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1.
Arch Dis Child ; 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38471743

ABSTRACT

OBJECTIVE: To assess efficacy and tolerability of semaglutide as a weight loss treatment for children living with comorbid obesity. DESIGN: Retrospective observational study of the first 50 children from a weight management service treated with semaglutide for at least 6 months. SETTING: A tertiary paediatric multidisciplinary weight management clinic in a UK hospital. PATIENTS: Aged 10-18 years old with a body mass index (BMI) SD score (SDS) >2 with a weight-related comorbidity (including insulin resistance (defined as homeostatic model assessment for insulin resistance >4), type 2 diabetes, metabolic-associated fatty liver disease, obstructive sleep apnoea or hypertension). INTERVENTIONS: Once-weekly injectable semaglutide titrated over 8 weeks to a final dose of 1 mg in addition to dietary and lifestyle advice. MAIN OUTCOME MEASURES: Primary outcome measures were change in weight, BMI SDS and percentage body weight. Secondary outcomes were side effects and cessation of treatment. RESULTS: After 6 months of treatment, statistically significant decreases in BMI SDS (0.32±0.27, p<0.001) and body weight (7.03±7.50 kg, p<0.001) were seen. Mean percentage total weight loss was 6.4±6.3% (p<0.001). For the 14 patients for whom 12-month data were available, statistically significant decreases were seen in mean BMI SDS (0.54±0.52, p<0.001). Mean body weight decreased by 9.7±10.8 kg (p<0.001). Percentage total weight loss at 12 months was 8.9±10.0% (p<0.001). Mild gastrointestinal side effects were common. One patient developed gallstones. Five patients discontinued treatment due to side effects. CONCLUSION: Semaglutide appears to be a safe and effective weight loss adjunct when used in a multidisciplinary weight management clinic.

2.
J Trauma Acute Care Surg ; 96(2): 305-312, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37381144

ABSTRACT

BACKGROUND: Emergency general surgery (EGS) admissions account for a large proportion of surgical care and represent the majority of surgical patients who suffer in-hospital mortality. Health care systems continue to experience growing demand for emergency services: one way in which this is being increasingly addressed is dedicated subspecialty teams for emergency surgical admissions, most commonly termed "emergency general surgery" in the United Kingdom. This study aims to understand the impact of the emergency general surgery model of care on outcomes from emergency laparotomies. METHODS: Data was obtained from the National Emergency Laparotomy Audit database. Patients were dichotomized into EGS hospital or non-EGS hospital. Emergency general surgery hospital is defined as a hospital where >50% of in-hours emergency laparotomy operating is performed by an emergency general surgeon. The primary outcome was in-hospital mortality. Secondary outcomes were intensive therapy unit (ITU) length of stay and duration of hospital stay. A propensity score weighting approach was used to reduce confounding and selection bias. RESULTS: There were 115,509 patients from 175 hospitals included in the final analysis. The EGS hospital care group included 5,789 patients versus 109,720 patients in the non-EGS group. Following propensity score weighting, mean standardized mean difference reduced from 0.055 to <0.001. In-hospital mortality was similar (10.8% vs. 11.1%, p = 0.094), with mean length of stay (16.7 days vs. 16.1 days, p < 0.001) and ITU stay (2.8 days vs. 2.6 days, p < 0.001) persistently longer in patients treated in EGS systems. CONCLUSION: No significant association between the emergency surgery hospital model of care and in-hospital mortality in emergency laparotomy patients was seen. There is a significant association between the emergency surgery hospital model of care and an increased length of ITU stay and overall hospital stay. Further studies are required to examine the impact of changing models of EGS delivery in the United Kingdom. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.


Subject(s)
Emergency Medical Services , General Surgery , Humans , Models, Organizational , Emergency Treatment , Laparotomy , United Kingdom , Hospital Mortality , Emergencies , Retrospective Studies , Emergency Service, Hospital
3.
Saudi J Biol Sci ; 30(11): 103791, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37711971

ABSTRACT

Isolation and amplification of nucleic acid (DNA) is considered a vital and potent instrument in molecular biological research. However, its functioning outside of a laboratory setting is difficult because of complex procedures that demand expert personnel and expensive equipment in addition to the fulfillment of several additional requirements. DNA isolation from minute insects is sometimes difficult, making diagnostic and genotyping procedures problematic. Thus, the current work offers a high-throughput, cost-effective, straightforward, and faster approach for isolating DNA from the aphid Myzus persicae. Intriguingly, two-step DNA extraction process yielded a high yield of extremely pure genomic DNA and required only 10 s to complete. PCR investigation aiming at amplifying the non-synonymous R81T region on the loop D site of the nAChR gene of M. persicae was subsequently utilized to successfully validate the recovered DNA. Moreover, the proposed method was compared in terms of yield and purity with conventionally used DNA isolation methods including, phenol:chloroform, salt out, and commercially available kits. In conclusion, this newly developed method would enable researchers to quickly process many biological samples used to analyze genetic diversity, mutant screening, and large spectrum diagnosis both in laboratory and field conditions.

4.
Surg Endosc ; 37(10): 7608-7615, 2023 10.
Article in English | MEDLINE | ID: mdl-37474827

ABSTRACT

BACKGROUND: The adoption of new surgical technologies is inevitably accompanied by a learning curve. With the increasing adoption of robotic techniques in benign foregut surgery, it is imperative to define optimal learning pathways, to ensure a clinically safe introduction of such a technique. The aim of this study was to assess the learning curve for robotic hiatal hernia repair with a pre-defined adoption process and proctoring. METHODS: The learning curve was assessed in four surgeons in a high-volume tertiary referral centre, performing over a 100 hiatal hernia repairs annually. The robotic adoption process included simulation-based training and a multi-day wet lab-based course, followed by robotic operations proctored by robotic upper GI experts. CUSUM analysis was performed to assess changes in operating time in sequential cases. RESULTS: Each surgeon (A, B, C and D) performed between 22 and 32 cases, including a total of 109 patients. Overall, 40 cases were identified as 'complex' (36.7%), including 16 revisional cases (16/109, 14.7%). With CUSUM analysis inflection points for operating time were seen after 7 (surgeon B) to 15 cases (surgeon B). CONCLUSION: The learning curve for robotic laparoscopic fundoplication may be as little as 7-15 cases in the setting of a clearly organized learning pathway with proctoring. By integrating these organized learning pathways learning curves may be shortened, ensuring patient safety, preventing detrimental outcomes due to longer learning curves, and accelerating adoption and integration of novel surgical techniques.


Subject(s)
Hernia, Hiatal , Laparoscopy , Robotic Surgical Procedures , Humans , Learning Curve , Robotic Surgical Procedures/methods , Hernia, Hiatal/surgery , Laparoscopy/methods , Operative Time , United Kingdom , Retrospective Studies
6.
Langenbecks Arch Surg ; 408(1): 62, 2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36692646

ABSTRACT

PURPOSE: Emergency general surgery patients undergoing laparoscopic surgery are at reduced risk of mortality and may require reduced length of critical care stay. This study investigated the effect of laparoscopy on high-risk patients' post-operative care requirements. METHODS: Data were retrieved for all patients entered into the NELA database between 2013 and 2018. Only high-risk surgical patients (P-POSSUM predicted mortality risk of ≥ 5%) were included. Patients undergoing laparoscopic and open emergency general surgical procedures were compared using a propensity score weighting approach. Outcome measures included total length of critical care (level 3) stay, overall length of stay and inpatient mortality. RESULTS: A total of 66,517 high-risk patients received emergency major abdominal surgery. A laparoscopic procedure was attempted in 6998 (10.5%); of these, the procedure was competed laparoscopically in 3492 (49.9%) and converted to open in 3506 (50.1%). Following inverse probability treatment weighting adjustment for patient disease and treatment characteristics, high-risk patients undergoing laparoscopic surgery had a shorter median ICU stay (1 day vs 2 days p < 0.001), overall hospital length of stay (11 days vs 14 days p < 0.001) and a lower inpatient mortality (16.0% vs 18.8%, p < 0.001). They were also less likely to have a prolonged ICU stay with an OR of 0.78 (95% CI 0.74-0.83, p < 0.001). CONCLUSION: The results of this study suggest that in patients at high risk of post-operative mortality, laparoscopic emergency bowel surgery leads to a reduced length of critical care stay, overall length of stay and inpatient mortality compared to traditional laparotomy.


Subject(s)
Laparoscopy , Humans , Length of Stay , Laparoscopy/methods , Laparotomy/adverse effects , Outcome Assessment, Health Care , Critical Care , Retrospective Studies , Postoperative Complications/etiology , Treatment Outcome
7.
Ann Surg ; 277(5): e1124-e1129, 2023 05 01.
Article in English | MEDLINE | ID: mdl-34954757

ABSTRACT

OBJECTIVE: We utilized a population dataset to compare outcomes for patients where surgery was independently performed by trainees to cases led by a consultant. SUMMARY OF BACKGROUND DATA: Emergency laparotomy is a common, high-risk, procedure. Although trainee involvement to improve future surgeons' experience and ability in the management of such cases is crucial, some studies have suggested this is to the detriment of patient outcomes. In the UK, appropriately skilled trainees may be entrusted to perform emergency laparotomy without supervision of a consultant (attending). METHODS: Patients who underwent emergency laparotomy between 2013 and 2018 were identified from the National Emergency Laparotomy Audit of England and Wales. To reduce selection and confounding bias, the inverse probability of treatment weighting approach was used, allowing robust comparison of trainee-led and consultant-led laparotomy cases accounting for eighteen variables, including details of patient, treatment, pathology, and preoperative mortality risk. Groups were compared for mortality and length of stay. RESULTS: A total of 111,583 patients were included in the study. The operating surgeon was a consultant in 103,462 cases (92.7%) and atrainee in 8121 cases (7.3%). Mortality at discharge was 11.6%. Trainees were less likely to operate on high-risk and colorectal cases. After weighting, mortality (12.2% vs 11.6%, P = 0.338) was equivalent between trainee- and consultant-led cases. Median length of stay was 11 (interquartile range 7, 19) versus 11 (7, 20) days ( P = 0.004), respectively. Trainee-led operations reported fewer cases of blood loss >500mL (9.1% vs 11.1%, P < 0.001). CONCLUSIONS: Major laparotomy maybe safely entrusted to appropriately skilled trainees without impacting patient outcomes.


Subject(s)
Laparotomy , Surgeons , Humans , Propensity Score , Consultants , Treatment Outcome
8.
Ann Surg ; 277(2): 267-274, 2023 02 01.
Article in English | MEDLINE | ID: mdl-33630434

ABSTRACT

OBJECTIVE: The aim of this study was to develop a predictive model for overall survival after esophagectomy using pre/postoperative clinical data and machine learning. SUMMARY BACKGROUND DATA: For patients with esophageal cancer, accurately predicting long-term survival after esophagectomy is challenging. This study investigated survival prediction after esophagectomy using a RandomSurvival Forest (RSF) model derived from routine data from a large, well-curated, national dataset. METHODS: Patients diagnosed with esophageal adenocarcinoma or squamous cell carcinoma between 2012 and 2018 in England and Wales who underwent an esophagectomy were included. Prediction models for overall survival were developed using the RSF method and Cox regression from 41 patient and disease characteristics. Calibration and discrimination (time-dependent area under the curve) were validated internally using bootstrap resampling. RESULTS: The study analyzed 6399 patients, with 2625 deaths during follow-up. Median follow-up was 41 months. Overall survival was 47.1% at 5 years. The final RSF model included 14 variables and had excellent discrimination with a 5-year time-dependent area under the receiver operator curve of 83.9% [95% confidence interval (CI) 82.6%-84.9%], compared to 82.3% (95% CI 81.1%-83.3%) for the Cox model. The most important variables were lymph node involvement, pT stage, circumferential resection margin involvement (tumor at < 1 mm from cut edge) and age. There was a wide range of survival estimates even within TNM staging groups, with quintiles of prediction within Stage 3b ranging from 12.2% to 44.7% survival at 5 years. CONCLUSIONS: An RSF model for long-term survival after esophagectomy exhibited excellent discrimination and well-calibrated predictions. At a patient level, it provides more accuracy than TNM staging alone and could help in the delivery of tailored treatment and follow-up.


Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Humans , Lymph Node Excision/methods , Esophagectomy/methods , Carcinoma, Squamous Cell/surgery , Neoplasm Staging
10.
Cancers (Basel) ; 14(5)2022 Feb 24.
Article in English | MEDLINE | ID: mdl-35267476

ABSTRACT

Oesophageal cancer (OC) is the ninth most common cancer worldwide. Patients receive neoadjuvant therapy (NAT) as standard of care, but less than 20% of patients with oesophageal adenocarcinoma (OAC) or a third of oesophageal squamous cell carcinoma (OSCC) patients, obtain a clinically meaningful response. Developing a method of determining a patient's response to NAT before treatment will allow rational treatment decisions to be made, thus improving patient outcome and quality of life. (1) Background: To determine the use and accuracy of microRNAs as biomarkers of response to NAT in patients with OAC or OSCC. (2) Methods: MEDLINE, EMBASE, Web of Science and the Cochrane library were searched to identify studies investigating microRNAs in treatment naïve biopsies to predict response to NAT in OC patients. (3) Results: A panel of 20 microRNAs were identified as predictors of good or poor response to NAT, from 15 studies. Specifically, miR-99b, miR-451 and miR-505 showed the strongest ability to predict response in OAC patients along with miR-193b in OSCC patients. (4) Conclusions: MicroRNAs are valuable biomarkers of response to NAT in OC. Research is needed to understand the effects different types of chemotherapy and chemoradiotherapy have on the predictive value of microRNAs; studies also require greater standardization in how response is defined.

11.
Surg Endosc ; 36(6): 4499-4506, 2022 06.
Article in English | MEDLINE | ID: mdl-34724578

ABSTRACT

BACKGROUND: There is limited evidence regarding the overall feasibility and success rates of the laparoscopic approach in major emergency surgery, despite its potential to improve outcomes. This study aims to investigate the association between patient, procedural, and surgical factors and likelihood of successful laparoscopic completion in emergency major surgery and derive a predictive model to aid clinical decision-making. METHOD: All patients recorded in the NELA emergency laparotomy database 1 December 2013-31 November 2018 who underwent laparoscopically attempted surgery were included. A retrospective cohort multivariable regression analysis was conducted for the outcome of conversion to open surgery. A predictive model was developed and internally validated. RESULTS: Of 118,355 patients, 17,040 (7.7%) underwent attempted laparoscopic surgery, of which 7.915 (46.4%) were converted to open surgery. Procedure type was the strongest predictor of conversion (compared to washout as reference, small bowel resection OR 25.93 (95% CI 20.42-32.94), right colectomy OR 6.92 (5.5-8.71)). Diagnostic [free pus, blood, or blood OR 3.67 (3.29-4.1)] and surgeon [subspecialist surgeon OR 0.56 (0.52-0.61)] factors were also significant, whereas age, gender, and pre-operative mortality risk were not. A derived predictive model had high internal validity, C-index 0.758 (95% CI 0.748-0.768), and is available for free-use online. CONCLUSION: Surgical, patient, and diagnostic variables can be used to predict likelihood of laparoscopic success with a high degree of accuracy. This information can be used to inform peri-operative decision-making and patient selection.


Subject(s)
Laparoscopy , Colectomy/methods , Conversion to Open Surgery , Feasibility Studies , Humans , Laparoscopy/methods , Laparotomy/methods , Retrospective Studies
12.
Ann Surg ; 275(6): 1103-1111, 2022 06 01.
Article in English | MEDLINE | ID: mdl-33914486

ABSTRACT

OBJECTIVE: To determine the relationship between BC, specifically low skeletal muscle mass (sarcopenia) and poor muscle quality (myosteatosis) and outcomes in emergency laparotomy patients. BACKGROUND: Emergency laparotomy has one of the highest morbidity and mortality rates of all surgical interventions. BC objectively identifies patients at risk of adverse outcomes in elective cancer cohorts, however, evidence is lacking in emergency surgery. METHODS: An observational cohort study of patients undergoing emergency laparotomy at ten English hospitals was performed. BC analyses were performed at the third lumbar vertebrae level using preoperative computed tomography images to quantify skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SM-RA). Sex-specific SMI and SM-RA were determined, with the lower tertile splits defining sarcopenia (low SMI) and myosteatosis (low SM-RA). Accuracy of mortality risk prediction, incorporating SMI and SM-RA variables into risk models was assessed with regression modeling. RESULTS: Six hundred ten patients were included. Sarcopenia and myosteatosis were both associated with increased risk of morbidity (52.1% vs 45.1%, P = 0.028; 57.5% vs 42.6%, P = 0.014), 30-day (9.5% vs 3.6%, P = 0.010; 14.9% vs 3.4%, P < 0.001), and 1-year mortality (27.4% vs 11.5%, P < 0.001; 29.7% vs 12.5%, P < 0.001). Risk-adjusted 30-day mortality was significantly increased by sarcopenia [OR 2.56 (95% CI 1.12-5.84), P = 0.026] and myosteatosis [OR 4.26 (2.01-9.06), P < 0.001], similarly at 1-year [OR 2.66 (95% CI 1.57-4.52), P < 0.001; OR2.08 (95%CI 1.26-3.41), P = 0.004]. BC data increased discrimination of an existing mortality risk-prediction model (AUC 0.838, 95% CI 0.835-0.84). CONCLUSION: Sarcopenia and myosteatosis are associated with increased adverse outcomes in emergency laparotomy patients.


Subject(s)
Sarcopenia , Cohort Studies , Female , Humans , Laparotomy/adverse effects , Male , Muscle, Skeletal/diagnostic imaging , Sarcopenia/complications , Tomography, X-Ray Computed/methods
13.
Br J Surg ; 109(2): 227-236, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34910129

ABSTRACT

BACKGROUND: Perioperative chemotherapy is widely used in the treatment of oesophagogastric adenocarcinoma (OGAC) with a substantial survival benefit over surgery alone. However, the postoperative part of these regimens is given in less than half of patients, reflecting uncertainty among clinicians about its benefit and poor postoperative patient fitness. This study estimated the effect of postoperative chemotherapy after surgery for OGAC using a large population-based data set. METHODS: Patients with adenocarcinoma of the oesophagus, gastro-oesophageal junction or stomach diagnosed between 2012 and 2018, who underwent preoperative chemotherapy followed by surgery, were identified from a national-level audit in England and Wales. Postoperative therapy was defined as the receipt of systemic chemotherapy within 90 days of surgery. The effectiveness of postoperative chemotherapy compared with observation was estimated using inverse propensity treatment weighting. RESULTS: Postoperative chemotherapy was given to 1593 of 4139 patients (38.5 per cent) included in the study. Almost all patients received platinum-based triplet regimens (4004 patients, 96.7 per cent), with FLOT used in 3.3 per cent. Patients who received postoperative chemotherapy were younger, with a lower ASA grade, and were less likely to have surgical complications, with similar tumour characteristics. After weighting, the median survival time after postoperative chemotherapy was 62.7 months compared with 50.4 months without chemotherapy (hazard ratio 0.84, 95 per cent c.i. 0.77 to 0.94; P = 0.001). CONCLUSION: This study has shown that postoperative chemotherapy improves overall survival in patients with OGAC treated with preoperative chemotherapy and surgery.


Subject(s)
Adenocarcinoma/drug therapy , Chemotherapy, Adjuvant , Esophageal Neoplasms/drug therapy , Esophagogastric Junction , Postoperative Care/methods , Preoperative Care/methods , Stomach Neoplasms/drug therapy , Adenocarcinoma/surgery , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy, Adjuvant , Esophageal Neoplasms/surgery , Esophagogastric Junction/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Stomach Neoplasms/surgery , Survival Analysis
14.
PLoS One ; 16(10): e0258201, 2021.
Article in English | MEDLINE | ID: mdl-34669698

ABSTRACT

Myzus persicae is a globally important pest with the ability to adjust to a wide range of environmental situations, and many molecular technologies have been developed and applied to understand the biology and/or control this pest insect directly. Reverse-transcription quantitative real-time PCR (RT-qPCR) is a primary molecular technology that is used to quantify gene expression. Choosing a stable reference gene is significantly important for precisely clarifying the expression level of the target gene. Actin and 18S have been recommended as stable compounds for real-time RT-qPCR in M. persicae under the tested biotic and abiotic conditions. In this study, we checked the stability of Actin and 18S by analyzing the relative expression levels of the cytochrome 450 monooxygenase family member genes CYP6CY3 and CYP6-1, carboxylesterase gene E4 and vacuolar protein sorting gene VPS11 via RT-qPCR under various conditions. The expression levels of these four target genes were normalized using both Actin and 18S individually and the combination of these two genes. Our results confirmed that Actin and 18S can be used as reference genes to normalize the expression of target genes under insecticide treatment and starvation in M. persicae. However, at the developmental stages of M. persicae, the expression of the four tested target genes was normalized stably by Actin but not 18S, with the latter presenting a problematic change with the developmental stages. Thus, the stability of reference genes in response to diverse biotic and abiotic factors should be evaluated before each RT-qPCR experiment.


Subject(s)
Actins/genetics , Aphids/genetics , Genes, Insect , RNA, Ribosomal, 18S/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Animals , Aphids/growth & development , Gene Expression Regulation, Developmental/drug effects , Insecticides/toxicity , Niacinamide/analogs & derivatives , Niacinamide/toxicity , Reference Standards , Triazines/toxicity
15.
J Surg Oncol ; 124(8): 1306-1316, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34463378

ABSTRACT

BACKGROUND: Sarcopenia (low skeletal muscle mass), myosteatosis (low skeletal muscle radiation-attenuation) and fitness are independently associated with postoperative outcomes in oesophago-gastric cancer. This study aimed to investigate (1) the effect of neoadjuvant therapy (NAT) on sarcopenia, myosteatosis and cardiopulmonary exercise testing (CPET), (2) the relationship between these parameters, and (3) their association with postoperative morbidity and survival. METHODS: Body composition analysis used single slice computed tomography (CT) images from chest (superior to aortic arch) and abdominal CT scans (third lumbar vertebrae). Oxygen uptake at anaerobic threshold (VO2 at AT) and at peak exercise (VO2 Peak) were measured using CPET. Measurements were performed before and after NAT and an adjusted regression model assessed their association. RESULTS: Of the 184 patients recruited, 100 underwent surgical resection. Following NAT skeletal muscle mass, radiation-attenuation and fitness reduced significantly (p < 0.001). When adjusted for age, sex, and body mass index, only pectoralis muscle mass was associated with VO2 Peak (p = 0.001). VO2 at AT and Peak were associated with 1-year survival, while neither sarcopenia nor myosteatosis were associated with morbidity or survival. CONCLUSION: Skeletal muscle and CPET variables reduced following NAT and were positively associated with each other. Cardiorespiratory function significantly contributes to short-term survival after oesophago-gastric cancer surgery.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Digestive System Surgical Procedures/adverse effects , Esophageal Neoplasms/therapy , Exercise Test/methods , Neoadjuvant Therapy/adverse effects , Sarcopenia/pathology , Stomach Neoplasms/therapy , Aged , Aged, 80 and over , Combined Modality Therapy , Digestive System Surgical Procedures/mortality , Esophageal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoadjuvant Therapy/mortality , Prognosis , Sarcopenia/diagnostic imaging , Sarcopenia/etiology , Stomach Neoplasms/pathology , Survival Rate , Tomography, X-Ray Computed
16.
Cancers (Basel) ; 13(14)2021 Jul 06.
Article in English | MEDLINE | ID: mdl-34298611

ABSTRACT

Neoadjuvant therapy followed by surgery is the standard of care for locally advanced esophageal adenocarcinoma (EAC). Unfortunately, response to neoadjuvant chemotherapy (NAC) is poor (20-37%), as is the overall survival benefit at five years (9%). The EAC genome is complex and heterogeneous between patients, and it is not yet understood whether specific mutational patterns may result in chemotherapy sensitivity or resistance. To identify associations between genomic events and response to NAC in EAC, a comparative genomic analysis was performed in 65 patients with extensive clinical and pathological annotation using whole-genome sequencing (WGS). We defined response using Mandard Tumor Regression Grade (TRG), with responders classified as TRG1-2 (n = 27) and non-responders classified as TRG4-5 (n =38). We report a higher non-synonymous mutation burden in responders (median 2.08/Mb vs. 1.70/Mb, p = 0.036) and elevated copy number variation in non-responders (282 vs. 136/patient, p < 0.001). We identified copy number variants unique to each group in our cohort, with cell cycle (CDKN2A, CCND1), c-Myc (MYC), RTK/PIK3 (KRAS, EGFR) and gastrointestinal differentiation (GATA6) pathway genes being specifically altered in non-responders. Of note, NAV3 mutations were exclusively present in the non-responder group with a frequency of 22%. Thus, lower mutation burden, higher chromosomal instability and specific copy number alterations are associated with resistance to NAC.

17.
Dis Esophagus ; 34(7)2021 Jul 12.
Article in English | MEDLINE | ID: mdl-33458741

ABSTRACT

BACKGROUND: There are a variety of surgical and endoscopic interventions available to treat gastroesophageal reflux disease. There is, however, no consensus on which approach is best.The aim of this national audit is to describe the current variation in the UK clinical practice in relation to anti-reflux surgery (ARS) and to report adherence to available clinical guidelines. METHODS: This national audit will be conducted at centers across the UK using the secure online web platform ALEA. The study will comprise two parts: a registration questionnaire and a prospective multicenter audit of ARS. All participating centers will be required to complete the registration questionnaire comprising details regarding pre-, peri-, and post-operative care pathways and whether or not these are standardized within each center. Following this, a 12-month multicenter prospective audit will be undertaken to capture data including patient demographics, predominant symptoms, preoperative investigations, surgery indication, intraoperative details, and postoperative outcomes within the first 90 days.Local teams will retain access to their own data to facilitate local quality improvement. The full dataset will be reported at national and international scientific congresses and will contribute to peer-reviewed publications and national quality improvement initiatives. CONCLUSIONS: This study will identify and explore variation in the processes and outcomes following ARS within the UK using a collaborative cohort methodology. The results generated by this audit will facilitate local and national quality improvement initiatives and generate new possibilities for future research in anti-reflux interventions.


Subject(s)
Digestive System Surgical Procedures , Gastroesophageal Reflux , Hernia, Hiatal , Laparoscopy , Fundoplication , Gastroesophageal Reflux/surgery , Hernia, Hiatal/surgery , Humans , Treatment Outcome , United Kingdom
18.
Eur J Surg Oncol ; 46(12): 2248-2256, 2020 12.
Article in English | MEDLINE | ID: mdl-32694054

ABSTRACT

BACKGROUND: Esophageal cancer is increasingly common and carries a poor prognosis. The optimal treatment modality for locally advanced cancer is unknown, with current guidance recommending either neoadjuvant chemotherapy (CT) or chemoradiotherapy (CRT) followed by surgery. There is a lack of adequately powered trials comparing CT against CRT. We retrospectively compared CT versus CRT using a propensity score weighting approach. METHODS: Demographic, disease, treatment and outcome data were retrieved from a local database for patients who received neoadjuvant CT or CRT followed by surgery. Inverse probability of treatment weighting (IPTW) was used to balance groups using a propensity score-weighting approach. Groups were assessed for differences in postoperative outcomes and survival. Kaplan-Meier and non-parametric tests were used to compare survival and outcome data as appropriate. RESULTS: Data for 284 patients were retrieved. Following IPTW groups were well matched. No significant differences were seen for postoperative complications (CT 64.9% vs. CRT 63.3%, p = 0.807), including major complications (24.0% vs. 23.6%, p = 0.943) and anastomotic leak (7.8% vs. 5.6%, p = 0.526). Significantly higher rates of clinical regression and complete pathological response were seen following CRT (p = 0.002 for both). Rates of R0 resection were higher with CRT, CT 79.1% vs. CRT 93.1%, p = 0.006. There was no difference between groups for overall or disease-free survival. CONCLUSION: This study suggests that the significant improvements in local tumour response seen after neoadjuvant CRT compared to CT may not translate to different survival outcomes. However, it must be stressed that adequately powered prospective trials are still lacking.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy/methods , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma/therapy , Esophagectomy , Neoadjuvant Therapy , Postoperative Complications/epidemiology , Adenocarcinoma/pathology , Aged , Capecitabine/administration & dosage , Disease-Free Survival , Docetaxel/administration & dosage , Epirubicin/administration & dosage , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Esophagogastric Junction/pathology , Female , Fluorouracil/administration & dosage , Hospital Mortality , Humans , Length of Stay , Leucovorin/administration & dosage , Lymph Node Excision , Male , Middle Aged , Neoplasm Staging , Oxaliplatin/administration & dosage , Propensity Score , Survival Rate , Treatment Outcome
19.
J Phys Condens Matter ; 32(21): 215401, 2020 May 13.
Article in English | MEDLINE | ID: mdl-31978908

ABSTRACT

An isostructural phase transition and a cubic to tetragonal phase transition in spin-frustrated pyrochlore Dy2Ti2O7 (DTO) at 35 GPa and 46 GPa, respectively, were detected by x-ray diffraction (XRD) and Raman spectroscopy studies at room temperature under high pressure. The band gap of DTO gradually increased with the increasing pressure up to 20 GPa, after which it narrowed significantly around 35 GPa, and further manifested with a slight discontinuity around 46 GPa. Below 35 GPa, the evolution of band gap with pressure maintained a close relationship with the Ti-O bond length and the distortion of TiO6 octahedron. The remarkable narrowing of the band gap around 35 GPa implied the changes of the band structure and confirmed the isostructural phase transition. These findings provide an in-depth understanding of the evolution of the structure and the band gap of DTO under high pressure.

20.
Adv Sci (Weinh) ; 6(19): 1901132, 2019 Oct 02.
Article in English | MEDLINE | ID: mdl-31592421

ABSTRACT

Inverse photoconductivity (IPC) is a unique photoresponse behavior that exists in few photoconductors in which electrical conductivity decreases with irradiation, and has great potential applications in the development of photonic devices and nonvolatile memories with low power consumption. However, it is still challenging to design and achieve IPC in most materials of interest. In this study, pressure-driven photoconductivity is investigated in n-type WO3 nanocuboids functionalized with p-type CuO nanoparticles under visible illumination and an interesting pressure-induced IPC accompanying a structural phase transition is found. Native and structural distortion induced oxygen vacancies assist the charge carrier trapping and favor the persistent positive photoconductivity beyond 6.4 GPa. The change in photoconductivity is mainly related to a phase transition and the associated changes in the bandgap, the trapping of charge carriers, the WO6 octahedral distortion, and the electron-hole pair recombination process. A unique reversible transition from positive to inverse photoconductivity is observed during compression and decompression. The origin of the IPC is intimately connected to the depletion of the conduction channels by electron trapping and the chromic property of WO3. This synergistic rationale may afford a simple and powerful method to improve the optomechanical performance of any hybrid material.

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