Assessment and management after corrosive ingestion: when is specialist centre referral needed? A 10-year UK experience.

BACKGROUND: Corrosive ingestion injuries are rare but clinically significant events, potentially associated with high morbidity and mortality. The low volume of cases limits guideline development. We report a 10-year experience of our tertiary centre focusing on cases requiring specialist care. METHODS: All adults treated following corrosive ingestion between 2010 and 2020 were included. Blood results, imaging and endoscopic findings were reviewed. Patients were stratified based on endoscopic findings. Emergency and delayed management was analysed along with short and long-term outcomes. Predictive value of early outcome indicators was investigated. RESULTS: Eighty-one patients were included, with an average follow-up of 5 years. Patients with injuries ≤ Zargar 2A (n = 15) had long-term outcomes similar to the ones with negative endoscopic findings (n = 51). All fifteen patients suffering injuries Zargar ≥ 2B required ITU and four died (26.6%). All deaths occurred within 50 days of ingestion, had Zargar grade ≥ 3 and airway involvement. Five patients (33%) required emergency operations, two of which died. All Zargar ≥ 2B injury survivors (n = 11) developed strictures and/or tracheo-esophageal fistulae (18%), required multiple admissions and prolonged nutritional support; five required delayed resections. Zargar grade ≥ 2B, airway damage, and increased CRP on admission correlated with unfavourable outcomes. CONCLUSION: Corrosive ingestion injuries up to Zargar 2A do not cause long-term sequelae and can be managed locally. Injuries > 2B bear high mortality and will cause sequelae. Early identification of severe injuries and transfer to specialist centres with multidisciplinary ITU, OG, thoracic and ENT expertise is recommended.

Near-Infrared Fluorescence Cholangiography can be a Useful Adjunct during Emergency Cholecystectomies.

Background. Emergency cholecystectomy is the gold standard treatment for acute cholecystitis according to National Institute for Health and Care Excellence recommendations. The procedure is feasible but carries a higher risk of iatrogenic injury to the bile duct, which should be considered preventable. Intraoperative fluorescence cholangiography following injection of indocyanine green (ICG) has been reported to aid identification of the extrahepatic bile duct. Data on its feasibility in the context of emergency cholecystectomies are missing. Materials and Methods. Fluorescent ICG was used intraoperatively to enhance the biliary anatomy during 33 consecutive emergency laparoscopic cholecystectomies at our institution. Primary outcomes of surgery were considered the length of hospital stay, conversion to open and complications rate, including bile duct injury. Secondary outcome was operating time. A historical population of emergency cholecystectomies was used as control. Results. There were no common bile duct injuries, no adverse effects from ICG, no conversion to open surgery and no deaths. 90% of patients went home within 48 hours after the operation in the absence of complications. ICG demonstrated intraoperative biliary anatomy allowing greater confidence to the surgeon performing emergency cholecystectomies. Six patients were operated beyond 72 hours from admission, without experiencing any complication Clavien-Dindo ≥3. ICG population had the same post-operative hospitalisation and complications rate of the control group, with a shorter operating time. Conclusion. Intraoperative augmented visualisation of biliary anatomy with ICG cholangiography can be a useful technology tool, with the potential to extend the 72 hours window of safety for emergency cholecystectomies.

Minimally invasive total adventitial resection of the cardia for tumours of the oesophagogastric junction.

PURPOSE: A cohort study analysing phases and outcomes of the learning curve required to master minimally invasive total adventitial resection of the cardia. METHODS: Data from 198 consecutive oesophagectomies performed by a single surgeon was collected prospectively. Patients' stratification reflected chronologically and technically the four main phases of the learning curve: open surgery (open total adventitial resection of the cardia (TARC), n = 45), hybrid Ivor Lewis oesophagectomy (HILO, n = 50), laparoscopic-thoracoscopic assisted (LTA, n = 56) and totally minimally invasive TARC (TMI TARC, n = 47). Operating time, hospital stay, specimen lymph nodes and resection margins were analysed. Five-year survival was the main long-term outcome measured. RESULTS: Overall 5-year survival was 45%. Perioperative mortality was 1.5% (n = 3). Hospital stay was 22 ± 23 days. Specimen lymph node median was 20 (range: 15-26). Resection margins were negative (R = 0, American College of Pathologists) in 193 cases (97.4%). Five-year survival in the four phases was 37.8%, 44.9%, 42.9% and 55.3%, showing a positive trend towards the end of the learning curve (p = 0.024). Median specimen lymph nodes was 20 (range: 15-22) for open TARC, 18.5 (13-25) for HILO, 19.5 (15-25) for LTA and 23 (18-30) for TMI TARC (p = 0.006). TMI TARC, adenocarcinoma, R >0, T >2, N >0 and LyRa (ratio positive/total specimen nodes) were associated with survival on univariate analysis. T >2 and LyRa independently predicted worse survival on multivariate analysis. CUSUM analysis showed surgical proficiency gain since laparoscopy was introduced. CONCLUSION: Mastering minimally invasive TARC requires a long learning curve. TMI TARC is safe and oncologically appropriate and may benefit long-term survival: it should be validated by randomised trials as a standardised anatomical resection for tumours of the oesophagogastric junction.

Functionalised thermally induced phase separation (TIPS) microparticles enabled for "click" chemistry.

Due to their homogeneity, tuneable properties, low cost and ease of manufacture, thermally induced phase separation (TIPS) polymeric microparticles are emerging as an exciting class of injectable device for the treatment of damaged tissue or complex diseases, such as cancer. However, relatively little work has explored enhancing surface functionalisation of this system. Herein, we present the functionalisation of TIPS microparticles with both small molecules and an antibody fragment of Herceptin™, via a heterobifunctional pyridazinedione linker capable of participating in SPAAC "click" chemistry, and compare it to the traditional method of preparing active-targeted microparticle systems, that is, physisorption of antibodies to the microparticle surface. Antigen-binding assays demonstrated that functionalisation of microparticles with Herceptin Fab, via a pyridazinedione linker, provided an enhanced avidity to HER2+ when compared to traditional physisorption methods.

The Effect of Film Thickness on the Gas Sensing Properties of Ultra-Thin TiO2 Films Deposited by Atomic Layer Deposition.

Analyte sensitivity for gas sensors based on semiconducting metal oxides should be highly dependent on the film thickness, particularly when that thickness is on the order of the Debye length. This thickness dependence has previously been demonstrated for SnO2 and inferred for TiO2. In this paper, TiO2 thin films have been prepared by Atomic Layer Deposition (ALD) using titanium isopropoxide and water as precursors. The deposition process was performed on standard alumina gas sensor platforms and microscope slides (for analysis purposes), at a temperature of 200 °C. The TiO2 films were exposed to different concentrations of CO, CH4, NO2, NH3 and SO2 to evaluate their gas sensitivities. These experiments showed that the TiO2 film thickness played a dominant role within the conduction mechanism and the pattern of response for the electrical resistance towards CH4 and NH3 exposure indicated typical n-type semiconducting behavior. The effect of relative humidity on the gas sensitivity has also been demonstrated.

Pancreatic stellate cells regulate blood vessel density in the stroma of pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVES: The vascular heterogeneity of pancreatic ductal adenocarcinoma (PDAC) has never been characterised. We analysed the heterogeneous vascular density of human PDAC along with its prognostic correlation. METHODS: Tissue Microarrays of 87 patients with different pancreatico-biliary pathologies were analysed in an automated manner (Ariol™) after CD31 staining to assess vascular density in juxta-tumoral and panstromal compartments. In vitro and ex vivo assays were carried out to assess the role of PSC. RESULTS: PDAC has a distinct vascular density and distribution of vessels compared to cholangiocarcinoma. The PDAC juxta-tumoral stroma was hypovascular and the normal adjacent rim was hypervascular compared to the panstromal compartment. These features adversely affected patient prognosis, suggesting a model for spatio-temporal PDAC evolution. Mice aortic rings and 3D organotypic cultures demonstrated pro- and anti-angiogenic signalling from activated PSC and cancer cells respectively. ATRA-induced quiescence suppressed the pro-angiogenic activity of PSC. CONCLUSION: Human PDAC has variable vascularity at microscopic level suggesting that novel stromal directed therapies would need to be determined by pathological characteristics.

Imbalance of desmoplastic stromal cell numbers drives aggressive cancer processes.

Epithelial tissues have sparse stroma, in contrast to their corresponding tumours. The effect of cancer cells on stromal cells is well recognized. Increasingly, stromal components, such as endothelial and immune cells, are considered indispensable for cancer progression. The role of desmoplastic stroma, in contrast, is poorly understood. Targeting such cellular components within the tumour is attractive. Recent evidence strongly points towards a dynamic stromal cell participation in cancer progression that impacts patient prognosis. The role of specific desmoplastic stromal cells, such as stellate cells and myofibroblasts in pancreatic, oesophageal and skin cancers, was studied in bio-engineered, physiomimetic organotypic cultures and by regression analysis. For pancreatic cancer, the maximal effect on increasing cancer cell proliferation and invasion, as well as decreasing cancer cell apoptosis, occurs when stromal (pancreatic stellate cells) cells constitute the majority of the cellular population (maximal effect at a stromal cell proportion of 0.66-0.83), accompanied by change in expression of key molecules such as E-cadherin and ß-catenin. Gene-expression microarrays, across three tumour types, indicate that stromal cells consistently and significantly alter global cancer cell functions such as cell cycle, cell-cell signalling, cell movement, cell death and inflammatory response. However, these changes are mediated through cancer type-specific alteration of expression, with very few common targets across tumour types. As highlighted by these in vitro data, the reciprocal relationship of E-cadherin and polymeric immunoglobulin receptor (PIGR) expression in cancer cells could be shown, in vivo, to be dependent on the stromal content of human pancreatic cancer. These studies demonstrate that context-specific cancer-stroma crosstalk requires to be precisely defined for effective therapeutic targeting. These data may be relevant to non-malignant processes where epithelial cells interact with stromal cells, such as chronic inflammatory and fibrotic conditions.

Impelling Factors for Contracting COVID-19 Among Surgical Professionals During the Pandemic: A Multinational Cohort Study.

Background: Medical workers, including surgical professionals working in coronavirus disease 2019 (COVID-19) treating hospitals, were under enormous stress during the pandemic. This global study investigated factors endowing COVID-19 amongst surgical professionals and students. Methods: This global cross-sectional survey was made live on February 18, 2021 and closed for analysis on March 13, 2021. It was freely shared on social and scientific media platforms and was sent via email groups and circulated through a personal network of authors. Chi-square test for independence, and binary logistic regression analysis were carried out on determining predictors of surgical professionals contracting COVID-19. Results: This survey captured the response of 520 surgical professionals from 66 countries. Of the professionals, 92.5% (481/520) reported practising in hospitals managing COVID-19 patients. More than one-fourth (25.6%) of the respondents (133/520) reported suffering from COVID-19 which was more frequent in surgical professionals practising in public sector healthcare institutions (P = 0.001). Thirty-seven percent of those who reported never contracting COVID-19 (139/376) reported being still asked to practice self-isolation and wear a shield without the diagnosis (P = 0.001). Of those who did not contract COVID-19, 75.7% (283/376) were vaccinated (P < 0.001). Surgical professionals undergoing practice in the private sector (odds ratio (OR): 0.33; 95% confidence interval (CI): 0.14 - 0.77; P = 0.011) and receiving two doses of vaccine (OR: 0.55; 95% CI: 0.32 - 0.95; P = 0.031) were identified to enjoy decreased odds of contracting COVID-19. Only 6.9% of those who reported not contracting COVID-19 (26/376) were calculated to have the highest "overall composite level of harm" score (P < 0.001). Conclusions: High prevalence of respondents got COVID-19, which was more frequent in participants working in public sector hospitals. Those who reported contracting COVID-19 were calculated to have the highest level of harm score. Self-isolation or shield, getting two doses of vaccines decreases the odds of contracting COVID-19.

The global level of harm among surgical professionals during the COVID-19 pandemic: A multinational cross-sectional cohort study.

BACKGROUND: Health care workers, including surgical professionals, experienced psychological burnout and physical harm during the coronavirus 2019 pandemic. This global survey investigated the coronavirus 2019 pandemic impact on psychological and physical health. METHODS: We conducted a global cross-sectional survey between February 18, 2021 and March 13, 2021. The primary outcome was to assess the psychological burnout, fulfillment, and self-reported physical level of harm. A validated Stanford Professional Fulfilment Index score with a self-reported physical level of harm was employed. We used a practical overall composite level of harm score to calculate the level of harm gradient 1-4, combining psychological burnout with self-reported physical level of harm score. RESULTS: A total of 545 participants from 66 countries participated. The final analysis included 520 (95.4%) surgical professionals barring medical students. Most of the participants (81.3%) were professionally unfulfilled. The psychological burnout was evident in 57.7% and was significantly common in those <50 years (P = .002) and those working in the public sector (P = .005). Approximately 41.7% of respondents showed changes in the physical health with self-remedy and no impact on work, whereas 14.9% reported changes to their physical health with <2 weeks off work, and 10.1% reported changes in physical health requiring >2 weeks off work. Severe harm (level of harm 4) was detected in 10.6%, whereas moderate harm (level of harm 3) affected 40.2% of the participants. Low and no harm (level of harm 2 and level of harm 1) represented 27.5% and 21.7%, respectively. CONCLUSION: Our study showed that high levels of psychological burnout, professional unfulfillment, work exhaustion, and severe level of harm was more frequent in younger professionals working in the public sector. The findings correlated with a high level of harm in surgical professionals impacting surgical services.

ρ-Kinase inhibition reduces early microvascular leukocyte accumulation in the rat kidney following ischemia-reperfusion injury: roles of nitric oxide and blood flow.

AIM: To study whether microvascular leukocyte accumulation after rat renal ischemia and reperfusion (IR) is decreased by Rho kinase inhibition, independently of effects upon nitric oxide (NO) and renal blood flow. METHODS: Male Wistar rats were subjected to 60 min of ischemia by bilateral clamping and 60 min of reperfusion of the renal arteries, or a sham procedure. Haemodynamics were monitored and microsphere blood flow to the kidneys was measured. The infusion of the Rho kinase inhibitor (Y27632) was commenced before clamping and IR. The NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), was administered after the start of reperfusion whilst the dopamine-1 receptor agonist fenoldopam, a renal vasodilator, was infused during the reperfusion period. Digital imaging microscopy analysis of cryosections was done to determine leukocyte accumulation and vasodilator-stimulated phosphoprotein serine 239 phosphorylation (p-VASP ser 239), a marker of endothelial NO. RESULTS: Leukocytes (60-70% neutrophils) accumulated within blood vessels in the corticomedullary junction and medulla of the kidney. Leukocyte accumulation was markedly reduced by the Rho kinase inhibitor but not by fenoldopam. However, both drugs improved renal blood flow and microvascular expression of p-VASP ser 239 in the corticomedullary junction and medulla, which were decreased following IR. L-NAME treatment of IR animals pretreated with the Rho kinase inhibitor reduced blood flow and p-VASP ser 239 expression and increased leukocyte accumulation. CONCLUSION: Early microvascular leukocyte accumulation in the corticomedullary junction and medulla of the rat kidney after IR is ameliorated by Rho kinase inhibition. This effect is partly independent upon attenuation of decreased NO and renal blood flow.