure and patients who underwent emergency inpatient cholecystectomy, herniorrhaphy, or bariatric surgery in 2016 were included. Data were collected from January to December 2016, and data were analyzed from March to July 2020. Exposures: Health outcome county rank as defined by the Robert Wood Johnson Foundation. Main Outcomes and Measures: The primary outcome was the proportional surgical ratio (PSR), which was the disparity in surgical access defined as the observed number of surgical procedures in the 5 LRCs relative to the expected number of procedures using the 5 HRCs as the standardized reference population. Results: In 2016, approximately 1.9 million adults lived in the 5 HRCs, while approximately 246 854 lived in the 5 LRCs. A total of 28 924 inpatient general surgical procedures were performed, with 4521 being performed in those living in the 5 LRCs and 24 403 in those living in the 5 HRCs. The rate of general surgery in the 5 HRCs was 13.09 procedures per 1000 population. Using the 5 HRCs as the reference, the PSR for the 5 LRCs was 1.40 (95% CI, 1.35-1.44). For emergent/urgent cholecystectomy, the PSR for the 5 LRCs was 2.26 (95% CI, 2.02-2.51), and the PSR for emergent/urgent herniorrhaphy was 1.83 (95% CI, 1.33-2.45). Age-adjusted rate of obesity (body mass index [calculated as weight in kilograms divided by height in meters squared] greater than 30), on average, was 36.6% (SD, 3.4) in the 5 LRCs vs 25.4% (SD, 4.6) in the 5 HRCs (P = .002). The rate of bariatric surgery in the 5 HRCs was 33.07 per 10 000 population with obesity. For the 5 LRCs, the PSR was 0.60 (95% CI, 0.51-0.69). Conclusions and Relevance: The PSR is a systematic approach to define potential disparities in surgical access and should be useful for identifying, investigating, and monitoring interventions intended to mitigate disparities in surgical access that effects the health of vulnerable populations.