Informing the surgical workforce pathway: how rural community characteristics matter.

INTRODUCTION: Rural areas worldwide face a general surgeon shortage, limiting rural populations' access to surgical care. While individual and practice-related factors have been well-studied in the US, we need a better understanding of the role of community characteristics in surgeons' location choices. This study aimed to understand the deeper meanings surgeons associated with community characteristics in order to inform efforts spanning the rural surgeon workforce pathway, from early educational exposures, and undergraduate and graduate medical education, to recruitment and retention. METHODS: We conducted a qualitative, descriptive interview study with general surgeons in the Midwestern US about the role and meaning of community characteristics, exploring their backgrounds, education, practice location choices, and future plans. We focused on rural surgeons and used an urban comparison group. We used convenience and snowball sampling, then conducted interviews in-person and via phone, and digitally recorded and professionally transcribed them. We coded inductively and continued collecting data until reaching code saturation. We used thematic network analysis to organize codes and draw conclusions. RESULTS: A total of 37 general surgeons (22 rural and 15 urban) participated. Interviews totaled over 52 hours. Three global themes described how rural surgeons associated different, often deeper, meanings with certain community characteristics compared to their urban colleagues: physical environment symbolism, health resources' relationship to scope of practice, and implications of intense role overlap (professional and personal roles). All interviewees spoke to all three themes, but the meanings they found differed importantly between urban and rural surgeons. Physical landscapes and community infrastructure were representative of autonomy and freedom for rural surgeons. They also shared how facilities, equipment, staff, staff education, and surgical partners combined to create different scopes of practice than their urban counterparts experienced. Often, rural surgeons found these resources dictated when they needed to transfer patients to higher-acuity facilities. Rural surgeons experienced role overlap intensely, as they cared for patients who were also friends and neighbors. CONCLUSION: Rural surgeons associated different meanings with certain community characteristics than their urban counterparts. As they work with prospective rural surgeons, educators and rural communities should highlight how health resources can translate into desired scopes of practice. They also should share with trainees the realities of role overlap, both how intense and stressful it can be but also how gratifying. Educators should include the rural social context in medical and surgical education, looking for even more opportunities to collaborate with rural communities to provide learners with firsthand experiences of rural environments, resources, and role overlap.

Open Payments Data Analysis of General and Fellowship-trained Surgeons Receiving Industry General Payments From 2016 to 2020: Payment Disparities and COVID-19 Pandemic Impact.

OBJECTIVE: To characterize industry nonresearch payments made to general and fellowship-trained surgeons between 2016 and 2020. BACKGROUND: The Centers for Medicare & Medicaid Services Open Payments Data (OPD) reports industry payments made to physicians related to drugs and medical devices. General payments are those not associated with research. METHODS: OPD data were queried for general and fellowship-trained surgeons who received general payments from 2016 to 2020. Payments' nature, amount, company, covered product, and location were collected. Surgeons' demographics, subspecialty, and leadership roles in hospitals, societies, and editorial boards were evaluated. RESULTS: From 2016 to 2020, 44,700 general and fellowship-trained surgeons were paid $535,425,543 in 1,440,850 general payments. The median payment was $29.18. The most frequent payments were for food and beverage (76.6%) and travel and lodging (15.6%); however, the highest dollar payments were for consulting fees ($93,128,401; 17.4%), education ($88,404,531; 16.5%), royalty or license ($87,471,238; 16.3%), and travel and lodging ($66,333,149; 12.4%). Five companies made half of all payments ($265,654,522; 49.6%): Intuitive Surgical ($128,517,411; 24%), Boston Scientific ($48,094,570; 9%), Edwards Lifesciences ($41,835,544, 7.8%), Medtronic Vascular ($33,607,136; 6.3%), and W. L. Gore & Associates ($16,626,371; 3.1%). Medical devices comprised 74.7% of payments ($399,897,217), followed by drugs and biologicals ($33,945,300; 6.3%). Texas, California, Florida, New York, and Pennsylvania received the most payments; however, the top dollar payments were in California ($65,702,579; 12.3%), Michigan ($52,990,904, 9.9%), Texas ($39,362,131; 7.4%), Maryland ($37,611,959; 7%), and Florida ($33,417,093, 6.2%). General surgery received the highest total payments ($245,031,174; 45.8%), followed by thoracic surgery ($167,806,514; 31.3%) and vascular surgery ($60,781,266; 11.4%). A total of 10,361 surgeons were paid >$5000, of which 1614 were women (15.6%); in this group, men received higher payments than women (means, $53,446 vs $22,571; P <0.001) and thoracic surgeons received highest payments (mean, $76,381; NS, P =0.14). A total of 120 surgeons were paid >$500,000 ($203,011,672; 38%)-5 non-Hispanic White (NHW) women (4.2%) and 82 NHW (68.3%), 24 Asian (20%), 7 Hispanic (5.8%), and 2 Black (1.7%) men; in this group, men received higher payments than women (means, $1,735,570 vs $684,224), and NHW men received payments double those of other men (means, $2,049,554 vs $955,368; NS, P =0.087). Among these 120 highly paid surgeons (>$500,000), 55 held hospital and departmental leadership roles, 30 were leaders in surgical societies, 27 authored clinical guidelines, and 16 served on journal editorial boards. During COVID-19, 2020 experienced half the number of payments than the preceding 3 years. CONCLUSIONS: General and fellowship-trained surgeons received substantial industry nonresearch payments. The highest-paid recipients were men. Further work is warranted in assessing how race, gender, and leadership roles influence the nature of industry payments and surgical practice. A significant decline in payments was observed early during the COVID-19 pandemic.

Emerging From the Pandemic: How Has Academic Surgery Changed?

Academic surgery has changed along with the rest of the world in response to the COVID pandemic. With increasing rates of vaccination against COVID over the past 2 y, we have slowly but steadily made progress toward controlling the spread of the virus. Surgeons, academic surgery departments, health systems, and trainees are all attempting to establish a new normal in various domains-clinical, research, teaching, and in their personal lives. How has the pandemic changed these areas? At the 2022 Academic Surgical Congress Hot Topics session, we attempted to address these issues.

Age-related next-generation sequencing mutational analysis in 1196 melanomas.

BACKGROUND AND OBJECTIVES: Melanoma mutational burden is high and approximately 50% have oncogenic mutations in BRAF. We sought to evaluate age-related mutational differences in melanoma. METHODS: We analyzed melanoma samples in the Genomics Evidence Neoplasia Information Exchange database. Targetable mutations were identified using the Precision Oncology Knowledge Base (OncoKB). RESULTS: We found 1194 patients with a common set of 30 genes. The top mutated genes in patients <40 years old (y/o) (n = 98) were BRAF (59%), TP53 (31%), NRAS (17%), and PTEN (14%); in 40-59 y/o (n = 354) were BRAF (51%), NRAS (30%), TP53 (26%), and APC (13%); and in ≥60 y/o (n = 742) were BRAF (38%), NRAS (33%), TP53 (26%), and KDR (19%). BRAF mutations were almost mutually exclusive from NRAS mutations in <40 y/o (58/59). Mutational burden increased with age, with means of 2.39, 2.92, and 3.67 mutations per sample in patients <40, 40-59, and ≥60 y/o, respectively (p < 0.0001). There were 10 targetable mutations meeting OncoKB criteria for melanoma: BRAF (level 1), RET (level 1), KIT (level 2), NRAS (level 3A), TP53 (level 3A), and FGFR2, MET, PTEN, PIK3CA, and KRAS (level 4). CONCLUSIONS: Mutations in melanoma have age-related differences and demonstrates potential targetable mutations for personalized therapies.

Surgical Management of Melanoma: Advances and Updates.

PURPOSE OF REVIEW: To review and update surgeons about the evolving complexities in the surgical management of melanoma including lymph node staging and treatment. RECENT FINDINGS: Primary resection with adequate margins continues to be the standard of care for localized cutaneous melanoma. Sentinel lymph node biopsy is confirmed to be a powerful tool due to its prognostic value and informative guidance for adjuvant treatments and surveillance. Due to the lack of benefit in melanoma-specific survival and distant metastasis-free survival, completion lymph node dissection is not performed routinely after a positive sentinel lymph node biopsy. Neoadjuvant systemic treatment approaches for advanced loco-regional disease show promise in phase I and II clinical trial data, and phase III studies. The surgical management of cutaneous melanoma continues to evolve with further de-escalation of the extent of excision of primary melanomas and the management of lymph node disease.

Recent Evolution in the Management of Lymph Node Metastases in Melanoma.

INTRODUCTION: Based upon two large randomized international clinical trials (German Dermatologic Cooperative Oncology Group (DeCOG-SLT) and Multicenter Selective Lymphadenectomy Trial II (MSLT-II)) published in 2016 and 2017, respectively, active surveillance has been demonstrated to have equivalent survival outcomes to completion lymphadenectomy (CLND) for a subset of patients who have microscopic lymph node disease. In this study, the changes in national practice patterns were examined regarding the utilization of CLND after positive sentinel lymph node biopsy (SLNB). METHODS: Using the National Cancer Database, CLND utilization was examined in SLN-positive patients diagnosed with melanoma between 2012 and 2016. A hierarchal logistical regression model with hospital-level random intercepts was constructed to examine the factors associated with SLNB followed by observation vs. SLNB with CLND. RESULTS: Of the 148,982 patients identified, 43% (n = 63,358) underwent SLNB and 10.3% (n = 6,551) had a SLNB with microscopic disease. CLND was performed for 57% (n = 2,817) of these patients. Patients were more likely to undergo CLND if they were ≤ 55 years of age (OR, 1.454; p ≤ 0.0001), ages 56 - 65 (OR, 1.127; p = 0.026), Charlson Deyo Score = 0 (OR, 2.088; p = 0.043), or were diagnosed with melanoma in 2012 (OR, 2.259, p ≤ 0.0001). CONCLUSIONS: The utilization of CLND among patients with microscopic nodal melanoma was significantly lower in 2016 compared to 2012. Younger age, lack of comorbidities, and primary tumor location on the trunk or head/neck were associated with higher utilization of CLND.

Metastatic Tumor-in-a-Dish, a Novel Multicellular Organoid to Study Lung Colonization and Predict Therapeutic Response.

Metastasis is a major cause of cancer-related deaths. A dearth of preclinical models that recapitulate the metastatic microenvironment has impeded the development of therapeutic agents that are effective against metastatic disease. Because the majority of solid tumors metastasize to the lung, we developed a multicellular lung organoid that mimics the lung microenvironment with air sac-like structures and production of lung surfactant protein. We used these cultures, called primitive lung-in-a-dish (PLiD), to recreate metastatic disease using primary and established cancer cells. The metastatic tumor-in-a-dish (mTiD) cultures resemble the architecture of metastatic tumors in the lung, including angiogenesis. Pretreating PLiD with tumor exosomes enhanced cancer cell colonization. We next tested the response of primary and established cancer cells to current chemotherapeutic agents and an anti-VEGF antibody in mTiD against cancer cells in two-dimensional (2D) or 3D cultures. The response of primary patient-derived colon and ovarian tumor cells to therapy in mTiD cultures matched the response of the patient in the clinic, but not in 2D or single-cell-type 3D cultures. The sensitive mTiD cultures also produced significantly lower circulating markers for cancer similar to that seen in patients who responded to therapy. Thus, we have developed a novel method for lung colonization in vitro, a final stage in tumor metastasis. Moreover, the technique has significant utility in precision/personalized medicine, wherein this phenotypic screen can be coupled with current DNA pharmacogenetics to identify the ideal therapeutic agent, thereby increasing the probability of response to treatment while reducing unnecessary side effects. SIGNIFICANCE: A lung organoid that exhibits characteristics of a normal human lung is developed to study the biology of metastatic disease and therapeutic intervention.

Morbidity and mortality of synchronous hepatectomy with cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

BACKGROUND: Liver resection in conjunction with partial colectomy for colon cancer is considered acceptable treatment for isolated metastasis to the liver. This method is unstudied in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for carcinomatosis due to colon cancer and high grade appendiceal cancer. METHODS: A retrospective chart review included patients from 2005 to 2016 undergoing CRS/HIPEC. Cancers other than colorectal adenocarcinoma and high grade appendiceal carcinoma were excluded. Patients were divided into hepatectomy and non-hepatectomy groups. Data was collected by chart review from electronic medical records to assess morbidity and mortality, as well as oncologic outcomes of included patients. RESULTS: The average patient age, length of stay, and sex were similar between groups. For those in the hepatectomy group, 80% underwent minor hepatectomy, and 20% underwent major hepatectomy. The comprehensive complication index (CCI) scores ranged from 0 (no complications), to 100 (death). The average CCI between study groups was similar (27.29 vs. 17.41, P=0.09). Hepatectomy was associated with a higher rate of Clavien-Dindo classifications (CDCs) of III or greater. Complications included pressor requirement, renal failure, blood transfusions, TPN, pleural effusions and leaks requiring drain placement, respiratory failure, UTI, new onset atrial fibrillation, wound infections, and death. CONCLUSIONS: Patients who underwent CRS/HIPEC and hepatectomy for colorectal and high grade appendiceal carcinomatosis had more severe complications at similar rates to non-hepatectomy patients. Complication rates should be considered when selecting patients for aggressive surgical intervention.

Pathological Response and Survival in Triple-Negative Breast Cancer Following Neoadjuvant Carboplatin plus Docetaxel.

PURPOSE: Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC. PATIENTS AND METHODS: One-hundred and ninety patients with stage I-III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan-Meier method. RESULTS: Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14-0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10-0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS. CONCLUSIONS: Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.

Speed Mentoring: An Innovative Method to Meet the Needs of the Young Surgeon.

OBJECTIVE: Speed mentoring has recently been used by several medical organizations as a strategy to establish mentoring relationships, which are felt to be critically important in the development of the surgeon. This study assesses a surgical speed-mentoring program at the 2015 American College of Surgeons (ACS) Clinical Congress. DESIGN: A steering committee designed the speed-mentoring program to match 60 ACS Resident and Associate Society mentees with a mix of junior and senior leadership of ACS. Each mentee met with 5 mentors for 10 minutes each during the 1 hour session. After participation in the activity, surveys were provided to assess the event. The survey included forced-choice questions using Likert-scales as well as open-ended questions. Mentor and mentee responses were compared using Medcalc software using comparison of means and comparison of proportion, with p < 0.05 considered significant. SETTING: The study was undertaken at the 2015 ACS Clinical Congress. PARTICIPANTS: A total of 60 mentors and 49 mentees participated in the inaugural ACS Speed-Mentoring activity. The postactivity survey was completed by 54 mentors (90%) and 39 mentees (79.5%). RESULTS: There was a high level of satisfaction with the activity, with 100% of mentors and mentees stating that they would recommend the activity to a colleague. There was overall high satisfaction with the organization of the session by both the mentors and the mentees although the mentors were more likely to feel that they needed more time for each interaction. More mentees (93%) than mentors (68.5%) felt they were likely to develop a mentoring relationship with one of their matches outside of the organized session. CONCLUSIONS: We demonstrated that a speed-mentoring event at a national surgical meeting offers an effective platform for mentoring and is mutually beneficial to both mentors and mentees. Data collected here will be used to modify and improve the design of future speed-mentoring sessions.

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts.

PURPOSE: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. EXPERIMENTAL DESIGN: The study population includes 190 patients with stage I-III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated. RESULTS: Among 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. CONCLUSIONS: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline-taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649-57. ©2016 AACR.

Impact of neoadjuvant chemotherapy on axillary nodal involvement in patients with clinically node negative triple negative breast cancer.

BACKGROUND: We evaluated the impact of Neoadjuvant Chemotherapy (NAC) versus primary surgery (PS) on axillary disease burden/surgery in clinically node negative Triple Negative Breast Cancer (TNBC). METHODS: Two hundred forty-three Stage I-III TNBC patients have enrolled on an IRB approved multisite prospective registry. Clinical and treatment information was collected. RESULTS: One hundred fifty-five patients with clinically node negative TNBC were identified. 47%, 49%, and 4% of patients had T1, T2, and T3 disease, respectively. Patients underwent PS (103/155, 66%) or NAC (52/155, 34%) at the discretion of treating physicians. 17% of PS and 0% of NAC patients were node positive at surgery (P=0.006). For T2 disease, 32% of PS and 0% of NAC patients were node positive at surgery (P=0.001). NAC patients had a lower chance of positive SLNB (0% vs. 12%, P=0.004) and undergoing ALND (2% vs. 22%, P=0.001) than PS patients. CONCLUSION: In this clinically node negative TNBC cohort, all NAC-treated patients were node negative at surgery, whereas 17% of PS patients had involved axillary nodes. NAC should be considered for clinically node negative TNBC to reduce the extent of axillary surgery even if breast conservation is not planned.

Honokiol inhibits melanoma stem cells by targeting notch signaling.

Melanoma is an aggressive disease with limited therapeutic options. Here, we determined the effects of honokiol (HNK), a biphenolic natural compound on melanoma cells and stemness. HNK significantly inhibited melanoma cell proliferation, viability, clonogenicity and induced autophagy. In addition, HNK significantly inhibited melanosphere formation in a dose dependent manner. Western blot analyses also demonstrated reduction in stem cell markers CD271, CD166, Jarid1b, and ABCB5. We next examined the effect of HNK on Notch signaling, a pathway involved in stem cell self-renewal. Four different Notch receptors exist in cells, which when cleaved by a series of enzymatic reactions catalyzed by Tumor Necrosis Factor-α-Converting Enzyme (TACE) and γ-secretase protein complex, results in the release of the Notch intracellular domain (NICD), which then translocates to the nucleus and induces target gene expression. Western blot analyses demonstrated that in HNK treated cells there is a significant reduction in the expression of cleaved Notch-2. In addition, there was a reduction in the expression of downstream target proteins, Hes-1 and cyclin D1. Moreover, HNK treatment suppressed the expression of TACE and γ-secretase complex proteins in melanoma cells. To confirm that suppression of Notch-2 activation is critical for HNK activity, we overexpressed NICD1, NICD2, and performed HNK treatment. NICD2, but not NICD1, partially restored the expression of Hes-1 and cyclin D1, and increased melanosphere formation. Taken together, these data suggest that HNK is a potent inhibitor of melanoma cells, in part, through the targeting of melanoma stem cells by suppressing Notch-2 signaling.

Honokiol affects melanoma cell growth by targeting the AMP-activated protein kinase signaling pathway.

BACKGROUND: Malignant melanoma is an aggressive form of skin cancer with limited effective therapeutic options. Melanoma research concentrates on maximizing the effect on cancer cells with minimal toxicity to normal cells. AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis and has been shown to control tumor progression regulating the cell cycle, protein synthesis, and cell growth and/or survival. Honokiol (HNK) is a biphenolic compound derived from Magnolia officinalis, a plant that has been used in traditional Chinese and Japanese medicine for the treatment of various pathological conditions. Recent studies have shown that HNK has antitumor activity with relatively low toxicity. In this study, we demonstrated that the growth inhibitory effects of HNK on melanoma and melanoma cancer stem cells were mediated through the activation of AMPK and hence AMPK signaling in melanoma cells. METHODS: We determined the effects of HNK treatment on various melanoma cell lines. HNK-induced cell growth inhibitory effects were determined using hexosaminidase assay. Protein expression studies were done by immunoblotting. Primary spheroid assay was used to assess stemness by growing single suspension cells in ultralow attachment plates. RESULTS: HNK is highly effective in inhibiting melanoma cells by attenuating protein kinase B/mammalian target of rapamycin and AMPK signaling. HNK showed significant inhibition of the spheroid-forming capacity of melanoma cells and, hence, stemness. HNK significantly decreased the number and size of melanospheres in a dose-dependent manner. Western blot analyses showed enhanced phosphorylation of AMPK in melanoma cells. Furthermore, HNK decreased the cellular adenosine triphosphate pool in a dose-dependent manner with maximum effects observed at 48 hours. CONCLUSIONS: The results suggest that HNK can target melanoma cells and mark them for cell death through AMPK signaling. Further studies are warranted for developing HNK as an effective chemopreventive/therapeutic agent in melanoma.

Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing.

NCCN guidelines recommend genetic testing for all triple-negative breast cancer (TNBC) patients aged ≤60 years. However, due to the lack of prospective information in unselected patients, these guidelines are not uniformly adopted by clinicians and insurance carriers. The aim of this study was to determine the prevalence of BRCA mutations and evaluate the utility of NCCN guidelines in unselected TNBC population. Stage I-IV TNBC patients were enrolled on a prospective registry at academic and community practices. All patients underwent BRCA1/2 testing. Significant family history (SFH) was defined >1 relative with breast cancer at age ≤50 or ≥1 relative with ovarian cancer. Mutation prevalence in the entire cohort and subgroups was calculated. 207 TNBC patients were enrolled between 2011 and 2013. Racial/ethnic distribution: Caucasian (80 %), African-American (14 %), Ashkenazi (1 %). Deleterious BRCA1/2 mutations were identified in 15.4 % (32/207) of patients (BRCA1:11.1 %, BRCA2:4.3 %). SFH reported by 36 % of patients. Mutation prevalence in patients with and without SFH was 31.6 and 6.1 %, respectively. When assessed by age at TNBC diagnosis, the mutation prevalences were 27.6 % (≤50 years), 11.4 % (51-60 years), and 4.9 % (≥61 years). Using SFH or age ≤50 as criteria, 25 and 34 % of mutations, respectively, were missed. Mutation prevalence in patients meeting NCCN guidelines was 18.3 % (32/175) and 0 % (0/32) in patients who did not meet guidelines (p = .0059). In this unselected academic and community population with negligible Ashkenazi representation, we observed an overall BRCA mutation prevalence rate of 15.4 %. BRCA testing based on NCCN guidelines identified all carriers supporting its routine application in clinical practice for TNBC.

Low grade B cell lymphoma arising in a background of multifocal extra-adrenal myelolipoma.

Myelolipomas are rare, benign, non-functioning tumors composed of an admixture of mature adipose tissue and hematopoietic elements. Extra-adrenal myelolipomas are extremely rare, but have been reported in multiple sites including the omentum, presacral, and retroperitoneal areas, along with the thorax, kidneys, liver and stomach. We report a case of a 68-year-old man with low-grade B-cell lymphoma arising in a background of recurrent multifocal extra-adrenal myelolipoma. Pathological evaluation of the lesion and bone marrow showed foci of lymphoid aggregate that were confirmed to be monoclonal B lymphoma by flow cytometry. To our knowledge, this is only the third reported case to feature such a rare combination of diseases. The clinical, radiological, and pathological differential diagnostic findings are discussed.

Axillary reverse mapping: a prospective study in women with clinically node negative and node positive breast cancer.

BACKGROUND: The primary aim of axillary reverse mapping (ARM) is to prevent lymphedema by preserving arm versus breast axillary lymphatics. Concerns regarding feasibility and oncologic safety have limited the adoption of the technique. This prospective study was undertaken to investigate ARM in clinically node negative and node positive breast cancer patients. METHODS: A total of 184 patients underwent 212 ARM procedures: 155 sentinel lymph node biopsies (SLNB) without axillary lymph node dissection (ALND) (group 1) and 57 ALNDs with/without SLNB (group 2). ARM lymphatics were not preserved if they were a SLN, directly entered a SLN, or were within ALND boundaries during ALND. RESULTS: SLN with radioisotope alone was successful in 92 % of procedures (181 of 197). ARM identification was 47 % (73 of 155) in group 1. Criteria were met in 30 % (47 of 155) for preservation, and 25 % (38 of 155) were preserved. Of those who met preservation criteria, 81 % (38 of 47) were preserved. In group 2, ARM identification was 72 % (41 of 57); 7 met criteria for preservation and were preserved. Of the ARM nodes, 10 % (22 of 212) were SLNs (crossover). ARM nodes contained metastatic disease in one crossover and two nonsentinel ARM nodes in clinically node positive patients with N2/N3 disease. CONCLUSIONS: ARM is a feasible technique for identification and preservation of axillary arm lymphatics with an acceptable incidence of SLN crossover. A larger sample size is needed to determine if ARM can reduce the incidence of lymphedema in patients undergoing SLNB alone and to confirm the absence of ARM metastases in clinically node negative patients undergoing ALND.

Honokiol induces cytotoxic and cytostatic effects in malignant melanoma cancer cells.

BACKGROUND: Melanomas are aggressive neoplasms with limited therapeutic options. Therefore, developing new therapies with low toxicity is of utmost importance. Honokiol is a natural compound that recently has shown promise as an effective anticancer agent. METHODS: The effect of honokiol on melanoma cancer cells was assessed in vitro. Proliferation and physiologic changes were determined using hexosaminidase assay and transmission electron microscopy. Protein expression was assessed by immunoblotting. RESULTS: Honokiol treatment inhibited cell proliferation and induced death. Electron microscopy showed autophagosome formation. Reduced levels of cyclin D1 accompanied cell-cycle arrest. Honokiol also decreased phosphorylation of AKT (known as protein kinase B) and mammalian target of rapamycin, and inhibited γ-secretase activity by down-regulating the expression of γ-secretase complex proteins, especially anterior pharynx-defective 1. CONCLUSIONS: Honokiol is highly effective in inhibiting melanoma cancer cells by attenuating AKT/mammalian target of rapamycin and Notch signaling. These studies warrant further clinical evaluation for honokiol alone or with present chemotherapeutic regimens for the treatment of melanomas.