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1.
J Minim Access Surg ; 19(1): 120-129, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36629221

RESUMEN

Background: Epiphrenic oesophageal diverticula are rare and often asymptomatic. When symptoms are present, minimally invasive diverticulectomy is considered the gold standard of treatment. While there is an agreement on the pre-operative assessment, no consensus is achieved when it comes to surgical technique. In the present study, we report our experience and propose a standardised approach to manage this rare oesophageal disorder. Materials and Methods: We prospectively analysed data of all consecutive patients who underwent three-dimensional (3D) laparoscopic distal oesophageal diverticulum resection during 2015-2020 at Upper gastrointestinal surgical department, St Thomas' Hospital, regarding pre-operative assessment, surgical technique, peri-and post-operative outcomes. Results: Six patients were submitted to 3D laparoscopic diverticulectomy, five of which with additional anterior myotomy and fundoplication and one with additional hiatal hernia repair only. Three patients followed a specific diet in preparation for surgery. Median pre-operative Eckardt symptom score was five. Two patients had normal manometry. Median operative time was 180 min, median estimated blood loss was <100 ml, neither intraoperative complications nor conversions to open approach occurred. All patients reported a complete resolution of symptoms directly after surgery. Median follow-up was 66 months. Five patients have none or minimal residual symptoms. One had recurrence requiring a revision operation for intermittent dysphagia. Conclusions: 3D laparoscopic diverticulectomy offers a reasonable chance of treatment in patients with epiphrenic diverticula. Optimal selection of patients, optimisation for surgery, gaining the surgical experience of carrying out these techniques and impact on short- and long-term results are issues that still remain under debate.

2.
Surg Endosc ; 36(8): 5753-5765, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35411459

RESUMEN

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.


Asunto(s)
Quemaduras Químicas , Cáusticos , Estenosis Esofágica , Adulto , Quemaduras Químicas/diagnóstico , Quemaduras Químicas/etiología , Quemaduras Químicas/cirugía , Cáusticos/toxicidad , Ingestión de Alimentos , Estenosis Esofágica/etiología , Humanos , Derivación y Consulta , Reino Unido
3.
Surg Innov ; 29(4): 526-531, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32936054

RESUMEN

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.


Asunto(s)
Conductos Biliares Extrahepáticos , Colecistectomía Laparoscópica , Conductos Biliares Extrahepáticos/lesiones , Conductos Biliares Extrahepáticos/cirugía , Colangiografía/métodos , Colecistectomía , Colecistectomía Laparoscópica/efectos adversos , Colecistectomía Laparoscópica/métodos , Fluorescencia , Humanos , Verde de Indocianina
4.
Langenbecks Arch Surg ; 406(7): 2273-2285, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33904977

RESUMEN

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.


Asunto(s)
Neoplasias Esofágicas , Esofagectomía , Cardias/cirugía , Estudios de Cohortes , Neoplasias Esofágicas/cirugía , Unión Esofagogástrica/cirugía , Humanos
5.
Org Biomol Chem ; 18(12): 2215-2218, 2020 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-32150198

RESUMEN

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.

6.
Sensors (Basel) ; 18(3)2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29494504

RESUMEN

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.

7.
Pancreatology ; 16(6): 995-1004, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27288147

RESUMEN

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.


Asunto(s)
Adenocarcinoma/patología , Vasos Sanguíneos/patología , Carcinoma Ductal Pancreático/patología , Células Estrelladas Pancreáticas/patología , Animales , Células Cultivadas , Colangiocarcinoma/patología , Humanos , Ratones , Análisis por Micromatrices , Microcirculación/efectos de los fármacos , Neovascularización Patológica/patología , Técnicas de Cultivo de Órganos , Pronóstico , Análisis de Supervivencia , Tretinoina/uso terapéutico , Microambiente Tumoral
8.
J Pathol ; 230(1): 107-17, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23359139

RESUMEN

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.


Asunto(s)
Matriz Extracelular/patología , Páncreas/patología , Neoplasias Pancreáticas/patología , Células del Estroma/patología , Apoptosis/fisiología , Línea Celular Tumoral , Supervivencia Celular/fisiología , Progresión de la Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/patología , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Miofibroblastos/metabolismo , Miofibroblastos/patología , Invasividad Neoplásica/patología , Técnicas de Cultivo de Órganos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Células Estrelladas Pancreáticas/metabolismo , Células Estrelladas Pancreáticas/patología , Transducción de Señal/fisiología , Células del Estroma/metabolismo , Análisis de Matrices Tisulares , Transcriptoma
9.
Poult Sci ; 102(2): 102368, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36566657

RESUMEN

Past antimicrobial misuse has led to the spread of antimicrobial resistance amongst pathogens, reportedly a major public health threat. Attempts to reduce the spread of antimicrobial resistant (AMR) bacteria are in place worldwide, among which finding alternatives to antimicrobials have a pivotal role. Such molecules could be used as "green alternatives" to reduce the bacterial load either by targeting specific bacterial groups or more generically, functioning as biocides when delivered in vivo. In this study, the effect of in-water peracetic acid as a broad-spectrum antibiotic alternative for broilers was assessed via hydrolysis of precursors sodium percarbonate and tetraacetylethylenediamine. Six equidistant peracetic acid levels were tested from 0 to 50 ppm using four pens per treatment and 4 birds per pen (i.e., 16 birds per treatment and 96 in total). Peracetic acid was administered daily from d 7 to 14 of age whilst measuring performance parameters and end-point bacterial concentration (qPCR) in crop, jejunum, and ceca, as well as crop 16S sequencing. PAA treatment, especially at 20, 30, and 40 ppm, increased body weight at d 14, and feed intake during PAA exposure compared to control (P < 0.05). PAA decreased bacterial concentration in the crop only (P < 0.05), which was correlated to better performance (P < 0.05). Although no differences in alpha- and beta-diversity were found, it was observed a reduction of Lactobacillus (P < 0.05) and Flectobacillus (P < 0.05) in most treatments compared to control, together with an increased abundance of predicted 4-aminobutanoate degradation (V) pathway. The analysis of the AMR genes did not point towards any systematic differences in gene abundance due to treatment administration. This, together with the rest of our observations could indicate that proximal gut microbiota modulation could result in performance amelioration. Thus, peracetic acid may be a valid antimicrobial alternative that could also positively affect performance.


Asunto(s)
Antiinfecciosos , Microbioma Gastrointestinal , Animales , Ácido Peracético/farmacología , Antibacterianos/farmacología , Pollos/microbiología , Farmacorresistencia Bacteriana , Antiinfecciosos/farmacología , Bacterias
10.
J Clin Med Res ; 15(4): 233-238, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37187715

RESUMEN

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.

11.
Surgery ; 171(6): 1494-1499, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35287957

RESUMEN

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.


Asunto(s)
Agotamiento Profesional , COVID-19 , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , COVID-19/epidemiología , Estudios Transversales , Personal de Salud , Humanos , Pandemias , SARS-CoV-2
12.
Nephron Exp Nephrol ; 118(4): e79-86, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21311198

RESUMEN

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.


Asunto(s)
Riñón/enzimología , Leucocitos/enzimología , Microcirculación/fisiología , Óxido Nítrico/fisiología , Inhibidores de Proteínas Quinasas/farmacología , Daño por Reperfusión/enzimología , Quinasas Asociadas a rho/antagonistas & inhibidores , Quinasas Asociadas a rho/fisiología , Amidas/farmacología , Amidas/uso terapéutico , Animales , Riñón/irrigación sanguínea , Leucocitos/efectos de los fármacos , Leucocitos/patología , Masculino , Microcirculación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Ratas , Ratas Wistar , Circulación Renal/efectos de los fármacos , Circulación Renal/fisiología , Daño por Reperfusión/tratamiento farmacológico
13.
Int J Surg Case Rep ; 82: 105917, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33936934

RESUMEN

INTRODUCTION AND IMPORTANCE: Heterotopic pancreas (HP) is defined as the presence of pancreatic tissue without anatomical and vascular continuity with the main body of the pancreas. HP typically remains asymptomatic, however complications such as acute pancreatitis can arise. Gastrointestinal involvement with coronavirus disease 2019 (COVID-19) is not uncommon and there are reported cases of associated pancreatitis. CASE PRESENTATION: A 31-year-old male presented to the Emergency department (ED) with a 3-day history of right iliac fossa pain. The patient was found to have COVID-19 and a planned laparoscopic appendectomy was later converted to a midline laparotomy when a mass close to the duodeno-jejunal (DJ) flexure was identified. Following a hand-sewn anastomosis the patient made a good post-operative recovery. Histology illustrated the presence of heterotopic pancreatic tissue within the small bowel with underlying fat necrosis typical of acute pancreatitis. Follow-up radiology supported the intraoperative finding of intestinal malrotation. CLINICAL DISCUSSION: Rarely the combined presence of intestinal malrotation and HP in patients has been noted. Heterotopic pancreatitis can present in a multitude of ways and it is a difficult diagnosis to make pre-operatively. Emerging literature documents the potential presentation of COVID-19 with acute pancreatitis. The expression of angiotensin-converting enzyme 2 (ACE2) receptors on the pancreas is believed to play a role. CONCLUSION: This is the first documented case of heterotopic pancreatitis with intestinal malrotation in a COVID-19 positive patient. We hypothesise that the COVID-19 infection contributed to the heterotopic pancreatitis.

14.
Pancreas ; 49(3): 313-325, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32168249

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) treatments have historically focused on targeting tumor cells directly. However, in pancreatic masses, the stroma encasing the malignant epithelial cells constitutes up to 80% to 90% of the tumor bulk. This extracellular matrix, which was previously neglected when designing cancer therapies, is now considered fundamental for tumor progression and drug delivery. Desmoplastic tissue is extensively cross-linked, resulting in tremendous tensile strength. This key pathological feature is procarcinogenic, linking PDAC and breast cancer (BC). Physical forces exerted onto cellular surfaces are detected intracellularly and transduced via biochemical messengers in a process called mechanotransduction. Mechanotransduction and tensional homeostasis are linked, with an integral role in influencing tumor growth, metastasis, and interactions with the immune system. It is essential to enhance our knowledge of these integral elements of parenchymal tumors. We aim to review the topic, with a special emphasis on desmoplastic processes and their importance in pancreatic and BC development and treatments, mindful that innovative diagnostic and therapeutic strategies cannot focus on biochemical pathways alone. We then focus on common therapeutic targets identified in both PDAC and BC models and/or patients, aiming to understand these treatments and draw similarities between the two tumors.


Asunto(s)
Neoplasias de la Mama/patología , Carcinoma Ductal Pancreático/patología , Matriz Extracelular/patología , Mecanotransducción Celular , Neoplasias Pancreáticas/patología , Células del Estroma/patología , Microambiente Tumoral , Animales , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/terapia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/terapia , Matriz Extracelular/metabolismo , Femenino , Humanos , Masculino , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Pronóstico , Células del Estroma/metabolismo , Resistencia a la Tracción
15.
Drug Deliv ; 26(1): 1115-1124, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31735095

RESUMEN

Prostate cancer is a leading cause of death in men and despite improved surgical procedures that aid tumor resection, the risk of recurrence after surgery as a result of positive resection margins remains significant. Adjuvant chemotherapy is often required but this is associated with toxicity. Improved ways of delivering highly toxic chemotherapeutic drugs in a more controlled and targeted manner after the prostate has been removed during surgery could reduce the risk of recurrence and avoid systemic toxicity. The aim of this study was to develop a novel drug-device combination tissue scaffold that can be used to deliver the chemotherapeutic agent, docetaxel, into the tissue cavity that is created following radical prostatectomy. The device component investigated consisted of highly porous, poly(dl-lactide-co-glycolide) microparticles made using thermally induced phase separation. A facile method was established for loading docetaxel with high efficiency within one hour. Sustained drug release was observed from the microparticles when placed into a dynamic system simulating tissue perfusion. The drug released from the microparticles into perfusates collected at regular time intervals inhibited colony formation and exhibited sustained cytotoxicity against 3D spheroids of PC3 prostate cancer cells over 10 days. In conclusion, this study demonstrates the concept of combining docetaxel with the biodegradable microparticles at the point of care is technically feasible for achieving an effective drug-device combination tissue scaffold. This approach could provide an effective new approach for delivering adjuvant chemotherapy following radical prostatectomy.


Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/química , Próstata/efectos de los fármacos , Andamios del Tejido/química , Línea Celular Tumoral , Quimioterapia Adyuvante/métodos , Docetaxel/administración & dosificación , Docetaxel/química , Humanos , Masculino , Células PC-3 , Prostatectomía/métodos , Neoplasias de la Próstata/tratamiento farmacológico
16.
Glob Chall ; 3(8): 1800117, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31565392

RESUMEN

Inspired by lotus leaves, self-floating Janus cotton fabric is successfully fabricated for solar steam generation with salt-rejecting property. The layer-selective soot-deposited fabrics not only act as a solar absorber but also provide the required superhydrophobicity for floating on the water. With a polyester protector, the prepared Janus evaporator exhibits a sustainable evaporation rate of 1.375 kW m-2 h-1 and an efficiency of 86.3% under 1 sun (1 kW m-2) and also performs well under low intensity and inclined radiation. Furthermore, no special apparatus and/or tedious processes are needed for preparing this device. With a cost of less than $1 per m2, this flexible Janus absorber is a promising tool for portable solar vapor generator.

17.
FEBS J ; 275(16): 4045-59, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18625007

RESUMEN

The Janus-faced atracotoxins are a unique family of excitatory peptide toxins that contain a rare vicinal disulfide bridge. Although lethal to a wide range of invertebrates, their molecular target has remained enigmatic for almost a decade. We demonstrate here that these toxins are selective, high-affinity blockers of invertebrate Ca(2+)-activated K(+) (K(Ca)) channels. Janus-faced atracotoxin (J-ACTX)-Hv1c, the prototypic member of this toxin family, selectively blocked K(Ca) channels in cockroach unpaired dorsal median neurons with an IC(50) of 2 nm, but it did not significantly affect a wide range of other voltage-activated K(+), Ca(2+) or Na(+) channel subtypes. J-ACTX-Hv1c blocked heterologously expressed cockroach large-conductance Ca(2+)-activated K(+) (pSlo) channels without a significant shift in the voltage dependence of activation. However, the block was voltage-dependent, indicating that the toxin probably acts as a pore blocker rather than a gating modifier. The molecular basis of the insect selectivity of J-ACTX-Hv1c was established by its failure to significantly inhibit mouse mSlo currents (IC(50) approximately 10 mum) and its lack of activity on rat dorsal root ganglion neuron K(Ca) channel currents. This study establishes the Janus-faced atracotoxins as valuable tools for the study of invertebrate K(Ca) channels and suggests that K(Ca) channels might be potential insecticide targets.


Asunto(s)
Insecticidas/química , Bloqueadores de los Canales de Potasio/química , Bloqueadores de los Canales de Potasio/toxicidad , Canales de Potasio Calcio-Activados/antagonistas & inhibidores , Venenos de Araña/química , Venenos de Araña/toxicidad , Secuencia de Aminoácidos , Animales , Línea Celular , Conductividad Eléctrica , Humanos , Insecticidas/toxicidad , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Neuronas/efectos de los fármacos , Neuronas/fisiología , Técnicas de Placa-Clamp , Periplaneta/citología , Periplaneta/efectos de los fármacos , Periplaneta/fisiología , Canales de Potasio con Entrada de Voltaje/metabolismo , Ratas , Homología de Secuencia de Aminoácido
18.
Clin Case Rep ; 6(9): 1665-1667, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30214737

RESUMEN

Postcesarean section complication rate is higher in LMIC (Low and Middle Income Countries) due to lack of resources and specialists availability. A completely or incompletely held infected placenta might underlie a dehiscent cesarean section wound. Humanitarian and local surgeons should consider this differential diagnosis and be ready to practice hysterectomies when needed.

19.
Trop Doct ; 48(3): 217-220, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29895213

RESUMEN

Surgical consent is one of the pillars of ethical conduct in Western world surgical practice. Recent studies have described the consenting processes for clinical trials in low- and middle-income countries (LMICs), but only a few have explored its practice before surgical procedures. The recent World Medical Association (WMA) Declaration of Lisbon recommends autonomy and independent decision-making. However, informed consent is influenced by cultural background, family structure, socioeconomic status, religion and education. The authors of the paper support the WMA recommendations, but agree the process for obtaining informed consent should be reviewed and developed to integrate in a culturally appropriate manner. This commentary reports the author's personal experience of surgical consent in Burundi and reviews the literature describing its practice and the specific challenges faced in Sub-Saharan Africa. Its aim is to encourage a debate among surgeons as to how surgical consent can be undertaken in different scenarios of LMICs.


Asunto(s)
Altruismo , Actitud Frente a la Salud , Características Culturales , Países en Desarrollo , Consentimiento Informado/normas , Procedimientos Quirúrgicos Operativos/normas , África del Sur del Sahara , Burundi , Humanos , Consentimiento Informado/ética , Pobreza , Procedimientos Quirúrgicos Operativos/ética
20.
J Surg Case Rep ; 2018(10): rjy293, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30386553

RESUMEN

Oesophageal adenocarcinoma following gastric band surgery has only been reported three times previously. The incidence is higher in morbidly obese patients, and its pathogenesis is correlated to reflux-induced microenvironmental changes. Bariatric surgery is transformative and its potential benefit for a substantial population is huge. Although no causal relationship with bariatric procedures has been evidenced to date, symptoms of adenocarcinoma-particularly anorexia, weight loss and dysphagia-can easily be overshadowed by alterations in eating patterns associated with weight-loss procedures. We report two cases of oesophageal adenocarcinoma in patients who had undergone a gastric banding procedure, and invite readers to consider the role that pre- and post-operative acid reflux dynamics may have precipitating neoplastic disease, and how endoscopic surveillance may play a role in prevention.

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