Surgical Margins After Neoadjuvant Radiation for Locally Advanced Vulvar Carcinoma: What is an Adequate Margin?

OBJECTIVE: We aim to explore whether the surgical tumor free margin is important for overall survival (OS) and local control in patients who undergo neoadjuvant radiation (RT) for vulvar cancer. METHODS: A retrospective review from 2004 to 2021 of patients who underwent RT followed by surgical resection was performed. Patients were categorized into groups based on margin status (no residual disease, >8 mm, close margins defined as 1 to 7 mm, or positive). Local control and OS were analyzed using the Kaplan-Meier with log rank test. Multivariate analysis was performed with cox hazards model. RESULTS: Eighty-three patients were included. A complete pathologic response (pCR) was found in 56% (n=46) of patients. The median follow-up time was 35 months (range: 4 to 216). The median OS for the entire cohort was 46 months (95% CI: 32.3-59.7). Having a pCR improved both OS and disease-free survival (DFS) compared with residual disease by 81 and 91 months, respectively (P<0.001). In the 2 patients with a margin >8 mm, there was no statistical difference in survival between those with close margins (46 vs. 25 mo, P=0.485). Factors that significantly impacted both OS and DFS were depth of invasion (DOI) and LVSI. On multivariate analysis of those with residual disease, there was no difference in OS or DFS by margin status but having a DOI >9 mm showed decreased OS (HR: 3.654; 95% CI: 1.317-10.135). CONCLUSIONS: In this cohort, response to RT, not margin status drives survival and recurrence. Given residual disease, the optimal margin is not clear, as there were only 2 patients with >8 mm margins. A close or positive margin had no impact on OS or local recurrence. A DOI >9 mm significantly impacts both OS and local recurrence even when accounting for other factors.

Lymph node dissection after neoadjuvant chemotherapy improves overall survival in clinical stage III endometrial cancer.

OBJECTIVE: To investigate whether performing a lymph node dissection during hysterectomy improves overall survival in patients with clinical stage III endometrial cancer who received neoadjuvant chemotherapy. METHODS: The National Cancer Database was queried to identify all patients with clinical stage III endometrial cancer who had undergone pre-operative chemotherapy as first course of treatment followed by hysterectomy with or without lymph node dissection between the years 2004 and 2020. Univariable and multivariable models were performed to investigate prognostic factors on overall survival. RESULTS: This study analyzed 2882 patients with clinical stage III endometrial cancer who received upfront chemotherapy. Among those who underwent lymph node dissection, 38% had positive lymph nodes. Factors found to be independently associated with improved survival included lymph node dissection (p<0.001), adjuvant radiation (p<0.001), histology (p<0.001), tumor grade (p<0.001), pathologic node status (p<0.001), age (p<0.001), type of insurance (p=0.027), and race (p<0.001). Patients who underwent lymph node dissection at time of hysterectomy had a significantly better overall survival (107 vs 85 months; p<0.001). Multivariate and propensity score analyses robustly demonstrated that lymph node dissection significantly improved overall survival (HR 0.69, 95% CI 0.57 to 0.84, p<0.001), even among patients with pathologically negative lymph nodes. CONCLUSION: Our study suggests that performing lymph node dissection at the time of hysterectomy is associated with improved overall survival in all patients with stage III endometrial cancer who receive upfront chemotherapy, regardless of age, race, insurance status, histologic subtype, tumor grade, pathologic node status, adjuvant radiation or chemotherapy. Notably, patients with high-risk disease may particularly benefit from this approach.

Bowel Perforation Caused by Biliary Stent Migration After ERCP: A Systematic Review.

GOALS: This systematic review aims to evaluate the risk factors, clinical features, and outcomes of bowel perforation caused by stent migration after endoscopic retrograde cholangiopancreatography (ERCP). BACKGROUND: Distal migration of biliary stents can occur after ERCP. Upon migration, most stents pass through the intestine without adverse events; however, bowel perforation has been reported. STUDY: A comprehensive literature search of PubMed, EMBASE, and Cochrane databases was conducted through October 2023 for articles that reported bowel perforation because of stent migration. Cases of incomplete stent migration and proximal stent migration were excluded. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to identify full-length articles in English reporting. RESULTS: Of 2041 articles retrieved on the initial search, 92 met the inclusion criteria. A total of 132 cases of bowel perforation occurred due to stent migration after ERCP (56.1% female; average age: 66 y). The median time from initial ERCP to perforation was 44.5 days (IQR 12.5-125.5). Most cases of perforation occurred in the small bowel (64.4%) compared with the colon (34.8%). Stents were mostly plastic (87.1%) with a median diameter of 10 Fr (IQR 8.5-10) and median length of 10.3 cm (IQR 715). Surgical management was pursued in 52.3% and endoscopic management in 42.4%. Bowel resection was required for 25.8% of patients. The overall mortality rate was 17.4%. CONCLUSION: In summary, this study demonstrates that bowel perforation after ERCP stent migration primarily occurs within 44.5 days and most frequently with a 10 Fr plastic biliary stent. The overall mortality rate was 17.4%. It is important for endoscopists to be mindful of this rare but serious adverse event.

The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study.

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).

Clinical Outcomes and Safety of Upper Endoscopy While on Glucagon-Like Peptide-1 Receptor Agonists.

Glucose-like peptide-1-receptor agonists (GLP-1RAs) have become integral to the management of type 2 diabetes and obesity. GLP-1RAs work in part through delaying gastric emptying, raising concerns about retained gastric contents (RGC) during esophagogastroduodenoscopy (EGD).1 The American Society of Anesthesiologists currently recommends holding GLP-1RAs for 1 dosing cycle before elective procedures, however, the American Gastroenterological Association (AGA) advocates proceeding with endoscopy in asymptomatic patients adhering to standard perioperative protocols without medication withholding and suggests implementing a liquid diet the day before endoscopy in lieu of stopping the medication.2,3 This variability in recommendations stems largely from a lack of GLP-1RA outcomes data from which to draw evidence-based conclusions.

Can an in-person hands-on applicator-based teaching session improve trainee knowledge and comfort with complex gynecologic brachytherapy?

INTRODUCTION: With the emergence of imaged-based planning and hybrid applicators the complexity of gynecologic brachytherapy has dramatically increased. Despite the known advantages of brachytherapy, notable national declines in utilization of brachytherapy have been documented. Clearly improved education in the sphere of gynecologic brachytherapy is needed. We hypothesize that a hands-on applicator-based training session would improve trainee comfort with gynecologic brachytherapy. METHODS AND MATERIALS: An in-person, applicator-based, hands-on training session was held with trainees from both radiation and gynecologic oncology programs. Trainees practiced assembling and handling applicators while receiving instruction on clinical scenarios in which various applicators are used in gynecologic cancer brachytherapy. Pre- and post-session, participants were administered an objective test of 10 pictorial-based case vignettes to quantify ability to select the correct applicator based on the interpretation of T2-weighted MR images. Participants additionally received a subjective survey to quantify comfort and experience with gynecologic brachytherapy using Likert-type question formatting. RESULTS: A total of 14 trainees participated. Most common case volume experience was 0-10 intracavitary (57%), 0-10 hybrid (71%), and 0-10 interstitial (71%). Pre-session, the most common answer to comfort level was "not comfortable still learning" for all brachytherapy types, and most common answer to largest gap in knowledge was all facets of brachytherapy. Average case-based test score was 3.5/10 pre-session versus 5.3/10 post-session (p = 0.028). Post-session, all respondents reported improved comfort level with brachytherapy. Post-session, most common answer to largest gap in knowledge was applicator/patient selection, and applicator/patient selection was also the largest area of identified improvement. 100% of participants felt repeating the session in the future would be helpful. CONCLUSIONS: Hands-on training with applicators improves both subjective and objective comfort with gynecologic brachytherapy. With 100% of participants requesting to implement this session into resident training, we suggest national opportunities might exist to expand educational processes and improve utilization of complex gynecologic brachytherapy in practice.

Comparative Effectiveness of Virtual Versus In-person Visits for Abdominal Pain During the COVID-19 Pandemic.

BACKGROUND AND AIMS: The COVID-19 pandemic has highlighted the importance of telemedicine in improving healthcare access and reducing costs. This study aimed to assess order compliance in the virtual versus in-person setting for the initial evaluation of abdominal pain (AP) prior to and during the pandemic. METHODS: A retrospective evaluation of virtual and in-person outpatient gastroenterology visits for AP were identified through natural language processing from January 2019 through September 2021 at the Cleveland Clinic main campus and regional hospitals in Ohio. We assessed the number and type of orders placed for patients and measured compliance through order completion. This study received Institutional Review Board approval (IRB 21-514). RESULTS: Among 20,356 patients at their initial visit, 79% had orders placed, of which 40% had pandemic in-person visits, 13% had pandemic virtual visits, and 47% had pre-pandemic in-person visits. Patients seen virtually were 65.1% less likely to complete orders compared to patients seen in-person (p < 0.001) during the pandemic. Patients seen in a pandemic virtual setting were 71.0% less likely to complete imaging orders (p < 0.001), 82.6% less likely to complete procedure orders (p < 0.001), and 60.5% less likely to complete lab orders (p < 0.001). CONCLUSION: Compared with in-person visits, patients seen virtually for their first presentation of AP were less likely to complete labs, imaging, and endoscopic evaluations. In-person visits were more successful with patient order completion during the pandemic. These findings highlight that virtual visits for AP, despite convenience, may compromise care delivery and warrant additional care coordination to achieve compliance with medical recommendations.

Treatment of Internal Mammary Nodes is Associated With Improved Overall Survival in Breast Cancer: A Meta-Analysis.

INTRODUCTION: The role of internal mammary nodal irradiation (IMNI) as a component of regional nodal radiotherapy is a controversial issue in breast radiation oncology with conflicting results presented in recent landmark trials. We thus created a meta-analysis of available data to better ascertain the potential benefit of IMNI. We hypothesize that with the increased power available within a meta-analysis, IMNI will prove to improve overall survival (OS) in breast cancer. METHODS: Literature search was conducted for prospective studies comparing IMNI to no IMNI. Primary endpoint was OS and secondary endpoints included local recurrence, regional recurrence, disease-free survival (DFS), breast cancer mortality (BCM), distant metastasis-free survival (DMFS), grade 2+ skin toxicity, cardiac events, and pneumonitis events. Subgroup analyses were performed for tumor location (medial/central vs. lateral), and nodal status (pN+ vs. pN0). Fixed-effect model was used if there was no heterogeneity, random-effects model otherwise. RESULTS: Four studies with a total of 5258 patients (IMNI: n=2592; control: n=2666) were included in the study. Pooled results showed IMNI significantly improved OS for all-comers (hazard ratio [HR]=0.89; 95% CI 0.81-0.97; P =0.008), as well as subgroups of pN+ with medial/central tumor location (HR=0.84; 95% CI 0.73-0.96; P =0.01) and pN+ with lateral tumor location (HR=0.87; 95% CI 0.77-0.99; P =0.04). There was no significant difference in OS for subgroups of pN0 and medial/central tumor location. There was no difference in local recurrence, but regional recurrence was significantly improved ( P =0.04). Endpoints of DFS (HR 0.91, 95% CI 0.84-0.99 P =0.03), BCM (HR 0.87, 95% CI 0.77-0.98, P =0.03), and DMFS (HR=0.87; 95% CI, 0.78-0.98; P =0.02) were all improved with IMNI. Grade 2+ skin toxicity, cardiac events and pneumonitis events were not significantly different between patient in the IMNI and no IMNI groups. CONCLUSION: Inclusion of IMN irradiation improves OS, DFS, BCM, and DMFS in breast cancer. Largest effect on OS was noted in the subgroup of patients with pN+ and medial/central tumor location.

Improved local control following dose-escalated stereotactic ablative radiation therapy (SABR) for metastatic sarcomas: An international multi-institutional experience.

BACKGROUND: We aimed to characterize local control (LC) and overall survival (OS) following stereotactic ablative radiation therapy (SABR) for extracranial sarcoma metastases. METHODS: A prospectively-maintained institutional registry was queried for patients with metastases from sarcoma primaries managed with SABR. Kaplan-Meier analysis was utilized for univariate analyses to assess potential prognostic factors regarding LC and OS. A Cox proportional hazards multivariate (MVA) model was employed to further assess initially identified independent variables. RESULTS: A total of 94 patients with 118 lesions with LC information were identified. Common metastatic sites treated were lung (77), non-spinal bone (15), and spine (10). The median biologically effective dose (BED4) was 175 Gy4 (range56.3 Gy4-360 Gy4) with a median dose/fractionation schedule of 50 Gy/5 fractions. One- and 2-year OS rates were 81.3 % (95 % CI: 71.2-88.1 %6) and 50.5 % (95 % CI: 38.6-61.3 %, respectively. On Cox MVA, advanced age and non-lung metastases were associated with inferior OS (p < 0.03) with patients with 0-2 of these risk factors having estimated 2-year OS of 65.1 %, 38.9 %, and N/A, respectively. One- and 2-year LC rates were 85.3 % (95 % CI: 77.7-90.9 %) and 78.2 % (95 % CI: 67.9-85.6 %), respectively. On MVA, only BED4 < 175 Gy was associated with inferior LC (hazard ratio (HR) = 3.33; p = 0.01). Ten of 118 treated lesions had treatment-related toxicities (all Grade 1-2). CONCLUSION: Age and lung vs. non-lung metastases were prognostic of OS and should be considered in patient selection for SABR. Dose escalation when feasible with BED4 ≥ 175 Gy is recommended given durable LC achieved without a subsequent increase in toxicity.

Clinical and Imaging Outcomes After Trigeminal Schwannoma Radiosurgery: Results From a Multicenter, International Cohort Study.

BACKGROUND AND OBJECTIVES: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS: The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION: SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.

The role of obesity in treatment planning for early-stage cervical cancer.

OBJECTIVES: Optimal management of obese patients with early-stage cervical cancer is debated despite evidence of non-inferior survival in obese patients undergoing radical hysterectomy with pelvic lymphadenectomy (RH) compared to primary radiation with or without radiosensitizing chemotherapy (RT). Objectives included describing patient factors affecting disposition to RH versus RT; comparing RH outcomes for obese (BMI >30 mg/m2) and non-obese patients; and comparing differences in recurrence free survival (RFS) and overall survival (OS). METHODS: This was a single institution cohort study of all cervical cancer patients who underwent RH or were candidates for RH based on clinical stage. Demographic, clinicopathologic and treatment outcomes were collected and analyzed. RESULTS: RT patients (n = 39, 15%) had a higher BMI (p = 0.004), older age (p < 0.001), more life-limiting comorbidities (LLC) (p < 0.001), larger tumor size (p = 0.001), and higher clinical stage (p = 0.013) compared to RH patients (n = 221, 85%). On multivariable survival analysis there was no difference in OS based on treatment modality; significant predictors of worse OS were larger tumor size, higher number of LLC and recurrence. Among the RH group, obese patients had a longer operative time (p = 0.01) and more LLC (p = 0.02); there were no differences in demographic or clinicopathologic characteristics, operative outcomes, RFS or OS compared to non-obese patients. CONCLUSION: In this cohort of RH-eligible cervical cancer patients, BMI was independently associated with disposition to RT. Studies demonstrate that RH is feasible and safe in obese patients with no difference in RFS or OS when compared to non-obese patients. Thus, the decision for disposition to RT should not be based on obesity alone.

Intracranial intraoperative radiotherapy (IORT): evaluation of electrocorticography and peri-operative seizure risk.

BACKGROUND: Intra-operative radiotherapy (IORT) for brain metastases (BMs) and primary brain tumors has emerged as an adjuvant radiation modality that allows for consolidation of care into a single anesthetic episode with surgical resection. Yet, there is a paucity of data regarding the impact that IORT may have on peri-operative and long-term seizure risk. METHODS: A retrospective analysis of patients receiving IORT during tumor resection was performed via registry including data regarding peri-operative anti-seizure medications and anesthetic agents. Intra-operative neuromonitoring was performed using electrocorticography (ECoG) captured before-, during-, and after-IORT then analyzed for evidence of seizure or significant baseline changes. Kaplan-Meir estimations were used for overall survival analysis relative to documented clinical seizure incidence post-IORT. RESULTS: Of the 24 consecutive patients treated with IORT during tumor resection included, 18 (75%) patients were diagnosed with BMs while 6 (25%) had newly-diagnosed glioblastoma. Mean and median survival times were 487 and 372 days, respectively. Clinical seizures occurred in 3 patients post-IORT, 2 BMs patients within 9 months and 1 glioblastoma patient at 14 months. IORT time represented 9.5% of anesthetic time. ECoG recordings were available for 5 patients (4 BMs; 1 glioblastoma), with mean recording durations of 13% of the total anesthetic time and no evidence of high-frequency oscillations or seizure activity. CONCLUSIONS: IORT is an option for delivery of definitive radiation in surgically resected brain tumors without increasing the peri-operative or long-term risk of seizure. ECoG data during the delivery of radiation fail to demonstrate any electrophysiological changes in response to ionizing radiation.

Is it enough to observe less than 2 cm sized gastric SET?

BACKGROUND AND AIMS: The recent surge in demand for screening endoscopy has led to an increased detection of gastric subepithelial tumors (SETs). According to current guideline, SETs less than 2 cm in size are recommended for periodic surveillance. In light of recent advancement in therapeutic endoscopy in resection of small SET, we analyzed the histopathological features and the effectiveness of endoscopic resection for these small SETs. METHODS: Retrospectively study was performed on 74 patients who underwent endoscopic resection of gastric small (≤ 2 cm) upper gastrointestinal tract SETs. The outcomes including histopathology and en bloc resection were analyzed. RESULTS: The mean SET size was 11.69 ± 5.11 mm. The mean procedure time was 81.26 ± 42.53 min. Of the 74 patients, 28 patients had leiomyomas, 26 had gastrointestinal stromal tumors (GISTs), 14 had ectopic pancreas, 4 had lipomas, and 2 had neuroendocrine tumors. Among those with GIST, two patients exhibited high-risk histology. All patients underwent successful and uneventful endoscopy. CONCLUSIONS: Endoscopic resection can be recommended even for the small gastric SETs. In our study, we found that SETs with a size of less than 2 cm have significant proportion of GISTs which harbor malignant transformation potential.

Mortality Trends, Outcomes, and Predictors of Portal Vein Thrombosis in Acute Pancreatitis Patients: A Propensity-Matched National Study.

BACKGROUND: Portal vein thrombosis (PVT) is a rare complication of acute pancreatitis (AP) and might be associated with worse outcomes. We aimed to study trends, outcomes, and predictors of PVT in AP patients. METHODS: The National Inpatient Sample database was utilized to identify the adult patients (≥ 18 years) with primary diagnosis of AP from 2004 to 2013 using International Classification of Disease, Ninth Revision. Patients with and without PVT were entered into propensity matching model based on baseline variables. Outcomes were compared between both groups and predictors of PVT in AP were identified. RESULTS: Among the total of 2,389,337 AP cases, 7046 (0.3%) had associated PVT. The overall mortality of AP decreased throughout the study period (p trend ≤ 0.0001), whereas mortality of AP with PVT remained stable (1-5.7%, p trend = 0.3). After propensity matching, AP patients with PVT patients had significantly higher in-hospital mortality (3.3% vs. 1.2%), AKI (13.4% vs. 7.7%), shock (6.9% vs. 2.5%), and need for mechanical ventilation (9.2% vs. 2.5%) along with mean higher cost of hospitalization and length of stay (p < 0.001 for all). Lower age (Odd ratio [OR] 0.99), female (OR 0.75), and gallstone pancreatitis (OR 0.79) were negative predictors, whereas alcoholic pancreatitis (OR 1.51), cirrhosis (OR 2.19), CCI > 2 (OR 1.81), and chronic pancreatitis (OR 2.28) were positive predictors of PVT (p < 0.001 for all) in AP patients. CONCLUSION: PVT in AP is associated with significantly higher risk of death, AKI, shock, and need for mechanical ventilation. Chronic and alcoholic pancreatitis is associated with higher risk of PVT in AP.

Is Substantial Lymphovascular Space Invasion Prognostic in Patients With Pathologically Lymph Node-Negative Endometrial Cancer?

PURPOSE: Lymphovascular space invasion (LVSI) predicts for higher rates of recurrence and increased mortality in endometrial cancer. Using 3-tier LVSI scoring, a PORTEC-1 and -2 trials analysis demonstrated that substantial LVSI was associated with worse locoregional (LR-DFS) and distant metastasis disease-free survival (DM-DFS), and these patients possibly benefited from external beam radiation therapy (EBRT). Furthermore, LVSI is a predictor for lymph node (LN) involvement, but the significance of substantial LVSI is unknown in patients with a pathologically negative LN assessment. We aimed to evaluate clinical outcomes of these patients in relation to the 3-tier LVSI scoring system. METHODS AND MATERIALS: We performed a single-institutional retrospective review of patients with stage I endometrioid-type endometrial cancer who underwent surgical staging with pathologically negative LN evaluation from 2017 to 2019 with 3-tier LVSI scoring (none, focal, or substantial). Clinical outcomes (LR-DFS, DM-DFS, and overall survival) were analyzed using the Kaplan-Meier method. RESULTS: A total of 335 patients with pathologically LN-negative stage I endometrioid-type endometrial carcinoma were identified. Substantial LVSI was present in 17.6% of patients; 39.7% of patients received adjuvant vaginal brachytherapy and 6.9% of patients received EBRT. Adjuvant radiation treatment varied by LVSI status. In patients with focal LVSI, 81.0% received vaginal brachytherapy. Among patients with substantial LVSI, 57.9% received vaginal brachytherapy alone, and 31.6% of patients received EBRT. The 2-year LR-DFS rates were 92.5%, 98.0%, and 91.4% for no LVSI, focal LVSI, and substantial LVSI, respectively. The 2-year DM-DFS rates were 95.5%, 93.3%, and 93.8% for no LVSI, focal LVSI, and substantial LVSI, respectively. CONCLUSIONS: In our institutional study, patients with pathologically LN-negative stage I endometrial cancer with substantial LVSI had similar rates of LR-DFS and DM-DFS compared with patients with none or focal LVSI. These findings highlight the need for multi-institutional studies to validate the prognostic value of substantial LVSI in this patient population.

Efficacy and safety of double- versus single-balloon retrograde enteroscopy.

INTRODUCTION: Data on the safety and efficacy of double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE) are conflicting. We aimed to compare the efficacy and safety of retrograde DBE to SBE. METHODS: We performed a retrospective analysis of all patients who underwent retrograde DBE or SBE at a large tertiary referral center from 2008 to December 2018. Outcomes assessed included technical success, diagnostic yield, therapeutics, depth of insertion, and procedural duration. RESULTS: A total of 523 (403 DBE, 120 SBE) patients underwent retrograde enteroscopy during the study period. The mean age was 59.4 ± 17.24 and 59.57 ± 16.94 years in DBE and SBE groups, respectively. There was no difference in technical success (91.0% vs. 92.5%, P = 0.85), diagnostic yield (40.9% vs. 40.8%, P = 0.95), and therapeutics (17.1% vs. 19.1%, P = 0.61) between DBE and SBE. Compared to SBE, DBE had significantly shorter mean procedure time (26.5 ± 34.5 min vs. 34.8 ± 29.4 min, P = 0.01) and higher maximal depth of insertion from ileocecal valve (108.1 ± 84.1 cm vs. 73.3 ± 63.4 cm, P = 0.001). Safety events were rare and similar in both groups. CONCLUSION: Retrograde DBE is associated with a significantly higher depth of insertion and shorter procedural duration, but similar diagnostic yield and technical success compared to SBE.

Prevalence of neonicotinoid insecticides in paired private-well tap water and human urine samples in a region of intense agriculture overlying vulnerable aquifers in eastern Iowa.

A pilot study among farming households in eastern Iowa was conducted to assess human exposure to neonicotinoids (NEOs). The study was in a region with intense crop and livestock production and where groundwater is vulnerable to surface-applied contaminants. In addition to paired outdoor (hydrant) water and indoor (tap) water samples from private wells, urine samples were collected from 47 adult male pesticide applicators along with the completions of dietary and occupational surveys. Estimated Daily Intake (EDI) were then calculated to examine exposures for different aged family members. NEOs were detected in 53% of outdoor and 55% of indoor samples, with two or more NEOs in 13% of samples. Clothianidin was the most frequently detected NEO in water samples. Human exposure was ubiquitous in urine samples. A median of 10 different NEOs and/or metabolites were detected in urine, with clothianidin, nitenpyram, thiamethoxam, 6-chloronicotinic acid, and thiacloprid amide detected in every urine samples analyzed. Dinotefuran, imidaclothiz, acetamiprid-N-desmethyl, and N-desmethyl thiamethoxam were found in ≥70% of urine samples. Observed water intake for study participants and EDIs were below the chronic reference doses (CRfD) and acceptable daily intake (ADI) standards for all NEOs indicating minimal risk from ingestion of tap water. The study results indicate that while the consumption of private well tap water provides a human exposure pathway, the companion urine results provide evidence that diet and/or other exposure pathways (e.g., occupational, house dust) may contribute to exposure more than water contamination. Further biomonitoring research is needed to better understand the scale of human exposure from different sources.

Factors associated with ductal carcinoma in situ (DCIS) treatment patterns and patient-reported outcomes across a large integrated health network.

PURPOSE: To examine associations between ductal carcinoma in situ (DCIS) patients' characteristics, treating locations and DCIS treatments received and to pilot assessing quality-of-life (QoL) values among DCIS patients with diverse backgrounds. METHODS: We performed a retrospective tumor registry review of all patients diagnosed and treated with DCIS from 2018 to 2019 in the UPMC-integrated network throughout central and western Pennsylvania. Demographics, clinical information, and administered treatments were compiled from tumor registry records. We categorized contextual factors such as different hospital setting (academic vs. community), socioeconomic status based on the neighborhood deprivation index (NDI) as well as age and race. QoL survey was administered to DCIS patients with diverse backgrounds via QoL questionnaire breast cancer module 23 and qualitative assessment questions. RESULTS: A total of 912 patients were reviewed. There were no treatment differences noted for age, race, or NDI. Mastectomy rate was higher in academic sites than community sites (29 vs. 20.4%; p = 0.0045), while hormone therapy (HT) utilization rate was higher in community sites (74 vs. 62%; p = 0.0012). QoL survey response rate was 32%. Only HT side effects negatively affected in QoL scores and there was no significant difference in QoL domains and decision-making process between races, age, NDI, treatment groups, and treatment locations. CONCLUSION: Our integrated health network did not show chronically noted disparities arising from social determinates of health for DCIS treatments by implementing clinical pathways and system-wide peer review. Also, we demonstrated feasibility in collecting QoL for DCIS women with diverse backgrounds and different socioeconomic statuses.

Concurrent immunoradiation for HPV-associated oropharyngeal squamous cell carcinoma.

OBJECTIVES: Current trials for HPV-associated oropharyngeal SCCs (OP-SCCs) are evaluating treatment de-escalation including use of concurrent immunotherapy with radiation therapy (I-RT). Given limited prospective data following I-RT, we aimed to examine this question utilizing the National Cancer Data Base (NCDB). METHODS: The NCDB was queried for patients with HPV-associated OP-SCCs eligible for current de-escalation studies with AJCC 7th edition T1-T2/N1-N2b and T3/N0-N2b disease. Patients were stratified into I-RT, concurrent chemoradiation (C-RT), and radiation therapy alone (RT) arms. Kaplan-Meier analysis was utilized to compare overall survival (OS) between treatment arms followed by a Cox multivariate (MVA) proportional hazards model controlling for tumor and patient characteristics and propensity-score analyses with inverse probability treatment weighting (IPTW). RESULTS: We identified 4768 patients; 313 received I-RT, 3660 patients received C-RT, and 795 received RT. Median age was 62 years (range 27-90) with a median Charlson-Deyo co-morbidity score of 0 (range: 0-3). The vast majority were cN1-N2a (88.8%) and 26.5% were cT3. On MVA, inferior 3-year and 8-year OS was noted following I-RT (81.6% and 70.5%) vs. C-RT (90.6% and 79.4%) (HR = 1.69 (95% CI: 1.29-2.21); p < 0.0001) with no significant difference vs. RT (88.1% and 75.8%) (HR = 1.07; p = 0.80). This was also maintained on IPTW-analysis (HR = 1.62 (95% CI: 1.23-2.15); p = 0.001). CONCLUSIONS: I-RT was associated with significantly poorer OS vs. C-RT with no benefit compared to RT for HPV-associated OP-SCCs. I-RT is not recommended outside of currently accruing clinical trials.