Prenatal exposure to per- and polyfluoroalkyl substances and early childhood adiposity and cardiometabolic health in the Healthy Start study.

BACKGROUND/OBJECTIVES: Observational and experimental studies have suggested that prenatal exposure to per- and polyfluoroalkyl substances (PFAS) can increase childhood adiposity and cardiometabolic disruption. However, most previous studies have used weight-based measures that cannot distinguish between fat mass and lean mass. We evaluated associations of prenatal PFAS exposure with precisely measured body composition and cardiometabolic biomarkers in early childhood. SUBJECTS: 373 eligible mother-infant pairs in the Healthy Start longitudinal cohort. METHODS: We used multiple linear regression and Bayesian kernel machine regression models to estimate associations between five PFAS in maternal mid-pregnancy serum, and early childhood adiposity via air displacement plethysmography. Secondary outcomes included body mass index, waist circumference, and fasting serum lipids, glucose, insulin and adipokines. Models were adjusted for potential confounders and effect modification by child sex was evaluated. RESULTS: The median age of children at assessment was 4.6 years. Prenatal concentration of perfluorooctanoate (PFOA) was positively associated with percent fat mass (0.89% per log2-unit increase, 95% CI: 0.15, 1.64), while perfluorononanoate (PFNA) was positively associated with fat mass index and body mass index. Cardiometabolic markers in blood were generally not associated with prenatal PFAS in this population. Mixture models confirmed the importance of PFNA and PFOA in predicting percent fat mass, while PFNA was most important for fat mass index, body mass index, and waist circumference. There were no significant effects of the five PFAS as a mixture, potentially due to opposing effects of different PFAS. CONCLUSIONS: Our results agree with previous studies showing that prenatal serum concentrations of certain PFAS are positively associated with early childhood adiposity. Notably, associations were stronger for measures incorporating precisely measured fat mass compared to measures of body size or weight. Early life increases in adiposity may precede the development of adverse cardiometabolic health outcomes in children exposed to PFAS during gestation.

Maternal Diet Quality During Pregnancy and Offspring Hepatic Fat in Early Childhood: The Healthy Start Study.

BACKGROUND: Overnutrition in utero may increase offspring risk of nonalcoholic fatty liver disease (NAFLD), but the specific contribution of maternal diet quality during pregnancy to this association remains understudied in humans. OBJECTIVES: This study aimed to examine the associations of maternal diet quality during pregnancy with offspring hepatic fat in early childhood (median: 5 y old, range: 4-8 y old). METHODS: Data were from 278 mother-child pairs in the longitudinal, Colorado-based Healthy Start Study. Multiple 24-h recalls were collected from mothers during pregnancy on a monthly basis (median: 3 recalls, range: 1-8 recalls starting after enrollment), and used to estimate maternal usual nutrient intakes and dietary pattern scores [Healthy Eating Index-2010 (HEI-2010), Dietary Inflammatory Index (DII), and Relative Mediterranean Diet Score (rMED)]. Offspring hepatic fat was measured in early childhood by MRI. Associations of maternal dietary predictors during pregnancy with offspring log-transformed hepatic fat were assessed using linear regression models adjusted for offspring demographics, maternal/perinatal confounders, and maternal total energy intake. RESULTS: Higher maternal fiber intake and rMED scores during pregnancy were associated with lower offspring hepatic fat in early childhood in fully adjusted models [Back-transformed ß (95% CI): 0.82 (0.72, 0.94) per 5 g/1000 kcal fiber; 0.93 (0.88, 0.99) per 1 SD for rMED]. In contrast, higher maternal total sugar and added sugar intakes, and DII scores were associated with higher offspring hepatic fat [Back-transformed ß (95% CI): 1.18 (1.05, 1.32) per 5% kcal/d added sugar; 1.08 (0.99, 1.18) per 1 SD for DII]. Analyses of dietary pattern subcomponents also revealed that lower maternal intakes of green vegetables and legumes and higher intake of "empty calories" were associated with higher offspring hepatic fat in early childhood. CONCLUSIONS: Poorer maternal diet quality during pregnancy was associated with greater offspring susceptibility to hepatic fat in early childhood. Our findings provide insights into potential perinatal targets for the primordial prevention of pediatric NAFLD.

Impact of the COVID-19 pandemic on children's sleep habits: an ECHO study.

BACKGROUND: Sleep in childhood is affected by behavioral, environmental, and parental factors. We propose that these factors were altered during the COVID-19 pandemic. This study investigates sleep habit changes during the pandemic in 528 children 4-12 years old in the US, leveraging data from the Environmental Influences on Child Health Outcomes (ECHO) Program. METHODS: Data collection occurred in July 2019-March 2020 (pre-pandemic) and two pandemic periods: December 2020-April 2021 and May-August 2021. Qualitative interviews were performed in 38 participants. RESULTS: We found no changes in sleep duration, but a shift to later sleep midpoint during the pandemic periods. There was an increase in latency at the first pandemic collection period but no increase in the frequency of bedtime resistance, and a reduced frequency of naps during the pandemic. Qualitative interviews revealed that parents prioritized routines to maintain sleep duration but were more flexible regarding timing. Children from racial/ethnic minoritized communities slept less at night, had later sleep midpoint, and napped more frequently across all collection periods, warranting in-depth investigation to examine and address root causes. CONCLUSIONS: The COVID-19 pandemic significantly impacted children sleep, but parental knowledge of the importance of sleep might have played a significant protective role. IMPACT: During the COVID-19 pandemic, US children changed their sleep habits, going to bed and waking up later, but their sleep duration did not change. Sleep latency was longer. Parental knowledge of sleep importance might have played a protective role. Regardless of data collection periods, children from racial/ethnic minoritized communities slept less and went to bed later. This is one of the first study on this topic in the US, including prospective pre-pandemic qualitative and quantitative data on sleep habits. Our findings highlight the pandemic long-term impact on childhood sleep. Results warrants further investigations on implications for overall childhood health.

Early-life exposure to residential black carbon and childhood cardiometabolic health.

BACKGROUND: Early life exposure to air pollution, such as particulate matter ≤2.5 µm (PM2.5), may be associated with obesity and adverse cardiometabolic health outcomes in childhood. However, the toxicity of PM2.5 varies according to its chemical composition. Black carbon (BC) is a constituent of PM2.5, but few studies have examined its impact on childhood cardiometabolic health. Therefore, we examined relationships between prenatal and early childhood exposure to BC and markers of adiposity and cardiometabolic health in early childhood. METHODS: This study included 578 mother-child pairs enrolled in the Healthy Start study (2009-2014) living in the Denver-metro area. Using a spatiotemporal prediction model, we assessed average residential black carbon levels during pregnancy and in the year prior to the early childhood follow-up visit at approximately 5 years old. We estimated associations between prenatal and early childhood BC and indicators of adiposity and cardiometabolic biomarkers in early childhood (mean 4.8 years; range, 4.0, 8.3), using linear regression. RESULTS: We found higher early childhood BC was associated with higher percent fat mass, fat mass index, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR), and lower leptin and waist circumference at approximately 5 years old, after adjusting for covariates. For example, per interquartile range (IQR) increase in early childhood BC (IQR, 0.49 µg/m3) there was 3.32% higher fat mass (95% CI; 2.05, 4.49). Generally, we did not find consistent evidence of associations between prenatal BC and cardiometabolic health outcomes in early childhood, except for an inverse association between prenatal BC and adiponectin, an adipocyte-secreted hormone typically inversely associated with adiposity. CONCLUSIONS: Higher early childhood, but not in utero, ambient concentrations of black carbon, a component of air pollution, were associated with greater adiposity and altered insulin homeostasis at approximately 5 years old. Future studies should examine whether these changes persist later in life.

An epigenome-wide association study of child appetitive traits and DNA methylation.

The etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4-5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors.

De-implementation of Axillary Dissection in Women With Breast Cancer is Largely Driven By Site-level Contextual Effects.

OBJECTIVE: To assess the contribution of unknown institutional factors (contextual effects) in the de-implementation of cALND in women with breast cancer. SUMMARY OF BACKGROUND DATA: Women included in the National Cancer Database with invasive breast carcinoma from 2012 to 2016 that underwent upfront lumpectomy and were found to have a positive sentinel node. METHODS: A multivariable mixed effects logistic regression model with a random intercept for site was used to determine the effect of patient, tumor, and institutional variables on the risk of cALND. Reference effect measureswere used to describe and compare the contribution of contextual effects to the variation in cALND use to that of measured variables. RESULTS: By 2016, cALND was still performed in at least 50% of the patients in a quarter of the institutions. Black race, younger women and those with larger or hormone negative tumors were more likely to undergo cALND. However, the width of the 90% reference effect measures range for the contextual effects exceeded that of the measured site, tumor, time, and patient demographics, suggesting institutional contextual effects were the major drivers of cALND de-implementation. For instance, a woman at an institution with low-risk of performing cALND would have 74% reduced odds of havinga cALND than if she was treated at a median-risk institution, while a patient at a high-risk institution had 3.91 times the odds. CONCLUSION: Compared to known patient, tumor, and institutional factors, contextual effects had a higher contribution to the variation in cALND use.

Adjuvant Therapy for Stage III Melanoma Without Immediate Completion Lymph Node Dissection.

INTRODUCTION: For patients with stage III melanoma with occult lymph node metastasis, the use of adjuvant therapy is increasing, and completion lymph node dissection (CLND) is decreasing. We sought to evaluate the use of modern adjuvant therapy and outcomes for patients with stage III melanoma who did not undergo CLND. METHODS: Patients with a positive SLNB from 2015 to 2020 who did not undergo CLND were evaluated retrospectively. Nodal recurrence, recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and melanoma-specific survival were evaluated. RESULTS: Among 90 patients, 56 (62%) received adjuvant therapy and 34 (38%) underwent observation alone. Patients who received adjuvant therapy were younger (mean age: 53 vs. 65, p < 0.001) and had higher overall stage (Stage IIIb/c 75% vs. 54%, p = 0.041). Disease recurred in 12 of 34 patients (35%) in the observation group and 11 of 56 patients (20%) in the adjuvant therapy group. The most common first site of recurrence was distant recurrence alone (5/34 patients) in the observation group and nodal recurrence alone (8/90 patients) in the adjuvant therapy group. Despite more adverse nodal features in the adjuvant therapy group, 24-month nodal recurrence rate and RFS were not significantly different between the adjuvant and observation cohorts (nodal recurrence rate: 26% vs. 20%, p = 0.68; RFS: 75% vs. 61%, p = 0.39). Among patients with stage IIIb/c disease, adjuvant therapy was associated with a significantly improved 24-month DMFS (86% vs. 59%, p = 0.04). CONCLUSIONS: In this early report, modern adjuvant therapy in patients who forego CLND is associated with longer DMFS among patients with stage IIIb/c disease.

Ambient air pollution during pregnancy and DNA methylation in umbilical cord blood, with potential mediation of associations with infant adiposity: The Healthy Start study.

BACKGROUND: Prenatal exposure to ambient air pollution has been associated with adverse offspring health outcomes. Childhood health effects of prenatal exposures may be mediated through changes to DNA methylation detectable at birth. METHODS: Among 429 non-smoking women in a cohort study of mother-infant pairs in Colorado, USA, we estimated associations between prenatal exposure to ambient fine particulate matter (PM2.5) and ozone (O3), and epigenome-wide DNA methylation of umbilical cord blood cells at delivery (2010-2014). We calculated average PM2.5 and O3 in each trimester of pregnancy and the full pregnancy using inverse-distance-weighted interpolation. We fit linear regression models adjusted for potential confounders and cell proportions to estimate associations between air pollutants and methylation at each of 432,943 CpGs. Differentially methylated regions (DMRs) were identified using comb-p. Previously in this cohort, we reported positive associations between 3rd trimester O3 exposure and infant adiposity at 5 months of age. Here, we quantified the potential for mediation of that association by changes in DNA methylation in cord blood. RESULTS: We identified several DMRs for each pollutant and period of pregnancy. The greatest number of significant DMRs were associated with third trimester PM2.5 (21 DMRs). No single CpGs were associated with air pollutants at a false discovery rate <0.05. We found that up to 8% of the effect of 3rd trimester O3 on 5-month adiposity may be mediated by locus-specific methylation changes, but mediation estimates were not statistically significant. CONCLUSIONS: Differentially methylated regions in cord blood were identified in association with maternal exposure to PM2.5 and O3. Genes annotated to the significant sites played roles in cardiometabolic disease, immune function and inflammation, and neurologic disorders. We found limited evidence of mediation by DNA methylation of associations between third trimester O3 exposure and 5-month infant adiposity.

The Volume-Outcome Effect Calls for Centralization of Care in Esophageal Adenocarcinoma: Results From a Large National Cancer Registry.

INTRODUCTION: Using the National Cancer Database, we assessed the relationship between facility overall esophageal adenocarcinoma (EAC) case volume and survival. METHODS: We categorized facilities into volume quintiles based on annual EAC patient volume and performed a multivariable Cox proportional hazards regression between facility patient volume and survival. RESULTS: In a cohort of 116,675 patients, facilities with higher vs lower (≥25 vs 1-4 cases) annual EAC patient volume demonstrated improved survival (adjusted hazard ratio: 0.80. 95% confidence interval: 0.70-0.91). DISCUSSION: This robust volume-outcome effect calls for centralization of care for EAC patients at high annual case volume facilities.

Controversial Role of Adjuvant Therapy in Node-Negative Invasive Intraductal Papillary Mucinous Neoplasm.

BACKGROUND: Adjuvant chemotherapy and/or chemoradiation [chemo(radiation)] is considered the standard of care for resected patients with pancreatic adenocarcinoma. However, invasive carcinoma arising from an intraductal papillary mucinous neoplasm (IPMN) seems to have different biologic behavior and prognosis. Retrospective data suggest a survival benefit of adjuvant chemo(radiation) for resected invasive IPMNs with metastatic nodal disease; however, it is unclear whether this remains valid for node-negative patients. PATIENTS AND METHODS: To compare the outcome of patients with invasive IPMNs who received adjuvant chemo(radiation) with that of those treated with surgery alone, we queried the National Cancer Database regarding data of patients who underwent pancreatic resection for invasive IPMN between 2006 and 2015. A propensity score analysis was conducted to balance covariates between treatment groups. RESULTS: For the study, 492 patients were eligible, of whom 267 (54.3%) received adjuvant chemo(radiation). Estimated 1- and 3-year overall survival rates were 88.9% and 73.5% versus 93.2% and 72.8% for patients who did or did not receive adjuvant chemo(radiation), respectively. Among patients with negative nodal stage, there was no difference in overall survival between patients who received versus patients who did not receive adjuvant chemo(radiation) (P = 0.973). In contrast, among patients with positive nodal disease, those who received adjuvant chemo(radiation) had significantly better OS compared with those who did not (P = 0.001). CONCLUSIONS: In patients with resected invasive IPMNs, adjuvant chemo(radiation) was associated with significantly improved overall survival only in presence of nodal metastases. This finding can help clinicians to select adjuvant treatment in a patient-tailored fashion.

Induction Chemotherapy Plus Neoadjuvant Chemoradiation for Esophageal and Gastroesophageal Junction Adenocarcinoma.

BACKGROUND: Neoadjuvant chemotherapy with concurrent radiotherapy (nCRT) is an accepted treatment regimen for patients with potentially curable esophageal and gastroesophageal junction (GEJ) adenocarcinoma. The purpose of this study is to evaluate whether induction chemotherapy (IC) before nCRT is associated with improved pathologic complete response (pCR) and overall survival (OS) when compared with patients who received nCRT alone for esophageal and GEJ adenocarcinoma. METHODS: Using the National Cancer Database (NCDB), patients who received nCRT and curative-intent esophagectomy for esophageal or GEJ adenocarcinoma from 2006 to 2015 were included. Chemotherapy and radiation therapy start dates were used to define cohorts who received IC before nCRT (IC + nCRT) versus those who only received concurrent nCRT before surgery. Propensity weighting was conducted to balance patient, disease, and facility covariates between groups. RESULTS: 12,460 patients met inclusion criteria, of whom 11,880 (95%) received nCRT and 580 (5%) received IC + nCRT. Following propensity weighting, OS was significantly improved among patients who received IC + nCRT versus nCRT (HR 0.82; 95% CI 0.74-0.92; p < 0.001) with median OS for the IC + nCRT cohort of 3.38 years versus 2.45 years for nCRT. For patients diagnosed from 2013 to 2015, IC + nCRT was also associated with higher odds of pCR compared with nCRT (OR 1.59; 95% CI 1.14-2.21; p = 0.007). CONCLUSION: IC + nCRT was associated with a significant OS benefit as well as higher pCR rate in the more modern patient cohort. These results merit consideration of a sufficiently powered prospective multiinstitutional trial to further evaluate these observed differences.

Implementation of Minimally Invasive Pancreaticoduodenectomy at Low and High-Volume Centers.

BACKGROUND: There is a need to better define the safety of implementing the use of minimally invasive pancreaticoduodenectomy (MIPD) in order to provide evidence for safe application. The objective of this study was to evaluate the mortality associated with the implementation of MIPD across low and high-volume facilities using the National Cancer Database (NCDB). METHODS: Patients in the NCDB with pancreatic cancer diagnosed from 2010-2016 undergoing MIPD were selected. Cumulative MIPD volume for each facility was calculated from the number of MIPD cases performed each year prior to and including the year of a patient's operation. A random effects logistic regression model was used to examine the adjusted association between log-transformed cumulative MIPD volume and 90-day mortality. RESULTS: After controlling for patient, tumor and facility-related variables, there was decreased 90-day mortality as the cumulative MIPD volume increased (OR 0.81; 95% CI 0.69-0.95; P = 0.009). Average annual open pancreaticoduodenectomy (PD) volume was independently protective throughout the implementation phase (OR 0.98; 95% CI 0.97-0.99; P = 0.049). This equates to an average predicted probability of 90-day mortality for the first 5 cumulative MIPD cases of 7.51% at a low-volume facility (5 open PDs per year) versus 4.39% at a high-volume facility (50 open PDs per year). CONCLUSIONS: Using the NCDB, 90-day mortality following MIPD decreased with higher cumulative facility MIPD case volume. Although higher cumulative MIPD case volume was associated with reduced 90-day mortality at both low and high-volume facilities, the higher mortality during the implementation of MIPD is magnified at low-volume facilities. This retrospective analysis demonstrates that MIPD can be safely implemented with low mortality at facilities with high-volume open PD programs.

Exposure to ambient air pollution during pregnancy and inflammatory biomarkers in maternal and umbilical cord blood: The Healthy Start study.

BACKGROUND: Air pollution exposure during pregnancy has been associated with adverse pregnancy and birth outcomes. Inflammation has been proposed as a potential link. We estimated associations between air pollution exposure during pregnancy and inflammatory biomarkers in maternal and cord blood. We evaluated whether maternal inflammation was associated with infant outcomes. METHODS: Among 515 mother-infant dyads in the Healthy Start study (2009-2014), trimester-long, 7- and 30-day average concentrations of particulate matter ≤2.5 µm (PM2.5) and ozone (O3) during pregnancy were estimated, using inverse-distance-weighted interpolation. Inflammatory biomarkers were measured in maternal blood in mid-pregnancy (C-reactive protein [CRP], Interleukin [IL]-6, and tumor necrosis factor-α [TNFα]) and in cord blood at delivery (CRP, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 [MCP-1], and TNFα). We used linear regression to estimate associations between pollutants and inflammatory biomarkers and maternal inflammatory biomarkers and infant weight and body composition. RESULTS: There were positive associations between PM2.5 during certain exposure periods and maternal IL-6 and TNFα. There were negative associations between recent O3 and maternal CRP, IL-6, and TNFα and positive associations between trimester-long O3 exposure and maternal inflammatory biomarkers, though some 95% confidence intervals included the null. Patterns were inconsistent for associations between PM2.5 and O3 and cord blood inflammatory biomarkers. No consistent associations between maternal inflammatory biomarkers and infant outcomes were identified. CONCLUSIONS: Air pollution exposure during pregnancy may impact maternal inflammation. Further investigations should examine the health consequences for women and infants of elevated inflammatory biomarkers associated with air pollution exposure during pregnancy.

Understanding gastroesophageal reflux disease in children.

ABSTRACT: Gastroesophageal reflux disease (GERD) is a common disorder with increasing prevalence in children. The diagnosis and management of GERD remains a challenge because of its nonspecific symptomatology from infancy through adolescence. Certain presenting alarm symptoms warrant a further, more extensive workup. Treatment of pediatric GERD begins with lifestyle and nonpharmacologic management, including postural adjustments, dietary changes, and weight loss if indicated. Pharmacologic interventions can be prescribed to relieve symptoms for patients whose disease does not respond to lifestyle management. Patients with refractory symptoms can be managed with surgical intervention. Complications may arise if GERD remains untreated, ranging from worsening oral health to failure to thrive.

Utility of Quantitative SPECT/CT Lymphoscintigraphy in Guiding Sentinel Lymph Node Biopsy in Head and Neck Melanoma.

PURPOSE: To investigate the use of advanced SPECT/CT quantification in guiding surgical selection of positive sentinel lymph nodes (SLNs) in head and neck melanoma. METHODS: We retrospectively reviewed data from patients with cutaneous head and neck melanoma who underwent lymphoscintigraphy with SPECT/CT prior to SLN biopsy (SLNB). Quantification of radiotracer uptake from SPECT/CT data was performed using in-house segmentation software. SLNs identified using SPECT/CT were compared to SLNs identified surgically using an intraoperative γ-probe. A radioactivity count threshold using SPECT/CT for detecting a positive SLN was calculated. RESULTS: One hundred and five patients were included. Median number of SLNs detected was 3/patient with SPECT/CT and 2/patient with intraoperative γ-probe. The hottest node identified by SPECT/CT and intraoperative γ-probe were identical in 85% of patients. All 20 histologically positive SLNs were identified by SPECT/CT and γ-probe. On follow-up, all nodal recurrences occurred at lymph node levels with the hottest node identified by SPECT/CT and either the hottest or second hottest node identified by γ-probe during SLNB. Using our data, a SPECT/CT radioactivity count threshold of 20% would eliminate the unnecessary removal of 11% of SPECT/CT identified nodes and 12% of intraoperatively detected nodes. CONCLUSION: Utilizing SPECT/CT quantification, we propose that a radioactivity count threshold can be developed to help guide the selective removal of lymph nodes in head and neck SLNB. Furthermore, the nodal level containing the hottest node identified by SPECT/CT quantification must be thoroughly investigated for SLNs and undergo careful follow-up and surveillance for recurrence.

Dextrose-Containing Carrier Solution for Hyperthermic Intraperitoneal Chemotherapy: Increased Intraoperative Hyperglycemia and Postoperative Complications.

PURPOSE: Intraoperative hyperglycemia is associated with infectious complications in general surgery patients. This study aimed to determine if the use of lactated Ringer's (LR) carrier solution during hyperthermic intraperitoneal chemotherapy (HIPEC) would lower the incidence of intraoperative hyperglycemia and improve postoperative outcomes when compared with a standard 1.5% dextrose peritoneal dialysate carrier solution. PATIENTS AND METHODS: This is a retrospective cohort study of 134 patients who underwent HIPEC at the University of Colorado. Perioperative glucose levels and outcomes were compared between patients who were perfused with 1.5% dextrose peritoneal dialysate carrier solution (n = 68) versus LR carrier solution (n = 66). RESULTS: The study population consisted of patients undergoing HIPEC for appendiceal (50%), colorectal (34%), mesothelioma (8%), and ovarian cancer (5%). Intraoperative severe hyperglycemia (glucose ≥ 180 mg/dL) was significantly more common among patients perfused with a dextrose-containing carrier solution versus those perfused with LR (88% vs. 21%; p < 0.001). Patients in the dextrose cohort had significantly more severe complications (39% vs. 12%; p = 0.034), infectious complications (35% vs. 15%; p = 0.011), and organ space infections (18% vs. 5%: p = 0.026) than the LR cohort. On multivariable analysis, dextrose-containing carrier solution was significantly associated with an increased risk of postoperative infectious complications (HR 5.16; p = 0.006). CONCLUSIONS: Intraoperative hyperglycemia is common when dextrose-containing carrier solution is used during HIPEC, and severe intraoperative hyperglycemia is strongly associated with an increased risk for infectious of complications following HIPEC. LR carrier solution should be routinely used to reduce intraoperative hyperglycemia and its associated risks.

Conversion to open surgery during minimally invasive esophagectomy portends worse short-term outcomes: an analysis of the National Cancer Database.

OBJECTIVE: The objectives were to determine factors associated with conversion to open surgery in patients with esophageal cancer who underwent minimally invasive esophagectomy (MIE, including laparo-thoracoscopic and robotic) and the impact of conversion to open surgery on patient outcomes. METHODS: We included patients from the National Cancer Database with esophageal and gastroesophageal junction cancer who underwent MIE from 2010 to 2015. Patient-, tumor-, and facility-related characteristics as well as short-term and oncologic outcomes were compared between patients who were converted to open surgery and those who underwent successful MIE without conversion to open surgery. Multivariable logistic regression models were used to analyze risk factors for conversion to open surgery from attempted MIE. RESULTS: 7306 patients underwent attempted MIE. Of these patients, 82 of 1487 (5.2%) robotic-assisted esophagectomies were converted to open, compared to 691 of 5737 (12.0%) laparo-thoracoscopic esophagectomies (p < 0.001). Conversion rates decreased significantly over the study period (ptrend = 0.010). Patient age, tumor size, and nodal involvement were independently associated with conversion. Facility minimally invasive cumulative volume and robotic approach were associated with decreased conversion rates. Patients whose MIEs were converted had increased 90-day mortality [Odds Ratio (OR) 1.49; 95% Confidence Interval (CI) 1.10, 2.02], prolonged hospital stay (OR 1.39; 95% CI 1.17, 1.66), and higher rates of unplanned readmission (OR 1.67; 95% CI 1.27, 2.20). No significant differences were found in surgical margins or number of lymph nodes harvested. CONCLUSION: Patients undergoing attempted MIE requiring conversion to open surgery had significantly worse short-term outcomes including postoperative mortality. Patient factors and hospital experience contribute to conversion rates. These findings should inform surgeons and patients considering esophagectomy for cancer.

Increasing omission of radiation therapy and sentinel node biopsy in elderly patients with early stage, hormone-positive breast cancer.

Prospective evidence demonstrates that there is limited benefit of axillary staging with sentinel lymph node biopsy (SLNB) or radiation therapy (RT) in patients over age 70 with clinical stage I, hormone-positive breast cancer. The clinical impact of this literature is unknown. Our hypothesis is that omission of SLNB and RT has increased over time in these patients, and patient and tumor characteristics can predict when omission strategies are used. A single-center tumor registry was queried for all patients over age 70 with ER+, Her2/neu-negative, clinical T1N0 invasive breast cancer from 2009 to 2017, who underwent breast conservation (n = 141). Date of treatment, age, tumor characteristics, use of SLNB, and use of RT were evaluated. The trend of treatment strategy over time was evaluated. Multivariable analysis was performed on the subgroup of patients after publication of the long-term follow-up CALGB 9343 data1 . Patients undergoing treatment with omission of RT and SLNB increased over the study period (P = .0006). Patients who did not receive RT were older (78.76 years ± 5.48 vs 73.37 ± 3.63, P < .01). There was no difference between tumor grade and size between uses of RT. Of patients who received SLNB (n = 84), only 3 (3.5%) had a positive LN. On multivariable analysis of patients who were treated after publication of the CALGB 9343 data (2014-2017), only age was predictive of being treated with RT (OR, 0.77; 95% CI, 0.67-0.88). Omission of both RT and SLNB are increasing in clinical practice in appropriately selected patients. The likelihood that patients are offered omission of these interventions increases with age. Low nodal positivity rates suggest that this strategy may be underutilized. Tumor grade and size were not predictive of omission of RT in this group of low-risk patients. Long-term data are needed as these approaches are increasingly adopted.

Comparing Short-term and Oncologic Outcomes of Minimally Invasive Versus Open Pancreaticoduodenectomy Across Low and High Volume Centers.

OBJECTIVE: To compare short-term and oncologic outcomes of patients with cancer who underwent open pancreaticoduodenectomy (OPD) versus minimally invasive pancreaticoduodenectomy (MIPD) using the National Cancer Database. SUMMARY BACKGROUND DATA: MIPD, including laparoscopic and robotic approaches, has continued to gain acceptance despite prior reports of increased short-term mortality when compared with OPD. METHODS: Patients with pancreatic cancer diagnosed from 2010 to 2015 undergoing curative intent resection were selected from the National Cancer Database. Patients submitted to OPD were compared with those submitted to MIPD. Laparoscopic and robotic approaches were included in the MIPD cohort. The primary outcome was 90-day mortality; secondary outcomes included 30-day mortality, hospital length of stay, unplanned 30-day readmission, surgical margins, number of lymph nodes harvested, and receipt of adjuvant chemotherapy. Propensity score-weighted random effects logistic regression models were used to examine the adjusted association between surgical approach and the specified outcomes. RESULTS: Between 2010 and 2015, 22,013 patients underwent OPD or MIPD for pancreatic cancer and 3754 (17.1%) were performed minimally invasively. On multivariable analysis, there was no difference in 90-day mortality between MIPD and OPD (OR, 0.92; 95% CI, 0.75-1.14). Patients undergoing MIPD were less likely to stay in the hospital for a prolonged time (OR, 0.75; 95% CI, 0.68-0.82). 30-day mortality, unplanned readmissions, margins, lymph nodes harvested, and receipt of adjuvant chemotherapy were equivalent between groups. Regardless of surgical approach, patients operated on at high volume centers had reduced 90-day mortality. CONCLUSION: Patients selected to receive MIPD for cancer have equivalent short-term and oncologic outcomes, when compared with patients who undergo OPD.

Postbiopsy Pigmentation is Prognostic in Head and Neck Melanoma.

PURPOSE: To assess postbiopsy pigmentation (PBP) as a prognostic feature in patients with cutaneous head and neck (H&N) melanoma. METHODS: Retrospective review of patients undergoing sentinel lymph node biopsy (SLNB) for H&N melanoma (1998-2018). PBP was defined as visible remaining pigment at the scar or biopsy site that was documented on physical exam by both a medical oncologist and a surgeon at initial consultation. Variables associated with disease-free survival (DFS) and overall survival (OS) were analyzed using multivariable Cox proportional hazards models. RESULTS: Among 300 patients, 34.3% (n = 103) had PBP and 44.7% (n = 134) had microscopic residual disease on final pathology after wide local excision. Prognostic factors associated with DFS included advanced age, tumor depth, ulceration, PBP, and positive SLNB (p < 0.05). Patients with PBP fared worse than their counterparts without PBP in 5-year DFS [44.1% (31.1-56.3%) vs. 73.0% (64.1-80.0%); p < 0.001] and 5-year OS [65.0% (50.0-76.6%) vs. 83.6% (75.7-89.2%); p = 0.005]. After multivariable adjustment, PBP remained associated with shorter DFS [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.01-2.93; p = 0.047], but was not prognostic of OS. CONCLUSIONS: In patients with H&N melanoma, PBP is associated with significantly shorter DFS. Patients with PBP may warrant greater consideration for SLNB and closer postoperative surveillance.