Racial Disparities in Breast Cancer Genetic Testing May be Mitigated by Counseling.

BACKGROUND: Currently, racial disparities exist in access to genetic testing. Recent developments have helped narrow the gap in accessibility. The purpose of this study was to determine whether racial disparities in genetic consultation attendance and completion of genetic testing persist, and, if so, factors that contribute to under-utilization of these resources. METHODS: A single-institution retrospective review of breast patients referred for genetic counseling between 2017 and 2019 was performed. Univariate and multivariate logistic regression evaluated factors associated with genetic counseling attendance and genetic testing. RESULTS: A total of 596 patients were referred for genetic counseling: 433 (72.7%) white; 138 (23.2%) black; and 25 (4.2%) other or unknown. In multivariate analysis, black patients, patients without breast cancer family history, and patients without a current cancer diagnosis, classified as high risk, were significantly less likely to attend their genetics appointment (p = 0.010, p = 0.007, p = 0.005, respectively). Age, insurance type, distance from facility, and need for chemotherapy did not significantly impact consult completion rate. Of the patients who completed a genetic consult, 84.4% (n = 248) had genetic testing and 17.7% (n = 44) had a pathogenic variant. For patients who attended counseling, there were no significant factors that were predictive with receipt of genetic testing. CONCLUSIONS: In this study, there was a significant association between race and attending genetic counseling. Once counseled, most patients went on to receive genetic testing, and racial disparities in testing disappeared, emphasizing the value of providing additional education about the importance and purpose of genetic testing.

A Supportive Culture Maintains General Surgery Wellness.

Social restrictions during the pandemic required creative solutions for incorporating interns into a demanding residency, building relationships, and fostering resiliency. We hypothesized that resident-driven initiatives focused on inclusion would overcome a lack of in-person events. An anonymous survey was administered to all surgery residents to assess burnout pre- and post-wellness interventions. Assessment scores were analyzed with Mann-U Whitney and Kruskal-Wallis tests. The surveys were completed by 71.6% (n = 53) and 48.6% (n = 36) of residents, respectively, and demonstrated high metrics for wellness measures. There were no significant differences on the 6-month post-assessment, suggesting interventions preserved high ratings. The PGY1 subgroup demonstrated improvement in the ability to identify a faculty mentor (P < .01) and had reduced burnout measures (P < .05). Surgical resident wellness is not dependent on department-wide gatherings; rather, resident-driven interventions in the workspace and intimate social support demonstrated an impact on wellness and reduced burnout.

The anti-proliferative effects of a frankincense extract in a window of opportunity phase ia clinical trial for patients with breast cancer.

PURPOSE: Boswellic acids, active components of frankincense, suppress tumor proliferation in vitro with a strong clinical trial safety profile in patients with inflammatory diseases. We performed a Phase Ia window of opportunity trial of Boswellia serrata (B. serrata) in patients with breast cancer to evaluate its biologic activity and safety. METHODS: Patients with invasive breast cancer were treated pre-operatively with B. Serrata (2400 mg/day PO) until the night before surgery for a median of 11 days (SD 6 days; range: 5-23 days). Paraffin-embedded sections from pretreatment diagnostic core biopsies and post-treatment surgical excisions were evaluated using a tunnel assay and immunohistochemistry staining with Ki-67 antibodies. A non-intervention retrospective control arm consisting of core and surgical tissue specimens from untreated patients was used to compare patients treated with B. Serrata. The change in proliferation and apoptosis between diagnostic core specimens and surgical specimens was compared between the control and treatment groups using a two-tailed paired t-test. RESULTS: Twenty-two patients were enrolled, of which 20 received treatment, and 18 had sufficient tissue for IHC. There was an increase in percent change in proliferation from core biopsy to surgical excision in the control group (n = 18) of 54.6 ± 21.4%. In the B. serrata-treated group there was a reduction in proliferation between core biopsy and excision (n = 18) of 13.8 ± 11.7%. This difference was statistically significant between the control and B. serrata-treated groups (p = 0.008). There was no difference in change in apoptosis. There were no serious adverse events related to the drug. CONCLUSION: Boswellia serrata inhibited breast cancer proliferation and was well-tolerated in a Phase Ia window of opportunity trial.

Neoadjuvant Chemotherapy is Associated With Decreased Survival in Early-Stage Gastric Cancer.

BACKGROUND: Although randomized controlled trials on neoadjuvant chemotherapy for gastric cancer have included some T1-staged tumors, overall survival (OS) has not been analyzed for this subset. Due to the low negative predictive value of clinical staging and the benefits of neoadjuvant chemotherapy for locally advanced disease, identifying patient groups with early-stage gastric cancer that may benefit from neoadjuvant chemotherapy is of merit. AIMS: The objective of this study was to evaluate the relationship between OS and sequence of surgical therapy for clinical T1 gastric cancer. METHODS: The 2017 National Cancer Database was used to compare patients who had surgery-first and those who received neoadjuvant chemotherapy for T1-stage gastric cancer. OS was analyzed using a parametric regression survival-time model adjusted for covariates. The effects of these covariates on OS based on surgical sequence were examined. RESULTS: 11,219 patients were included, of which 10,191 underwent surgery as their first or only treatment. When adjusted for covariates, neoadjuvant chemotherapy followed by curative-intent surgery was significantly associated with increased risk of death (HR 1.15, 95% CI 1.01-1.31, P = .030). In multivariate analysis, clinical N0 stage, non-minorities, and patients with high socioeconomic status had improved OS if they did not have neoadjuvant chemotherapy and instead had upfront surgery. CONCLUSION: Neoadjuvant chemotherapy is associated with decreased OS for early-stage gastric adenocarcinoma, even for patients with clinically positive nodal disease. In addition, the lack of survival improvement with a surgery-first approach in patients with disparities deserves further study.

Secreted frizzled related-protein 2 is prognostic for human pancreatic cancer patient survival and is associated with fibrosis.

Pancreatic adenocarcinoma (PDAC) is one of the deadliest cancers, with five-year survival rates of 9%. We hypothesized that secreted frizzled-related protein 2 (SFRP2) may influence stromal growth in pancreatic cancer, since it increases fibrosis and collagen production in non-neoplastic pathologies. We assessed SFRP2 value as a biomarker and assessed its function in PDAC. SFRP2 gene expression in patients with PDAC was analyzed using TCGA data. Disease free survival (DFS) was analyzed using Kaplan Meier test. The effect of KRAS inhibition on SFRP2 expression in PDAC cells was assessed. The associations of stromal content with SFPR2 mRNA and protein with fibrosis were analyzed. The role of SFRP2 in mesenchymal transformation was assessed by western blot in fibroblasts. Of all cancers in TCGA, SFRP2 levels were highest in PDAC, and higher in PDAC than normal tissues (n= 234, p= 0.0003). High SFRP2 levels correlated with decreased DFS (p= 0.0097). KRAS inhibition reduced SFRP2 levels. Spearman correlation was 0.81 between stromal RNA and SFRP2 in human PDAC, and 0.75 between fibrosis and SFRP2 levels in PDAC tumors. SFRP2-treated fibroblasts displayed mesenchymal characteristics. SFRP2 is prognostic for PDAC survival, regulated by KRAS, and associated with PDAC fibrosis.

The impact of nurse navigation on timeliness to treatment for benign high-risk breast pathology.

PURPOSE: High-risk breast pathology is a breast cancer risk factor for which timely treatment is crucial. Nurse navigation programs have been implemented to minimize delays in patient care. This study evaluated nurse navigation in terms of timeliness to surgery for patients with high-risk breast pathology. METHODS: This was a single-institution, retrospective review of patients with identified high-risk breast pathology undergoing lumpectomy between January 2017 and June 2019. Patients were stratified into cohorts based on periods with and without nurse navigation. Preoperative and postoperative time to care as well as demographic and tumor characteristics were compared using univariate and multivariate analysis. RESULTS: 100 patients had assigned nurse navigators and 29 patients did not. Nurse navigation was associated with reduced time from referral to date of surgery (DOS) by 16.9 days (p = 0.003). Patients > 75 years had a shorter time to first appointment (p = 0.03), and patients with Medicare insurance had a reduced time from referral to DOS (p = 0.005). 20% of all patients were upstaged to cancer on final surgical pathology. CONCLUSION: Nurse navigation was significantly associated with decreased time to care for patients with high-risk breast pathology undergoing lumpectomy. We recommend nurse navigation programs as part of a comprehensive approach for patients with high-risk breast pathology.

An Early-Stage Colon Cancer Develops Intrabiliary Growth Type Metastasis 7 Years After Curative Colectomy.

Although liver metastasis commonly occurs in patients with colorectal cancer (CRC), it is infrequent that it presents several years after curative resection for early-stage disease. Even more unusual is development of intrabiliary growth type metastasis rather than parenchymal metastasis. When this occurs, it can be mistaken for cholangiocarcinoma. We present a case in a patient with history of pT1N0M0 CRC treated with sigmoidectomy 7 years previously who presented with abdominal pain and MRI revealing left hepatic ductal dilation with no accompanying mass. With a recent normal colonoscopy and carcinoembryonic antigen, he was diagnosed with cholangiocarcinoma. Anatomic hepatic resection was performed, and final pathology with immunohistochemistry revealed staining consistent with CRC metastasis rather than cholangiocarcinoma. Intrabiliary growth type metastasis is a rare occurrence, which leads to its misdiagnosis. Patients with an intrabiliary tumor and a history of CRC should have immunohistochemistry to confirm the diagnosis to ensure appropriate adjuvant treatment and counseling.

The Effect of Goal-Directed Fluid Administration on Outcomes After Pancreatic Surgery.

BACKGROUND: We evaluated the effect of an Enhanced Recovery After Surgery protocol on intraoperative fluid administration and postoperative outcomes in pancreatic surgery. METHODS: Pancreatic cancer resections at our institution from 2012 to 2018 were grouped according to pre- or post-protocol initiation. Preoperative characteristics and postoperative outcomes were compared with Fisher's exact test and chi-square for categorical variables, and Mann-Whitney U test for continuous variables. Further analysis separated patients that had a Whipple from those who had distal pancreatectomy. RESULTS: A total of 263 patients underwent pancreatic cancer resection during the study period (169 Whipples, 84 DPs, 92 pre-ERAS and 171 post-ERAS). Intraoperative fluid administration significantly decreased after protocol implementation (mean 6,277 ml vs. 3870 ml, p < 0.001). This held true when separating patients that had a Whipple procedure from those that had a DP (6,929 ml vs. 4,513 ml, p < 0.001, 5,060 ml vs. 2,833 cc, p = 0.002, respectively). Intensive care unit (ICU) admission (41.3% vs. 20.5%, p < 0.001) and length of stay (9.4 vs. 8.1 days, p < 0.01) were significantly reduced after ERAS implementation for all patients and in Whipple patients alone (47.5% vs. 23.6%, p = 0.002 and 10.7 vs. 6.6 days, p = 0.004). DP patients also had significantly decreased ICU admissions (41.3% vs. 20.5%, p = 0.045). All other postoperative outcomes were not significantly different. CONCLUSION: For patients undergoing pancreatic cancer resection, goal-directed fluid management is associated with decreased intraoperative fluid administration, decreased ICU admission, and decreased length of stay without an increase in postoperative complications or readmission.

Distal Pancreatectomy for Pancreatitis in the Modern Era.

INTRODUCTION: Distal pancreatectomy has not been well examined in the modern era to guide management for pancreatitis. We evaluated this heterogeneous group and the preoperative factors associated with clinically relevant postoperative pancreatic fistula (CR-POPF). METHODS: Patients undergoing distal pancreatectomy at a single academic institution from August 2012 to January 2020 were evaluated. Univariate and multivariate logistic regressions were conducted between preoperative factors and CR-POPF. RESULTS: One hundred and thirty patients underwent distal pancreatectomy. Indication for operative management included chronic pancreatitis and/or pseudotumor in 24.6% (n = 32), disconnected left pancreatic remnant in 31.5% (n = 41), chronic distal pseudocyst in 20.8% (n = 27), and distal necrosis in 13.8% (n = 18). Significant complications (Clavien-Dindo grade ≥ III) were seen in 34% of patients. After surgery, 34.2% developed diabetes, 40% had persistent opioid use, and 22.3% had CR-POPF. In multivariate analysis, male sex was significantly associated with CR-POPF (odds ratio 3.1, P = 0.037), and having a preoperative, therapeutic endoscopic retrograde cholangiopancreatography was protective (odds ratio 0.28, P = 0.020). CONCLUSIONS: Distal pancreatectomy is undertaken in pancreatitis with high morbidity. Female sex and preoperative, therapeutic endoscopic retrograde cholangiopancreatography were significant protective factors for CR-POPF. The natural history of this approach is relevant for those with distal pancreatitis failing medical management.

Music Therapy in Dialysis Access Procedures With Moderate Sedation.

BACKGROUND: The aim was to evaluate the effects of music on patients' anxiety and satisfaction after undergoing dialysis access procedures under moderate sedation. METHODS: Patients (n = 30) undergoing moderate sedation for dialysis access procedures were evaluated at a single institution. Each patient filled out a survey preoperatively and postoperatively using the short form State-Trait Anxiety Inventory (STAI-6). Patient-selected music was provided by using a MP3 player with noise canceling headphones. RESULTS: Postoperatively, 77% of patients perceived music intervention as very or extremely helpful in decreasing anxiety during the procedure. Further, 93% of patients were somewhat or very satisfied with their procedure. The average pain rating was 3.1 on a scale of 0-10, in which 70% of patients had no to mild pain and 30% of patients rated moderate to severe pain. In comparison to prior procedures without music, 63% of patients rated better experience with the music intervention, 37% rated a similar experience, and 3.7% rated having a worse experience. Approximately, 93% of patients were willing to repeat procedure with music and would recommend it to other patients. Preoperative anxiety average score was 35.6 ± 13 and was reduced postoperatively to 28.9 ± 12.9 (P = .006). Preoperatively, 23% of patients rated high anxiety and postoperatively only 6.7% of patients rated high anxiety (P = .016). CONCLUSION: Music is an easy, feasible, inexpensive intervention that may reduce patients' anxiety and improve satisfaction during moderate sedation procedures and in the postoperative period.

Devices to enhance organ perfusion during cardiopulmonary resuscitation.

INTRODUCTION: The recommended method of cardiopulmonary resuscitation (CPR) has been closed-chest cardiac compressions, but the development of CPR adjunctive devices has called into question the efficacy and role of these adjunctive devices. In this review, we provide a comprehensive evaluation and discussion on the commercially available noninvasive CPR adjuncts used during out-of-hospital cardiac arrest (OHCA). AREAS COVERED: We review the three most common CPR adjunctive devices: the piston mechanism, the load distributing band, and the impedance threshold device. All three CPR adjunctive devices have preclinical data to support their use during cardiac arrest. In clinical trials, limited data show improvement in survival and neurologic recovery for these devices, and there is insufficient high-level evidence to support their use over manual chest compressions. However, there is a role for them when adequate manual chest compressions are not feasible. EXPERT OPINION: The commercially available CPR adjuncts do not consistently show improved outcomes in the literature. There is still a need for research and development into innovative solutions to improve OHCA survival and neurologic recovery. Efforts focused on increasing the speed of CPR initiation and increasing perfusion to the cerebral and coronary vasculature have the potential to advance resuscitative practices.

Prognostic factors for residual occult disease in shave margins during partial mastectomy.

PURPOSE: Shave margins have been shown to decrease positive final margins in partial mastectomy. We investigated prognostic factors associated with residual disease in shave margins. METHODS: Patients with invasive breast carcinoma and ductal carcinoma in situ (DCIS) who had circumferential shave margins excised during lumpectomy were abstracted from a retrospective database from 2015 to 2018. We defined residual occult disease (ROD) as either (1) residual disease in a shave margin when the initial lumpectomy specimen had negative margins or (2) residual disease in a shave margin that did not correspond with the positive lumpectomy margin. We identified the frequency of ROD and conducted logistic regression analysis to identify associated prognostic factors. RESULTS: 166 Patients (139 invasive carcinoma, 27 DCIS) were included with median follow-up of 28 months (9-50 months). Residual occult disease existed in 34 (24.5%) with invasive carcinoma and 8 (29.6%) with DCIS. In univariate analyses of the invasive group, invasive lobular carcinoma and a positive initial, non-corresponding lumpectomy margin were predictive of ROD (OR 3.63, p = 0.04, OR 3.48, p = 0.003 respectively). In multivariate analysis, a positive lumpectomy margin remained significant, p = 0.007. No variables were associated with ROD in DCIS. CONCLUSION: Residual occult disease was shown to be a frequent event in this analysis of lumpectomy with circumferential shave margins. Having a positive initial lumpectomy margin was predictive of ROD in a non-corresponding margin. Surgeons should consider not being selective in their shave margins or margin of re-excision if shave margins were not obtained in their initial surgery.

Overcoming PD-1 Inhibitor Resistance with a Monoclonal Antibody to Secreted Frizzled-Related Protein 2 in Metastatic Osteosarcoma.

Secreted frizzled-related protein 2 (SFRP2) promotes the migration/invasion of metastatic osteosarcoma (OS) cells and tube formation by endothelial cells. However, its function on T-cells is unknown. We hypothesized that blocking SFRP2 with a humanized monoclonal antibody (hSFRP2 mAb) can restore immunity by reducing CD38 and PD-1 levels, ultimately overcoming resistance to PD-1 inhibitors. Treating two metastatic murine OS cell lines in vivo, RF420 and RF577, with hSFRP2 mAb alone led to a significant reduction in the number of lung metastases, compared to IgG1 control treatment. While PD-1 mAb alone had minimal effect, hSFRP2 mAb combination with PD-1 mAb had an additive antimetastatic effect. This effect was accompanied by lower SFRP2 levels in serum, lower CD38 levels in tumor-infiltrating lymphocytes and T-cells, and lower PD-1 levels in T-cells. In vitro data confirmed that SFRP2 promotes NFATc3, CD38 and PD-1 expression in T-cells, while hSFRP2 mAb treatment counteracts these effects and increases NAD+ levels. hSFRP2 mAb treatment further rescued the suppression of T-cell proliferation by tumor cells in a co-culture model. Finally, hSFRP2 mAb induced apoptosis in RF420 and RF577 OS cells but not in T-cells. Thus, hSFRP2 mAb therapy could potentially overcome PD-1 inhibitor resistance in metastatic osteosarcoma.

Travel distance and overall survival in hepatocellular cancer care.

BACKGROUND: Our objective was to assess the relationship between overall survival (OS) and distance travelled to the treating facility for patients undergoing liver resection for hepatocellular carcinoma and to determine whether this relationship was dependent upon the structural factors of the treating facility. METHODS: Using National Cancer Database, we focused on extremes of travel: Local (<12.5 miles to treating facility) and Travel (≥50 miles). We analyzed OS with Cox models; we estimated stratified models to assess interaction between distance and facility characteristics (volume, academic status). RESULTS: We included 6860 patients. After correction for confounding, distance travelled was not associated with OS (p = 0.444). However, Travel patients treated at high-volume, academic centers had worse OS compared to Local patients (HR 1.54, 95%CI 1.07-2.21); this association was not seen for patients treated at low volume, academic centers (p = 0.708) high volume non-academic centers (p = 0.174) or low volume non-academic centers (p = 515). CONCLUSION: For those patients treated at high-volume, academic centers, living far from the facility was associated with worse OS. The reasons for this association should be investigated further.

Travel distance and its interaction with patient and hospital factors in pancreas cancer care.

BACKGROUND: Although volume-outcome literature supports regionalization for complex procedures, travel may be burdensome. We assessed the relationship between overall survival and travel distance for patients undergoing pancreatic resection for adenocarcinoma. METHODS: We analyzed the Fall 2018 National Cancer Database Public Use File. We defined distance traveled as a categorical variable (<12.5 miles, 12.5-50mi, and >50mi). We analyzed overall survival (OS) as a function of distance traveled using the log rank test and Cox proportional hazards models; we estimated stratified models to assess for interaction between distance and other relevant covariates. RESULTS: In adjusted analysis of 39,089 patients, greater distance was associated with decreased OS (p = 0.0029). We found interactions between distance and center type, comorbidities, and age. Distance traveled was a negative factor for patients treated at low-volume academic centers (but not high-volume academic or non-academic centers). Additionally, distance traveled was a negative factor for OS in young, healthy patients but not geriatric, ill patients. CONCLUSION: Traveling more than 12.5 miles for pancreatic resection was associated with worse OS. Prior to regionalization, evaluation of local resources may be necessary.

What is Elective Oncologic Surgery in the Time of COVID-19? A Literature Review of the Impact of Surgical Delays on Outcomes in Patients with Cancer.

BACKGROUND: The impact of the COVID-19 pandemic has spread beyond those infected with SARS-CoV-2. Its widespread consequences have affected cancer patients whose surgeries may be delayed in order to minimize exposure and conserve resources. METHODS: Experts in each surgical oncology subspecialty were selected to perform a review of the relevant literature. Articles were obtained through PubMed searches in each cancer subtype using the following terms: delay to surgery, time to surgery, outcomes, and survival. RESULTS: Delays in surgery > 4 weeks in breast cancer, ductal carcinoma in situ, T1 pancreatic cancer, ovarian cancer, and pediatric osteosarcoma, negatively impacted survival. Studies on hepatocellular cancer, colon cancer, and melanoma (Stage I) demonstrated reduced survival with delays > 3 months. CONCLUSION: Studies have shown that short-term surgical delays can result in negative impacts on patient outcomes in multiple cancer types as well as in situ carcinoma. Conversely, other cancers such as gastric cancer, advanced melanoma and pancreatic cancer, well-differentiated thyroid cancer, and several genitourinary cancers demonstrated no significant outcome differences with surgical delays.

Comparison of discharge silver concentrations from electrolytic plating and metallic replacement silver recovery units.

Silver-based photographic X-ray film is made of solid crystals of silver chloride or silver bromide suspended in a gelatin and then coated on a film. During the X-ray developing process, the image is processed and the nonimage areas containing solid silver chloride or silver bromide crystals are removed in a solution called the fixer. There may be local environmental regulations that regulate the amount of silver discharged from a facility. To meet these regulations, many facilities have added silver recovery units to their processes. Two different types of recovery processes are in use in a large hospital and three clinics under study. All of the units were claimed by their respective manufacturers to be able to recover silver down to concentrations of 5 mg/L. This concentration would ensure that the building that houses each unit would meet the local county limit of 0.5 mg/L silver for total building silver discharge. The hypothesis for this research is that one system, newer and more expensive, consisting of so-called electrolytic plating units (EPUs) (which are followed by so-called metallic replacement units [MRUs] as a backup), will have better silver recovery than MRUs alone. A total of six units were sampled, three EPUs (in combination with MRUs) and three MRUs. The units were sampled once or twice a day for 10 days for a total of 17 samples from each. The samples then were analyzed by inductively coupled plasma spectroscopy, and an analysis of variance was performed on the results. The range for the electrolytic plating unit/metallic replacement unit combinations was 0.20-99.9 mg/L (mean of 35.15 mg/L; median of 33.8 mg/L). The range for the MRUs alone was 7.2-1112 mg/L (mean of 565.5 mg/L; median of 720 mg/L). Many individual results exceeded 5 mg/L, such that extensive dilution would be required to ensure the building effluent did not exceed 0.5 mg/L. It is suggested that the metallic replacement units be changed to EPUs (with metallic replacement backup units) because they had better silver recovery. Also, the EPU combinations need to be sampled regularly to ensure that their silver concentrations are at acceptable levels.