Adjuvant imatinib in high-risk resected gastrointestinal stromal tumors: Merely delaying the inevitable?

INTRODUCTION: Patients with high-risk resected gastrointestinal stromal tumors (GIST) receiving adjuvant imatinib have improved recurrence-free survival (RFS), however whether a complete cytocidal effect exists is unknown. We investigated this using a normalized recurrence timeline measured from end of oncologic treatment (EOOT), defined as the later of resection or end of adjuvant therapy. METHODS: We reviewed patients with resected high-risk GIST at our cancer center from 2003 to 2018. RFS (measured from resection and EOOT), overall survival (OS), and time to imatinib resistance (TTIR) were analyzed using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. The performance of the Memorial Sloan Kettering (MSK) GIST nomogram was assessed. RESULTS: We identified 86 patients with high-risk GIST with a median 106 months of postsurgical follow-up. One-third (n = 29; 34%) did not receive adjuvant imatinib, while 57 (66%) did for a median of 3 years. The MSK nomogram-predicted 5-year RFS for patients receiving adjuvant imatinib was similar to those who did not (29% vs. 31%, p = 0.64). When RFS was measured from EOOT, the MSK-predicted RFS was independently associated with EOOT RFS (hazard ratio 0.22, p = 0.02), while adjuvant imatinib receipt and duration were not. Neither receipt nor duration of adjuvant imatinib were associated with TTIR or OS (all p > 0.05). CONCLUSIONS: Treatment with adjuvant imatinib delays, but does not clearly impact ultimate recurrence, TTIR, or OS, suggesting many patients with high-risk GIST may receive adjuvant imatinib unnecessarily. Additional studies are needed to establish the benefit of adjuvant therapy versus initiating therapy at first radiographic recurrence.

Outcomes of Late-Line Systemic Treatment in GIST: Does Sequence Matter?

Ripretinib and avapritinib have demonstrated activity in the late-line treatment of gastrointestinal stomal tumors (GISTs). We investigated whether patients previously treated with ripretinib benefit from avapritinib, and vice versa. Patients diagnosed with metastatic/unresectable GIST and treated with both drugs at two institutions in 2000-2021 were included. Patients were grouped by drug sequence: ripretinib-avapritinib (RA) or avapritinib-ripretinib (AR). Radiographic response was evaluated using RECIST 1.1. Kaplan-Meier and log-rank tests were used to compare time-to-progression (TTP) and overall survival (OS). Thirty-four patients (17 per group) were identified, with a median age of 48 years. The most common primary site was the small bowel (17/34, 50%), followed by the stomach (10/34, 29.4%). Baseline characteristics and tumor mutations were not significantly different between groups. Response rates (RRs) for ripretinib were 18% for RA and 12% for AR; RRs for avapritinib were 12% for AR and 18% for RA. Median TTPs for ripretinib were 3.65 months (95%CI 2-5.95) for RA and 4.73 months (1.87-15.84) for AR. Median TTPs for avapritinib were 5.39 months (2.86-18.99) for AR and 4.11 months (1.91-11.4) for RA. Median OS rates following RA or AR initiation were 29.63 (95%CI 13.8-50.53) and 33.7 (20.03-50.57) months, respectively. Both ripretinib and avapritinib were efficacious in the late-line treatment of GIST, with no evidence that efficacy depended on sequencing.

Referral and treatment patterns in pancreatic acinar cell carcinoma: A regional population-level analysis.

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas. We evaluated the effect disease stage, surgical intervention, and institutional volume status plays in survival. METHODS: We queried the Oregon State Cancer Registry for patients with PACC from 1997 to 2018. Treatment and referral patterns were analyzed, and overall survival (OS) was evaluated with Kaplan-Meier and Cox-proportional hazard analysis. RESULTS: 43 patients were identified. Median OS was 33.1 and 7.1 months in those with locoregional and metastatic disease respectively (p â€‹= â€‹0.008). Surgical intervention was associated with improved OS (hazard ratio 0.28, p â€‹< â€‹0.0001). High volume center (HVC) care trended towards improving OS. While the majority of cases were diagnosed at low volume centers (74%), referral to HVCs was rare (n â€‹= â€‹4) and limited to advanced (stage III/IV) disease. CONCLUSION: Stage and surgical resection influence survival outcomes in PACC, more data is needed to delineate the impact of institutional volume status.

Targeting the RNA-Binding Protein HuR in Cancer.

The RNA-binding protein human antigen R (HuR) is a well-established regulator of gene expression at the posttranscriptional level. Its dysregulation has been implicated in various human diseases, particularly cancer. In cancer, HuR is considered "active" when it shows increased subcellular localization in the cytoplasm, in addition to its normal nuclear localization. Cytoplasmic HuR plays a crucial role in stabilizing and enhancing the translation of prosurvival mRNAs that are involved in stress responses relevant to cancer progression, such as hypoxia, radiotherapy, and chemotherapy. In general, due to HuR's abundance and function in cancer cells compared with normal cells, it is an appealing target for oncology research. Exploiting the principles underlying HuR's role in tumorigenesis and resistance to stressors, targeting HuR has the potential for synergy with existing and novel oncologic therapies. This review aims to explore HuR's role in homeostasis and cancer pathophysiology, as well as current targeting strategies, which include silencing HuR expression, preventing its translocation and dimerization from the nucleus to the cytoplasm, and inhibiting mRNA binding. Furthermore, this review will discuss recent studies investigating the potential synergy between HuR inhibition and traditional chemotherapeutics.

Neoadjuvant therapy does not impact the biliary microbiome in patients with pancreatic cancer.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) often impinges on the biliary tree and obstruction necessitates stent placement increasing the risk of surgical site infections (SSIs). We sought to explore the impact of neoadjuvant therapy on the biliary microbiome and SSI risk in patients undergoing resection. METHODS: A retrospective analysis was performed on 346 patients with PDAC who underwent resection at our institution from 2008 to 2021. Univariate and multivariate methods were utilized for analysis. RESULTS: Biliary stenting rates were similar between groups but resulted in increased bile culture positivity (97% vs. 15%, p < 0.001). Culture positivity did not differ between upfront resection or neoadjuvant chemotherapy (NAC) (77% vs. 80%, p = 0.60). NAC-alone versus neoadjuvant chemoradiotherapy did not impact biliary positivity (80% vs. 79%, p = 0.91), nor did 5-fluorouracil versus gemcitabine-based regimens (73% vs. 85%, p = 0.19). While biliary stenting increased incisional SSI risk (odds ratios [OR]: 3.87, p = 0.001), NAC did not (OR: 0.83, p = 0.54). Upfront resection, NAC, and chemoradiotherapy were not associated with biliary organism-specific changes or antibiotic resistance patterns. CONCLUSIONS: Biliary stenting is the greatest predictor for positive biliary cultures and SSIs in resected PDAC patients. Neither NAC nor radiotherapy impact bile culture positivity, speciation, rates, or antibiotic resistance patterns, and perioperative antibiotic prophylaxis should not differ.

High-volume centers are associated with higher receipt of combined therapy in stage III pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at a locally advanced stage with vascular involvement which was previously viewed as a contraindication to resection. However, high-volume centers are increasingly capable of resecting complex tumors. We aimed to explore patterns of treatment that are uncharacterized on a population level. METHODS: A statewide registry was queried from 2003 to 2018 for stage III PDAC. Stepwise logistic regression and Kaplan-Meier were used for statistical analysis. RESULTS: We identified 424 eligible patients. 348 (82%) received chemotherapy, 17 (4.0%) received resection, and 59 (13.9%) received both; median survival was 10.7, 8.7, and 22.7 months, respectively (P < 0.001). High-volume centers (≥20 cases per year; OR 5.40 [95% CI: 2.76, 10.58], P < 0.001) and later year of diagnosis (OR 1.12/year [95% CI: 1.04, 1.20], P = 0.004) were associated with higher odds of receiving combined therapy. CONCLUSION: PDAC patients with vascular involvement who receive both systemic chemotherapy and surgical resection have improved overall survival. High-volume centers are independently associated with higher odds of receiving combined systemic therapy and surgical resection.

Delayed adjuvant endocrine therapy is associated with decreased recurrence-free survival following neoadjuvant chemotherapy for breast cancer.

BACKGROUND: In hormone receptor-positive breast cancer (HRPBC), endocrine therapy is often initiated after adjuvant radiotherapy given concerns of radiation fibrosis. No studies have investigated how this may impact outcomes in high-risk patients undergoing neoadjuvant chemotherapy (NAC). METHODS: Females with nonmetastatic HRPBC receiving NAC from 2011 to 2017 were identified from our multi-institutional database. Interval from surgery to endocrine therapy (ISET) was calculated in weeks. Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: Of 280 patients, 179 (64%) received adjuvant radiotherapy; all deaths (n = 25) and 90% (n = 27) of recurrences occurred in this group, which was the focus of subsequent analysis. Median follow-up was 49 months. Recurrences were predominantly distant metastases (n = 21, 81%). Median ISET was 12 weeks (range 0-55 weeks). On multivariable analysis, ISET >14 weeks was independently associated with worse RFS (HR 3.20, 95% C.I. 1.22-8.40, P = 0.02) but not OS (HR 2.15, 95% C.I. 0.75-6.15, P = 0.15). CONCLUSION: In patients with HRPBC treated with NAC and adjuvant radiation, increasing ISET is associated with adverse oncologic outcomes.

Bedside vs webside: Assessing patient-reported experiences for in-person and telemedicine-based perioperative evaluations.

BACKGROUND: Though telemedicine has been identified as safe and feasible, data on patient reported experiences (PREs) are lacking. We sought to compare PREs between in-person and telemedicine-based perioperative care. METHODS: Patients evaluated from August-November 2021 were prospectively surveyed to assess experiences and satisfaction with care rendered during in-person and telemedicine-based encounters. Patient and hernia characteristics, encounter related plans, and PREs were compared between in-person and telemedicine-based care. RESULTS: Of 109 respondents (86% response rate), 55% (n = 60) utilized telemedicine-based perioperative care. Indirect costs were lower for patients using telemedicine-based services, including work absence (3% vs. 33%, P < 0.001), lost wages (0% vs. 14%, P = 0.003), and requirements for hotel accommodations (0% vs. 12%, P = 0.007). PREs related to telemedicine-based care were non-inferior to in-person care across all measured domains (P > 0.4). CONCLUSIONS: Telemedicine-based care yields significant cost-savings over in-person care with similar patient satisfaction. These findings suggest that systems should focus on optimization of perioperative telemedicine services.

Care at high-volume centers is associated with improved outcomes for patients with pancreatic neuroendocrine tumors: A population-level analysis.

BACKGROUND AND OBJECTIVES: Primary resection and debulking of liver metastases have been associated with improved survival in pancreatic neuroendocrine tumors (PNETs). The treatment patterns and outcomes differences between low-volume (LV) institutions and high-volume (HV) institutions remains unstudied. METHODS: A statewide cancer registry was queried for patients with nonfunctional PNET from 1997 to 2018. LV institutions were defined as treating <5 newly diagnosed patients with PNET per year, while HV institutions treated ≥5. RESULTS: We identified 647 patients: 393 with locoregional (n = 236 HV care, n = 157 LV care) and 254 with metastatic disease (n = 116 HV care, n = 138 LV care). Patients with HV care had improved disease-specific survival (DSS) compared to patients with LV care for both locoregional (median 63 vs. 32 months, p < 0.001) and metastatic disease (median 25 vs. 12 months, p < 0.001). In patients with metastatic disease, primary resection (hazard ratio [HR]: 0.55, p = 0.003) and HV institution (HR: 0.63, p = 0.002) were independently associated with improved DSS. Furthermore, diagnosis at a HV center was independently associated with higher odds of receiving primary site surgery (odds ratio [OR]: 2.59, p = 0.01) and metastasectomy (OR: 2.51, p = 0.03). CONCLUSIONS: Care at HV centers is associated with improved DSS in PNET. We recommend referral of all patients with PNETs to HV centers.

Hepatectomy is associated with improved oncologic outcomes in recurrent colorectal liver metastases: A propensity-matched analysis.

BACKGROUND: Following resection of colorectal liver metastasis, most patients have disease recurrence, most commonly intrahepatic. Although the role of resection in colorectal liver metastasis is well-established, there have been limited investigations assessing the benefit of repeat hepatic resection compared with systemic treatment alone for intrahepatic recurrence. METHODS: A retrospective single-institution cohort study of patients with recurrent colorectal liver metastasis following curative-intent hepatectomy was performed from 2003 to 2019. The oncologic outcomes, including post-recurrence overall survival, were evaluated using Kaplan-Meier and Cox proportional hazards modeling. Patients undergoing repeat hepatic resection were propensity-matched with patients receiving systemic treatment alone based on relevant clinicopathologic variables. RESULTS: There were 338 patients treated with hepatic resection for colorectal liver metastasis over the study period. Liver recurrence was observed in 147 (43%) patients at a median time of 10 months from prior resection, with a median post-recurrence overall survival of 29 months. There were 37 patients managed with repeat hepatic resection; 33 (89%) received perioperative chemotherapy. On propensity matching, there were no significant clinicopathologic differences between 37 patients having repeat hepatic resection and 37 patients treated with systemic treatment alone. Repeat hepatic resection was independently associated with improved 5-year post-recurrence overall survival compared with systemic treatment alone (median overall survival 41 vs 35 months, 5-year overall survival 19% vs 3%, P = .048). CONCLUSION: Disease characteristics of patients with intrahepatic recurrence of colorectal liver metastasis, specifically the number of liver lesions and size of the largest lesion, are most predictive of survival and response to systemic therapy. Patients who recur with oligometastatic liver disease experience improved outcomes and derive benefit from curative-intent repeat hepatic resection with integrated perioperative systemic therapy.

Socioeconomic and Geographic Disparities in the Referral and Treatment of Pancreatic Cancer at High-Volume Centers.

Importance: Treatment at high-volume centers (HVCs) has been associated with improved overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC); however, it is unclear how patterns of referral affect these findings. Objective: To understand the relative contributions of treatment site and selection bias in driving differences in outcomes in patients with PDAC and to characterize socioeconomic factors associated with referral to HVCs. Design, Setting, Participants: A population-based retrospective review of the Oregon State Cancer Registry was performed from 1997 to 2019 with a median 4.3 months of follow-up. Study participants were all patients diagnosed with PDAC in Oregon from 1997 to 2018 (n = 8026). Exposures: The primary exposures studied were diagnosis and treatment at HVCs (20 or more pancreatectomies for PDAC per year), low-volume centers ([LVCs] less than 20 per year), or both. Main Outcomes and Measures: OS and treatment patterns (eg, receipt of chemotherapy and primary site surgery) were evaluated with Kaplan-Meier analysis and logistic regression, respectively. Results: Eight thousand twenty-six patients (male, 4142 [52%]; mean age, 71 years) were identified (n = 3419 locoregional, n = 4607 metastatic). Patients receiving first-course treatment at a combination of HVCs and LVCs demonstrated improved median OS for locoregional and metastatic disease (16.6 [95% CI, 15.3-17.9] and 6.1 [95% CI, 4.9-7.3] months, respectively) vs patients receiving HVC only (11.5 [95% CI, 10.7-12.3] and 3.9 [95% CI, 3.5-4.3] months, respectively) or LVC-only treatment (8.2 [95% CI, 7.7-8.7] and 2.1 [95% CI, 1.9-2.3] months, respectively; all P < .001). No differences existed in disease burden by volume status of diagnosing institution. When stratifying by site of diagnosis, HVC-associated improvements in median OS were smaller (locoregional: 10.4 [95% CI, 9.5-11.2] vs 9.9 [95% CI, 9.4-10.4] months; P = .03; metastatic: 3.6 vs 2.7 months, P < .001) than when stratifying by the volume status of treating centers, indicating selection bias during referral. A total of 94% (n = 1103) of patients diagnosed at an HVC received HVC treatment vs 18% (n = 985) of LVC diagnoses. Among patients diagnosed at LVCs, later year of diagnosis and higher estimated income were independently associated with higher odds of subsequent HVC treatment, while older age, metastatic disease, and farther distance from HVC were independently associated with lower odds. Conclusions and Relevance: LVC-to-HVC referrals for PDAC experienced improved OS vs HVC- or LVC-only care. While disease-related features prompting referral may partially account for this finding, socioeconomic and geographic disparities in referral worsen OS for disadvantaged patients. Measures to improve access to HVCs are encouraged.

Patient-performed at-home surgical drain removal is safe and feasible following hernia repair and abdominal wall reconstruction.

BACKGROUND: Traditionally, surgical drains are considered a relative contraindication to telemedicine-based postoperative care. We sought to assess the safety, feasibility, and outcomes of an at-home patient-performed surgical drain removal pilot program. METHODS: A prospective cohort study among patients who were discharged with surgical drains was performed. Patients discharged with drains were given the option for in-clinic, provider-performed removal, or at-home, patient-performed drain removal. Patient demographics, health characteristics, perioperative metrics, and operative outcomes were compared and analyzed. RESULTS: A total of 68 encounters with drain removal were included (at-home: 28%, n = 19; in-clinic: 72%, n = 49), with both groups having similar demographics, except for age (median age of telemedicine-based at-home: 50 vs in-clinic: 62 years, p = 0.03). Patients who opted into at-home, patient-performed drain removal were more likely to have drain removal occur earlier (9 vs 13 days for in-clinic, p < 0.001). In-clinic removal resulted in increased encounters with surgical nursing staff and increased travel time, with no significant difference in complication burden. CONCLUSIONS: Patient-performed at-home drain removal is safe and allows for more timely drain removal.

Circulating Neoplastic-Immune Hybrid Cells Predict Metastatic Progression in Uveal Melanoma.

Background: Uveal melanoma is an aggressive cancer with high metastatic risk. Recently, we identified a circulating cancer cell population that co-expresses neoplastic and leukocyte antigens, termed circulating hybrid cells (CHCs). In other cancers, CHCs are more numerous and better predict oncologic outcomes compared to circulating tumor cells (CTCs). We sought to investigate the potential of CHCs as a prognostic biomarker in uveal melanoma. Methods: We isolated peripheral blood monocular cells from uveal melanoma patients at the time of primary treatment and used antibodies against leukocyte and melanoma markers to identify and enumerate CHCs and CTCs by immunocytochemistry. Results: Using a multi-marker approach to capture the heterogeneous disseminated tumor cell population, detection of CHCs was highly sensitive in uveal melanoma patients regardless of disease stage. CHCs were detected in 100% of stage I-III uveal melanoma patients (entire cohort, n = 68), whereas CTCs were detected in 58.8% of patients. CHCs were detected at levels statically higher than CTCs across all stages (p = 0.05). Moreover, CHC levels, but not CTCs, predicted 3 year progression-free survival (p < 0.03) and overall survival (p < 0.04). Conclusion: CHCs are a novel and promising prognostic biomarker in uveal melanoma.

Circulating Cells with Macrophage-like Characteristics in Cancer: The Importance of Circulating Neoplastic-Immune Hybrid Cells in Cancer.

Cancer remains a significant cause of mortality in developed countries, due in part to difficulties in early detection, understanding disease biology, and assessing treatment response. If effectively harnessed, circulating biomarkers promise to fulfill these needs through non-invasive "liquid" biopsy. While tumors disseminate genetic material and cellular debris into circulation, identifying clinically relevant information from these analytes has proven difficult. In contrast, cell-based circulating biomarkers have multiple advantages, including a source for tumor DNA and protein, and as a cellular reflection of the evolving tumor. While circulating tumor cells (CTCs) have dominated the circulating cell biomarker field, their clinical utility beyond that of prognostication has remained elusive, due to their rarity. Recently, two novel populations of circulating tumor-immune hybrid cells in cancer have been characterized: cancer-associated macrophage-like cells (CAMLs) and circulating hybrid cells (CHCs). CAMLs are macrophage-like cells containing phagocytosed tumor material, while CHCs can result from cell fusion between cancer and immune cells and play a role in the metastatic cascade. Both are detected in higher numbers than CTCs in peripheral blood and demonstrate utility in prognostication and assessing treatment response. Additionally, both cell populations are heterogeneous in their genetic, transcriptomic, and proteomic signatures, and thus have the potential to inform on heterogeneity within tumors. Herein, we review the advances in this exciting field.

Ten-Year Survivorship in Patients with Metastatic Gastrointestinal Stromal Tumors.

INTRODUCTION: Patients developing metastatic gastrointestinal stromal tumors (mGIST) have heterogenous disease biology and oncologic outcomes; prognostic factors are incompletely characterized. We sought to evaluate predictors of 10-year metastatic survivorship in the era of tyrosine kinase inhibitor (TKI) therapy. METHODS: We reviewed patients with mGIST treated at our Comprehensive Cancer Center from 2003 to 2019, including only patients with either mortality or 10 years of follow-up. Ten-year survivorship was evaluated with logistic regression. RESULTS: We identified 109 patients with a median age of 57 years at mGIST diagnosis. Synchronous disease was present in 57% (n = 62) of patients; liver (n = 48, 44%), peritoneum (n = 40, 37%), and liver + peritoneum (n = 18, 17%) were the most common sites. Forty-six (42%) patients were 10-year mGIST survivors. Following mGIST diagnosis, radiographic progression occurred within 2 years in 53% (n = 58) of patients, 2-5 years in 16% (n = 17), and 5-10 years in 16% (n = 17), with median survival of 32, 76, and 173 months, respectively. Seventeen (16%) patients had not progressed by 10 years. Fifty-two (47%) patients underwent metastasectomy, which was associated with improved progression-free survival (hazard ratio 0.63, p = 0.04). In patients experiencing progression, factors independently associated with 10-year survivorship were age (odds ratio [OR] 0.96, p = 0.03) and time to progression (OR 1.71/year, p < 0.001). CONCLUSIONS: Ten-year survivorship is achievable in mGIST in the era of TKIs and is associated with younger age and longer time to first progression, while metastasectomy is associated with longer time to first progression. The role of metastasectomy in the management of patients with disease progression receiving TKI therapy merits further study.

Disparities in Electronic Screening for Cancer-Related Psychosocial Distress May Promote Systemic Barriers to Quality Oncologic Care.

BACKGROUND: Screening for cancer-related psychosocial distress is an integral yet laborious component of quality oncologic care. Automated preappointment screening through online patient portals (Portal, MyChart) is efficient compared with paper-based screening, but unstudied. We hypothesized that patient access to and engagement with EHR-based screening would positively correlate with factors associated with digital literacy (eg, age, socioeconomic status). METHODS: Screening-eligible oncology patients seen at our Comprehensive Cancer Center from 2014 through 2019 were identified. Patients with active Portals were offered distress screening. Portal and screening participation were analyzed via multivariable logistic regression. Household income in US dollars and educational attainment were estimated utilizing zip code and census data. RESULTS: Of 17,982 patients, 10,279 (57%) had active Portals and were offered distress screening. On multivariable analysis, older age (odds ratio [OR], 0.97/year; P<.001); male gender (OR, 0.89; P<.001); Black (OR, 0.47; P<.001), Hawaiian/Pacific Islander (OR, 1.54; P=.007), and Native American/Alaskan Native race (OR, 0.67; P=.04); Hispanic ethnicity (OR, 0.76; P<.001); and Medicare (OR, 0.59; P<.001), Veteran's Affairs/military (OR, 0.09; P<.01), Medicaid (OR, 0.34; P<.001), or no insurance coverage (OR, 0.57; P<.001) were independently associated with lower odds of being offered distress screening; increasing income (OR, 1.05/$10,000; P<.001) and educational attainment (OR, 1.03/percent likelihood of bachelor's degree or higher; P<.001) were independently associated with higher odds. In patients offered electronic screening, participation rate was 36.6% (n=3,758). Higher educational attainment (OR, 1.01; P=.03) was independently associated with participation, whereas Black race (OR, 0.58; P=.004), Hispanic ethnicity (OR, 0.68; P=.01), non-English primary language (OR, 0.67; P=.03), and Medicaid insurance (OR, 0.78; P<.001) were independently associated with nonparticipation. CONCLUSIONS: Electronic portal-based screening for cancer-related psychosocial distress leads to underscreening of vulnerable populations. At institutions using electronic distress screening workflows, supplemental screening for patients unable or unwilling to engage with electronic screening is recommended to ensure efficient yet equal-opportunity distress screening.

Variation in adoption of skin and nipple sparing mastectomy: An opportunity to enhance patient outcomes.

BACKGROUND: Nipple-sparing mastectomies (NSM) for breast cancer are under-utilized. We sought to investigate NSM utilization. METHODS: Females with nonmetastatic breast cancer undergoing mastectomy in the Legacy Health System from 2007 to 2020 were identified. Multivariable logistic regression was utilized to evaluate odds of receiving NSM. RESULTS: Three-thousand-four-hundred-seventeen mastectomies were performed with 772 undergoing NSM. On multivariable analysis, later year (OR 1.22/year, P < 0.001), neoadjuvant chemotherapy (OR 1.33, P = 0.04), HR+ (OR 1.61, P = 0.001) and surgeon volume (OR 1.16/10 yearly mastectomies, P < 0.001) were independently associated with increased odds of receiving a NSM while age (OR 0.94/year, P < 0.001), IDC (OR 0.58, P = 0.01), T3/T4 stage (OR 0.36, P = 0.009), and clinical node positivity (OR 0.63, P = 0.003) were independently associated with decreased odds. Surgeon volume was not associated with odds of receiving a non-NSM with reconstruction (OR 1.01 P = 0.48). CONCLUSION: NSM is under-utilized by low-volume breast surgeons. Understanding barriers to adoption is an is an opportunity to enhance patient-centered outcomes.

The RNA-Binding Protein HuR Posttranscriptionally Regulates the Protumorigenic Activator YAP1 in Pancreatic Ductal Adenocarcinoma.

Yes-associated protein 1 (YAP1) is indispensable for the development of mutant KRAS-driven pancreatic ductal adenocarcinoma (PDAC). High YAP1 mRNA is a prognostic marker for worse overall survival in patient samples; however, the regulatory mechanisms that mediate its overexpression are not well understood. YAP1 genetic alterations are rare in PDAC, suggesting that its dysregulation is likely not due to genetic events. HuR is an RNA-binding protein whose inhibition impacts many cancer-associated pathways, including the "conserved YAP1 signature" as demonstrated by gene set enrichment analysis. Screening publicly available and internal ribonucleoprotein immunoprecipitation (RNP-IP) RNA sequencing (RNA-Seq) data sets, we discovered that YAP1 is a high-confidence target, which was validated in vitro with independent RNP-IPs and 3' untranslated region (UTR) binding assays. In accordance with our RNA sequencing analysis, transient inhibition (e.g., small interfering RNA [siRNA] and small-molecular inhibition) and CRISPR knockout of HuR significantly reduced expression of YAP1 and its transcriptional targets. We used these data to develop a HuR activity signature (HAS), in which high expression predicts significantly worse overall and disease-free survival in patient samples. Importantly, the signature strongly correlates with YAP1 mRNA expression. These findings highlight a novel mechanism of YAP1 regulation, which may explain how tumor cells maintain YAP1 mRNA expression at dynamic times during pancreatic tumorigenesis.

Outcomes of Telemedicine-Based Consultation among Rural Patients Referred for Abdominal Wall Reconstruction and Hernia Repair.

BACKGROUND: Perioperative telemedicine use has increased as a result of the COVID-19 pandemic and may improve access to surgical care. However, studies assessing outcomes in populations at risk for digital-health disparities are lacking. We sought to characterize the pre- and postoperative outcomes for rural patient populations being assessed for hernia repair and abdominal wall reconstruction with telehealth. METHODS: Patients undergoing telehealth evaluation from March 2020 through May 2021 were identified. Rurality was identified by zip code of residence. Rural and urban patients were compared based on demographics, diagnosis, treatment plan, and visit characteristics and outcomes. Downstream care use related to supplementary in-person referral, and diagnostic testing was assessed. RESULTS: Three hundred-seventy-three (196 preoperative, 177 postoperative) telehealth encounters occurred during the study period (rural: 28% of all encounters). Rural patients were more likely to present with recurrent or incisional hernias (90.0 vs 72.7%, p = 0.02) and advanced comorbidities (American Society of Anesthesiologists status score > 2: 73.1 vs 52.1%, p = 0.009). Rural patients derived significant benefits related to time saved commuting, with median distances of 299 and 293 km for pre- and postoperative encounters, respectively. Downstream care use was 6.1% (N = 23) for additional in-person evaluations and 3.4% (N = 13) for further diagnostic testing, with no difference by rurality. CONCLUSIONS: Perioperative telehealth can safely be implemented for rural populations seeking hernia repair and may be an effective method for reducing disparities. Downstream care use related to additional in-person referral or diagnostic testing was minimally impacted in both the preoperative and postoperative settings. These findings suggest that rurality should not deter surgeons from providing telemedicine-based surgical consultation for hernia repair.