Initiation of Breast Cancer Screening at a Later Age May Disproportionately Impact Minority Groups: Review of Ohio Data (1996-2022).

Among women with breast cancer, delays in diagnosis and earlier presentation have been documented among minority women. Consequently, initiation of breast cancer screening at a later age may disproportionately harm minority groups. This study seeks to determine whether minority women face a higher proportional risk of younger age breast cancer than their White peers. Using publicly available data from the Ohio Department of Public Health Data Warehouse, we constructed a database allowing for retrospective evaluation of all breast cancer patients in the state of Ohio from 1996 to 2020. White women represented the bulk of total breast cancer cases in each age group and overall; however, the proportion of cancers attributable to White women increased in each successively older cohort group: 80.7% of cases under age 40 up to 91.3% of the 80 or older group. By a significant margin, the opposite is true in minority groups with African American women accounting for 15% of cases under the age of 40, trending down to 7.8% of the 80 and older group. Comparison of the proportions of these groups demonstrates statistically significant proportional decreases among minority groups and statistically significant increases among White women. Our findings suggest that women of color in the Ohio population face a disproportionately high risk of being diagnosed with younger age breast cancer and support the findings of other authors who recommend tailoring breast cancer screening by racial cohort. Efforts should be made to promote younger-age screening for minority women to prevent disproportionate harm.

Creation of an Application to Increase Surgical Resident Operative Case Coverage.

PURPOSE: Studies have shown that the confidence of surgical residents to perform procedures after completing residency can be affected by their volume of operative experiences. Many surgical residencies span multiple hospitals with a multitude of attendings providing additional educational opportunities available via cross-coverage. This study aims to evaluate the use of a mobile application (app) for operative cross-coverage to improve surgical opportunities in a large surgical residency program and decrease the number of uncovered cases. METHODS: An app allowing for uncovered cases to be sent to all surgical residents was used starting March 2022. A survey was completed by residents pre- and postapp implementation. A retrospective chart review was conducted of all general surgery procedures at the 2 major hospital systems 4 months before and after implementation to evaluate resident case coverage. RESULTS: In the preapp survey, 71% (27/38) of residents noted cross-covering 1 or more cases a month with 90% (34/38) reporting, they were unaware of all cases available. In the postapp survey, 100% of residents reported better awareness of available cases, 97% (35/36) reported uncovered cases were more easily accessible, 100% felt the app simplified finding coverage, and 100% wanted to continue the app long-term. On retrospective review, 7210 cases were identified in the preapp and postapp period with an increased volume of cases in the postapp period. After implementation of the case coverage app, there was a significant increase in total case coverage (p = <0.001) as well as a significant increase in coverage of endoscopic (p = 0.007), laparoscopic (p = 0.025), open (p = 0.015) and robotic cases (p = <0.001). CONCLUSIONS: This study shows the impact that technological innovation can play in the education and operative experiences of surgical residents. This can be used to improve operative experiences of residents in various surgical fields in any training program throughout the country.

Thriving in the Virtual Era: An Organized Approach to Improve Program Visibility and Virtual Residency Interview Process.

OBJECTIVE: Since residency interviews became virtual due to COVID-19, and likely continue in the future, programs must find ways to improve their non-traditional recruiting methods. The objective of this study was to evaluate effectiveness of a structured, non-traditional approach on visibility and perception of the program as well as virtual interview experience. METHODS: The focus of our approach was to ensure constant engagement while maintaining all pre-interview communication as resident-led and informal. The program focused on improving visibility and outreach through an organized utilization of social media platforms highlighting people and local culture. The virtual interview process was restructured with resident-led virtual meet and greets followed by small group discussions and providing virtual hospital tours, videos, and slides of the program's culture and expectationson the interview day. Perception of the program and the new approach to the interview process was assessed via an anonymous survey. RESULTS: The program's visibility was measured via social media analytics with an increase in reach on Facebook from 0/post to as high as 4200/post and engagement 2/post to nearly 600/post. Tweet Impressions from approximately 350/mo to 11,000/mo with the increase in new Followers/month by 532.5%. Increase in total number of applicants in 2021 of 16% compared to average between 2018 and 2020. Survey response rate was 66.1%; of those 53.8% of interviewees attended a virtual meet and greet session. Perceptions of interviewees on our program was exclusively positive. Specific characteristics of the program that would make students rank us higher were program's culture, people, academics, and clinical experiences they would get as residents. CONCLUSIONS: The exponential increase in our program's visibility and exclusively positive program assessment suggest that a structured approach utilizing social media and virtual technologies could improve both the recruitment and the virtual interview process while maintaining positive perceptions of the program.

Blood-Based Multi-Cancer Detection Using a Novel Variant Calling Assay (DEEPGENTM): Early Clinical Results.

This is an early clinical analysis of the DEEPGENTM platform for cancer detection. Newly diagnosed cancer patients and individuals with no known malignancy were included in a prospective open-label case-controlled study (NCT03517332). Plasma cfDNA that was extracted from peripheral blood was sequenced and data were processed using machine-learning algorithms to derive cancer prediction scores. A total of 260 cancer patients and 415 controls were included in the study. Overall, sensitivity for all cancers was 57% (95% CI: 52, 64) at 95% specificity, and 43% (95% CI: 37, 49) at 99% specificity. With 51% sensitivity and 95% specificity for all stage 1 cancers, the stage-specific sensitivities trended to improve with higher stages. Early results from this preliminary clinical, prospective evaluation of the DEEPGENTM liquid biopsy platform suggests the platform offers a clinically relevant ability to differentiate individuals with and without known cancer, even at early stages of cancer.

Initial Surgical Treatment for Breast Cancer and the Distance Traveled for Care.

BACKGROUND: Geography may influence the operative decision-making in breast cancer treatment. This study evaluates the relationship between distance to treating facility and the initial breast cancer surgery selected, identifying the characteristics of women who travel for surgery. METHODS: Utilizing Florida state inpatient and ambulatory surgery databases, we identified female breast cancer patients who underwent surgical treatment from January 1 to December 31, 2013. Patients were subgrouped by distance to treatment facility. The primary outcome was the initial surgical treatment choice. Regression models were used to identify factors associated with greater distance to initial treatment. RESULTS: The final sample included 12 786 patients who underwent lumpectomy, mastectomy alone, or mastectomy with reconstruction. Compared to women who traveled < 4.0 miles, women who traveled > 14.0 miles were younger (P < .001), more often identified as white with private insurance (P < .001) and were less likely to have three or more medical comorbidities (P < .001). With increased travel to treatment, the frequency of lumpectomy decreased (P < .001), while the frequency of mastectomy with reconstruction increased (P < .001). Increasing age in years (adjusted odds ratio (AOR) = .98 [95% CI = .98-.99]) and identifying as nonwhite with private (AOR = .70 [.61-.80]) or public insurance (AOR = .64 [.56-.73]) was associated with less frequently travelling for initial breast cancer surgery. DISCUSSION: The relationship between the initial surgical treatment for breast cancer and the distance traveled for care highlights a disparity between those who can and cannot travel for treatment.

Breast Cancer Stage at Presentation in Ohio: The Effect of Medicaid Expansion and the Affordable Care Act.

Patients presenting with localized breast cancer have a five-year survival of 99 per cent, whereas survival falls to 27 per cent in advanced disease. This obviates the importance of early diagnosis and treatment. Our study evaluates the impact of Ohio's Medicaid expansion and the passage of the Affordable Care Act (ACA) on the stage at which Ohioans were diagnosed with breast cancer. Data were collected for 3056 patients presenting with breast cancer between 2006 and 2016 in the Dayton area. Patients were divided into groups based on cancer stage. The percentage of patients presenting with advanced disease (stage 3 or 4) was compared both before and after ACA implementation and Ohio Medicaid expansion. These results were also compared with statewide data maintained by the Ohio Department of Health. Compared with pre-ACA, the number of uninsured patients post-ACA was noted to fall 83 per cent, the number of patients presenting with Medicaid increased by five times, and the proportion of patients younger than 65 years presenting with breast cancer increased by approximately 7 per cent. These changes notwithstanding, no difference was identified in the percentage of patients presenting with advanced breast cancer before and after ACA implementation or Ohio Medicaid expansion (P = 0.56). Statewide data similarly demonstrated no change (P = 0.88). Improved insurance access had a smaller-than-anticipated impact on the stage at which Ohioans presented with breast cancer. As significant morbidity and mortality can be avoided by earlier presentation, additional research is appropriate to identify factors affecting patients' decision to seek breast cancer screening and care.

Minimally Invasive Esophagectomy Utilizing a Stapled Side-to-Side Anastomosis is Safe in the Western Patient Population.

BACKGROUND: There has been an increased utilization of minimally invasive esophagectomy (MIE) in an effort to reduce morbidity, decrease length of stay, and improve quality of life. However, there are limited large series of patients undergoing MIE from the United States and no standardized approach. We reviewed our experience with MIE utilizing a stapled side-to-side anastomosis during a 7.5-year period. STUDY DESIGN: A retrospective review of prospectively maintained databases for patients undergoing planned esophagectomy were reviewed from 2007 to 2015. Esophagogastric anastomoses were performed via a 6-cm linear stapled side-to-side method. Demographics, comorbidities, surgical approach, pathology data, and postoperative morbidities were recorded and reviewed. RESULTS: A MIE was attempted in 303 of 315 (96 %) patients, and a total minimally invasive approach was completed in 293 of 315 (93 %) patients. Location of anastomosis was predominantly in the neck, with 244 patients (77.5 %) undergoing a total minimally invasive McKeown approach (n = 231). A total, minimally invasive Ivor-Lewis was completed in 60 patients (19.1 %). Anastomotic leak was identified in 24 patients (7.6 %). Rates of anastomotic leak were 4.4 % for Ivor-Lewis and 8.5 % for McKeown resection. Median length of stay was 8 days, and in-hospital mortality occurred in only three patients (n = 1 %). Ninety-day follow-up demonstrated a 4.1 % stricture rate requiring dilatation. CONCLUSIONS: In the Western patient population, MIE utilizing a 6-cm stapled side-to-side anastomosis is associated with low rates of anastomotic leak, stricture, and mortality.

Total laparoscopic resection for advanced gastric cancer is safe and feasible in the Western population.

BACKGROUND: There is debate surrounding the use of laparoscopic resection for advanced gastric cancer in the Western population. Here we aim to assess the feasibility and short-term outcomes of laparoscopic gastrectomy in consecutive patients in a Western population. METHODS: From 2012 to 2014, retrospective review of 28 patients with clinically staged advanced gastric cancer (≥T3 or ≥N1) treated with laparoscopic resection. RESULTS: Sixty-one percentage of patients were male. Median age was 67 years (range 35-86). Median BMI was 26.5 (range 19.4-46.1). Resection types were proximal (n = 2), distal (n = 14), and total (n = 12). Twenty-six (93 %) patients underwent D2 lymphadenectomy. Four patients underwent conversion to open. Median blood loss was 125 mL (range 30-300). Median LOS was 7 days (range 4-16). Of postoperative complications, five were minor: arrhythmia (n = 1), surgical site infection (n = 3), in-hospital fall (n = 1); and four were major (intra-abdominal abscess, stricture, PE, and anastomotic bleed). T stages were Tx (n = 1), T2 (n = 3), T3 (n = 18), and T4 (n = 6). N stages were N0 (n = 4), N1 (n = 8), N2 (n = 1), and N3 (n = 15). Median tumor size was 5.8 cm (range 0-9.5). Median lymph node yield was 22 (range 6-53). All margins were negative. Median follow-up was 12.8 months (range 2-27). Six patients have died of progressive disease. CONCLUSION: Following total laparoscopic resection for advanced gastric cancer, oncologic endpoints, postoperative course, and early cancer-specific follow-up are excellent. The results demonstrated here support the routine use of these techniques in the Western patient population.

Association Between Clinically Staged Node-Negative Esophageal Adenocarcinoma and Overall Survival Benefit From Neoadjuvant Chemoradiation.

IMPORTANCE: While neoadjuvant chemoradiation for esophageal cancer improves oncologic outcomes for a broad group of patients with locally advanced and/or node-positive tumors, it is less clear which specific subset of patients derives most benefit in terms of overall survival (OS). OBJECTIVE: To determine whether neoadjuvant chemoradiation based on esophageal adenocarcinoma histology has similar oncologic outcomes for patients treated with surgery alone when stratified by clinical nodal status. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis using the American College of Surgeons National Cancer Database from 1998 to 2006. Patients with esophageal adenocarcinoma histology and clinical stage T1bN1-N3 or T2-T4aN-/+M0 were divided into 2 treatment groups: (1) neoadjuvant chemoradiation followed by surgery and (2) surgery alone. Subset analysis within each treatment group was performed for clinically node-negative patients (cN-) vs node-positive patients (cN+) in conjunction with pathological nodal status. A propensity score-adjusted analysis, which included patient demographics, comorbidity status, and clinical T stage, was also performed. MAIN OUTCOME AND MEASURES: The primary outcome was 3-year OS. Secondary outcomes included margin status, postoperative length of stay, unplanned readmission rate, and 30-day mortality. RESULTS: A total of 1309 patients were identified, of whom 539 received neoadjuvant chemoradiation followed by surgery and 770 received surgery alone. Of the 1309 patients, 41.2% (n = 539) received neoadjuvant chemoradiation and 47.2% (n = 618) were cN+. Median follow-up for the entire cohort was 73.3 months (interquartile range, 64.1-93.5 months). The 3-year OS was better for neoadjuvant chemoradiation followed by surgery compared with surgery alone (49% vs 38%, respectively; P < .001). Stratifying based on clinical nodal status, the propensity score-adjusted OS was significantly better for cN+ patients who received neoadjuvant chemoradiation (hazard ratio, 0.52; 95% CI, 0.42-0.66; P < .001). In contrast, there was no difference in OS for cN- patients based on treatment (hazard ratio, 0.84; 95% CI, 0.65-1.10; P = .22). CONCLUSIONS AND RELEVANCE: Patients with cN+ esophageal adenocarcinoma benefit significantly from neoadjuvant chemoradiation. However, patients with cN- tumors treated with neoadjuvant chemoradiation plus surgery do not derive a significant OS benefit compared with surgery alone. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN- disease.

Biopsy techniques for soft tissue and bowel sarcomas.

There is overlap in the clinical presentation of benign soft tissue tumors and soft tissue sarcomas. A preoperative sarcoma diagnosis would allow for consideration for neoadjuvant therapy, including preoperative radiation, as well as optimal surgical treatment planning, and patient counseling. Image guided core needle biopsy is a low morbidity, cost-effective, highly accurate approach for obtaining a definitive pathologic diagnosis. Any biopsy approach should minimize the potential for tumor seeding of otherwise uninvolved anatomic structures.

Laparoscopic distal, subtotal gastrectomy for advanced gastric cancer.

The objective of this study was to show laparoscopic subtotal, distal gastrectomy with D2 lymphadenectomy as a safe and appropriate method for the resection of advanced gastric cancer. This study was conducted at a designated NCI Cancer Center. Subjects of the study were patients with advanced gastric malignancy, including transmural penetration of the tumor and/or nodal disease, requiring subtotal, distal gastrectomy. The main outcome measure is a description of the technique of a laparoscopic subtotal, distal gastrectomy for antral and distal body tumors. In conclusion, the laparoscopic approach to advanced gastric malignancy with a subtotal, distal gastrectomy and D2 lymphadenectomy is a safe, oncologically appropriate procedure which provides excellent outcomes.

Ablative therapy for esophageal dysplasia and early malignancy: focus on RFA.

Ablative therapies have been utilized with increasing frequency for the treatment of Barrett's esophagus with and without dysplasia. Multiple modalities are available for topical ablation of the esophagus, but radiofrequency ablation (RFA) remains the most commonly used. There have been significant advances in technique since the introduction of RFA. The aim of this paper is to review the indications, techniques, outcomes, and most common complications following esophageal ablation with RFA.

Hospital-based, acute care encounters after radiofrequency ablation of hepatic tumours.

BACKGROUND: The use of radiofrequency ablation (RFA) for cancer is increasing; however, post-discharge outcomes have not been well described. The aim of the present study was to determine rates of hospital-based, acute care utilization within 30 days of discharge after RFA. METHODS: Using state-level data from California, patients were identified who were at least 40 years of age who underwent RFA of hepatic tumours without a concurrent liver resection from 2007-2011. Our primary outcome was hospital readmissions or emergency department visits within 30 days of discharge. A multivariable regression model was constructed to identify patient factors associated with these events. RESULTS: The final sample included 1764 patients treated at 100 centres. Hospital readmissions (11.3/100 discharges), emergency department visits (6.0/100 discharges) and overall acute care utilization (17.3/100 discharges) were common. Most encounters occurred within 10 days of discharge for diagnoses related to the procedure. Patients with renal failure [adjusted odds ratio (AOR) = 1.98 (1.11-3.53)], obesity [AOR = 1.69 (1.03-2.77)], drug abuse [AOR = 2.95 (1.40-6.21)] or those experiencing a complication [AOR = 1.52 (1.07-2.15)] were more likely to have a hospital-based acute care encounter within 30 days of discharge. CONCLUSIONS: Hospital-based acute care after RFA is common. Patients should be counselled regarding the potential for acute care utilization and interventions targeted to high-risk populations.

Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen-induced cellular senescence.

Estrogen signaling plays an important role in breast carcinogenesis. An increased understanding of estrogen gene targets and their effects will allow for more directed and effective therapies for individuals with breast cancer, particularly those with estrogen receptor positive tumors resistant to tamoxifen therapy. Here, we identify YPEL3 as a growth suppressive protein downregulated by estrogen in estrogen receptor positive breast cancer cell lines. Estrogen repression of YPEL3 expression was found to be independent of p53 but dependent on estrogen receptor alpha expression. Importantly, YPEL3 expression, which is induced by the removal of estrogen or treatment with tamoxifen triggers cellular senescence in MCF-7 cells while loss of YPEL3 increases the growth rate of MCF-7 cells. Taken together these findings suggest that YPEL3 may represent a potential target for directed hormonal therapy for estrogen receptor positive breast cancer patients.

Senescence-associated gene YPEL3 is downregulated in human colon tumors.

BACKGROUND: Previous work has demonstrated YPEL3 to be a growth-suppressive protein that acts through a pathway of cellular senescence. We set out to determine whether human colon tumors demonstrated downregulation of YPEL3. METHODS: We collected colon tumor samples with matched normal control samples and analyzed them for YPEL3 gene expression by reverse transcriptase-polymerase chain reaction and CpG hypermethylation of the YPEL3 promoter by base-specific polymerase chain reaction analysis. Colon cancer cell lines (Caco-2 and HCT116(-/-) p53) were used to assess YPEL3 gene expression after treatment with 5-azadeoxycytidine or trichostatin A. RESULTS: Reverse transcriptase-polymerase chain reaction analysis demonstrated a decrease in YPEL3 expression in tumor samples when compared to their patient-matched normal tissue. We determined that DNA methylation of the YPEL3 promoter CpG island does not play a role in YPEL3 regulation in human colon tumors or colon cancer cells lines, consistent with the inability of 5-azadeoxycytidine treatment to induce YPEL3 expression in colon cancer cell lines. In contrast, colon cell line results suggest that histone acetylation may play a role in YPEL3 regulation in colon cancer. CONCLUSIONS: YPEL3 is preferentially downregulated in human colon adenocarcinomas. DNA hypermethylation does not appear to be the mechanism of YPEL3 downregulation in this subset of collected patient samples or in colon cell lines. Histone acetylation may be a relevant epigenetic modulator of YPEL3 in colon adenocarcinomas. Future investigation of YPEL3 and its role in colon cancer signaling and development may lead to increased understanding and alternative treatment options for this disease.

Why YPEL3 represents a novel tumor suppressor.

Yippee-like 3 (YPEL3) was reported in 2004 as one of five family members of the Yippee protein with conservation in species down to slime molds. While reports of other YPEL family members have surfaced our laboratory was the first to report that YPEL3 is induced by the p53 tumor suppressor. Furthermore we demonstrated that YPEL3 is growth suppressive, triggering cellular senescence in human cell lines and is down-regulated in several human tumors. Studies with mouse YPEL3, originally named small unstable apoptotic protein (SUAP), confirmed that the gene encodes a growth suppressive highly unstable protein. In this review we show that transcriptionally active forms of p73 and p63, family members of p53, can transactivate the human YPEL3 gene. While there are several reported YPEL3 transcripts and potentially 2 protein isoforms, no clear protein structure has been reported. As evidence mounts that YPEL3 is a tumor suppressor gene, studies aimed at understanding its biological function, regulation of gene expression and impact on tumorigenesis will help.