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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. Gene silencing, protein interaction, and transgenesis technology reveal ETHYLENE RESPONSE FACTOR 070 participates in ethylene-mediated inhibition of flowering in Pak-choi. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Achieving margin negative resection is a significant determinant of outcome in pancreatic adenocarcinoma (PDA). However, because of the fibrotic nature of PDA, it can be difficult to discriminate fibrosis from active disease intra-operatively. We sought to determine if post-hoc video review of robotic pancreatico-duodenectomy (RPD) could predict the portal/superior mesenteric vein (PV/SMV) margin status on final pathology. Experienced pancreatic surgeons, blinded to patient and operative variables, reviewed the PV/SMV margin for available RPD videos of consecutive PDA patients from 9/2012 through 6/2017. 107 RPD videos were reviewed. Of 76 patients (71%) predicted to have a negative vein margin on video review, 20 patients (26%) had a pathologic positive margin. 25 of 31 patients (81%) predicted to have positive margin on video review were positive on pathology. The specificity of video prediction was 90.3% with a sensitivity of 55.6% and an accuracy of 75.7%. Post-hoc video review prediction is unable to reliably predict a positive (R1) margin at the portal vein/SMV, suggesting that intra-operative clinical assessment may be suboptimal in determining the need for more extensive resections. [ABSTRACT FROM AUTHOR]

Abstract Background NSQIP data show that half of distal pancreatectomies (DP) are performed by a minimally invasive approach (MIS). Advantages have been demonstrated for MIS DP, yet comparative cost data are limited. Outcomes and cost were compared in patients undergoing open (ODP), laparoscopic (LDP), and robotic (RDP) approaches at a single institution. Methods A retrospective review was performed on patients undergoing DP between 1/2010-5/2016. Analysis was intention-to-treat, and cost was available after 1/2013. Results DP was performed in 374 patients: ODP = 85, LDP = 93, and RDP = 196. Operating time was lowest in the RDP cohort (p < 0.0001). ODP had higher estimated blood loss (p < 0.0001) and transfusions (p < 0.0001) than LDP and RDP. LDP had greater conversions to open procedures than RDP (p = 0.001). Postoperative outcomes were similar between groups. Length of stay was higher in the ODP group (p = 0.0001) than LDP and RDP. Overall cost for the ODP was higher than the RDP and LDP group (p = 0.002). On multivariate analysis, RDP reduced LOS (ODP: Odds = 6.5 [p = 0.0001] and LDP: Odds = 2.1 [p = 0.036]) and total cost (ODP: Odds = 5.7 [p = 0.002] and LDP: Odds = 2.8 [p = 0.042]) independently of all demographics and illness covariates. Conclusions A robotic approach is associated with reduced length of stay and cost compared to open and laparoscopic procedures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We sought to investigate whether robotic pancreatoduodenectomy (RPD) mitigates adverse outcomes in patients with high-risk morphometric features compared to the open approach (OPD). Morphometric parameters for RPD and OPDs were measured by two blinded radiologists. The morphometric parameter best correlating with adverse outcomes was identified and used in multivariable models to evaluate the impact of surgical approach (open vs. robotic) on outcomes of patients with high-risk morphometric features. Of 282 PDs available for morphometric analysis, 134 (47.5%) underwent RPD. Average Psoas Density demonstrated the most frequent association with adverse outcomes, with correlations to prolonged LOS (ρ= -0.154, p=0.01), severe complications (ρ= -0.159, p=0.007), readmission (ρ= -0.16, p=0.007), and discharge to home (ρ= 0.2, p<0.001). On multivariable analysis of patients with high-risk morphometric features (defined as APD ≤ 50th percentile), RPD was associated with a reduction in the likelihood of prolonged LOS (OR 0.27, p = 0.015) and a trend towards discharge home versus a rehab facility or nursing home (OR 2.26, p = 0.061). This study confirms the association between morphometrics and outcomes following PD, and suggests that the robotic approach may be associated with improved outcomes in PD patients with high-risk morphometric features. [ABSTRACT FROM AUTHOR]

Background Postpancreatectomy hemorrhage (PPH) is a serious and life threatening complication following pancreaticoduodenectomy. The objective was to determine whether PPH incidence is elevated in a series of robotic pancreatoduodenectomy (RPD) from a high-volume institution and if video review can identify technical factors associated with PPH. Methods A retrospective review of RPDs from October 2008 to March 2016 was performed. PPH was classified by established international criteria. Technical factors from RPD resection were ascertained using video analysis. Clinical and technical variables were analyzed using multivariate analysis. Results Of 400 patients who underwent RPD PPH occurred in 19 (4.8%) and 168 (42%) had videos available to review. The technique of RPD was consistent but a falciform flap was performed routinely after RPD#181 and flaps were performed less (37.5% vs 75%) in the pseudoaneurysm group ( p = 0.033). On univariate analysis of technical variables, gastroduodenal artery (GDA) mishandling and suture ligation were positive predictors of pseudoaneurysm formation while falciform flap placement was a negative predictor (all p < 0.05). GDA suture ligation remained significant on multivariate analysis ( p = 0.006). A negative relationship was found between pseudoaneurysm occurrence and time ( ρ = −0.533; p < 0.05). Conclusions PPH in a large series of RPD is similar to reported rates in historical open control series; however, pseudoaneurysm is less common with increasing experience. Video review is a useful tool in identifying technical variables during in RPD. [ABSTRACT FROM AUTHOR]

Background Lumbar spinal stenosis is a common diagnosis in elderly individuals, and the rates of surgery have risen all over the world. The optimal approach to provide satisfactory decompression and minimize complications for lumbar spinal stenosis remains controversial. Objective The purpose of this study was to evaluate the surgical outcome of interspinous spacers versus decompressive laminectomy in the management of degenerative lumbar canal stenosis. Patients and Methods Our prospective, comparative study included 2 groups of patients who were operated on in Ain Shams University Hospitals between January 2010 and December 2014. In the first group, 28 patients underwent decompression and additional implantation of an interspinous spacer (ISP). In the second group, 25 patients underwent decompressive laminectomy (DL). Results Our statistical results revealed no significant difference in outcome between the 2 groups regarding visual analog scale score for leg pain and Oswestry Low Back Pain Disability Index. However, the improvement (visual analog scale score) for back pain was better in the DL group. Complication and reoperation rates were higher in the ISP group. Conclusion Although decompression and additional implantation of an ISP are safe procedures, they do not show better improvement in clinical outcome as compared with decompressive laminectomy. [ABSTRACT FROM AUTHOR]

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 H 2 O 2 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.

Patients who undergo resection for non-invasive IPMN are at risk for long-term recurrence. Further evidence is needed to identify evidence-based surveillance strategies based on the risk of recurrence. We performed a systematic review of the current literature regarding recurrence patterns following resection of non-invasive IPMN to summarize evidence-based recommendations for surveillance. Among the 61 studies reviewed, a total of 8779 patients underwent resection for non-invasive IPMN. The pooled overall median follow-up time was 49.5 months (IQR: 38.5-57.7) and ranged between 14.1 months and 114 months. The overall median recurrence rate for patients with resected non-invasive IPMN was 8.8% (IQR: 5.0, 15.6) and ranged from 0% to 27.6%. Among the 33 studies reporting the time to recurrence, the overall median time to recurrence was 24 months (IQR: 17, 46). Existing literature on recurrence rates and post-resection surveillance strategies for patients with resected non-invasive IPMN varies greatly. Patients with resected non-invasive IPMN appear to be at risk for long-term recurrence and should undergo routine surveillance.

Background: Mucinous cystic neoplasms of the liver (MCN-L) including biliary cystadenomas (BCA) and biliary cystadenocarcinomas (BCAC) are rare cystic lesions that comprise less than 5% of all liver cysts and affect only a small subset of individuals. We herein review the current evidence regarding the clinical presentation, imaging characteristics, tumor markers, pathological findings, clinical management, and prognosis of MCN-L., Methods: A comprehensive review of the literature was performed using MEDLINE/Pubmed and Web of Science databases. In PubMed, the terms "biliary cystadenoma," "biliary cystadenocarcinoma," and "non parasitic hepatic cysts" were queried to identify the most recent data on MCN-L., Results: US imaging, CT, and MRI, as well as consideration of clinicopathological features, are required to appropriately characterize and diagnose hepatic cystic tumors. BCA are premalignant lesions and cannot be reliably differentiated from BCAC based on imaging alone. As such, both types of lesions should be treated with margin-negative surgical resection. Following surgical resection, recurrence is fairly low among patients with BCA and BCAC. Despite having worse long-term outcomes than BCA, the prognosis following surgical resection of BCAC still remains more favorable than other primary malignant liver tumors., Conclusion: MCN-L are rare cystic liver tumors that include BCA and BCAC, which can be difficult to differentiate based on imaging alone. Surgical resection remains the mainstay of management for MCN-L with recurrence being generally uncommon. Future multi-institutional studies are still required to better understand the biology behind BCA and BCAC to improve the care of patients with MCN-L., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Socioeconomic status can often dictate access to timely surgical care and postoperative outcomes. We sought to analyze the impact of county-level poverty duration on hepatopancreaticobiliary cancer outcomes., Methods: Patients diagnosed with hepatopancreaticobiliary cancer were identified from the Surveillance, Epidemiology, and End Results-Medicare 2010 to 2015 database linked with county-level poverty from the American Community Survey and the US Department of Agriculture between 1980 to 2010. Counties were categorized as never high-poverty, intermittent high-poverty, and persistent poverty. Hierarchical generalized linear models and accelerated failure time models with Weibull distribution were used to assess diagnosis, treatment, textbook outcomes, and survival., Results: Among 41,077 patients, 1,758 (4.3%) lived in persistent poverty. Counties exposed to greater durations of poverty had increased proportions of non-Hispanic Black patients (never high-poverty: 7.6%, intermittent high-poverty: 20.4%, persistent poverty: 23.2%), uninsured patients (never high-poverty: 0.5%, intermittent high-poverty: 0.5%, persistent poverty: 0.9%), and patients with a rural residence (never high-poverty: 0.6%, intermittent high-poverty: 2.4%, persistent poverty: 11.5%). Individuals residing in persistent poverty had lower odds of undergoing resection (odds ratio 0.82, 95% confidence interval 0.66-0.98), achieving textbook outcomes (odds ratio 0.54, 95% confidence interval 0.34-0.84), and increased cancer-specific mortality (hazard ratio 1.07, 95% CI 1.00-1.15) (all P < .05). Non-Hispanic Black patients were less likely to present with early-stage disease (odds ratio 0.86, 95% confidence interval 0.79-0.95) and undergo surgical treatment (odds ratio 0.58, 95% confidence interval 0.52-0.66) compared to non-Hispanic White patients (both P < .01). Notably, non-Hispanic White patients in persistent poverty were more likely to present with early-stage disease (odds ratio 1.30, 95% confidence interval 1.12-1.52) and undergo surgery for localized disease (odds ratio 1.36, 95% confidence interval 1.06-1.74) compared to non-Hispanic Black patients in never high-poverty (both P < .05)., Conclusion: Duration of poverty was associated with lower odds of receipt of surgical treatment, achievement of textbook outcomes, and worse cancer-specific survival. Non-Hispanic Black patients were at particular risk of suboptimal outcomes, highlighting the impact of structural racism independent of socioeconomic status., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Almost one-third of patients with colorectal cancer (CRC) experience recurrence after resection. Adherence to surveillance guidelines largely dictates efficacy in early detection of recurrence. We sought to assess and compare adherence to postoperative surveillance guidelines for colonoscopy, imaging, and Carcinoembryonic Antigen (CEA)., Methods: PubMed, Medline, Embase, Scopus, Cochrane, Web of Science, and CINAHL were systematically searched. Random-effects meta-analysis was performed and pooled adherence to each surveillance strategy was assessed for CEA, imaging, and colonoscopy., Results: Overall 14 studies (55,895 patients) met the inclusion criteria. Adherence to colonoscopy guidelines was the highest (70%, 95%CI 67-73), followed by imaging (63%, 95%CI 47-80), and CEA (54%; 95%CI 42-66). Among 7 (50%) studies that examined adherence to the American Society of Clinical Oncology guidelines, compliance with colonoscopy was the highest (73%; 95% CI 70-76), followed by imaging (58%; 95% CI 37-78), and CEA (45%; 95%CI 37-52). Of note, guideline adherence to CEA testing was much lower than colonoscopy among patients with colon (OR 0.21; 95%CI 0.20-0.22) and rectal cancer (OR 0.25; 95%CI 0.23-0.28) (both p < 0.05). This was also noted when compared with imaging recommendations among older patients (OR = 0.62; 95%CI 0.42-0.93) and patients with stage II, (OR = 0.80; 95%CI 0.76-0.84) and stage III disease (OR = 0.88; 95%CI 0.82-0.94) (all p < 0.05)., Conclusion: While guideline adherence to postoperative surveillance with colonoscopy was high, adherence to CEA testing and imaging surveillance strategies was markedly lower following CRC resection. Future studies should investigate avenues to improve compliance with surveillance guidelines among health care providers and patients to optimize postoperative follow-up for CRC., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Radioembolization (RE) with 90Yttrium (Y90) has generally been used to treat patients with advanced disease. Recent data suggest, however, that RE is also safe and feasible to treat patients with early or intermediate stage disease. We herein review the current evidence regarding the use of RE with Y90 for patients with HCC., Methods: A comprehensive review of the literature was performed using MEDLINE/PubMed and Web of Science databases with a search end date of August 1, 2022., Results: Patients with HCC are often treated according to the BCLC staging system. Among patients with early-stage HCC (BCLC A), intermediate-stage HCC (BCLC B), and advanced-stage HCC (BCLC C), RE with Y90 has demonstrated promising results with comparable overall survival, time to disease progression, and radiological response compared with other standard of care treatment modalities. Moreover, Y90 RE can be used as a downstaging treatment modality for patients with advanced HCC who have a disease burden that is initially outside LT criteria. Radiation lobectomy (RL) has been described as a treatment modality with the intent of treating the ipsilateral liver that harbors the HCC, while also causing compensatory hypertrophy of the future liver remnant (FLR)., Conclusion: While initially considered as a palliative option for HCC patients, Y90 RE has emerged as an important part of the multi-modality care of patients with HCC across a wide spectrum of clinical indications., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background: Receipt of adjuvant therapy for gallbladder adenocarcinoma (GBAC) is associated with a survival benefit. This study sought to identify whether delays in initiation of adjuvant therapy among patients with resected GBAC impacts long-term survival., Methods: Patients with stage II and III GBAC who underwent a curative-intent resection followed by adjuvant chemotherapy or chemoradiation between 2004 and 2017 were queried from the National Cancer Data Base. Descriptive statistics and multivariate models were constructed to determine the relationship between timely (<12 weeks) and delayed (>12 weeks) adjuvant therapy and overall survival (OS)., Results: A total of 871 patients with GBAC were identified. The median time to receipt of adjuvant chemotherapy was 67 days and the median time to receipt of adjuvant chemoradiation was 69 days. After controlling for all factors, treatment at an Academic/Research center was the only variable associated with timely receipt of adjuvant therapy. However, after controlling for clinically relevant factors, the timing of adjuvant therapy did not impact OS (delayed: HR 0.93, 95% CI: 0.46-1.85; P = .83)., Conclusion: Current guidelines support the use of adjuvant therapy following resection of GBAC. This national cohort study demonstrates that delays in adjuvant therapy >12 weeks did not impact long-term survival., (© 2022 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

(1) Background: Cancer screening tests discover cancer at early stages, even before symptoms appear. When abnormal tissues or a malignant mass is found early, treatment and cure rates are improved. In late stages, the cancer may have grown and metastasized. This can negatively affect cancer treatment and reduce the overall survival rate. Screening tests are performed when a person is asymptomatic. Public awareness about cancer screening is crucial for the success of cancer screening programs and for consequently decreasing the morbidity and mortality rate due to cancer. (2) Aim: Assess the knowledge and perception of the community regarding cancer screening in Saudi Arabia. (3) Methodology: A descriptive cross-sectional study targeting the general population of Saudi Arabia was conducted from January to June 2022. The data were collected using a structured validated electronic questionnaire. The study questionnaire covered participants' personal data, medical history, source of data, and participants' knowledge, attitude, and practice items. The questionnaire was used as a digital survey and was distributed electronically to the target population. (4) Results: A total of 1313 participants completed the study questionnaire. The participants' ages ranged from 18 to 67 years, with a mean age of 28.3 ± 11.4 years old. Overall, 60.4% of the study participants knew about cancer screening. Regarding the benefits of cancer screening, 91.8% of the participants reported knowing that the early detection of cancer helps treatment, and 81.1% knew that the early detection of cancer improves treatment outcomes. Moreover, 441 (33.6%) of the participants had good knowledge regarding cancer and cancer screening, while 872 (66.4%) had poor levels of knowledge. Furthermore, 106 (8.1%) of the participants underwent cancer screening. (5) Conclusions: The study results revealed that participants' awareness regarding cancer and cancer screening was low, especially for approaches to reduce cancer risk. Additionally, the study participants' practice regarding cancer screening was low. The health care authority should plan for population-based efficacious cancer screening programs. In addition, cancer screening information and the benefits of early detection can be disseminated through social media to target the desired populations.

Background: Partial pancreatic resection is a known risk factor for new-onset pancreatogenic diabetes mellitus (P-DM). The long-term incidence of P-DM and its clinical impact after partial pancreatic resection remains unknown. The primary objective of this study is to determine the long-term incidence of P-DM and its clinical impact after partial pancreatic resection., Study Design: The Medicare 100% Standard Analytic File (2013 to 2017) was queried for all patients who underwent partial pancreatic resection (pancreaticoduodenectomy, distal pancreatectomy). The primary outcome was the development of postoperative P-DM after surgery., Results: Among 4,255 patients who underwent a pancreaticoduodenectomy or distal pancreatectomy, with a median follow-up of 10.8 months, the incidence of P-DM was 20.3% (n=863) and occurred at a median of 3.6 months after surgery. For patients with at least a 3-year follow-up, 32.2% of patients developed P-DM. Risk factors for developing P-DM included male sex (odds ratio [OR] 1.32, 95% CI 1.13 to 1.54), undergoing a distal pancreatectomy (OR 1.98, 95% CI 1.68 to 2.35), having a malignant diagnosis (OR 1.65, 95% CI 1.34 to 2.04), a family history of diabetes (OR 2.06, 95% CI 1.43 to 2.97; all p < 0.001), and being classified as prediabetic in the preoperative setting (OR 1.57, 95% CI 1.18 to 2.08; p = 0.002). Patients who developed P-DM were more commonly readmitted within 90 days of surgery and had higher postoperative healthcare expenditures in the year after surgery ($24,440 US dollars vs $16,130 US dollars; both p < 0.001) vs patients without P-DM., Conclusions: Approximately 1 in 5 Medicare beneficiaries who undergo a pancreatic resection develop P-DM after pancreatic resection. Appropriate screening and improved patient education should be conducted for these patients, in particular, for those with identified risk factors.

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., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The initiation of adjuvant chemotherapy for pancreatic adenocarcinoma within 12 weeks after surgery is recommended by the National Comprehensive Cancer Network. This study seeks to identify factors associated with delayed adjuvant chemotherapy and whether delays impact survival in under-resourced populations., Methods: Patients with nonmetastatic pancreatic adenocarcinoma who received a definitive resection followed by adjuvant chemotherapy between 2006 and 2017 were queried from the National Cancer Database. Multivariate logistic regression models were constructed to determine the relationship between socioeconomic/clinical variables and delayed adjuvant chemotherapy. Kaplan Meier curves compared survival between under-resourced patients receiving delayed versus timely adjuvant chemotherapy., Results: Among 25,008 patients, timely adjuvant chemotherapy varied by stage (stage 1: 67.9% vs stage 2: 75.8% vs stage 3: 89.2%; P < .001). Older age (odds ratio 1.02, 95% confidence interval 1.02-1.03; P < .001), Non-Hispanic Black race (odds ratio 1.25, 95% confidence interval 1.11-1.41; P < .001), increasing comorbidity score (odds ratio 1.18, 95% confidence interval 1.12-1.23; P < .001), 30-day readmission (odds ratio 1.45, 95% confidence interval 1.28-1.63; P < .001), and undergoing a Whipple (odds ratio 1.30, 95% confidence interval 1.16-1.44; P < .001) were associated with delayed adjuvant chemotherapy. Conversely, the highest neighborhood median income quartile (odds ratio 0.84, 95% confidence interval 0.73-0.97; P = .021), private insurance (odds ratio 0.59, 95% confidence interval 0.46-0.76; P < .001), Medicare (odds ratio 0.68, 95% confidence interval 0.52-0.88; P = .003), and receipt of neoadjuvant therapy (odds ratio 0.05, 95% confidence interval 0.04-0.06; P < .001) were associated with timely adjuvant chemotherapy. Non-Hispanic Black patients and patients with the lowest neighborhood education had worse overall survival when receiving delayed versus timely adjuvant chemotherapy., Conclusion: Timely adjuvant chemotherapy for pancreatic adenocarcinoma was only achieved in 73.3% of patients. Age, race, comorbidities, median income, and insurance were identified as barriers. Delayed adjuvant chemotherapy was associated with worse survival among under-resourced populations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Breast cancer is the leading cause of cancer death among Hispanic women. Unfortunately, few studies disaggregate Hispanic patients by race to understand its implications on treatment and clinical outcomes such as mortality. The aim of this study is to examine surgical management and overall mortality among different subgroups of women who self-identify as Hispanic., Methods: Hispanic female patients, ages 18-90, stages I-III, diagnosed with breast cancer between 2010 and 2015 from the National Cancer Data Base were identified. The study cohort was divided into three ethnoracial categories: (1) Hispanic White (HW), 2) Hispanic Black (HB), and 3) Hispanic Other (HO). Descriptive statistics and multivariate models were constructed to determine the relationship between sociodemographic factors, clinical variables, surgical management, and mortality when disaggregated by race., Results: There were 56,675 Hispanic women who met the study criteria. Most where HW (n=50,599, 89.3%) and the rest were HB (n=1,334, 2.4%) and HO (n=4,742, 8.3%). There was no difference between the three groups on receipt of breast conservation therapy (P=0.12). HB (48.5%) and HO (46.6%) women were more likely to undergo reconstruction than those who identified as HW (38.7%) (P<0.001). Additionally, HB (38.3%) women were more likely to undergo tissue-based reconstruction than HW (29.0%) and HO women (30%) (P=0.0008). There was no difference between the groups in the utilization of contralateral prophylactic mastectomy (CPM) (P=0.078). On multivariable analysis, there was no difference in mortality between HB and HW patients (HR 1.18, 95%CI 0.92-1.51; Ref HW). However, HO women had a 24% relative risk reduction in mortality (HR 0.76, 95% CI 0.63-0.92; HW ref)., Conclusion: Findings from this study suggest there are ethnoracial disparities in reconstruction utilization and mortality among Hispanic women. Future studies should examine how culture, language, healthcare access, and patient preferences contribute to these disparities., (© 2021. W. Montague Cobb-NMA Health Institute.)

Objectives: Physicians are increasingly recommending neoadjuvant therapy (NT) before surgery for pancreatic ductal adenocarcinoma (PDAC). However, patient preferences for and opinions regarding NT are poorly understood., Methods: Survivors and caregivers from a national PDAC patient advocacy organization completed an online survey assessing preferences for NT versus surgery first (SF) and factors influencing their decision making., Results: Among 54 participants, 74.1% had a personal history of PDAC. While most patients preferred SF for resectable disease, NT was the preferred treatment approach for borderline resectable, locally advanced, and resectable cancers with high carbohydrate antigen 19-9. The most important factor influencing patient decision making regarding NT was its impact on overall survival while the least important was published national guidelines. The most preferred rationale for NT was ability to downstage to surgical resection and early treatment of micrometastatic disease., Conclusions: Among a national cohort of PDAC survivors and caregivers, the majority preferred SF for resectable PDAC, whereas NT was preferred when the resectability of a tumor was in question. The impact of NT on quantity and quality of life, as well as the likelihood of achieving surgical resection, was most highly valued by participants., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients with liver-only metastatic pancreatic adenocarcinoma have traditionally been offered palliative chemotherapy alone. Recent studies have explored the role of surgical resection among patients with limited metastatic disease. National practice patterns and the impact of surgery among these patients remains unknown., Methods: The National Cancer Database was queried for all patients with pancreatic adenocarcinoma between 2010 and 2015. The primary outcome was overall survival from the time of diagnosis. Patients with liver-only metastatic disease were included. Univariable and multivariable logistic regression models were constructed to determine the association of patient, hospital, and regional factors with receipt of surgical resection. A propensity score-matched cohort (1:1) was generated by matching patient- and tumor-related factors (age, sex, race, comorbidity burden, primary tumor site, primary tumor size) among patients with liver-only stage IV pancreatic adenocarcinoma who received chemotherapy alone compared to those who received chemotherapy and underwent pancreatectomy and liver metastatectomy., Results: Among 312,426 patients who met the study criteria, one half (n = 140,043, 50.4%) had stage IV disease; metastatic sites included bone (n = 5493, 3.1%), brain (n = 620, 0.4%), lung (n = 16,580, 9.5%), and liver (n = 62,444, 35.7%). Patients with stage IV disease were more likely to be younger (odds ratio: 1.10, 95% confidence interval: 1.0-1.2; P = .03) and have poorly (odds ratio: 2.1, 95% confidence interval: 1.8-2.5; P < .001) or undifferentiated (odds ratio: 3.1, 95% confidence interval: 2.3-4.1; P < .001) tumors. Among stage IV patients with liver-only disease (n = 47,785, 14.9%), 891 patients (1.9%) underwent pancreatic resection. Patients who underwent resection were more likely to be younger (odds ratio 1.4, 95% confidence interval: 1.0-1.8; P = .03) and treated at an academic/research center (odds ratio 2.1, 95% confidence interval: 1.2-3.5; P = .006). Median overall survival among patients who underwent resection was 10.74 months versus 3.4 months among patients who did not undergo resection. After controlling for patient and disease-related factors, patients who underwent surgical resection had a lower risk of death versus patients who did not undergo surgery (hazard ratio: 0.5, 95% confidence interval: 0.4-0.6; P < .001). After propensity score matching, patients who received multimodality treatment for liver-only metastatic pancreatic adenocarcinoma (surgery, chemotherapy) had a longer median overall survival (15.6 months vs 8.1 months) compared to those who received chemotherapy alone (P < .001)., Conclusion: This study suggests that pancreatic resection in patients with liver metastases, in combination with chemotherapy and/or chemoradiation, may be associated with improved survival in well-selected patients. However, attempts at an aggressive surgical approach for patients with liver-only stage IV pancreatic adenocarcinoma patients should only be performed only under a well-designed prospective clinical trial., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Neighborhood factors may influence cancer care through physical, economic, and social means. This study assesses the impact of neighborhood socioeconomic status on diagnosis, treatment, and survival in pancreatic cancer., Methods: Patients with pancreatic adenocarcinoma were identified in the 2010-2016 Surveillance Epidemiology and End Results database. Neighborhood socioeconomic status (divided into tertiles) was based on an National Cancer Institute census tract-level composite score, including income, education, housing, and employment. Multivariate models predicted metastasis at time of diagnosis and receipt of surgery for early-stage disease. Overall survival compared via Kaplan-Meier and Cox proportional hazards., Results: Fifteen thousand four hundred and thirty-six patients (29.7%) lived in low neighborhood socioeconomic status, 17,509 (33.7%) in middle neighborhood socioeconomic status, and 19,010 (36.6%) in high neighborhood socioeconomic status areas. On multivariate analysis, neighborhood socioeconomic status was not associated with metastatic disease at diagnosis (low neighborhood socioeconomic status odds ratio 1.02, 95% confidence interval 0.97-1.07; ref: high neighborhood socioeconomic status). However, low neighborhood socioeconomic status was associated with decreased likelihood of surgery for localized/regional disease (odds ratio 0.60, 95% confidence interval 0.54-0.68; ref: high neighborhood socioeconomic status) and worse overall survival (low neighborhood socioeconomic status hazard ratio 1.18, 95% confidence interval 1.15-1.21; ref: high neighborhood socioeconomic status)., Conclusion: Patients from resource-poor neighborhoods are less likely to receive stage-appropriate therapy for pancreatic cancer and have an 18% higher risk of death., (Copyright © 2021. Published by Elsevier Inc.)

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., (© 2021. Society of Surgical Oncology.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The utilization of cancer-directed treatment for patients with all stages of pancreatic cancer in the USA is unknown. This study sought to examine national practice patterns and identify patient, hospital, regional, and other factors associated with disparities in the use of guideline-concordant cancer-directed therapy., Methods: Patients diagnosed with PDAC between 2004 and 2015 were queried from the National Cancer Data Base. Standard of care cancer-directed treatment was defined as surgical resection plus chemotherapy or chemoradiation for patients with stage 1 and 2 disease, chemotherapy for patients with metastatic disease (stage 4), and chemotherapy with or without surgery or chemoradiation for patients with locally advanced stage 3 disease., Results: A total of 336,629 patients with stage 1 (n = 38,443, 11.4%), stage 2 (n = 93,923, 27.9%), stage 3 (n = 37,492, 11.1%), or stage 4 metastatic (n = 166,771, 49.5%) disease were identified. Adherence with stage-specific standard of care treatment occurred in only 45.3% (n = 152,560) of patients among the entire cohort and varied by stage of disease (stage 1: 14.6% vs. stage 2: 39.9% vs. stage 3: 67.6%, vs. stage 4: 50.9%). Older age (OR 0.95, 95%CI 0.94-0.95; p < 0.001), female sex (OR 0.94, 95%CI 0.943-0.97; p < 0.001), African Americans (OR 0.89, 95%CI 0.87-0.91; P < 0.001), and increasing comorbidity burden (Charlson-Deyo score ≥3: OR 0.52, 95%CI 0.50-0.55; P < 0.001) were associated with a lower likelihood of receiving stage-specific standard of care treatment. Conversely, treatment at a high-volume center (quartile 4: OR: 1.13, 95%CI 1.10-1.16; P < 0.001) and higher education level (OR 1.32, 95%CI 1.28-1.36; p < 0.001) was associated with higher likelihood of receiving stage-specific standard of care treatment. Patients who received standard of care treatment had a 47% lower risk of death compared with patients who did not receive standard of care treatment (HR 0.53, 95%CI 0.52-0.53; P < 0.001)., Conclusion: Pancreatic adenocarcinoma is a complex disease requiring a multi-disciplinary approach for optimal outcomes. Receipt of stage-specific standard of care treatment for PDAC is associated with improved long-term oncological outcomes, but is only achieved in less than half of patients. Further studies are needed to evaluate interventions to address these treatment disparities for patients with PDAC., (© 2021. The Society for Surgery of the Alimentary Tract.)

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., (© 2021. Society of Surgical Oncology.)

Purpose: Low socioeconomic status (SES) is associated with advanced stage, lower-quality care, and higher mortality among breast cancer patients. The purpose of this study is to examine the association between neighborhood SES (nSES), surgical management, and disease-specific mortality in de novo metastatic breast cancer (MBC) patients in the Surveillance, Epidemiology, and End Results (SEER) Program., Methods: MBC patients ages 18 to 85+ years diagnosed from 2010 through 2016 were identified in SEER. The cohort was divided into low, middle, and high nSES based on the NCI census tract-level index. Univariable and multivariable analyses were used to examine the relationship between nSES, surgery, and disease specific mortality in MBC patients., Results: There were 24,532 de novo MBC patients who met study criteria, with 28.7 % undergoing surgery. Over the study period, surgery utilization decreased across all nSES groups. However, lower nSES was associated with a higher odds of undergoing surgery (low OR 1.25 [1.15-1.36] p < 0.001; middle OR 1.09 [1.01-1.18] p = 0.022; ref high). Living in an area with lower SES was associated with a worse disease specific mortality (low HR 1.24 [1.25, 1.44; ], middle 1.20 [1.1-1.29]: ref high). Specifically, there was a 9.26 month mean survival differences between the lowest (41.02 ± 0.47 months) and highest (50.28 ± 0.47 months) nSES groups., Conclusion: These results suggest area of residence may contribute to differences in surgical management and clinical outcomes among de novo MBC patients. Future studies should examine the contributions of patient characteristics and preferences within the context of surgeon recommendations., Competing Interests: Declaration of competing interest Oindrila Bhattacharyya declares that she has no conflict of interest. Yaming Li declares that she has no conflict of interest. James L. Fisher declares that he has no conflict of interest. Allan Tsung declares that he has no conflict of interest. Mariam Eskander declares that she has no conflict of interest. Ahmad Hamad declares that he has no conflict of interest. Samilia Obeng-Gyasi declares that she has no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2021. Society of Surgical Oncology.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Pre-operative exercise therapy improves outcomes for many patients who undergo surgery. Despite the well-known effects on tolerance to systemic perturbation, the mechanisms by which pre-operative exercise protects the organ that is operated on from inflammatory injury are unclear. Here, we show that four-week aerobic pre-operative exercise significantly attenuates liver injury and inflammation from ischaemia and reperfusion in mice. Remarkably, these beneficial effects last for seven more days after completing pre-operative exercising. We find that exercise specifically drives Kupffer cells toward an anti-inflammatory phenotype with trained immunity via metabolic reprogramming. Mechanistically, exercise-induced HMGB1 release enhances itaconate metabolism in the tricarboxylic acid cycle that impacts Kupffer cells in an NRF2-dependent manner. Therefore, these metabolites and cellular/molecular targets can be investigated as potential exercise-mimicking pharmaceutical candidates to protect against liver injury during surgery.

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.

The objective of the present work was the selection of cultivar, suitable medium and explant type for callus, root production, ascorbic acid, total ascorbic acid, dehydroascorbic and total protein of non-heading Chinese cabbage in two cultivars 'Caixin' and 'Suzhouqing'. We compared 10 types of MS media supplemented with 0.0, 1.0, 2.0 and 3.0 mg/l TDZ; 0.0, 0.25, 0.50 and 1.0 mg/l NAA and 0.0, 5.0, 7.5 and 9.0 mg/l AgNO 3 and 5 kinds of explants as embryo, leaf, root, cotyledon and hypocotyl. Maximum frequency of callus fresh weight was recorded with hypocotyl explant, which were cultured on MS + 2.0 mg/l TDZ + 1.0 mg/l NAA + 9.0 mg/l AgNO 3 in 'Suzhouqing', optimum callus dry weight was obtained on the same media. The highest result for root fresh and dry weight recorded with 'Caixin' with MS + 3.0 mg/l TDZ + 1.0 mg/l NAA + 9.0 mg/l AgNO 3 when we used embryo as explant. The highest ascorbic acid content was found with callus cultured on MS + 1.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO 3 , when used leaf explant in 'Caixin' or root in 'Suzhouqing', and there were no significant difference between them. While the highest value of total AsA content was registered with callus cultured on MS + 2.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO 3 extracted from cotyledon in 'Caixin'. The highest content of DHA was registered with MS + 2.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO 3 with cotyledon in 'Caixin'. Also, in 'Caixin' MS + 3.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO 3 recorded the highest value of total protein content with embryo explant.

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.

Introduction: The safety, efficacy, and learning curve for robotic pancreatoduodenecomy has been reported; however, the outcomes and learning curve of robotic pancreatoduodenecomy with vascular resections remain unknown. Our aim was to evaluate the outcomes of robotic pancreatoduodenecomy with vascular resections compared with robotic pancreatoduodenecomy without vascular resection and to identify the learning curve and benchmarks for improved performance during robotic pancreatoduodenecomy with vascular resections., Methods: A retrospective review of consecutive patients who underwent robotic pancreatoduodenecomy with vascular resections and robotic pancreatoduodenecomy between 2011 and 2017. Patients were analyzed consecutively, and a cumulative sum analysis was performed to detect improvements in performance over time., Results: Of 380 consecutive robotic pancreatoduodenecomy patients, 50 (13%) underwent robotic pancreatoduodenecomy with vascular resections. Compared with robotic pancreatoduodenecomy, robotic pancreatoduodenecomy with vascular resections were more likely to have had pancreatic adenocarcinoma (84% vs 42%) and had received neoadjuvant therapy (35% vs 65%, P < .01). Robotic pancreatoduodenecomy with vascular resections operative time revealed a steady, significant decrease (Rho = -0.38, p = .006) with marked initial improvement after the first 8 cases and maturation of the learning curve after 35 cases. A significant decrease in duration of the hospital stay was observed throughout the experience (Rho = -0.528, P < .0001), whereas margin status, pancreatic fistula, major morbidity, and mortality remained constant and comparable to robotic pancreatoduodenecomy alone., Conclusion: Robotic pancreatoduodenectomy with vascular resections is safe and feasible. For surgeons who have surpassed the learning curve of robotic pancreatoduodenectomy, it appears that improvements in performance of robotic pancreatoduodenecomy with vascular resections can be observed after 35 cases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDA) is associated with a hypercoagulable state, resulting in a high risk of venous thromboembolism (VTE). Risk of VTE is well established for patients receiving chemotherapy for advanced disease and during the perioperative period for patients undergoing surgical resection. However, data are lacking for patients undergoing neoadjuvant treatment followed by resection, who may have a unique risk of VTE because of exposure to both chemotherapy and surgery., Methods: The study included patients with PDA who underwent neoadjuvant therapy followed by surgery from 2007 to June 2017. Development of VTE was evaluated from the start of treatment through the 90-day postoperative period. Risk factors including demographic, treatment, and laboratory variables were evaluated., Results: The study investigated 426 patients receiving neoadjuvant therapy before surgical resection. Of these patients, 20% had a VTE within 90 days postoperatively (n = 87), and 70% of the VTE occurred during the postoperative period. The VTE included pulmonary embolism (30%), deep vein thrombosis (33%), and thrombosis of the portal vein (PV)/superior mesenteric vein (SMV) (40%). A pretreatment hemoglobin level lower than 10 g/dL and a platelet count higher than 443 were independently associated with VTE during neoadjuvant treatment. The independent predictors of postoperative VTE were a body mass index higher than 35 kg/m 2 , a preoperative platelet-to-lymphocyte ratio higher than 260, resection with distal pancreatectomy with celiac axis resection/total pancreatectomy, PV/SMV resection, and longer operative times. Development of VTE was associated with worse overall and disease-free survival and an independent predictor of survival and decreased likelihood of receiving adjuvant chemotherapy., Conclusions: Venous thromboembolism during neoadjuvant therapy and the subsequent perioperative period is common and has a significant impact on outcome. Further study into novel thromboprophylaxis measures or protocols during neoadjuvant treatment and the perioperative period is warranted.

Background: Serum carbohydrate antigen 19-9 (CA19-9) correlates with response to therapy and overall survival (OS) for patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to define the chronologic relationship between CA19-9 elevation and radiographic recurrence to develop a model that can predict the risk of recurrence (RFS) and prognosis during interval surveillance for patients with resected PDAC., Methods: A retrospective review examined patients undergoing surgery for pancreatic adenocarcinoma from January 2010 to May 2016. Their CA19-9 levels were classified at diagnosis, after surgery, and at 6-month surveillance intervals. Recurrence was defined by radiographic evidence. The CA19-9 levels were correlated with RFS and OS at every time point using multivariate analysis., Results: The study examined 525 patients. Five patterns of CA19-9 were identified: normal ("nonsecretors," 18.5%), always elevated, and high at diagnosis but normal after resection involving three patterns with varied behavior during surveillance. These five patterns had implications for RFS and OS. When elevation of CA19-9, as assessed at 6-month intervals, was analyzed relative to detection of radiographic disease, CA19-9 had poor positive predictive value (average, 35%) but high negative predictive value (average, 92%) for radiographic recurrence. Conditional RFS showed that CA19-9 elevation did not equal radiographic recurrence but predicted subsequent RFS. Additionally, conditional OS showed that CA19-9 elevation alone was predictive at each time point., Conclusion: This study showed that CA19-9 patterns beyond the post-resection period predict RFS and OS. High CA19-9 frequently is discordant with recurrence on imaging and may precede it by more than 6 months. At each surveillance interval, CA19-9 is predictive of prognosis, which may help in counseling patients and could be used to direct protocols of salvage chemotherapy.

Background: Both FOLFIRINOX and gemcitabine/nab-paclitaxel (G-nP) are used increasingly in the neoadjuvant treatment (NAT) of pancreatic ductal adenocarcinoma (PDA). This study aimed to compare neoadjuvant FOLFIRINOX and G-nP in the treatment of resectable (R) and borderline resectable (BR) head PDA., Methods: A single-institution retrospective review of R and BR patients undergoing pancreaticoduodenectomy after NAT with FOLFIRINOX or G-nP was performed. Comparative analysis was performed using inverse-probability-weighted (IPW) estimators. The end points of the study were overall survival (OS) and an 80% reduction in CA19-9 with NAT., Results: In this study, 193 patients were analyzed, with 73 patients receiving FOLFIRINOX and 120 patients receiving G-nP. The median OS was 38.7 months for FOLFIRINOX versus 28.6 months for G-nP (p = 0.214). The patients who received FOLFIRINOX were younger and had fewer comorbidities, more BR disease, and larger tumors than those treated with G-nP (all p < 0.05). The two regimens were equally effective in achieving an 80% decline in CA19-9 (p = 0.8). The R0 resection rates were similar (80%), but FOLFIRINOX was associated with a reduction in pN1 disease (56% vs. 72%; p = 0.028). The receipt of adjuvant therapy was similar (74 vs. 75%; p = 0.79). In the Cox regression analysis with adjustment for baseline and treatment-related variables (FOLFIRINOX vs. G-nP, age, gender, computed tomography (CT) tumor size, BR vs. R, pre-NAT CA19-9), regimen type was not associated with a survival benefit. In the IPW analysis of 166 patients, however, the average treatment effect of FOLFIRINOX was to increase OS by 4.9 months compared with G-nP (p = 0.012)., Conclusions: Both FOLFIRINOX and G-nP are viable options for neoadjuvant treatment of PDA. In this study, neoadjuvant FOLFIRINOX was associated with a 4.9-month improvement in survival compared with G-nP after adjustment for covariates.

Background: Adoption of robotics in general surgery has expanded but there is no mandatory national standardized curriculum for general surgery residents (GSR)., Methods: A survey was administered to all GSRs in 2014 addressing future practice and robotic experience. A non-mandatory robotic curriculum was available for residents to train. Compliance was assessed. In 2016, the same survey was re-administered. Barriers to completing the curriculum were identified., Results: Interest in improving robotic skills remained high (2014 = 97.8% vs 2016 = 95.9%, p = 0.608), and the majority planned to incorporate robotics into future practice (77.8% vs 69.4%; p = 0.358). Only 11 residents (18%) voluntarily completed the curriculum while 36 (60%) started but did not complete. A trend toward increased procedure participation was seen (60.0%-77.6%, p = 0.066). The perceived barriers to completion of the curriculum were length of time required (80%) and lack of access to a simulator (60%)., Conclusions: A structured robotic training curriculum that is non-mandatory is insufficient in helping residents gain fundamental robotic skills., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Overexpression of HER2 protein and amplification of the ERBB2 gene has been observed in various adenocarcinomas, providing a therapeutic target that can be used to extend the survival of a select cohort of patients. Anti-HER2 therapy has been successfully applied to gastric and colorectal cancers, but its use and potential benefit in small intestinal carcinomas is not well characterized. We applied anti-HER2 therapy to an ERBB2 -amplified advanced duodenal adenocarcinoma, adding trastuzumab to FOLFOX in the neoadjuvant setting. A 61-year-old woman with an advanced duodenal cancer harboring an ERBB2 amplification received preoperative trastuzumab and FOLFOX. Restaging revealed significant tumor downstaging with no metastasis. After multidisciplinary assessment, she underwent pancreaticoduodenectomy. Final pathologic analysis revealed no residual invasive adenocarcinoma, consistent with a complete neoadjuvant treatment response. This case report emphasizes the need for further molecular characterization of small bowel cancers; genetic alterations may provide therapeutic targets to improve the prognosis of these rare and aggressive malignancies., (Copyright © 2017 by the National Comprehensive Cancer Network.)

Purpose of Review: The purpose of this review is to highlight the recent advances in food desensitization in children with food allergy., Recent Findings: Recent advancements in epicutaneous, sublingual, and oral immunotherapy for food allergy in the future may offer children with food allergy and their families a viable option to reduce risk or severity of anaphylaxis with phase III trials ongoing for two of these treatment modalities. Food allergy prevalence in children is estimated to be up to 8%. These children are at risk of significant allergic reactions and anaphylaxis. Food avoidance and use of antihistamines or epinephrine has been the standard of care for these patients. This approach also has a significant socioeconomic effects on patients and their families. Recent advancements in understanding food allergy have allowed for exploring new methods of treatment. There is an increasing interest in oral immunotherapy, epicutaneous immunotherapy, or sublingual immunotherapy for food allergy. There have been also innovative approaches to immunotherapy by modification of food allergens (to make them less allergenic while maintain their immunogenicity) or adding adjunctive treatments (probiotics, anti-IgE, etc.) to increase efficacy or safety.

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Dementia is a major public health problem among the elderly in developed countries and a growing problem in the underdeveloped countries. There are no published data on dementia in any of the Arabic countries. The aim of this study was to determine the different sub-types of dementia among Qataris., Methods: A retrospective and prospective ongoing hospital-based study in which all medical records of the patients with diagnosis of dementia seen at the Hamad General Hospital, Doha, Qatar, between June 1997 and June 2003, whether inpatient or outpatient were reviewed. Dementia was defined according to diagnostic and statistical manual (DSM) IV criteria. Those who had dementia were evaluated by a psychologist, psychiatrist, neurologist and a geriatrician. All had brain computerized tomography, magnetic resonance imaging or both and routine blood tests. Finally, they were classified into sub-types according to the cause of dementia., Results: Out of 300 patients, 134 fulfilled the inclusion criteria, most of them were illiterate, married and non-smokers. Among those dementia sub-types were: Alzheimer disease (AD) 39 (29%), vascular dementia (VaD) 30 (22%), mixed AD and VaD 20 (15%) and Parkinson's disease with dementia 8 (6%) were noted. The rest of them had dementia due to other medical conditions., Conclusion: Our study showed that AD is more prevalent than VaD. It also showed that patients and their families seek medical help late due to the general belief among the public that forgetfulness and other associated cognitive impairment are part of the normal aging process. The emergence of new drugs and advancement in the prevention of cerebrovascular diseases makes early diagnosis of dementia sub-type important. A community based study, to show the real prevalence and incidence of sub-types of dementia, is highly indicated. These data are necessary for planning and setting up community services and health care programs for demented patients.

Varicella-zoster virus (VZV) infection has not often been related to the development of Guillain Barre Syndrome (GBS). However, the close temporal relationship noted between varicella infection and the onset of GBS suggests the participation of VZV in the etiopathogenesis of GBS. Very few cases have been reported showing this relationship. This report describes 2 cases highly suggestive of this association.