ETHYLENE RESPONSE FACTOR 070 inhibits flowering in Pak-choi by indirectly impairing BcLEAFY expression.

APETALA2/ethylene responsive factors respond to ethylene and participate in many biological and physiological processes, such as plant morphogenesis, stress resistance, and hormone signal transduction. Ethylene responsive factor 070 (BcERF070) is important in flowering. However, the underlying molecular mechanisms of BcERF070 in floral transition in response to ethylene signaling have not been fully characterized. Herein, we explored the function of BcERF070 in Pak-choi [Brassica campestris (syn. Brassica rapa) ssp. chinensis]. Ethylene treatment induced BcERF070 expression and delayed flowering in Pak-choi. Silencing of BcERF070 induced flowering in Pak-choi. BcERF070 interacted with major latex protein-like 328 (BcMLP328), which forms a complex with helix-loop-helix protein 30 (BcbHLH30) to enhance the transcriptional activity of BcbHLH30 on LEAFY (BcLFY), ultimately promoting flowering. However, BcERF070 impaired the BcMLP328-BcbHLH30 complex activation of LEAFY (BcLFY), ultimately inhibiting flowering in Pak-choi. BcERF070 directly promoted the expression of the flowering inhibitor gene B-box 29 (BcBBX29) and delayed flowering by reducing FLOWERING LOCUS T (BcFT) expression. These results suggest that BcERF070 mediates ethylene-reduced flowering by impairing the BcMLP328-BcbHLH30 complex activation of BcLFY and by directly promoting the gene expression of the flowering inhibition factor BcBBX29 to repress BcFT expression. The findings contribute to understanding the molecular mechanisms underlying floral transition in response to ethylene in plants.

QTL mapping and candidate gene analysis reveal two major loci regulating green leaf color in non-heading Chinese cabbage.

KEY MESSAGE: Two major-effect QTL GlcA07.1 and GlcA09.1 for green leaf color were fine mapped into 170.25 kb and 191.41 kb intervals on chromosomes A07 and A09, respectively, and were validated by transcriptome analysis. Non-heading Chinese cabbage (NHCC) is a leafy vegetable with a wide range of green colors. Understanding the genetic mechanism behind broad spectrum of green may facilitate the breeding of high-quality NHCC. Here, we used F2 and F7:8 recombination inbred line (RIL) population from a cross between Wutacai (dark-green) and Erqing (lime-green) to undertake the genetic analysis and quantitative trait locus (QTL) mapping in NHCC. The genetic investigation of the F2 population revealed that the variation of green leaf color was controlled by two recessive genes. Six pigments associated with green leaf color, including total chlorophyll, chlorophyll a, chlorophyll b, total carotenoids, lutein, and carotene were quantified and applied for QTL mapping in the RIL population. A total of 7 QTL were detected across the whole genome. Among them, two major-effect QTL were mapped on chromosomes A07 (GlcA07.1) and A09 (GlcA09.1) corresponding to two QTL identified in the F2 population. The QTL GlcA07.1 and GlcA09.1 were further fine mapped into 170.25 kb and 191.41 kb genomic regions, respectively. By comparing gene expression level and gene annotation, BraC07g023810 and BraC07g023970 were proposed as the best candidates for GlcA07.1, while BraC09g052220 and BraC09g052270 were suggested for GlcA09.1. Two InDel molecular markers (GlcA07.1-BcGUN4 and GlcA09.1-BcSG1) associated with BraC07gA023810 and BraC09g052220 were developed and could effectively identify leaf color in natural NHCC accessions, suggesting their potential for marker-assisted leaf color selection in NHCC breeding.

Comparative Transcriptome Analysis Reveals the Protective Role of Melatonin during Salt Stress by Regulating the Photosynthesis and Ascorbic Acid Metabolism Pathways in Brassica campestris.

Salinity stress is a type of abiotic stress which negatively affects the signaling pathways and cellular compartments of plants. Melatonin (MT) has been found to be a bioactive compound that can mitigate these adverse effects, which makes it necessary to understand the function of MT and its role in salt stress. During this study, plants were treated exogenously with 100 µM of MT for 7 days and subjected to 200 mM of salt stress, and samples were collected after 1 and 7 days for different indicators and transcriptome analysis. The results showed that salt reduced chlorophyll contents and damaged the chloroplast structure, which was confirmed by the downregulation of key genes involved in the photosynthesis pathway after transcriptome analysis and qRT-PCR confirmation. Meanwhile, MT increased the chlorophyll contents, reduced the electrolyte leakage, and protected the chloroplast structure during salt stress by upregulating several photosynthesis pathway genes. MT also decreased the H2O2 level and increased the ascorbic acid contents and APX activity by upregulating genes involved in the ascorbic acid pathway during salt stress, as confirmed by the transcriptome and qRT-PCR analyses. Transcriptome profiling also showed that 321 and 441 DEGs were expressed after 1 and 7 days of treatment, respectively. The KEGG enrichment analysis showed that 76 DEGs were involved in the photosynthesis pathway, while 35 DEGs were involved in the ascorbic acid metabolism pathway, respectively. These results suggest that the exogenous application of MT in plants provides important insight into understanding MT-induced stress-responsive mechanisms and protecting Brassica campestris against salt stress by regulating the photosynthesis and ascorbic acid pathway genes.

Surgery-mediated tumor-promoting effects on the immune microenvironment.

Surgical resection continues to be the mainstay treatment for solid cancers even though chemotherapy and immunotherapy have significantly improved patient overall survival and progression-free survival. Numerous studies have shown that surgery induces the dissemination of circulating tumor cells (CTCs) and that the resultant inflammatory response promotes occult tumor growth and the metastatic process by forming a supportive tumor microenvironment (TME). Surgery-induced platelet activation is one of the initial responses to a wound and the formation of fibrin clots can provide the scaffold for recruited inflammatory cells. Activated platelets can also shield CTCs to protect them from blood shear forces and promote CTCs evasion of immune destruction. Similarly, neutrophils are recruited to the fibrin clot and enhance cancer metastatic dissemination and progression by forming neutrophil extracellular traps (NETs). Activated macrophages are also recruited to surgical sites to facilitate the metastatic spread. More importantly, the body's response to surgical insult results in the recruitment and expansion of immunosuppressive cell populations (i.e. myeloid-derived suppressor cells and regulatory T cells) and in the suppression of natural killer (NK) cells that contribute to postoperative cancer recurrence and metastasis. In this review, we seek to provide an overview of the pro-tumorigenic mechanisms resulting from surgery's impact on these cells in the TME. Further understanding of these events will allow for the development of perioperative therapeutic strategies to prevent surgery-associated metastasis.

BcMYB111 Responds to BcCBF2 and Induces Flavonol Biosynthesis to Enhance Tolerance under Cold Stress in Non-Heading Chinese Cabbage.

Flavonols have been shown to respond to a variety of abiotic stresses in plants, including cold stress. Higher total flavonoid content was found in non-heading Chinese cabbage (NHCC, Brassica campestris (syn. Brassica rapa) ssp. chinensis) after cold stress. A non-targeted metabolome analysis showed a significant increase in flavonol content, including that of quercetin and kaempferol. Here, we found that an R2R3-MYB transcription factor, BcMYB111, may play a role in this process. BcMYB111 was up-regulated in response to cold treatment, with an accompanying accumulation of flavonols. Then, it was found that BcMYB111 could regulate the synthesis of flavonols by directly binding to the promoters of BcF3H and BcFLS1. In the transgenic hairy roots of NHCC or stable transgenic Arabidopsis, overexpression of BcMYB111 increased flavonol synthesis and accumulation, while these were reduced in virus-induced gene silencing lines in NHCC. After cold stress, the higher proline content and lower malondialdehyde (MDA) content showed that there was less damage in transgenic Arabidopsis than in the wild-type (WT). The BcMYB111 transgenic lines performed better in terms of antioxidant capacity because of their lower H2O2 content and higher superoxide dismutase (SOD) and peroxidase (POD) enzyme activities. In addition, a key cold signaling gene, BcCBF2, could specifically bind to the DRE element and activate the expression of BcMYB111 in vitro and in vivo. The results suggested that BcMYB111 played a positive role in enhancing the flavonol synthesis and cold tolerance of NHCC. Taken together, these findings reveal that cold stress induces the accumulation of flavonols to increase tolerance via the pathway of BcCBF2-BcMYB111-BcF3H/BcFLS1 in NHCC.

Access Denied: Inequities in Clinical Trial Enrollment for Pancreatic Cancer.

BACKGROUND: The influence of social determinants of health (SDH) on participation in clinical trials for pancreatic cancer is not well understood. In this study, we describe trends and identify disparities in pancreatic cancer clinical trial enrollment. PATIENTS AND METHODS: This is a retrospective study of stage I-IV pancreatic cancer patients in the 2004-2016 National Cancer Database. Cohort was stratified into those enrolled in clinical trials during first course of treatment versus not enrolled. Bivariate analysis and logistic regression were used to understand the relationship between SDH and clinical trial participation. RESULTS: A total of 1127 patients (0.4%) enrolled in clinical trials versus 301,340 (99.6%) did not enroll. Enrollment increased over the study period (p < 0.001), but not for Black patients or patients on Medicaid. The majority enrolled had metastatic disease (65.8%). On multivariate analysis, in addition to year of diagnosis (p < 0.001), stage (p < 0.001), and Charlson score (p < 0.001), increasing age [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.96-0.97], non-white race (OR 0.54, CI 0.44-0.66), living in the South (OR 0.42, CI 0.35-0.51), and Medicaid, lack of insurance, or unknown insurance (0.41, CI 0.31-0.53) were predictors of lack of participation. Conversely, treatment at an academic center (OR 6.36, CI 5.4-7.4) and higher neighborhood education predicted enrollment (OR 2.0, CI 1.55-2.67 for < 7% with no high school degree versus > 21%). DISCUSSION: Age, race, insurance, and geography are barriers to clinical trial enrollment for pancreatic cancer patients. While overall enrollment increased, Black patients and patients on Medicaid remain underrepresented. After adjusting for cancer-specific factors, SDH are still associated with clinical trial enrollment, suggesting need for targeted interventions.

Beta-blockers and Ambulatory Inotropic Therapy.

BACKGROUND: Continuous infusion of ambulatory inotropic therapy (AIT) is increasingly used in patients with end-stage heart failure (HF). There is a paucity of data concerning the concomitant use of beta-blockers (BB) in these patients. METHODS: We retrospectively reviewed all patients discharged from our institution on AIT. The cohort was stratified into 2 groups based on BB use. The 2 groups were compared for differences in hospitalizations due to HF, ventricular arrhythmias and ICD therapies (shock or antitachycardia pacing). RESULTS: Between 2010 and 2017, 349 patients were discharged on AIT (95% on milrinone); 74% were males with a mean age of 61 ± 14 years. BB were used in 195 (56%) patients, whereas 154 (44%) did not receive these medications. Patients in the BB group had longer duration of AIT support compared to those in the non-BB group (141 [1-2114] vs 68 [1-690] days). After adjusting for differences in baseline characteristics and indication for AIT, patients in the BB group had significantly lower rates of hospitalizations due to HF (hazard ratio [HR] 0.61 (0.43-0.86); P = 0.005), ventricular arrhythmias (HR 0.34 [0.15-0.74]; P = 0.007) and ICD therapies (HR 0.24 [0.07-0.79]; P = 0.02). CONCLUSION: In patients with end-stage HF on AIT, the use of BB with inotropes was associated with fewer hospitalizations due to HF and fewer ventricular arrhythmias.

Does CT scanning after pancreatoduodenectomy reduce readmission rates: an analysis of 900 resections at a high-volume center.

BACKGROUND: Pancreatoduodenectomy (PD) remains associated with significant complication and readmission rates. Infection constitutes a significant proportion of morbidity. We aim to evaluate whether CT scans performed prior to discharge for suspected infection prevents readmission. METHODS: A retrospective review of patients undergoing PD at a tertiary referral center from 2010 to 2018. RESULTS: A total of 982 patients underwent PD: 74% had no clinical infection at the index admission. Of the non-infected patients, 59% exhibited leukocytosis, 27% underwent a CT scan, and 33.6% were readmitted. Of the non-infected patients, 148 (20.3%) experienced major complications, and this was the strongest predictor of readmission (OR: 10.5, [95% CI: 6.5-17], p = 0.0001). In the non-infected patients who had major complications, CT scanning was predictive of lower risk of readmission (OR: 0.38, [95% CI: 0.17-0.83], p = 0.015). Leukocytosis was also found to be predictive of lower risk of readmission (OR: 0.42, [95% CI: 0.18-0.98], p = 0.044). These findings did not hold true for those who had yet to experience major complications on their index admission. CONCLUSION: CT scanning without evidence of infection was associated with reduction of readmission in the cohort with major complications and showed a trend towards preventing readmission in the overall cohort. Development of clinical algorithms to maximize the utility of this test is warranted.

Myths, misconceptions, and hesitancy in people residing in Qatar toward mRNA COVID-19 vaccines: An experience exchange from Qatar University health center.

The hesitancy in taking COVID-19 vaccines is a complex process influenced by several factors, including individual, social, and cultural. Health literacy and community awareness around mRNA COVID-19 vaccines are critical for successfully combating the pandemic. Healthcare professionals, including family physicians and nurses, can help increase community awareness and mitigate some misconceptions and hesitancy regarding mRNA COVID-19 vaccines in people's attitudes. Therefore, in this study, we aimed to explore how the interaction between an individual's social identities such as gender, ethnicity, culture, knowledge, and belief impact their hesitancy and attitudes toward mRNA COVID-19 vaccines. We aimed to describe our experience in dealing with people residing in Qatar from the perspective of healthcare practitioners from the Qatar University Health Center during the period when mRNA COVID-19 vaccines was introduced in a time frame of 6 months (April to October, 2021). We identified several factors associated with the reluctance to receive mRNA COVID-19 vaccines once vaccination services were available, affordable, and accessible to everyone in Qatar (Table 1). Most individuals were hesitant and refused to take mRNA COVID-19 vaccines owing to the unjustified myths and fear about potential side effects of vaccines in general and unknown long-term effects of vaccination, especially among women who were uneducated. We believe we have been able to put forth a fair, unbiased, and balanced argument between an individual's right to take or refuse the vaccine and the overall benefits to the public and community health in terms of the overall community immunity when the vast majority of the population will be vaccinated. Our experience could assist in developing culturally sensitive and tailored community outreach programs to increase community awareness as it is the cornerstone on which public health can fight the irrational myths, fear, misconceptions, vaccine hesitancy, and improve vaccination coverages. Moreover, our shared experiences might be able to better prepare future launching of pandemic vaccination campaigns in order to minimize vaccine hesitancy.

Oncologic Outcomes After Robotic Pancreatic Resections Are Not Inferior to Open Surgery.

OBJECTIVE: Compare oncologic outcomes after open and robotic pancreatic resections for pancreatic adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: Receipt of adjuvant chemotherapy improves survival after resected PDAC. Complications after pancreatectomy have been shown to prohibit the administration of adjuvant chemotherapy and survival. We examined the effect of surgical approach on receipt of adjuvant chemotherapy, complications, and overall survival after pancreatectomy. METHODS: A single-institution retrospective review of all patients with PDAC who underwent robotic or open pancreatectomy from 2011 to 2016 with 24-month follow-up. RESULTS: Four hundred fifty-six patients underwent resection: 226 robotic and 230 open. No significant difference was identified in major complications or receipt of adjuvant chemotherapy between robotic and open pancreatectomy, nor was approach an independent predictor of these outcomes. Robotic pancreatectomy patients had a shorter length of stay than patients who underwent open pancreatectomy (7 days vs 9 days; P < 0.001). Additionally, wound infection rate (32.3% vs 12.4%, P < 0.0001) and transfusion (39.6% vs 12.4%, P < 0.0001) was improved in robotic pancreatectomy group with no differences in perioperative mortality. Improved median overall survival approached statistical significance for the robotic cohort (25.6 months vs 23.9 months; P = 0.055); however, on multivariable analysis the robotic approach predicted overall survival, (hazard ratio 0.77, P = 0.041). Robotic approach was an independent predictor of decreased blood loss and less transfusions than the open approach. CONCLUSIONS: Robotic pancreatectomy was not inferior compared to open pancreatectomy in a high-volume experienced center for oncologic outcomes and due to decreased blood loss and transfusion may have improved survival.

Hormone receptor-positive breast cancer and black race: does sex matter?

PURPOSE: Black breast cancer patients have worse clinical outcomes than their White counterparts. There are few studies comparing clinical outcomes between Black male breast cancer (MBC) and female breast cancer (FBC) patients. The objective of this study is to examine differences in presentation, treatment, and mortality between Black MBC and FBC. METHODS: The National Cancer Database was queried for all Black MBC and FBC patients, ages 18-90, with hormone receptor-positive breast cancer diagnosed between 2010 and 2016. Hormone receptor positivity was defined as estrogen receptor-positive, progesterone-positive and HER 2-negative cancer. Sociodemographic and clinical variables were compared between MBC and FBC patients on bivariable analysis. After propensity score matching, overall survival was evaluated using the log-rank test and Cox proportional hazards. RESULTS: Compared to FBC patients, MBC patients had higher rates of metastatic disease (stage 4, MBC 4.4% vs. FBC 2.6%, p < 0.001), larger tumors (tumor size < 2 cm, MBC 32.1 vs. FBC 49.1%, p < 0.001) and a higher percentage of poorly differentiated tumors (grade 3, MBC 28.5% vs. FBC 21.4%, p < 0.001). MBC patients had lower rates of hormone therapy (MBC 66.4% vs. FBC 80.7%, p < 0.001) and neoadjuvant chemotherapy (MBC 5.8% vs. FBC 7.5%, p = 0.05) than FBC. On propensity score matched analysis, Black MBC patients had a higher overall mortality (p25 of 60 months vs. 74 months) compared to FBC patients (p = 0.0260). CONCLUSION: Among hormone receptor-positive Black MBC and FBC patients, there are sex-based disparities in stage, hormone therapy use and overall survival.

Guide to Enhanced Recovery for Cancer Patients Undergoing Surgery: Pancreaticoduodenectomy.

INTRODUCTION: Pancreaticoduodenectomy (PD) is a highly complex operation with high rates of morbidity and significant potential for perioperative mortality. Enhanced recovery after surgery protocols following PD aim to standardize post-operative clinical pathways in an effort to decrease surgical stress, minimize practice variation, and accelerate postoperative recovery. We reviewed current evidence and provide recommendations for enhanced recovery after PD protocols. METHODS: Current evidence regarding enhanced recovery after PD were reviewed. Recommendations for enhanced recovery after PD protocols are provided based on evidence and expert opinion. RESULTS: Key clinical factors required for a enhanced recovery after PD protocol to reduce postoperative complications and promote a faster recovery include patient and provider education, preoperative oral nutrition until 2-3 h prior to surgery, goal-directed intravenous fluid management, early advancement of oral diet, multimodal analgesia, early mobilization, normoglycemia, and early removal of intra-abdominal drains when clinically indicated. A PD specific protocol has been shown to reduce rates of PD-specific and overall complications as well as shorten postoperative hospital length of stay. CONCLUSION: The key facilitator to a successful enhanced recovery after PD protocol is careful multi-disciplinary planning with input from all stakeholders. Evidenced-based enhanced recovery protocols have been shown to reduce postoperative morbidity and accelerate postoperative recovery following PD.

Is Textbook Oncologic Outcome a Valid Hospital-Quality Metric after High-Risk Surgical Oncology Procedures?

BACKGROUND: "Textbook oncologic outcome" (TOO) is a composite quality measure representing the "ideal" outcome for patients undergoing cancer surgery. This study sought to assess the validity of TOO as a metric to evaluate hospital quality. METHODS: Patients who underwent curative-intent resection of gastric, pancreatic, colon, rectal, lung, esophageal, bladder, or ovarian cancer were identified in the National Cancer Database (2006-2017). Cancer site-specific TOO was defined as adequate lymph node yield, R0 resection, non-length-of-stay outlier, no hospital readmission, and receipt of guideline-concordant chemotherapy and/or radiation. Mixed-effects analyses estimated the adjusted TOO rate for each hospital stratified by cancer site. The association between hospital adjusted TOO rates and 5-year overall survival was assessed using mixed-effects Cox proportional hazards analyses. RESULTS: Among 852,988 cancer resections, the TOO rate varied across cancer sites as follows: stomach (31.8%), pancreas (25%), colon (66.9%), rectum (33.6%), lung (35.1%), esophagus (31.2%), bladder (43%), and ovary (44.7%). After characterization of adjusted hospital TOO rates into quintiles, an incremental improvement in overall survival was observed, with higher adjusted TOO rates. Similarly, with the adjusted hospital TOO rate treated as a continuous variable, there was a significant 4% to 12% improvement in overall survival for every 10% increase in the adjusted hospital TOO rate for gastric (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.85-0.91), pancreatic (HR, 0.90; 95% CI, 0.88-0.93), colon (0.93; 95% CI, 0.91-0.94), rectal (HR, 0.90; 95% CI, 0.87-0.93), lung (HR, 0.96; 95% CI, 0.95-0.97), esophageal (HR, 0.93; 95% CI, 0.90-0.95), bladder (HR, 0.94; 95% CI, 0.91-0.97), and ovarian (HR, 0.96; 95% CI, 0.94-0.98) cancer. CONCLUSIONS: A direct association exists between adjusted hospital TOO rates and survival after high-risk cancer procedures. As a valid hospital metric, TOO can be used to compare the overall quality of cancer care across hospitals.

Will It Play in Peoria? A Pilot Study of a Robotic Skills Curriculum for Surgical Oncology Fellows.

INTRODUCTION: To implement a mastery-based robotic surgery curriculum using virtual reality (VR) and inanimate reality (IR) drills at multiple Complex General Surgical Oncology (CGSO) fellowships. PATIENTS AND METHODS: A prospective study of curriculum feasibility and efficacy was conducted at four CGSO fellowship sites. All sites had simulators, and kits were provided to perform 19 biotissue drills. Fellows from three non-UPMC sites (n = 15) in 2016-2018 were compared with fellows from University of Pittsburgh (UPMC; n = 15) where the curriculum was validated in 2014-2018. RESULTS: All fellows completed the pre- and post-test. There was no difference in pre-test scores between UPMC and non-UPMC sites. Only 7 of 15 non-UPMC fellows completed the VR curriculum (47% compliance) compared with all 15 UPMC fellows completing the VR curriculum (100% compliance). UPMC had higher curriculum times (217 versus 93 mins) and % mastery (86% versus 55%). Time spent on curriculum was associated with % mastery (p = 0.01). Both groups showed improvement between pre- and post-test. Post-test VR scores trended higher for UPMC (221 versus 180). Between the non-UPMC sites, there was a difference in compliance (p = 0.03) and % mastery (p = 0.03). Zero non-UPMC fellows performed the biotissue drills, while five contemporary UPMC fellows completed 253 biotissue drills. Approximately 140 UPMC faculty and 300 staff hours were spent on the pilot. CONCLUSIONS: A proficiency curriculum can result in improved robotic console skills. However, multiple barriers to implementation potentially exist, including availability of simulators, availability of a training robot, on-site support staff, and universal buy-in from fellows, faculty, and leadership.

Chronic Intravenous Inotropic Support as Palliative Therapy and Bridge Therapy for Patients With Advanced Heart Failure: A Single-Center Experience.

BACKGROUND: Many patients with American College of Cardiology/American Heart Association Stage D (advanced) heart failure are discharged home on chronic intravenous inotropic support (CIIS) as bridge to surgical therapy or as palliative therapy. This study analyzed the clinical trajectory of patients with advanced heart failure who were on home CIIS. METHODS: We conducted a single-institution, retrospective cohort study of patients on CIIS between 2010 and 2016 (n = 373), stratified by indication for initiation of inotropic support. Study outcomes were time from initiation of CIIS to cessation of therapy, time to death for patients who did not receive surgical therapy and rates of involvement with palliative care. RESULTS: Overall, patients received CIIS therapy for an average of 5.9 months (standard deviation [SD] 7.3). Patients on CIIS as palliative therapy died in an average of 6.2 months (SD 6.6) from the time of initiation of CIIS, and those on CIIS as bridge therapy who did not ultimately receive surgical therapy died after an average of 8.6 months (SD 9.3). Patients who received CIIS as bridge therapy were significantly less likely to receive palliative-care consultation than those on inotropes as palliative therapy, whether or not they underwent surgery. CONCLUSIONS: In this large cohort of patients with advanced HF, patients who on CIIS as palliative therapy survived for 6.2 months, on average, with wide variation among patients. Patients who were on CIIS as bridge therapy but did not ultimately receive surgical therapy received less palliative care despite the high mortality rate in this subgroup.

Comparison of lymph node evaluation and yield among patients undergoing open and minimally invasive surgery for gallbladder adenocarcinoma.

INTRODUCTION: Assessment of regional lymph nodes (LN) is essential for determining prognosis among patients with gallbladder cancer (GBC). The impact of surgical technique on LN yield has not been well explored. We investigated the impact of minimally invasive surgery (MIS; robotic or laparoscopic) on the evaluation and retrieval of regional LN for patients with GBC. METHODS: We queried the National Cancer Database (NCDB) to identify patients with GBC who underwent curative-intent surgery between 2010 and 2015. Patients with metastatic disease or those with missing data on surgical resection or LN evaluation were excluded. RESULTS: We identified 2014 patients who underwent an open (n = 1141, 56.6%) or MIS approach (n = 873, 43.4%) for GBC and met the inclusion criteria. Patients who underwent MIS were older (open: 68 years, IQR: 60, 75 vs. MIS: 70 years, IQR (61, 77); P = 0.02), and were more commonly treated at a comprehensive community cancer program (P < 0.001). Approximately 3 out of 4 patients (n = 1468, 72.9%) underwent an evaluation of regional LN, with nearly half of these patients (n = 607, 41.7%) having LN metastasis. Among patients who underwent a regional lymphadenectomy, average lymph node yield was 3 (IQR: 1, 6) and was similar between the two groups (P = 0.04). After controlling for all factors, operative approach was not associated with likelihood of receiving a lymphadenectomy during curative-intent resection (OR 0.81, 95% CI 0.63-1.04; P = 0.11). CONCLUSION: In conclusion, patients undergoing curative-intent resection for GBC had similar rates of lymph node evaluation and yield regardless of operative approach. Over one-quarter of patients did not undergo a lymphadenectomy at the time of surgery. Further studies are needed to identify barriers to lymph node evaluation and yield among patients undergoing surgery for gallbladder cancer. Presented at the 2019 2nd World Congress of the International Laparoscopic Liver Society, Tokyo, Japan.

Oral tolerance and allergy.

Food allergy prevalence is increasing in the developed world. It's estimated that each year in the US, anaphylaxis to food results in 30,000 emergency room visits and 150 deaths. Over the past few decades, there has been a tremendous effort to better understand the pathogenesis of food allergy and mechanisms of food tolerance. In this article we review the structural of the gastrointestinal immune system and mechanisms of natural tolerance to food. We then review the factors that may result in the IgE mediated hypersensitivity reaction to food allergens resulting in clinical food allergy. Lastly, we provide a brief review of the efforts to induce immune tolerance to patients with food allergy.

Mentorship and formal robotic proficiency skills curriculum improve subsequent generations' learning curve for the robotic distal pancreatectomy.

BACKGROUND: Minimally invasive distal pancreatectomy is the accepted standard of care. The robotic distal (RDP) learning curve is 20-40 surgeries with operating time (ORT) as the most significant factor. This study evaluates how formal mentorship and a robotic skills curriculum impact the learning curve for subsequent generation surgeons. METHODS: Consecutive RDP from 2008 to 2017 were evaluated. First Generation was two surgeons who started program without training or mentorship. Second Generation was the two surgeons who joined the program with mentorship. Third Generation was fellows who benefited from both formal training and mentorship. Multivariable models (MVA) were performed for ORT, clinically relevant pancreatic fistula (CR-POPF), and major complications (Clavien≥3). RESULTS: A total of 296 RDP were performed of which 187 did not include other procedures: First Generation (n = 71), Second Generation (n = 50), and Third Generation (n = 66). ORT decreased by generation (p < 0.001) without any differences in CR-POPF or Clavien≥3. On MVA, earlier generation (p = 0.019), pre-operative albumin (p = 0.001) and pancreatic adenocarcinoma (p = 0.019) were predictive of ORT. Increased BMI (p = 0.049) and neoadjuvant therapy (p = 0.046) were predictive of CR-POPF. Fellow participation at the console increased over time. CONCLUSION: Formal mentorship and a skills curriculum decreased the learning curve and complications were largely dependent on patient factors.

Mitigation of the Robotic Pancreaticoduodenectomy Learning Curve through comprehensive training.

BACKGROUND: There is an associated lag in achieving competency for robotic pancreaticoduodenectomy (PD), resulting in a learning curve. We hypothesize that the reported learning curve can be mitigated through a comprehensive graduated training protocol. METHODS: All patients (n = 237) who underwent an open (n = 197, 83.1%) or robotic (n = 40, 16.9%) PD between 2015-2019 were identified at The Ohio State University. The learning curve for operative time and surgical failure (defined as conversion to open, blood transfusion, or Clavien-Dindo complication grade ≥3) was analyzed using a risk adjusted cumulative summation technique. RESULTS: After 10 cases, operative time plateaued to a mean of 468.3 ± 96.3 minutes for robotic PD versus a mean of 332.5 ± 103.9 minutes for open PD (P < 0.001). There was no further apparent learning curve over time relative to rates of operative time or surgical failure. After propensity score-matching, patients undergoing robotic PD had a similar incidence of major complications, grade B/C postoperative pancreatic fistula, and delayed gastric emptying versus patients undergoing open PD (all P > 0.05). CONCLUSION: Completion of a comprehensive procedure-specific robotic training protocol for PD mitigated the learning curve for this operative approach by shifting the curve into the training/simulation phase rather than the live operating phase. These data hold important implications for the future training and accreditation of surgeons embarking on robotic PD.

Serum CA19-9 Response to Neoadjuvant Therapy Predicts Tumor Size Reduction and Survival in Pancreatic Adenocarcinoma.

BACKGROUND: The optimal cutoffs for carbohydrate antigen 19-9 (CA19-9) response after neoadjuvant therapy (NT) for pancreatic adenocarcinoma (PDAC) are not well characterized. This study aimed to analyze the relationship of serum CA19-9 to other markers of response and to identify thresholds correlating to outcomes. METHODS: A retrospective review of resected PDAC patients from 2010 to 2017 at an academic tertiary referral center was conducted. RESULTS: The analysis enrolled 250 subjects. Normalization and multiple cutoff points for CA19-9 response were assessed. Normalization was not associated with improved survival (35.17 vs. 29.43 months; p = 0.173). Although a response 45% or higher was associated with longer survival (35 vs. 20 months; p = 0.018), a response of 85% or higher was optimal (55.7 vs. 25.97 months; p < 0.0001). A response of 85% or higher remained a strong independent predictor of survival [hazard ratio (HR), 0.47; p = 0.007]. Subjects with a response of 85% or higher had received more NT cycles [3 (range 2-6) vs. 3 (range 2-4) cycles; p = 0.006] and fewer adjuvant cycles [4 (range 3-6) vs. 5 (range 3-6) cycles; p = 0.027]. Reduction in T-size correlated with a drop in CA19-9 and a size reduction of 25% or higher (56.97 vs. 28.17 months; p = 0.016) improved survival. A serum CA19-9 response of 85% or higher was a strong independent predictor of a reduction in T-size of 25% or higher (HR 2.40; p = 0.007). CONCLUSION: A CA19-9 response of 85% or higher is the optimal threshold for predicting survival. It is predictive of T-size reduction. Future NT trials should incorporate CA19-9 response as an end point.