For the Love of the Game: Calculating the Premium Associated With Academic Surgical Practice.

OBJECTIVE: We sought to determine the premium associated with a career in academic surgery, as measured by compensation normalized to the work relative value unit (wRVU). BACKGROUND: An academic surgical career embodying innovation and mentorship offers intrinsic rewards but is not well monetized. We know compensation for academic surgeons is less than their nonacademic counterparts, but the value of clinical effort, as normalized to the wRVU, between academic and nonacademic surgeons has not been well characterized. Thus, we analyzed the variations in the valuation of academic and nonacademic surgical work from 2010 to 2022. METHODS: We utilized Medical Group Management Association Provider Compensation data from 2010, 2014, 2018, and 2022 to compare academic and nonacademic surgeons. We analyzed raw total cash compensation (TCC), wRVU, TCC per wRVU (TCC/wRVU), and TCC to collections (TCCtColl). We calculated collections per wRVU (Coll/wRVU). We adjusted TCC and TCCtColl for inflation using the Consumer Price Index. Linear modeling for trend analysis was performed. RESULTS: Compared with nonacademic, academic surgeons had lower TCC (2010: $500,415.0±23,666 vs $631,515.5±23,948.2, -21%; 2022: $564,789.8±23,993.9 vs $628,247.4±15,753.2, -10%), despite higher wRVUs (2022: 9109.4±474.9 vs 8062.7±252.7) and higher Coll/wRVU (2022: 76.68±8.15 vs 71.80±6.10). Trend analysis indicated that TCC will converge in 2038 at an estimated $660,931. CONCLUSIONS: In 2022, academic surgeons had more clinical activity and superior organizational revenue capture, despite less total and normalized clinical compensation. On the basis of TCC/wRVUs, academia charges a premium of 16% over nonacademic surgery. However, trend analysis suggests that TCC will converge within the next 20 years.

Analysis of the Understanding and Worry about Lymphedema of Patients with Breast Cancer.

BACKGROUND: Lymphedema is a potential lifelong sequela of breast cancer treatment. We sought to: (1) evaluate the worry and knowledge of patients about lymphedema, (2) quantify patients reporting lymphedema education and screening, and (3) determine willingness to participate in lymphedema screening and prevention programs. PATIENTS AND METHODS: A survey evaluating lymphedema-related knowledge and worry was sent to patients treated for stage 0-III breast cancer. Exclusion criteria included > 10 years since diagnosis, missing clinical staging, and those without axillary surgery. Responses were linked with clinicopathologic information. RESULTS: Of 141 patients meeting inclusion criteria, 89% of those without lymphedema were not at all or slightly worried about lymphedema. Higher levels of worry were associated with clinical stage II-III disease [odds ratio (OR) 2.63, p = 0.03], a history of axillary lymph node dissection (ALND) (OR 4.58, p < 0.01), and employment (OR 2.21, p = 0.05). A total of 102 (72%) patients recalled receiving lymphedema education. Lymphedema knowledge was limited, with < 25% of respondents answering > 50% of the risk factor questions correctly. Worry and knowledge were not significantly associated. Of patients without lymphedema, 36% were interested in learning more about lymphedema and 64% were willing to participate in or learn more about a screening program. Most (66%) felt that lymphedema information should be provided before and after cancer treatment. DISCUSSION: A majority of our breast cancer survivors had limited knowledge about lymphedema risk factors. While most patients were not worried about developing lymphedema, higher worry was seen in patients with a higher clinical stage at diagnosis, ALND, and employment. Our findings suggest potential targets and timing for patient-centered educational interventions.

Academic Advancement in Global Surgery: Appointment, Promotion, and Tenure: Recommendations From the American Surgical Association Working Group on Global Surgery.

: There is growing interest in global surgery among US academic surgical departments. As academic global surgery is a relatively new field, departments may have minimal experience in evaluation of faculty contributions and how they integrate into the existing academic paradigm for promotion and tenure. The American Surgical Association Working Group on Global Surgery has developed recommendations for promotion and tenure in global surgery, highlighting criteria that: (1) would be similar to usual promotion and tenure criteria (eg, publications); (2) would likely be undervalued in current criteria (eg, training, administrative roles, or other activities that are conducted at low- and middle-income partner institutions and promote the partnerships upon which other global surgery activities depend); and (3) should not be considered (eg, mission trips or other clinical work, if not otherwise linked to funding, training, research, or building partnerships).

Ensuring Equity, Diversity, and Inclusion in Academic Surgery: An American Surgical Association White Paper.

OBJECTIVE: The leadership of the American Surgical Association (ASA) appointed a Task Force to objectively address issues related to equity, diversity, and inclusion with the discipline of academic surgery. SUMMARY OF BACKGROUND DATA: Surgeons and the discipline of surgery, particularly academic surgery, have a tradition of leadership both in medicine and society. Currently, we are being challenged to harness our innate curiosity, hard work, and perseverance to address the historically significant deficiencies within our field in the areas of diversity, equity, and inclusion. METHODS: The ASA leadership requested members to volunteer to serve on a Task Force to comprehensively address equity, diversity, and inclusion in academic surgery. Nine work groups reviewed the current literature, performed primary qualitative interviews, and distilled available guidelines and published primary source materials. A work product was created and published on the ASA Website and made available to the public. The full work product was summarized into this White Paper. RESULTS: The ASA has produced a handbook entitled: Ensuring Equity, Diversity, and Inclusion in Academic Surgery, which identifies issues and challenges, and develops a set of solutions and benchmarks to aid the academic surgical community in achieving these goals. CONCLUSION: Surgery must identify areas for improvement and work iteratively to address and correct past deficiencies. This requires honest and ongoing identification and correction of implicit and explicit biases. Increasing diversity in our departments, residencies, and universities will improve patient care, enhance productivity, augment community connections, and achieve our most fundamental ambition-doing good for our patients.

Nipple-Sparing Mastectomy is Not Associated with a Delay of Adjuvant Treatment.

BACKGROUND: High-volume single-institution studies support the oncologic safety of nipple sparing mastectomy (NSM). Concerns remain regarding the increased potential for complications, recurrence, and delays to subsequent adjuvant therapy. A national database was used to examine treatment and outcomes for NSM patients. METHODS: Women undergoing unilateral NSM or skin sparing mastectomy (SSM) for stage 0-4 breast cancer from 2004 to 2013 were identified from the National Cancer Database. Demographic and oncologic characteristics, short-term outcomes and time to local and systemic treatment were compared. RESULTS: NSM was performed on 8173 patients: 8.7% were node positive, and for stage 1-4 disease, 10.6% were triple negative (TN) and 15.3% were HER2-positive. NSM patients were less likely than SSM patients to receive chemotherapy [CT] (37.4 vs. 43.4%) or radiation [PMRT] (15.6 vs. 16.9%), and were also more likely to present with clinically early-stage disease. NSM patients with high-risk features were more likely to receive CT in the neoadjuvant [NCT] than adjuvant setting [AC] (OR 3.76, 1.81, and 1.99 for clinical N2/3, TN, and HER2-positive disease, all p < 0.001). On multivariate analysis, NSM patients had a higher rate of pathologic complete response [pCR] (OR 1.41, p < 0.001). Readmission rate, positive margin rate and time to CT, PMRT or hormonal therapy were not increased for NSM compared to SSM patients. CONCLUSIONS: Over one third of NSM patients received chemotherapy and/or radiation. NSM patients with high-risk features were more likely to receive NAC and obtain a pCR. NSM patients did not experience worse outcomes or delayed adjuvant therapy compared to SSM.

Intraoperative Radiotherapy for Breast Cancer Treatment in a Rural Community.

BACKGROUND: Access to health care poses particular challenges for patients living in rural communities. Intraoperative radiotherapy (IORT) offers a treatment alternative to traditional whole-breast radiation therapy (WBRT) for select patients. This study aimed to analyze the use of IORT for patients undergoing breast-conserving surgery at an academic institution located in a rural state. METHODS: A retrospective review analyzed all patients at a single institution with a diagnosis of ductal carcinoma in situ (DCIS) or invasive breast cancer from April 2012 to January 2017 who were undergoing breast-conserving surgery with either IORT or WBRT. Student's t test or Fisher's exact test was used to make statistical comparisons. RESULTS: Patients undergoing IORT (n = 117) were significantly older than patients treated with WBRT (n = 191) (65.6 vs 58.6 years; p < 0.001) and had smaller tumors on both preoperative imaging (1.04 vs 1.66 cm; p < 0.05) and final pathology (0.99 vs 1.48 cm; p < 0.05). Patients receiving IORT lived farther from the treating facility than patients treated with WBRT (67.2 vs 30.8 miles; p < 0.05). To account for biases created in the IORT selection criteria, subgroup analysis was performed for women receiving WBRT who fulfilled IORT selection criteria, and distance traveled remained significant (67.2 vs 31.4 miles; p < 0.05). Neither recurrence nor survival differed between the IORT and WBRT groups. Medicare reimbursement for IORT was approximately 50% more than for WBRT. CONCLUSIONS: For women from rural communities, IORT appears to be an attractive option because these women tend to be older and to live farther from the treatment facility.

Per oral endoscopic myotomy: early experience and safety of a multispecialty approach.

BACKGROUND: Per oral endoscopic myotomy (POEM) has gained increasing popularity for treating achalasia. A multidisciplinary approach may allow safe and early adoption of POEM into clinical practice. MATERIALS AND METHODS: We performed a retrospective review of our initial POEM cases. All procedures were performed by a team of interventional gastroenterologist and thoracic surgeon. We analyzed demographics, comorbidities, achalasia subtypes, length of hospital stay, duration of surgery, morbidity, mortality, length of myotomy, preoperative and postoperative Eckardt scores. RESULTS: Thirty-one consecutive patients underwent POEM during the 24-month period from January 2014 to December 2015. Eighteen patients (58%) had prior non-operative interventions. Average duration of follow-up was 9.6 months. Seventeen patients (66.8%) had follow-up of 12 months and longer. Average preoperative Eckardt score was 6.3 (3-10), median 6. Average postoperative Eckardt score was 1.4 (0-8), median 1, in 1 month and an average 2.2, median 1, in 1 year. Patients with type III achalasia were most refractory to treatment, while patients with type II had the best results. Average LOS was 1.3 days (1-5), median 1 day. Average DOS was 106 min (60-148), median 106. Average LOM was 13 cm (10-15), with median of 13 cm. We had one 30-day mortality secondary to coronary artery disease. Four patients had prior Heller myotomies and underwent a posterior myotomy during POEM, with outcomes similar to patients with no prior myotomy. CONCLUSIONS: We demonstrated safety and efficiency of a multispecialty approach for achalasia with POEM with a low rate of complications.

Poorly differentiated neuroendocrine carcinoma of the breast with Merkel cell features.

Neuroendocrine carcinoma of the breast is a rare tumor subtype comprising less than 1% of breast cancers in the United States. Merkel cell features within this rare subtype are even rarer. We report a neuroendocrine breast carcinoma with Merkel cell features. The patient underwent breast conservation therapy and a sentinel lymph node biopsy. Unfortunately, the tumor was extremely aggressive and at 5 weeks postoperatively she presented with widely metastatic disease. Due to the aggressive nature of this tumor, we reviewed the literature and treatment options for this rare variant of a rare subtype.

Surgical Management of Breast Cancer in 2010-2011 SEER Registries by Hormone and HER2 Receptor Status.

BACKGROUND: Although locoregional recurrence is known to affect overall survival for operable breast cancer, the impact of receptor status on locoregional control is debated. Currently, hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status are generally not considered relevant to surgical choice. This study examines recent population-level surgical trends with regard to receptor status. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) data to identify stage I-III female breast cancers diagnosed from 2010 to 2011. Patients were categorized by HR and HER2 receptor status. Univariate and multivariate logistic regressions were used to assess factors associated with undergoing mastectomy and the choice of contralateral prophylactic mastectomy (CPM). RESULTS: The overall mastectomy rate for the 87,504 women diagnosed in 2010-2011 was 43.4 %. On multivariate analysis, the odds of receiving mastectomy was greater for HER2-positive disease with either HR-negative or HR-positive status, than for women with HER2-negative/HR-positive disease (odds ratio 1.73 and 1. 31, respectively; all p values <0.001). Age, stage, marital status, race, and year of diagnosis also correlated with mastectomy. Triple-negative breast cancer (TNBC) was associated with CPM, while HER2 status was not. The mastectomy rate, which increased overall from 2006 to 2010, has continued to increase for stage III disease but has decreased for stage I disease. Mastectomy rates overall were lower in 2011 than 2010 (p = 0.012). CONCLUSIONS: HER2-positive disease and TNBC were independent predictors of more extensive surgery in this large, recent, population-based cohort. Although mastectomy rates have continued to increase for stage III disease, mastectomy rates overall were lower in 2011 than in previous years.

Receptor Tyrosine Kinase Expression Predicts Response to Sunitinib in Breast Cancer.

BACKGROUND: Preliminary data indicate that tyrosine kinase inhibitors (TKIs) function through rearranged during transfection (RET) in breast cancer. However, TKIs are not specific and can block several receptor tyrosine kinases (RTKs). This study used cell lines and primary breast cancer specimens to determine factors associated with TKI response. METHODS: Proliferation was assessed after short interfering RNA knockdown with or without sunitinib in breast cancer cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Breast cancer tissue and matched normal breast was obtained from 30 women with invasive breast carcinoma. Gene expression was assessed by reverse transcriptase-polymerase chain reaction. Fresh tissue was treated in vitro with sunitinib or control media for 30 min, and response was assessed by phosphorylation-specific western blot. RESULTS: The RTKs including epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR1-3), platelet-derived growth factor receptor (PDGFRa/b), and Kit were overexpressed in triple-negative breast tumors relative to HER2- and estrogen receptor-alpha (ERα)-positive tumors and normal breast tissue. Knockdown of EGFR reduced in vitro proliferation in MCF-7 and MDA-MB-231 but not in SKBR-3 or ZR-75-1 breast cancer cells. With the exception of RET, response to sunitinib was independent of RTK expression in all four cell lines. Both ERα-positive and low-EGFR-expressing tumors had an increased in vitro sunitinib response, as determined by alteration of Erk activation. Expression of other RTKs and additional clinical factors were not associated with response. CONCLUSION: Triple-negative breast cancers overexpress RTKs but have decreased in vitro response to the TKI sunitinib. In addition to RET, TKIs that block EGFR may increase the therapeutic efficacy of TKIs in breast cancer.

A novel animal model for locally advanced breast cancer.

BACKGROUND: Locally advanced breast cancer (LABC) poses complex management issues due to failure of response to chemotherapy and progression to local complications such as skin erosion, superinfection, and lymphedema. Most cell line and animal models are not adequate to study LABC. METHODS: A patient-derived xenograft (IOWA-1T) from a patient with LABC was characterized for expression profile, short tandem repeat profile, oncogenic mutations, xenograft growth, and response to therapy. RESULTS: Short tandem repeat profile authenticated the cell line as derived from a human woman. The primary tumor and derived xenografts were weakly estrogen receptor alpha positive (<5%), progesterone receptor negative, and HER2 nonamplified. Expression array profile compared to MCF-7 and BT-549 cell lines indicate that IOWA-1T was more closely related to basal breast cancer. IOWA-1T harbors a homozygous R248Q mutation of the TP53 gene; in vitro invasion assay was comparable to BT-549 and greater than MCF-7. IOWA-1T xenografts developed palpable tumors in 9.6 ± 1.6 days, compared to 49 ± 13 days for parallel experiments with BT-20 cells (p < 0.002). Tumor xenografts became locally advanced, growing to >2 cm in 21.6 ± 2 days, characterized by skin erosion necessitating euthanasia. The SUMO inhibitor anacardic acid inhibited the outgrowth of IOWA-1T xenografts, while doxorubicin had no effect on tumorigenesis. CONCLUSIONS: IOWA-1T is a novel cell line with an expression pattern consistent with basal breast cancer. Xenografts recapitulated LABC and provide a novel model for testing therapeutic drugs that may be effective in cases resistant to conventional chemotherapy.

Distinct pathways regulated by RET and estrogen receptor in luminal breast cancer demonstrate the biological basis for combination therapy.

OBJECTIVE: We investigated directed therapy based on TFAP2C-regulated pathways to inform new therapeutic approaches for treatment of luminal breast cancer. BACKGROUND: TFAP2C regulates the expression of genes characterizing the luminal phenotype including ESR1 and RET, but pathway cross talk and potential for distinct elements have not been characterized. METHODS: Activation of extracellular signal-regulated kinases (ERK) and AKT was assessed using phosphorylation-specific Western blot. Cell proliferation was measured with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] after siRNA (small interfering RNA) gene knockdown or drug treatment. Cell cycle, Ki-67, and cleaved caspase 3 were measured by fluorescence-activated cell sorting. Tumorigenesis was assessed in mice xenografts. RESULTS: Knockdown of TFAP2C or RET inhibited GDNF (glial cell line-derived neurotrophic factor)-mediated activation of ERK and AKT in MCF-7 cells. Similarly, sunitinib, a small-molecule inhibitor of RET, blocked GDNF-mediated activation of ERK and AKT. Inhibition of RET either by gene knockdown or by treatment with sunitinib or vandetanib reduced RET-dependent growth of luminal breast cancer cells. Interestingly, knockdown of TFAP2C, which controls both ER (estrogen receptor) and RET, demonstrated a greater effect on cell growth than either RET or ER alone. Parallel experiments using treatment with tamoxifen and sunitinib confirmed the increased effectiveness of dual inhibition of the ER and RET pathways in regulating cell growth. Whereas targeting the ER pathway altered cell proliferation, as measured by Ki-67 and S-phase, anti-RET primarily increased apoptosis, as demonstrated by cleaved caspase 3 and increased TUNEL (terminal deoxyneucleotidyl transferase dUTP nick end labeling) expression in xenografts. CONCLUSIONS: ER and RET primarily function through distinct pathways regulating proliferation and cell survival, respectively. The findings inform a therapeutic approach based on combination therapy with antiestrogen and anti-RET in luminal breast cancer.

Rate of contralateral prophylactic mastectomy is influenced by preoperative MRI recommendations.

BACKGROUND: Women with breast cancer increasingly undergo contralateral prophylactic mastectomy (CPM). We evaluated the relationship between preoperative magnetic resonance imaging (MRI) findings and CPM. Other clinicopathologic variables associated with CPM choice and the pathology found in the contralateral breast are also reported. METHODS: Newly diagnosed breast cancer patients were prospectively enrolled in the University of Iowa Breast Molecular Epidemiology Resource. Patients with stages 0-III breast cancer who underwent mastectomy for the index cancer were eligible for this analysis. Univariate logistic regression and a multivariate model were used to identify factors predictive of CPM. RESULTS: Among 134 patients (mean age 54.9 years), 53 (39.6 %) chose CPM. On univariate analysis, patients undergoing CPM were more likely to have a preoperative breast MRI (64.2 vs. 39.5 %, p = 0.006) and to have follow-up testing recommended for the contralateral breast (28.3 vs. 4.9 %, p = 0.001). Univariate analysis also associated CPM with younger age (p < 0.0001), BRCA testing (p < 0.0001), BRCA mutation (p = 0.034) and reconstruction performed (p = 0.001). Median age of youngest child at diagnosis varied significantly between the CPM (15.9 years) and non-CPM (24.3 years) groups (p = 0.0018). On multivariate analysis, MRI follow-up recommendation, young age, reconstruction and human epidermal growth factor receptor 2 (HER2) positivity of the index cancer were significantly associated with CPM. Of the CPM specimens, one (1.8 %) had ductal carcinoma-in situ, which had not been identified on MRI. CONCLUSIONS: Abnormal findings in the contralateral breast on preoperative MRI, as well as young age, reconstruction and HER2-positive status correlated with CPM choice in this cohort. Occult malignancy was rare.

ATA risk stratification in papillary thyroid microcarcinoma has low positive predictive value when identifying recurrence.

BACKGROUND: Rising incidence of papillary thyroid microcarcinomas (PTMC) has raised concerns for overdiagnosis. Utility of the American Thyroid Association Risk Stratification System (ATA-RSS) 2015 in predicting risk of disease recurrence in patients with PTMC was assessed. METHODS: Electronic health records of patients who underwent total thyroidectomy were queried. ATA-RSS 2015 risk stratification was performed on those with PTMC, and validity for predicting disease recurrence was calculated. RESULTS: With 10-year median follow up, recurrence was higher in PTMC patients with high/intermediate vs low ATA risk (33 â€‹% vs 4 â€‹%, p â€‹= â€‹0.002). Sensitivity of ATA-RSS for detecting recurrence was 60 â€‹%, specificity 90 â€‹%, PPV 33.3 â€‹%, NPV 96.6 â€‹%, and accuracy 88 â€‹%. When microscopic extrathyroidal extension (ETE) was excluded as an intermediate risk criterion, PPV improved to 50 â€‹% and accuracy improved to 92.5 â€‹% CONCLUSIONS: ATA-RSS 2015 predicts recurrence in PTMC with high NPV but low PPV. Exclusion of microscopic ETE improved PPV, which may help prevent overtreatment.

Epidemiology and survival outcomes of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinoma.

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine neoplasms are a rare subtype of neuroendocrine neoplasm consisting of ≥30% each of neuroendocrine and non-neuroendocrine differentiation. Neuroendocrine carcinomas are poorly differentiated neuroendocrine tumors. The epidemiology and prognosis of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas are not clearly defined in the literature. We sought to examine the presentation, patterns of care, and outcomes of patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. METHODS: We identified patients diagnosed with stage I-III colorectal (excluding appendix) mixed neuroendocrine-non-neuroendocrine neoplasms or neuroendocrine carcinomas with only one-lifetime cancer diagnosis who underwent surgical resection between 2010 and 2018 from the National Cancer Database. We performed bidirectional selection to identify variables to include in a multivariable Cox proportional hazards model. RESULTS: We identified 189 patients with a diagnosis of stage I to III colorectal mixed neuroendocrine-non-neuroendocrine neoplasms, 66% of whom had poorly differentiated tumors and 482 with neuroendocrine carcinomas. Among patients with stage III disease, 68% of patients with mixed neuroendocrine-non-neuroendocrine neoplasms and 54% of patients with neuroendocrine carcinomas received adjuvant chemotherapy. The median survival for the overall patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas cohorts were 38 and 42 months, respectively (P = .22), and the median survival for patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas with stage III disease were 30 and 25 months, respectively (P = .27). In multivariable analysis, fewer number of positive nodes and receipt of adjuvant chemotherapy were independently associated with decreased risk of mortality for patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. CONCLUSION: Adjuvant chemotherapy is associated with improved survival in stage III mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. Future studies are warranted to identify subsets of patients benefiting most from adjuvant therapy.

Hospital Accreditation Status and Treatment Differences Among Black Patients With Colon Cancer.

Importance: Hospital-level factors, such as hospital type or volume, have been demonstrated to play a role in treatment disparities for Black patients with cancer. However, data evaluating the association of hospital accreditation status with differences in treatment among Black patients with cancer are lacking. Objective: To evaluate the association of Commission on Cancer (CoC) hospital accreditation status with receipt of guideline-concordant care and mortality among non-Hispanic Black patients with colon cancer. Design, Setting, and Participants: This population-based cohort study used the National Program of Cancer Registries, which is a multicenter database with data from all 50 states and the District of Columbia, and covers 97% of the cancer population in the US. The participants included non-Hispanic Black patients aged 18 years or older diagnosed with colon cancer between January 1, 2018, and December 31, 2020. Race and ethnicity were abstracted from medical records as recorded by health care facilities and practitioners. The data were analyzed from December 7, 2023, to January 17, 2024. Exposure: CoC hospital accreditation. Main Outcome and Measures: Guideline-concordant care was defined as adequate lymphadenectomy during surgery for patients with stages I to III disease or chemotherapy administration for patients with stage III disease. Multivariable logistic regression models investigated associations with receipt of guideline-concordant care and Cox proportional hazards regression models assessed associations with 3-year cancer-specific mortality. Results: Of 17 249 non-Hispanic Black patients with colon cancer (mean [SD] age, 64.8 [12.8] years; 8724 females [50.6%]), 12 756 (74.0%; mean [SD] age, 64.7 [12.8] years) were treated at a CoC-accredited hospital and 4493 (26.0%; mean [SD] age, 65.1 [12.5] years) at a non-CoC-accredited hospital. Patients treated at CoC-accredited hospitals compared with those treated at non-CoC-accredited hospitals had higher odds of receiving guideline-concordant lymphadenectomy (adjusted odds ratio [AOR], 1.89; 95% CI, 1.69-2.11) and chemotherapy (AOR, 2.31; 95% CI, 1.97-2.72). Treatment at CoC-accredited hospitals was associated with lower cancer-specific mortality for patients with stages I to III disease who received surgery (adjusted hazard ratio [AHR], 0.87; 95% CI, 0.76-0.98) and for patients with stage III disease eligible for chemotherapy (AHR, 0.75; 95% CI, 0.59-0.96). Conclusions and Relevance: In this cohort study of non-Hispanic Black patients with colon cancer, patients treated at CoC-accredited hospitals compared with those treated at non-CoC-accredited hospitals were more likely to receive guideline-concordant care and have lower mortality risk. These findings suggest that increasing access to high-quality guideline-concordant care at CoC-accredited hospitals may reduce variations in cancer treatment and outcomes for underserved populations.

Social Vulnerability and Receipt of Guideline-Concordant Care among Patients with Colorectal Cancer.

BACKGROUND: Cancer outcome disparities have been reported in highly vulnerable communities. The objective of this study was to evaluate the association of social vulnerability with receipt of guideline-concordant care (GCC) and mortality risk for patients with colorectal cancer. STUDY DESIGN: This retrospective observational study identified patients with stage I-III colon or stage II-III rectal cancer between 2018 and 2020 from the National Program of Cancer Registries Database. Data were merged with the Centers for Disease Control and Prevention Social Vulnerability Index (SVI) at the county level. GCC was defined as stage-appropriate lymphadenectomy, radiation therapy, or systemic therapy. Multivariable logistic regression and Cox proportional hazards regression investigated associations of SVI, as a continuous and categorical variable stratified into quartiles, with GCC and 3-year cancer-specific mortality risk, respectively. RESULTS: Among 124,950 patients (colon, n=102,399; rectal, n=22,551), median SVI was 60.9 (IQR 35.0 to 79.5). Patients in the highest SVI quartile had 21% decreased odds of receiving GCC (95% CI 0.76 - 0.83). Treatment at Commission on Cancer (CoC) accredited hospitals was associated with increased GCC (OR 1.79; 95% CI 1.72 - 1.85). Although there was an inverse, decreasing association between SVI and probability of GCC, probability at non-CoC-accredited hospitals declined faster than at CoC-accredited hospitals (p<0.05). After adjusting for receipt of GCC, highly vulnerable patients treated at CoC-accredited hospitals had decreased mortality risk (HR 0.91; 95% CI 0.83 - 0.98). CONCLUSION: For highly vulnerable patients, treatment at CoC-accredited hospitals was associated with increased receipt of GCC and decreased mortality risk, which may reflect CoC-accreditation requirements for treatment guideline adherence, community engagement, and addressing barriers to care.

An MITF- and mTOR-dependent FLCN pathway suppresses TFE3-driven metastasis in melanoma.

Cancer cells have remarkable plasticity allowing them to acquire many biological states. Melanoma cells have the ability to switch from a proliferative melanocytic state to an invasive mesenchymal state and back again resulting in intratumoral heterogeneity. While microphthalmia-associated transcription factor (MITF) promotes the melanocytic phenotype, it is unclear what transcription factors drive the mesenchymal phenotype, and what mechanisms regulate the switch from the proliferative state to the mesenchymal state. We show that nuclear localization of the MITF paralog TFE3 correlates positively with metastatic potential in melanoma cell lines and tumors, and that deletion of TFE3 in MITF-low melanoma cell lines eliminates migration and metastatic ability. Further, we find that MITF suppresses the mesenchymal phenotype by activating expression of FNIP2, which encodes a component of an mTORC1-stimulated pathway promoting cytoplasmic retention and lysosomal degradation of TFE3. These findings point to the mTOR pathway and TFE3 as key regulators of melanoma plasticity.

Discriminating pheochromocytomas from other adrenal lesions: the dilemma of elevated catecholamines.

BACKGROUND: Screening tests for pheochromocytoma involve measuring levels of catecholamines in the urine or plasma, which have significant false-positive rates. We reviewed patients with adrenal masses and elevated levels of catecholamines to determine the value of different preoperative tests in diagnosing pheochromocytomas. METHODS: A retrospective chart review identified patients who underwent adrenalectomy between 1997 and 2011 with elevation of urine or serum catecholamines. A database of clinicopathologic factors was created including preoperative urine and plasma metanephrines, normetanephrines, vanillylmandelic acid, and fractionated catecholamines, and tumor dimensions on imaging and pathology. RESULTS: A total of 70 patients underwent adrenalectomy because of presence of an adrenal mass and elevation of catecholamines or normetanephrines or metanephrines. Of these, 46 had pathologically confirmed pheochromocytomas. To improve our ability to discriminate between pheochromocytoma and other pathology, we examined different combinations of clinicopathologic factors and catecholamine levels and found the best test was a scoring system. Points are awarded for a hierarchy of elevated normetanephrine, norepinephrine, metanephrines, with additional points received for age <50 and size on imaging >3.3 cm. A score of 2 is suggestive of pheochromocytoma, with a positive predictive value of 86-87%, while a score of 4 is diagnostic with positive predictive value of 100%. CONCLUSION: We found that urine/serum normetanephrine levels were the most valuable screening tool; however, a score examining the size of adrenal mass on preoperative CT, age, and either plasma or urine norepinephrine, metanephrine, and normetanephrine values leads to a higher positive predictive value, making this scoring system superior to individual lab tests.