Prolonged neutrophilia is associated with worse outcomes after Esophagectomy

Author(s):  
Ian C Bostock ◽  
Nicolas Zhou ◽  
Mara B Antonoff ◽  
Mariela Blum Murphy ◽  
Steven Lin ◽  
...  

Abstract Neutrophilia is a potential biomarker for postoperative complications and oncologic outcomes. There is a paucity of data regarding neutrophilia in patients with esophageal adenocarcinoma. Our Institutional Database was queried for esophageal adenocarcinoma patients who underwent esophagectomy from 2006 to 2019. Complete blood counts (CBC), demographic characteristics, perioperative and oncologic outcomes were evaluated. Two groups were created based on the presence of prolonged neutrophilia (PN, >7,000 absolute neutrophils 90 days after surgery). Univariate, multivariable, and survival analysis were performed (P-value < 0.05). We identified 686 patients with complete CBC data: 565 in the no prolonged neutrophilia (NPN) and 121 in the PN groups (17.6%). The mean age was 54 versus 48 years in the NPN and PN groups (P = 0.01). There was no difference in height, weight, gender, race, tumor size, histology, pTNM, PS, ASA, salvage procedure, neoadjuvant treatment and comorbidities. On multivariable analysis, the PN group had increased transfusions (19.8% vs. 11.9%; P = 0.02), aspiration (13.2% vs. 2.5%; P = 0.002), pulmonary embolus (3.3% vs. 0.4%; P = 0.02), cardiac arrest (5% vs. 0.4%; P = 0.02) and hematologic complications (23.1% vs. 12.6%; P = 0.01). After controlling for any postoperative complication, PN had increased distant recurrence (24% vs. 12.7%; hazard ration [HR]: 2.3, 95% confidence interval [CI] 1.42–3.9; P = 0.001) and decreased OS (33.8% vs. 49.7%, HR: 1.83, 95% CI: 1.19–2.81; P = 0.006); median follow up 77 months (46–109). PN was predictive of distant recurrence and decreased overall survival. Further work investigating these neutrophil populations represents a potential area for biomarker research, immunomodulation, and may guide postoperative surveillance strategies.

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Masakazu Goto ◽  
Yukiko Shibahara ◽  
Cristina Baciu ◽  
Frances Allison ◽  
Mathieu Derouet ◽  
...  

Abstract   Chemokines are major regulators of cell trafficking and adhesion. The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, have recently been reported as biomarkers in various cancers, including esophageal squamous cell carcinoma; however, there are few studies of these chemokines in esophageal adenocarcinoma (EAC). In this study, we investigated the relationship between expression of CXCL12, CXCR4 and CXCR7, and prognosis in patients with EAC. Methods This study examined 55 patients with EAC who were treated in Toronto General Hospital from 2001 to 2010. Tissue microarray immunohistochemistry was used to evaluate the expression of CXCL12, CXCR4 and CXCR7. Evaluation of immunohistochemistry was performed by a pathologist without knowledge of patients’ information and scored based on a semiquantitative scoring system. The average score from multiple cancer tissues on the microarray was utilized and patients were divided into high or low expression groups using the median score as a cutoff point. These results were compared with the patients’ clinicopathological features and survival. Results The score of CXCR7 was positively correlated with that of CXCL12 (r = 0.3154). High CXCR7 expression was significantly associated with lymphatic invasion (present vs absent, P = 0.005), higher number of lymph node metastases (pN0–1 vs pN2–3, P = 0.0014) and TNM stage (Stage I-II vs III-IV, P = 0.0168). Patients with high CXCR7 (n = 23) expression was associated with worse overall (OS) and disease-free survival (DFS) (P = 0.0221, 0.0090, respectively), and patients with high CXCL12 (n = 24) tended to have worse OS and DFS (P = 0.1091, 0.1477, respectively). High expression of both CXCR7 and CXCL12 was an independent prognostic factor for DFS on multivariable analysis (HR0.3, 95%CI: 0.1–0.8, P = 0.0115). Conclusion High CXCR7 expression was associated with poor prognosis in patients with EAC, and high expression of CXCR7 and its ligand CXCL12, had a stronger association on prognosis. Further study of this potential biomarker using whole tissue samples and larger sample size is warranted.


Objective: While the use of intraoperative laser angiography (SPY) is increasing in mastectomy patients, its impact in the operating room to change the type of reconstruction performed has not been well described. The purpose of this study is to investigate whether SPY angiography influences post-mastectomy reconstruction decisions and outcomes. Methods and materials: A retrospective analysis of mastectomy patients with reconstruction at a single institution was performed from 2015-2017.All patients underwent intraoperative SPY after mastectomy but prior to reconstruction. SPY results were defined as ‘good’, ‘questionable’, ‘bad’, or ‘had skin excised’. Complications within 60 days of surgery were compared between those whose SPY results did not change the type of reconstruction done versus those who did. Preoperative and intraoperative variables were entered into multivariable logistic regression models if significant at the univariate level. A p-value <0.05 was considered significant. Results: 267 mastectomies were identified, 42 underwent a change in the type of planned reconstruction due to intraoperative SPY results. Of the 42 breasts that underwent a change in reconstruction, 6 had a ‘good’ SPY result, 10 ‘questionable’, 25 ‘bad’, and 2 ‘had areas excised’ (p<0.01). After multivariable analysis, predictors of skin necrosis included patients with ‘questionable’ SPY results (p<0.01, OR: 8.1, 95%CI: 2.06 – 32.2) and smokers (p<0.01, OR:5.7, 95%CI: 1.5 – 21.2). Predictors of any complication included a change in reconstruction (p<0.05, OR:4.5, 95%CI: 1.4-14.9) and ‘questionable’ SPY result (p<0.01, OR: 4.4, 95%CI: 1.6-14.9). Conclusion: SPY angiography results strongly influence intraoperative surgical decisions regarding the type of reconstruction performed. Patients most at risk for flap necrosis and complication post-mastectomy are those with questionable SPY results.


2020 ◽  
Vol 13 (1) ◽  
pp. 658-666
Author(s):  
Tossapon Chamnankit ◽  
Parichat Ong-artborirak ◽  
Jukkrit Wangrath

Background: Elderly people with uncontrolled diabetes mellitus (DM) are at risk of falls, which can lead to injury and disability. Not much is known of informal caregivers’ awareness of falls in elderly patients with DM. Objective: This study aims to identify an association between caregiver’s awareness and falls in elderly patients with DM. Methods: A total of 136 pairs of DM patients and their respective family caregivers were recruited from a clinical service center at Chiang Mai University, Thailand. The questionnaire regarding the caregiver’s awareness of the risk of falls in elderly patients was given via a face-to-face interview. Each elderly patient was asked about their history of falls in the prior year, and the risk of falls was assessed by Time Up & Go (TUG) test. Logistic regression analysis was performed to determine association. Results: The mean age of the DM patients was 65.7 years. Sixty-two patients (45.6%) had fallen at least once in the prior year. The mean TUG test result was 12.67±1.83 second. Most caregivers demonstrated a high level of awareness regarding the risk of falls in elderly patients. The results of the multivariable analysis showed that three variables – balance problems, risk of falls assessed by TUG test, and scores of caregiver’s awareness of risk of falls – were significantly related to falls in the previous year among elderly patients with DM (p-value<0.05). Conclusion: The caregivers’ awareness of fall risk may influence fall occurrence among older adults with DM. An intervention program to improve awareness among informal caregivers should be considered for fall prevention in elderly people.


Author(s):  
Jae Young Moon ◽  
Min Ro Lee ◽  
Gi Won Ha

Abstract Background Transanal total mesorectal excision (TaTME) appears to have favorable surgical and pathological outcomes. However, the evidence on survival outcomes remains unclear. We performed a meta-analysis to compare long-term oncologic outcomes of TaTME with transabdominal TME for rectal cancer. Methods PubMed, EMBASE, and the Cochrane Library were searched. Data were pooled, and overall effect size was calculated using random-effects models. Outcome measures were overall survival (OS), disease-free survival (DFS), and local and distant recurrence. Results We included 11 nonrandomized studies that examined 2,143 patients for the meta-analysis. There were no significant differences between the two groups in OS, DFS, and local and distant recurrence with a RR of 0.65 (95% CI 0.39–1.09, I2 = 0%), 0.79 (95% CI 0.57–1.10, I2 = 0%), 1.14 (95% CI 0.44–2.91, I2 = 66%), and 0.75 (95% CI 0.40–1.41, I2 = 0%), respectively. Conclusion In terms of long-term oncologic outcomes, TaTME may be an alternative to transabdominal TME in patients with rectal cancer. Well-designed randomized trials are warranted to further verify these results.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abdelrahman Zamzam ◽  
Muzammil H. Syed ◽  
John Harlock ◽  
John Eikelboom ◽  
Krishna K. Singh ◽  
...  

AbstractPlasma levels of fatty acid binding protein 3 (pFABP3) are elevated in patients with peripheral artery disease (PAD). Since the kidney filters FABP3 from circulation, we investigated whether urinary fatty acid binding protein 3 (uFABP3) is associated with PAD, and also explored its potential as a diagnostic biomarker for this disease state. A total of 130 patients were recruited from outpatient clinics at St. Michael’s Hospital, comprising of 65 patients with PAD and 65 patients without PAD (non-PAD). Levels of uFABP3 normalized for urine creatinine (uFABP3/uCr) were 1.7-folds higher in patients with PAD [median (IQR) 4.41 (2.79–8.08)] compared with non-PAD controls [median (IQR) 2.49 (1.78–3.12), p-value = 0.001]. Subgroup analysis demonstrated no significant effect of cardiovascular risk factors (age, sex, hypertension, hypercholesteremia, diabetes and smoking) on uFABP3/uCr in both PAD and non-PAD patients. Spearmen correlation studies demonstrated a significant negative correlation between uFABP3/uCr and ABI (ρ = − 0.436; p-value = 0.001). Regression analysis demonstrated that uFABP3/Cr levels were associated with PAD independently of age, sex, hypercholesterolemia, smoking, prior history of coronary arterial disease and Estimated Glomerular Filtration rate (eGFR) [odds ratio: 2.34 (95% confidence interval: 1.47–3.75) p-value < 0.001]. Lastly, receiver operator curve (ROC) analysis demonstrated unadjusted area under the curve (AUC) for uFABP3/Cr of 0.79, which improved to 0.86 after adjusting for eGFR, age, hypercholesteremia, smoking and diabetes. In conclusion, our results demonstrate a strong association between uFABP3/Cr and PAD and suggest the potential of uFABP3/Cr in identifying patients with PAD.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 38-38
Author(s):  
Piers Boshier ◽  
Andrea Wirsching ◽  
Rajesh Krishnamoorthi ◽  
Michael Larsen ◽  
Shayan Irani ◽  
...  

Abstract Background Endoscopic therapy is considered to be comparable to esophagectomy with respect to oncologic outcomes in early (clinical stage T1) esophageal adenocarcinoma (EC). The current study aims to compare early outcomes and financial costs, associated with endoscopic versus surgical therapy for early EC. Methods Retrospective review of patients undergoing either endoscopic or surgical therapy for cT1 EC between 2010 and 2015 at a single high-volume center. To ensure comparability between treatment groups only those patients who were deemed medically fit to undergo esophagectomy, regardless of ultimate management, were included. Cost analysis was performed for each patient group and was compared to procedural outcomes. Results Forty-three patients met the inclusion criteria for this study (endoscopic therapy n = 20; esophagectomy n = 23). All patients who underwent endoscopic therapy had clinical stage T1A, whilst 15 patients in the esophagectomy group had T1B disease (P < 0.001). Patient groups were well matched for all other baseline characteristics (P > 0.05). For patients undergoing endoscopic therapy a median of six interventions were performed per patient (range 2–18). Same day discharge was achieved after 98% of all endoscopic procedures with 72% of cases performed under general anesthesia. Endoscopic dilations due to stricture formation were required in five (25%) patients after endoscopic therapy. Esophagectomy was associated with a median hospital stay of 9 (8–13) days and greater procedure specific morbidity compared to endoscopic therapy. Median treatment costs for patients undergoing esophagectomy were significantly greater than that incurred for patients receiving endoscopic therapy only ($53,849, 95%-confidence interval: 50,541–88,784 vs. $22,640, 95%CI: 18,754–46,705, P < 0.001). The minimum cost associated with esophagectomy in the current study was approximately four times greater than for endoscopic therapy ($40,410 vs. $9236). In comparison the maximum cost incurred for surgical and endoscopic therapy were $247,808 and $127,508 respectively. Overall costs were significantly correlated to either number and severity or postoperative complications or number of endoscopic procedures performed (P < 0.002). Conclusion In patients with early EC endoscopic therapy was associated with lower rates of procedure specific morbidity compared to esophagectomy. Despite an increased number of interventions and longer duration of therapy, overall costs were significantly lower in patients undergoing endoscopic therapy when compared to esophagectomy. Disclosure All authors have declared no conflicts of interest.


Author(s):  
Anika Tabassum ◽  
Md. Nazmus Samdani ◽  
Tarak Chandra Dhali ◽  
Rahat Alam ◽  
Foysal Ahammad ◽  
...  

Transporter associated with antigen processing 1 (TAP1) gene codes for a transporter protein, which is responsible for tumor antigen presentation in the MHC I or HLA complex. A defect in the gene results in an inadequate tumor tracking. TAP1 may also influence multi drug resistance, which is an extreme threat in providing treatment by drugs which are chemotherapeutic. The gene of TAP1 was analyzed bioinformatically. It gave us prognostic data as a confirmation of whether it should be used as a biomarker. The expression level and pattern analysis were conducted using ONCOMINE, GENT2 and GEPIA2 online platforms. Samples with different clinical outcomes were investigated for expression and promoter methylation analysis was done in cancer vs normal tissues using UALCAN. The copy number alteration and mutation frequency and expression in different cancer studies were analyzed using cBioPortal. The PrognoScan and KM plotter survival analysis of significant data (p-value&lt;0.05) was representing graphically. Pathway and Gene ontology analysis of gene correlated to TAP1 gene was presented using bar charts. After arranging the data in a single panel and correlating expression to prognosis, understanding mutational and alterations and comparing pathways, TAP1 may be a potential novel target to evade a threat against chemotherapy and the study gives new aspects to consider for immunotherapy in human breast, lung, liver and ovarian cancer.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 520-520
Author(s):  
Joseph A. Sparano ◽  
Anne M. O'Neill ◽  
Noah Graham ◽  
Donald W. Northfelt ◽  
Chau T. Dang ◽  
...  

520 Background: Systemic inflammation may contribute to cancer progression (PMC2803035), including recurrence of early breast cancer (PMC4828958). We hypothesized that inflammatory cytokines and/or chemokines may be associated with distant recurrence (DR). Methods: We performed a case:control study in women with stage II-III Her2-negative breast cancer, all of whom had surgery and adjuvant chemotherapy (doxorubicin/cyclophosphamide, then weekly paclitaxel) with/without bevacizumab, plus endocrine therapy if ER-positive (PMC6118403). Propensity score matching was used to identify approximately 250 case:control pairs (with/without DR). Serum samples obtained before adjuvant chemotherapy were analyzed using the MSD V-Plex Human Cytokine 36-Plex Kit for detection of human cytokines and chemokines involved in the Th1/Th2 pathway, chemotaxis, the Th17 pathway, angiogenesis, and immune system regulation. Conditional logistic regression analysis, with models fit via maximum likelihood, were used to estimate hazard ratios (HRs) and test for associations. Due to skewed nature of cytokines, HRs are reported on log base 2 scale. If adjusted for multiple testing including 36 markers, a p value of < 0.0014 would be required for statistical significance. Results: A total 249 matched pairs (498 patients) were identified. Covariates used for propensity score matching included age, menopausal status (post 54% vs. pre/peri 46%), ER/PR status (one/both pos 64% vs. both neg 36%) tumor size ( < = 2cm 17%, > 2-5cm 67%, > 5cm 16%) nodal status (neg 15%,1-3+ 32%, 4+ 53%), and grade (low 3%, int. 31%, high 66%). The only biomarker associated with a significantly increased DR risk when adjusted for multiple testing was the proinflammatory cytokine IL-6 (HR 1.37, 95% confidence intervals [CI] 1.15, 1.65, p = 0.0006). Others associated with a 2-sided p value < 0.05 included the chemokine MDC(macrophage-derived chemokine/CCL22) (1.90, 95% CI 1.17, 3.1, p = 0.0098), the T helper cell inflammatory cytokine IL-17A (HR 1.36, 95% CI 1.10, 1.67, p = 0.0052), and the cytokine VEGF-A (HR 1.13 for, 95% CI 1.01, 1.27, p = 0.037). There was no statistical interaction between VEGF-A and bevacizumab benefit. The median and mean value for IL-6 was 0.95 and 7.5 pg/ml (range 0.04-2761.24 pg/ml). Conclusions: This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher DR risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy. This provides a foundation for confirmatory validation of IL-6 as a prognostic biomarker, and potentially as a predictive biomarker for testing therapeutic interventions targeting the IL-6/JAK/STAT3 pathway. Supported by NCI U10CA180820,180794,180821; UG1CA189859,232760,233290, 233196; Komen Foundation; Breast Cancer Research Foundation. Clinical trial information: NCT00433511.


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