Archival single-cell genomics reveals persistent subclones during DCIS progression.

Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials. We validated our method by profiling 40,330 single cells from cell lines, a frozen tissue, and 27 FFPE samples from breast, lung, and prostate tumors stored for 3-31 years. Analysis of 10 patients with matched DCIS and cancers that recurred 2-16 years later show that many primary DCIS had already undergone whole-genome doubling and clonal diversification and that they shared genomic lineages with persistent subclones in the recurrences. Evolutionary analysis suggests that most DCIS cases in our cohort underwent an evolutionary bottleneck, and further identified chromosome aberrations in the persistent subclones that were associated with recurrence.

Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma.

Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor to invasive breast cancer (IBC). To understand the changes in the tumor microenvironment (TME) accompanying transition to IBC, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) and a 37-plex antibody staining panel to interrogate 79 clinically annotated surgical resections using machine learning tools for cell segmentation, pixel-based clustering, and object morphometrics. Comparison of normal breast with patient-matched DCIS and IBC revealed coordinated transitions between four TME states that were delineated based on the location and function of myoepithelium, fibroblasts, and immune cells. Surprisingly, myoepithelial disruption was more advanced in DCIS patients that did not develop IBC, suggesting this process could be protective against recurrence. Taken together, this HTAN Breast PreCancer Atlas study offers insight into drivers of IBC relapse and emphasizes the importance of the TME in regulating these processes.

Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression.

How tumor cells genetically lose antigenicity and evade immune checkpoints remains largely elusive. We report that tissue-specific expression of the human long noncoding RNA LINK-A in mouse mammary glands initiates metastatic mammary gland tumors, which phenotypically resemble human triple-negative breast cancer (TNBC). LINK-A expression facilitated crosstalk between phosphatidylinositol-(3,4,5)-trisphosphate and inhibitory G-protein-coupled receptor (GPCR) pathways, attenuating protein kinase A-mediated phosphorylation of the E3 ubiquitin ligase TRIM71. Consequently, LINK-A expression enhanced K48-polyubiquitination-mediated degradation of the antigen peptide-loading complex (PLC) and intrinsic tumor suppressors Rb and p53. Treatment with LINK-A locked nucleic acids or GPCR antagonists stabilized the PLC components, Rb and p53, and sensitized mammary gland tumors to immune checkpoint blockers. Patients with programmed ccll death protein-1(PD-1) blockade-resistant TNBC exhibited elevated LINK-A levels and downregulated PLC components. Hence we demonstrate lncRNA-dependent downregulation of antigenicity and intrinsic tumor suppression, which provides the basis for developing combinational immunotherapy treatment regimens and early TNBC prevention.

LncRNA CamK-A Regulates Ca2+-Signaling-Mediated Tumor Microenvironment Remodeling.

Cancer cells entail metabolic adaptation and microenvironmental remodeling to survive and progress. Both calcium (Ca2+) flux and Ca2+-dependent signaling play a crucial role in this process, although the underlying mechanism has yet to be elucidated. Through RNA screening, we identified one long noncoding RNA (lncRNA) named CamK-A (lncRNA for calcium-dependent kinase activation) in tumorigenesis. CamK-A is highly expressed in multiple human cancers and involved in cancer microenvironment remodeling via activation of Ca2+-triggered signaling. Mechanistically, CamK-A activates Ca2+/calmodulin-dependent kinase PNCK, which in turn phosphorylates IκBα and triggers calcium-dependent nuclear factor κB (NF-κB) activation. This regulation results in the tumor microenvironment remodeling, including macrophage recruitment, angiogenesis, and tumor progression. Notably, our human-patient-derived xenograft (PDX) model studies demonstrate that targeting CamK-A robustly impaired cancer development. Clinically, CamK-A expression coordinates with the activation of CaMK-NF-κB axis, and its high expression indicates poor patient survival rate, suggesting its role as a potential biomarker and therapeutic target.

Does preoperative symptom duration affect outcomes following per oral endoscopic myotomy (POEM)?

BACKGROUND: Per oral endoscopic myotomy (POEM) is a safe therapy for the treatment of achalasia. Long-term effects of untreated achalasia include worsening dysmotility and disruptions in esophageal anatomy, i.e., tortuosity and dilation. We hypothesize that long-standing achalasia prior to intervention will have worse outcomes following POEM than in patients with symptoms for shorter duration. METHODS: We retrospectively analyzed achalasia patients who underwent POEM at our institution from 2011 to 2023, categorizing them into symptom duration cohorts (< 1 year, 1-3 years, 4-10 years, > 10 years). Inclusion criteria comprised patients with documented achalasia diagnosis who received POEM treatment at our facility. Exclusion criteria encompassed individuals lacking data pertaining to achalasia diagnosis, the time frame before intervention, or those missing pre and postoperative Eckardt scores. POEM failure was defined as symptom recurrence, necessity for repeat intervention, or high postoperative Eckardt score. We compared demographic, preoperative, and postoperative outcomes across these cohorts, and employed multivariable logistic regression to explore the link between symptom duration and POEM response. RESULTS: During the study period, in our increased cohort 234 patients met inclusion criteria. 75 patients had symptoms for < 1 year, 78 patients had symptoms from 1 to 3 years, 47 patients had symptoms from 4 to 10 years, and 34 patients had symptoms > 10 years. Patient demographics such as age, sex, BMI, Charleson-Deyo-Comorbidity-Index, and diabetes did not differ amongst cohorts. High-resolution manometry data, including achalasia type, Median IRP, LES residual pressure, and Basal LES pressure did not differ between groups. Preoperative Eckardt scores ranged from 4 to 5 across groups (p 0.24). Patients endorsed an average of three total preoperative symptoms across groups (p 0.13). Patients with symptoms greater than 4 years had significantly more endoscopic interventions prior to POEM (37% vs, 68% p .001). There was no significant difference in post-procedure mean Eckardt scores between cohorts. All cohorts experienced the same number of post-POEM symptoms. Post-POEM manometric measurements remained consistent across cohorts. Similarly, there were no significant differences in terms of symptom recurrence, requirement for repeat interventions, or repeat POEM among the cohorts. Multivariable logistic regression analysis determined achalasia symptoms greater than a decade did not result in increased odds of having a higher postoperative Eckardt score, worse dysphagia, regurgitation, or weight loss. CONCLUSIONS: In this increased cohort, this data once again suggests that longer symptom duration is not associated with increased rates of POEM failure.

Extracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by Multiplexed Spatial Proteomics.

Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC (n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC.

Association of inflammation-related exposures and ovarian cancer survival in a multi-site cohort study of Black women.

BACKGROUND: An association was observed between an inflammation-related risk score (IRRS) and worse overall survival (OS) among a cohort of mostly White women with invasive epithelial ovarian cancer (EOC). Herein, we evaluated the association between the IRRS and OS among Black women with EOC, a population with higher frequencies of pro-inflammatory exposures and worse survival. METHODS: The analysis included 592 Black women diagnosed with EOC from the African American Cancer Epidemiology Study (AACES). Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of the IRRS and OS, adjusting for relevant covariates. Additional inflammation-related exposures, including the energy-adjusted Dietary Inflammatory Index (E-DIITM), were evaluated. RESULTS: A dose-response trend was observed showing higher IRRS was associated with worse OS (per quartile HR: 1.11, 95% CI: 1.01-1.22). Adding the E-DII to the model attenuated the association of IRRS with OS, and increasing E-DII, indicating a more pro-inflammatory diet, was associated with shorter OS (per quartile HR: 1.12, 95% CI: 1.02-1.24). Scoring high on both indices was associated with shorter OS (HR: 1.54, 95% CI: 1.16-2.06). CONCLUSION: Higher levels of inflammation-related exposures were associated with decreased EOC OS among Black women.

Accuracy in Polyp Size Measurement Among Surgeons, Gastroenterologists, Trainees, and Experts: A Prospective Video-Based Study.

INTRODUCTION: Polyp size determination plays an important role in endoscopic decision making and follow-up determination. However, there is a lack of knowledge of endoscopist accuracy for polyp sizing and efficacy of available tools for size measurement. Our aim was to compare the accuracy of visual assessment, snare, forceps, and virtual scale endoscope (VSE) in estimating polyp size among a diverse group of endoscopists. METHODS: We conducted a prospective video-based study. One hundred twenty polyps measured and recorded along with all available measurement tools were randomized to visual assessment, snare, forceps, or VSE group. Eleven endoscopists conducted video-based measurement using the randomized measurement tool. Primary outcome was relative accuracy in polyp size measurement compared with caliper measurement immediately postresection. RESULTS: One thousand three hundred twenty measurements were performed. VSE had statistically significantly higher relative accuracy when compared to forceps (79.3 vs 71.3%; P < 0.0001). Forceps had statistically significantly higher relative accuracy when compared to visual assessment (71.3 vs 63.6%; P = 0.0036). There was no statistically significant difference when comparing visual assessment and snare-based measurements (63.6 vs 62.8%; P = 0.797). Overall, 21.5% of polyps >5 mm were misclassified as ≤5 mm and 17.3% of polyps ≥10 mm were misclassified as <10 mm. VSE had the lowest percentage of polyps >5 mm misclassified as ≤5 mm (2.6%), polyps ≤5 mm misclassified as >5 mm (5.1%), and polyps <10 mm misclassified as ≥10 mm (1.7%). DISCUSSION: Visual size estimation of polyps is inaccurate independently of training level, sex, and specialty. Size measurement accuracy can be improved using forceps and yields the highest relative accuracy when an adaptive scale technology is used.

Survival of epithelial ovarian cancer in Black women: a society to cell approach in the African American cancer epidemiology study (AACES).

PURPOSE: The causes for the survival disparity among Black women with epithelial ovarian cancer (EOC) are likely multi-factorial. Here we describe the African American Cancer Epidemiology Study (AACES), the largest cohort of Black women with EOC. METHODS: AACES phase 2 (enrolled 2020 onward) is a multi-site, population-based study focused on overall survival (OS) of EOC. Rapid case ascertainment is used in ongoing patient recruitment in eight U.S. states, both northern and southern. Data collection is composed of a survey, biospecimens, and medical record abstraction. Results characterizing the survival experience of the phase 1 study population (enrolled 2010-2015) are presented. RESULTS: Thus far, ~ 650 patients with EOC have been enrolled in the AACES. The five-year OS of AACES participants approximates those of Black women in the Surveillance Epidemiology and End Results (SEER) registry who survive at least 10-month past diagnosis and is worse compared to white women in SEER, 49 vs. 60%, respectively. A high proportion of women in AACES have low levels of household income (45% < $25,000 annually), education (51% ≤ high school education), and insurance coverage (32% uninsured or Medicaid). Those followed annually differ from those without follow-up with higher levels of localized disease (28 vs 24%) and higher levels of optimal debulking status (73 vs 67%). CONCLUSION: AACES is well positioned to evaluate the contribution of social determinants of health to the poor survival of Black women with EOC and advance understanding of the multi-factorial causes of the ovarian cancer survival disparity in Black women.

A new method to accurately identify single nucleotide variants using small FFPE breast samples.

Most tissue collections of neoplasms are composed of formalin-fixed and paraffin-embedded (FFPE) excised tumor samples used for routine diagnostics. DNA sequencing is becoming increasingly important in cancer research and clinical management; however it is difficult to accurately sequence DNA from FFPE samples. We developed and validated a new bioinformatic pipeline to use existing variant-calling strategies to robustly identify somatic single nucleotide variants (SNVs) from whole exome sequencing using small amounts of DNA extracted from archival FFPE samples of breast cancers. We optimized this strategy using 28 pairs of technical replicates. After optimization, the mean similarity between replicates increased 5-fold, reaching 88% (range 0-100%), with a mean of 21.4 SNVs (range 1-68) per sample, representing a markedly superior performance to existing tools. We found that the SNV-identification accuracy declined when there was less than 40 ng of DNA available and that insertion-deletion variant calls are less reliable than single base substitutions. As the first application of the new algorithm, we compared samples of ductal carcinoma in situ of the breast to their adjacent invasive ductal carcinoma samples. We observed an increased number of mutations (paired-samples sign test, P < 0.05), and a higher genetic divergence in the invasive samples (paired-samples sign test, P < 0.01). Our method provides a significant improvement in detecting SNVs in FFPE samples over previous approaches.

Preoperative manometric data can predict symptom improvement after per oral endoscopic myotomy for treatment of achalasia.

BACKGROUND: While per oral endoscopic myotomy (POEM) has been shown to be efficacious in the treatment of achalasia, it can be difficult to predict who will have a robust and durable response. Historically, high lower esophageal sphincter pressures have been shown to predict a worse response to endoscopic therapies such as botox therapy. This study was designed to evaluate if modern preoperative manometric data could predict a response to therapy after POEM. METHODS: This was a retrospective study of 144 patients who underwent a POEM at a single institution by a single surgeon over an 8-year period (2014-2022) who had high-resolution manometry performed preoperatively and had an Eckardt symptom score performed both preoperatively and postoperatively. The achalasia type and integrated relaxation pressures (IRP) were then tested for potential correlation with need for any further achalasia interventions postoperatively as well as the degree of Eckardt score reduction using univariate analysis. RESULTS: The achalasia type on preoperatively manometry was not predictive of need for further interventions or degree of Eckardt score reduction (p = 0.74 and 0.44, respectively). A higher IRP was not predictive of need for further interventions however it was predictive of a greater reduction in postoperative Eckardt scores (p = 0.03) as shown by a nonzero regression slope. CONCLUSION: In this study, achalasia type was not a predictive factor in need for further interventions or degree of symptom relief. While IRP was not predictive of need for further interventions, a higher IRP did predict better symptomatic relief postoperatively. This result is opposite that of other endoscopic treatment modalities. Therefore, patients with higher IRP on high-resolution manometry would likely benefit from myotomy which provides significant symptomatic relief postoperatively.

Symptom duration is not associated with per oral endoscopic myotomy (POEM) failure.

INTRODUCTION: Per oral endoscopic myotomy (POEM) is a relatively novel technique to address achalasia; however, little is known about the efficacy of POEM for patients with long-standing achalasia. We hypothesize that patients with long-standing achalasia prior to intervention will be more recalcitrant to POEM than patients with symptoms for a short duration. METHODS: We performed a retrospective analysis of patients with achalasia who received a POEM at a single institution from 2012 to 2022. Patients were grouped into cohorts based on the time of symptom duration: < 1 year, 1-3 years, 4-10 years, > 10 years. POEM failure was defined as need for repeat intervention, symptom recurrence, and a high postoperative Eckart score. Demographic and clinical data were compared between cohorts. Measures of failure multivariable logistic regression analyzed the association between symptom duration and response to POEM. RESULTS: During the study period, 132 patients met inclusion criteria. Patient age at surgery, sex, BMI, Charleston-Deyo Comorbidity Index, and patients with diabetes with and without end organ complications, connective tissue diseases, and patients with ulcer diseases did not differ among cohorts. Patients who have had symptoms for greater than 10 years had significantly more endoscopic interventions prior to their POEM (30% vs, 60% p = 0.002). Patients in all cohorts experienced the same number of symptoms post-POEM. Manometric measurements did not vary across cohorts after POEM. Symptom recurrence, need for repeat endoscopic intervention, repeat surgical intervention, or repeat POEM also did not vary across cohorts. Having symptoms of achalasia > 10 years did not increase the odds POEM failure on multivariable logistical regression. CONCLUSIONS: These data suggest that longer symptom duration is not associated with increased rates of POEM failure. This is promising as clinicians should not exclude patients for POEM eligibility based on duration of symptoms alone.

Do preoperative endoscopic interventions predict symptom recurrence or reintervention after peroral endoscopic myotomy?

BACKGROUND: Studies assessing outcomes of patients undergoing peroral endoscopic myotomy (POEM) after botulinum injection or dilation have had various results with respect to failure, although this has not been differentiated between lack of clinical response and recurrence. We hypothesize that patients with previous endoscopic intervention(s) are more likely to recur than treatment-naïve patients. METHODS: This is a retrospective cohort study of patients that underwent POEM for achalasia at a single tertiary care center between 2011 and 2022. Patients were excluded if they had previous myotomy (POEM or Heller). The remaining patients were stratified into treatment-naïve patients (TN), those with previous botulinum injection (BTX), those with previous dilatation (BD), and those with both previous endoscopic interventions (BOTH). Primary outcome was recurrence indicated by clinical symptoms or need for repeat endoscopic intervention or surgery after originally having clinical resolution (Eckardt ≤ 3). Multivariate logistic regression using preoperative and intraoperative factors was completed to assess odds of recurrence. RESULTS: A total of 164 patients were included in the analysis, 90 TN, 34 BD, 28 BTX, and 12 BOTH. There were no other significant differences in demographics or in preoperative Eckardt score (p = 0.53). There was no difference in the proportion of patients that had postoperative manometry (p = 0.74), symptom recurrence (p = 0.59), surgical intervention (p = 0.16). BTX (14.3%) and BOTH (16.7%) patients had a higher rate of repeat endoscopic intervention than BD and TN patients (5.9% and 1.1%). In the logistic regression analysis, there was no association among the BTX, BD, or BOTH groups compared to the TN group. No odds ratios achieved statistical significance. CONCLUSIONS: There were no increased likelihood of recurrence with botulinum injection or dilatation prior to POEM, implying that they are similarly good candidates compared to treatment-naïve patients.

Preoperative patient factors and anatomy do not predict who will develop reflux after per oral endoscopic myotomy.

BACKGROUND: Per oral endoscopic myotomy (POEM) has been shown to be an efficacious and safe therapy for the treatment of achalasia. Compared to laparoscopic Heller myotomy however, no antireflux procedure is routinely combined with POEM and therefore the development of symptomatic or silent reflux is of concern. This study was designed to determine if various patient factors and anatomy would predict the development of gastroesophageal reflux disease post-operatively. METHODS: This was a retrospective cohort study of all patients who underwent a POEM at a single institution by a single surgeon over an eight-year period (2014-2022). It has been our practice to obtain a postoperative ambulatory pH test on all patients 6 months after POEM off all acid reducing medications. Patients without a postoperative ambulatory esophageal pH monitoring test were excluded. Age, sex, obesity (BMI > 30), achalasia type, presence of a hiatal hernia, history of prior endoscopic achalasia treatments or myotomy were analyzed using univariate analysis as predictive factors for the development of postoperative GERD (DeMeester score > 14.7 on ambulatory pH monitoring). RESULTS: There were 179 total patients included in the study with 42 patients (23.5%) having undergone postoperative ambulatory pH testing. The majority of patients (137 or 76.5%) were lost to follow up and did not undergo ambulatory pH testing. Twenty-three out of those 42 patients (55%) had evidence of GERD on ambulatory pH testing. Multiple preoperative patient characteristics including demographics, manometric results, EGD findings, and history of prior achalasia interventions did not correlate with the development of post-operative GERD. CONCLUSIONS: Despite the high rate of reflux after POEM, there does not appear to be any reliable preoperative indicators of which patients have a higher risk of developing post-operative GERD after POEM.

Enhanced gastric decompression for palliation of malignant bowel obstruction.

BACKGROUND: Malignant bowel obstruction (MBO) is a sequela of advanced intraabdominal cancer and has a profound impact on quality of life. Common therapy is endoscopic decompressive gastrostomy tube placement. Standard gastrostomy tubes are poorly designed to completely evacuate the dependent portions of the stomach due to their location on the anterior gastric wall. In our institution we have begun placing the ASPIRE Assist gastrostomy tube (ASPIRE Bariatrics, Exton, PA) which includes a 15 cm long, 30Fr fenestrated gastric tube extension for enhanced gastric decompression. This tube is FDA indicated for gastric decompression and marketed for endoscopic weight loss. The purpose of this study is to review our experience managing MBO utilizing the ASPIRE Assist tube. METHODS: This is a retrospective analysis of outcomes at a single institution. All decompressive endoscopic gastrostomy tubes placed by two surgeons between November 2019 and July 2021 were reviewed. Endoscopic placement was performed utilizing standard safe tract and Ponsky pull techniques. RESULTS: Fourteen patients were identified (10F:4 M), mean age 70 (range 35-89). Primary cancer diagnoses included gynecologic (8), colorectal (3), bladder (1), small bowel (1), peritoneal serous (1). During the 12 months before decompressive gastrostomy tube placement, mean number of hospital admissions for MBO was 1.6 (range 1-3). Following tube placement, twelve patients had no further hospital admissions for MBO over their lifespan of mean 270 days (range 8-679 days). One patient had 1 admission for MBO in the 12 months before tube placement and 3 admissions in the 4 months after placement. A second patient had 2 admissions in the 12 months before tube placement and 1 admission in their 54-day lifespan after placement. There were no major complications. CONCLUSIONS: Endoscopic placement of the ASPIRE Assist gastrostomy tube is safe for palliation of MBO and may improve gastric decompression compared with standard endoscopic gastrostomy tubes. Enhanced gastric decompression can better manage symptoms, reduce hospital encounters, and improve quality of life. Further study is needed, however, our initial data appears promising.

An analysis of publications originating from abstracts presented at the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Meeting.

BACKGROUND: Research presentation has benefits, including CV building, networking, and collaboration. A measurable standard for achievement is publication in a peer-reviewed journal. Expectations regarding the likelihood of publication are unknown for studies presented at a national surgical scientific meeting. This study aims to evaluate predictors of manuscript publication arising from abstracts presented at a national surgical scientific meeting. METHODS: Abstracts presented at the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Meeting 2019 were reviewed. Identification of published manuscripts was completed using MedLine, Embase, and Google Scholar 28 months after the presentation to allow for time for publication. Factors evaluated for association with publication included author and abstract measures. Descriptive analyses and multivariable statistics were performed. RESULTS: 724 abstracts (160 podiums, 564 posters) were included. Of the podium presentations, 128 (80%) were published in a median of 4 months after the presentation. On univariable and multivariable analyses, there was no association between publication and abstract topic, gender, degree, number of publications, or H-indices of first and senior authors. 154 (27.3%) poster presentations were published with a median of 13 months. On univariable analysis, there was a statistically significant difference regarding the abstract topic (p = 0.015) and senior author degree (p = 0.01) between published and unpublished posters. Multivariable analysis demonstrated that colorectal surgery (OR 2.52; CI 1.02-6.23) and metabolic/obesity (OR 2.53; CI 1.09-5.84) are associated with an increased odd of publication. There was an inverse association with female senior authors (OR 0.53; CI 0.29-0.98), while additional degrees (e.g., doctorate and/or master's degree) of the senior authors were associated with an increased publication rate (OR 1.80; CI 1.00-3.22). CONCLUSION: 80% of podiums but only 27% of posters were ultimately published. While some predictors of poster publication were noted, it is unclear if these are why these projects fail to publish. Future research is warranted to determine if there are effective strategies to increase poster publication rates.

Risk factors for adverse outcomes following paraesophageal hernia repair among obese patients.

BACKGROUND: Although obesity is an established risk factor for adverse outcomes after paraesophageal hernia repair (PEHR), many obese patients nonetheless receive PEHR. The purpose of this study was to explore risk factors for adverse outcomes of PEHR among this high-risk cohort. We hypothesized that obese patients may have other risk factors for adverse outcomes following PEHR. METHODS: A retrospective study of adult obese patients who underwent minimally invasive PEHR from 2017 to 2019 was performed. Patients were excluded for BMI < 30 or if they had concomitant bariatric surgery at time of PEHR. The primary outcome of interest was a composite adverse outcome (CAO) defined as having any of the four following outcomes after PEHR: persistent GERD > 30 d, persistent dysphagia > 30 d, recurrence, or reoperation. Chi-square and t-test analysis was used to compare demographic and clinical characteristics. Multivariable logistic regression analysis was used to evaluate independent predictors of CAO. RESULTS: In total, 139 patients met inclusion criteria with a median follow-up of 19.7 months (IQR 8.8-81). Among them, 51/139 (36.7%) patients had a CAO: 31/139 (22.4%) had persistent GERD, 20/139 (14.4%) had persistent dysphagia, 24/139 (17.3%) had recurrence, and 6/139 (4.3%) required reoperation. On unadjusted analysis, patients with a CAO were more likely to have a history of prior abdominal surgery (86.3% vs 70.5%, p = 0.04) and were less likely to have undergone a preoperative CT scan (27.5% vs 45.5%, p = 0.04). On multivariable analysis, previous abdominal surgery was independently associated with an increased likelihood of CAO whereas age and preoperative CT scan had a decreased likelihood of CAO. CONCLUSIONS: Although there were adverse outcomes among obese patients, minimally invasive PEHR may be feasible in a subset of patients at specialized centers. These findings may help guide the appropriate selection of obese patients for PEHR.

Multi-society consensus conference and guideline on the treatment of gastroesophageal reflux disease (GERD).

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common diseases in North America and globally. The aim of this guideline is to provide evidence-based recommendations regarding the most utilized and available endoscopic and surgical treatments for GERD. METHODS: Systematic literature reviews were conducted for 4 key questions regarding the surgical and endoscopic treatments for GERD in adults: preoperative evaluation, endoscopic vs surgical or medical treatment, complete vs partial fundoplication, and treatment for obesity (body mass index [BMI] ≥ 35 kg/m2) and concomitant GERD. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed. RESULTS: The consensus provided 13 recommendations. Through the development of these evidence-based recommendations, an algorithm was proposed for aid in the treatment of GERD. Patients with typical symptoms should undergo upper endoscopy, manometry, and pH-testing; additional testing may be required for patients with atypical or extra-esophageal symptoms. Patients with normal or abnormal findings on manometry should consider undergoing partial fundoplication. Magnetic sphincter augmentation or fundoplication are appropriate surgical procedures for adults with GERD. For patients who wish to avoid surgery, the Stretta procedure and transoral incisionless fundoplication (TIF 2.0) were found to have better outcomes than proton pump inhibitors alone. Patients with concomitant obesity were recommended to undergo either gastric bypass or fundoplication, although patients with severe comorbid disease or BMI > 50 should undergo Roux-en-Y gastric bypass for the additional benefits that follow weight loss. CONCLUSION: Using the recommendations an algorithm was developed by this panel, so that physicians may better counsel their patients with GERD. There are certain patient factors that have been excluded from included studies/trials, and so these recommendations should not replace surgeon-patient decision making. Engaging in the identified research areas may improve future care for GERD patients.

Prediction of Upstaging in Ductal Carcinoma in Situ Based on Mammographic Radiomic Features.

Background Improving diagnosis of ductal carcinoma in situ (DCIS) before surgery is important in choosing optimal patient management strategies. However, patients may harbor occult invasive disease not detected until definitive surgery. Purpose To assess the performance and clinical utility of mammographic radiomic features in the prediction of occult invasive cancer among women diagnosed with DCIS on the basis of core biopsy findings. Materials and Methods In this Health Insurance Portability and Accountability Act-compliant retrospective study, digital magnification mammographic images were collected from women who underwent breast core-needle biopsy for calcifications that was performed at a single institution between September 2008 and April 2017 and yielded a diagnosis of DCIS. The database query was directed at asymptomatic women with calcifications without a mass, architectural distortion, asymmetric density, or palpable disease. Logistic regression with regularization was used. Differences across training and internal test set by upstaging rate, age, lesion size, and estrogen and progesterone receptor status were assessed by using the Kruskal-Wallis or χ2 test. Results The study consisted of 700 women with DCIS (age range, 40-89 years; mean age, 59 years ± 10 [standard deviation]), including 114 with lesions (16.3%) upstaged to invasive cancer at subsequent surgery. The sample was split randomly into 400 women for the training set and 300 for the testing set (mean ages: training set, 59 years ± 10; test set, 59 years ± 10; P = .85). A total of 109 radiomic and four clinical features were extracted. The best model on the test set by using all radiomic and clinical features helped predict upstaging with an area under the receiver operating characteristic curve of 0.71 (95% CI: 0.62, 0.79). For a fixed high sensitivity (90%), the model yielded a specificity of 22%, a negative predictive value of 92%, and an odds ratio of 2.4 (95% CI: 1.8, 3.2). High specificity (90%) corresponded to a sensitivity of 37%, positive predictive value of 41%, and odds ratio of 5.0 (95% CI: 2.8, 9.0). Conclusion Machine learning models that use radiomic features applied to mammographic calcifications may help predict upstaging of ductal carcinoma in situ, which can refine clinical decision making and treatment planning. © RSNA, 2022.

A multi-modal exploration of heterogeneous physico-chemical properties of DCIS breast microcalcifications.

Ductal carcinoma in situ (DCIS) is frequently associated with breast calcification. This study combines multiple analytical techniques to investigate the heterogeneity of these calcifications at the micrometre scale. X-ray diffraction, scanning electron microscopy and Raman and Fourier-transform infrared spectroscopy were used to determine the physicochemical and crystallographic properties of type II breast calcifications located in formalin fixed paraffin embedded DCIS breast tissue samples. Multiple calcium phosphate phases were identified across the calcifications, distributed in different patterns. Hydroxyapatite was the dominant mineral, with magnesium whitlockite found at the calcification edge. Amorphous calcium phosphate and octacalcium phosphate were also identified close to the calcification edge at the apparent mineral/matrix barrier. Crystallographic features of hydroxyapatite also varied across the calcifications, with higher crystallinity centrally, and highest carbonate substitution at the calcification edge. Protein was also differentially distributed across the calcification and the surrounding soft tissue, with collagen and ß-pleated protein features present to differing extents. Combination of analytical techniques in this study was essential to understand the heterogeneity of breast calcifications and how this may link crystallographic and physicochemical properties of calcifications to the surrounding tissue microenvironment.