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BACKGROUND: Oesophageal cancer, in particular adenocarcinoma, has a strong male predominance. However, the impact of patient sex on operative and oncologic outcomes and recovery of health-related quality of life is poorly documented, and was the focus of this large multicentre cohort study. METHODS: All consecutive patients who underwent oncological oesophagectomy from 2009 to 2015 in the 20 European iNvestigation of SUrveillance after Resection for Esophageal cancer study group centres were assessed. Clinicopathologic variables, therapeutic approach, postoperative complications, survival and health-related quality of life data were compared between male and female patients. Multivariable analyses adjusted for age, sex, tumour histology, treatment protocol and major complications. Specific subgroup analyses comparing adenocarcinoma versus squamous cell cancer for all key outcomes were performed. RESULTS: Overall, 3974 patients were analysed, 3083 (77.6%) male and 891 (22.4%) female; adenocarcinoma was predominant in both groups, while squamous cell cancer was observed more commonly in female patients (39.8% versus 15.1%, P < 0.001). Multivariable analysis demonstrated improved outcomes in female patients for overall survival (HRmales 1.24, 95% c.i. 1.07 to 1.44) and disease-free survival (HRmales 1.22, 95% c.i. 1.05 to 1.43), which was caused by the adenocarcinoma subgroup, whereas this difference was not confirmed in squamous cell cancer. Male patients presented higher health-related quality of life functional scores but also a higher risk of financial problems, while female patients had lower overall summary scores and more persistent gastrointestinal symptoms. CONCLUSION: This study reveals uniquely that female sex is associated with more favourable long-term survival after curative treatment for oesophageal cancer, especially adenocarcinoma, although long-term overall and gastrointestinal health-related quality of life are poorer in women.
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Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Humanos , Masculino , Feminino , Qualidade de Vida , Estudos Retrospectivos , Estudos de Coortes , Carcinoma de Células Escamosas/cirurgiaRESUMO
OBJECTIVE: To determine the impact of operative approach [open (OE), hybrid minimally invasive (HMIE), and total minimally invasive (TMIE) esophagectomy] on operative and oncologic outcomes for patients treated with curative intent for esophageal and junctional cancer. BACKGROUND: The optimum oncologic surgical approach to esophageal and junctional cancer is unclear. METHODS: This secondary analysis of the European multicenter ENSURE study includes patients undergoing curative-intent esophagectomy for cancer between 2009 and 2015 across 20 high-volume centers. Primary endpoints were disease-free survival (DFS) and the incidence and location of disease recurrence. Secondary endpoints included among others R0 resection rate, lymph node yield, and overall survival (OS). RESULTS: In total, 3199 patients were included. Of these, 55% underwent OE, 17% HMIE, and 29% TMIE. DFS was independently increased post-TMIE [hazard ratio (HR): 0.86 (95% CI: 0.76-0.98), P = 0.022] compared with OE. Multivariable regression demonstrated no difference in absolute locoregional recurrence risk according to the operative approach [HMIE vs OE, odds ratio (OR): 0.79, P = 0.257; TMIE vs OE, OR: 0.84, P = 0.243]. The probability of systemic recurrence was independently increased post-HMIE (OR: 2.07, P = 0.031), but not TMIE (OR: 0.86, P = 0.508). R0 resection rates ( P = 0.005) and nodal yield ( P < 0.001) were independently increased after TMIE, but not HMIE ( P = 0.424; P = 0.512) compared with OE. OS was independently improved following both HMIE (HR: 0.79, P = 0.009) and TMIE (HR: 0.82, P = 0.003) as compared with OE. CONCLUSION: In this European multicenter study, TMIE was associated with improved surgical quality and DFS, whereas both TMIE and HMIE were associated with improved OS as compared with OE for esophageal cancer.
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Neoplasias Esofágicas , Esofagectomia , Recidiva Local de Neoplasia , Humanos , Esofagectomia/métodos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Masculino , Feminino , Recidiva Local de Neoplasia/epidemiologia , Pessoa de Meia-Idade , Idoso , Procedimentos Cirúrgicos Minimamente Invasivos , Taxa de Sobrevida , Europa (Continente)/epidemiologia , Intervalo Livre de Doença , Resultado do TratamentoRESUMO
Esophagectomy is an exemplar of complex oncological surgery and is associated with a relatively high risk of major morbidity and mortality. In the modern era, where specific complications are targeted in prevention and treatment pathways, and where the principles of enhanced recovery after surgery are espoused, optimum outcomes are targeted via a number of approaches. These include comprehensive clinical and physiological risk assessment, specialist perioperative care by a high-volume team, and multimodal inputs throughout the patient journey that aim to preserve or restore nutritional deficits, muscle mass and function.
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Neoplasias Esofágicas , Assistência Perioperatória , Humanos , Esofagectomia/efeitos adversos , Neoplasias Esofágicas/etiologiaRESUMO
BACKGROUND: Obesity, sarcopenia, and myosteatosis in inflammatory bowel disease may confer negative outcomes, but their prevalence and impact among patients with Crohn's disease (CD) have not been systematically studied. The aim of this study was to assess nutritional status and body composition among patients undergoing resectional surgery for CD and determine impact on operative outcomes. METHODS: Consecutive patients with CD undergoing resection from 2000 to 2018 were studied. Total, subcutaneous, and visceral fat areas and lean tissue area (LTA) and intramuscular adipose tissue (IMAT) were determined preoperatively by computed tomography at L3 using SliceOmatic (Tomovision, Canada). Univariable and multivariable linear, logistic, and Cox proportional hazards regression were performed. RESULTS: One hundred twenty-four consecutive patients were studied (ileocolonic disease 53%, nâ =â 62, biologic therapy 34.4% nâ =â 43). Mean fat mass was 22.7 kg, with visceral obesity evident in 23.9% (nâ =â 27). Increased fat stores were associated with reduced risk of emergency presentation but increased corticosteroid use (ß 9.09, standard error 3.49; Pâ =â .011). Mean LBM was 9.9 kg. Sarcopenia and myosteatosis were associated with impaired baseline nutritional markers. Myosteatosis markers IMAT (Pâ =â .002) and muscle attenuation (Pâ =â .0003) were associated with increased grade of complication. On multivariable analysis, IMAT was independently associated with increased postoperative morbidity (odds ratio [OR], 1.08; 95% confidence interval (CI), 1.01-1.16; Pâ =â .037) and comprehensive complications index (Pâ =â .029). Measures of adiposity were not associated with overall morbidity; however, increased visceral fat area independently predicted venous thromboembolism (OR, 1.02; 95% CI, 1.00-1.05; Pâ =â .028), and TFA was associated with increased wound infection (OR, 1.00; 95% CI, 1.00-1.01; Pâ =â .042) on multivariable analysis. CONCLUSION: Myosteatosis is associated with nutritional impairment and predicts increased overall postoperative morbidity following resection for CD. Despite its association with specific increased postoperative risks, increased adiposity does not increase overall morbidity, reflecting preservation of nutritional status and relatively more quiescent disease phenotype. Impaired muscle mass and function represent an appealing target for patient optimization to improve outcomes in the surgical management of CD.
Myosteatosis was predictive of postoperative morbidity following surgery for Crohn's Disease. Increased adiposity does not increase overall morbidity, reflecting a more quiescent disease phenotype. Obesity, myosteatosis, and sarcopenia represent appealing targets for patient optimization to improve outcomes surgical outcomes in Crohn's Disease.
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OBJECTIVE: This study aimed to compare clinicopathologic, oncologic, and health-related quality of life (HRQL) outcomes following neoadjuvant chemoradiation (nCRT) and chemotherapy (nCT) in the ENSURE international multicenter study. BACKGROUND: nCT and nCRT are the standards of care for locally advanced esophageal cancer (LAEC) treated with curative intent. However, no published randomized controlled trial to date has demonstrated the superiority of either approach. METHODS: ENSURE is an international multicenter study of consecutive patients undergoing surgery for LAEC (2009-2015) across 20 high-volume centers (NCT03461341). The primary outcome measure was overall survival (OS), secondary outcomes included histopathologic response, recurrence pattern, oncologic outcome, and HRQL in survivorship. RESULTS: A total of 2211 patients were studied (48% nCT, 52% nCRT). pCR was observed in 4.9% and 14.7% ( P <0.001), with R0 in 78.2% and 94.2% ( P <0.001) post nCT and nCRT, respectively. Postoperative morbidity was equivalent, but in-hospital mortality was independently increased [hazard ratio (HR)=2.73, 95% CI: 1.43-5.21, P= 0.002] following nCRT versus nCT. Probability of local recurrence was reduced (odds ratio=0.71, 95% CI: 0.54-0.93, P =0.012), and distant recurrence-free survival time reduced (HR=1.18, 95% CI: 1.02-1.37, P =0.023) after nCRT versus nCT, with no difference in OS among all patients (HR=1.10, 95% CI: 0.98-1.25, P =0.113). On subgroup analysis, patients who underwent R0 resection following nCT as compared with nCRT had improved OS (median: 60.7 months, 95% CI: 49.5-71.8 vs 40.8 months, 95% CI: 42.8-53.4, P <0.001). CONCLUSIONS: In this European multicenter study, nCRT compared with nCT was associated with reduced probability of local recurrence but reduced distant recurrence-free survival for patients with LAEC, without differences in OS. These data support tailored patient-specific decision-making in the overall approach to achieving optimum outcomes in LAEC.
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Adenocarcinoma , Neoplasias Esofágicas , Humanos , Adenocarcinoma/patologia , Quimiorradioterapia , Neoplasias Esofágicas/patologia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Qualidade de VidaRESUMO
BACKGROUND: Obesity can pose perioperative challenges related to obesity-associated co-morbidities and technical factors. However, the true impact of obesity on postoperative outcomes is not well established and reports are conflicting. The aim was to perform a systematic review and meta-analysis to explore the effect of obesity on perioperative outcomes for general surgery procedures in distinct obesity subtypes. METHODS: A systematic review was performed for studies reporting postoperative outcomes in relation to BMI in upper gastrointestinal, hepatobiliary and colorectal based on an electronic search using the Cochrane Library, Science Direct, PubMed and Embase up to January 2022. The primary outcome was the incidence of 30-day postoperative mortality among patients with obesity undergoing general surgical procedures in comparison to patients with normal range BMI. RESULTS: Sixty-two studies, including 1 886 326 patients, were eligible for inclusion. Overall, patients with obesity (including class I/II/II) had lower 30-day mortality rates in comparison to patients with a normal BMI (odds ratio (OR) 0.75, 95 per cent c.i. 0.66 to 0.86, P < 0.0001, I2 = 71 per cent); this was also observed specifically in emergency general surgery (OR 0.83, 95 per cent c.i. 0.79 to 0.87, P < 0.0000001, I2 = 7 per cent). Compared with normal BMI, obesity was positively associated with an increased risk of 30-day postoperative morbidity (OR 1.11, 95 per cent c.i. 1.04 to 1.19, P = 0.002, I2 = 85 per cent). However, there was no significant difference in postoperative morbidity rates between the cohorts of patients with a normal BMI and class I/II obesity (OR 0.98, 95 per cent c.i. 0.92 to 1.04, P = 0.542, I2 = 92 per cent). Overall, the cohort with obesity had a higher rate of postoperative wound infections compared with the non-obese group (OR 1.40, 95 per cent c.i. 1.24 to 1.59, P < 0.0001, I2 = 82 per cent). CONCLUSION: These data suggest a possible 'obesity paradox' and challenge the assumption that patients with obesity have higher postoperative mortality compared with patients with normal range BMI. Increased BMI alone is not associated with increased perioperative mortality in general surgery, highlighting the importance of more accurate body composition assessment, such as computed tomography anthropometrics, to support perioperative risk stratification and decision-making. REGISTRATION NUMBER: CRD42022337442 (PROSPERO https://www.crd.york.ac.uk/prospero/).
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Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Fatores de Risco , Obesidade/complicações , Comorbidade , Índice de Massa CorporalRESUMO
Importance: Postoperative urinary retention (POUR) is a well-recognized complication of inguinal hernia repair (IHR). A variable incidence of POUR has previously been reported in this context, and contradictory evidence surrounds potential risk factors. Objective: To ascertain the incidence of, explore risk factors for, and determine the health service outcomes of POUR following elective IHR. Design, Setting, and Participants: The Retention of Urine After Inguinal Hernia Elective Repair (RETAINER I) study, an international, prospective cohort study, recruited participants between March 1 and October 31, 2021. This study was conducted across 209 centers in 32 countries in a consecutive sample of adult patients undergoing elective IHR. Exposure: Open or minimally invasive IHR by any surgical technique, under local, neuraxial regional, or general anesthesia. Main Outcomes and Measures: The primary outcome was the incidence of POUR following elective IHR. Secondary outcomes were perioperative risk factors, management, clinical consequences, and health service outcomes of POUR. A preoperative International Prostate Symptom Score was measured in male patients. Results: In total, 4151 patients (3882 male and 269 female; median [IQR] age, 56 [43-68] years) were studied. Inguinal hernia repair was commenced via an open surgical approach in 82.2% of patients (n = 3414) and minimally invasive surgery in 17.8% (n = 737). The primary form of anesthesia was general in 40.9% of patients (n = 1696), neuraxial regional in 45.8% (n = 1902), and local in 10.7% (n = 446). Postoperative urinary retention occurred in 5.8% of male patients (n = 224), 2.97% of female patients (n = 8), and 9.5% (119 of 1252) of male patients aged 65 years or older. Risk factors for POUR after adjusted analyses included increasing age, anticholinergic medication, history of urinary retention, constipation, out-of-hours surgery, involvement of urinary bladder within the hernia, temporary intraoperative urethral catheterization, and increasing operative duration. Postoperative urinary retention was the primary reason for 27.8% of unplanned day-case surgery admissions (n = 74) and 51.8% of 30-day readmissions (n = 72). Conclusions: The findings of this cohort study suggest that 1 in 17 male patients, 1 in 11 male patients aged 65 years or older, and 1 in 34 female patients may develop POUR following IHR. These findings could inform preoperative patient counseling. In addition, awareness of modifiable risk factors may help to identify patients at increased risk of POUR who may benefit from perioperative risk mitigation strategies.
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Hérnia Inguinal , Laparoscopia , Retenção Urinária , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Retenção Urinária/epidemiologia , Retenção Urinária/etiologia , Retenção Urinária/cirurgia , Hérnia Inguinal/cirurgia , Hérnia Inguinal/complicações , Estudos de Coortes , Incidência , Estudos Prospectivos , Estudos Retrospectivos , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fatores de Risco , Anestesia GeralRESUMO
Roux-en-Y gastric-bypass (RYGB) induced alterations in intestinal morphology and gut-cell hormone expression profile in the bypassed biliopancreatic-limb (BPL) versus the alimentary-limbs (AL) are poorly characterised. This pilot study has therefore explored effects following RYGB in high-fat-diet (HFD) and normal-diet (ND) rats. Female Wistar rats (4-week-old) were fed HFD or ND for 23-weeks prior to RYGB or sham surgeries. Immunohistochemical analysis of excised tissue was conducted three-weeks post-surgery. After RYGB, intestinal morphology of the BPL in both HFD and ND groups was unchanged with exception of a small decrease in villi width in the ND-RYGB and crypt depth in the HFD-RYGB group. However, in the AL, villi width was decreased in ND-RYGB rats but increased in the HFD-RYGB group. In addition, crypt depth decreased after RYGB in the AL of HFD rats. GIP positive cells in either limb of both groups of rats were unchanged by RYGB. Similarly, there was little change in GLP-1 positive cells, apart from a small decrease of numbers in the villi of the BPL in HFD rats. RYGB increased GLP-2 cell numbers in the AL of ND-RYGB rats, including in both crypts and villi. This was associated with decreased numbers of cells expressing PYY in the AL of ND-RYGB rats. The BPL appears to maintain normal morphology and unchanged enteroendocrine cell populations despite being bypassed in RYGB-surgery. In contrast, in the AL, villi area is generally enhanced post-RYGB in ND rats with increased numbers of GLP-2 positive cells and decreased expression of PYY.
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Derivação Gástrica , Hormônios Gastrointestinais , Animais , Feminino , Ratos , Peptídeo 2 Semelhante ao Glucagon , Projetos Piloto , Ratos Wistar , Peptídeo YY/metabolismoRESUMO
The uptake of robotic surgery is rapidly increasing worldwide across surgical specialties. However, there is currently a much higher use of robotic surgery in the United States of America (USA) compared to the United Kingdom (UK) and Ireland. Reduced exposure to robotic surgery in training may lead to longer learning curves and worse patient outcomes. We aimed to identify whether any difference exists in exposure to robotic surgery during general surgical training between trainees in the USA, UK and Ireland. Over a 15-week period from September 2021, a survey was distributed through the professional networks of the research team. Participants were USA, UK or Irish trainees who were part of a formal general surgical training curriculum. 116 survey responses were received. US trainees (n = 34) had all had robotic simulator experience, compared to only 37.93% of UK (n = 58) and 75.00% of Irish (n = 24) trainees (p < 0.00001). 91.18% of US trainees had performed 15 or more cases as the console surgeon, compared to only 3.44% of UK and 16.67% of Irish trainees (p < 0.00001). Fifty UK trainees (86.21%) and 22 Irish trainees (91.67%) compared to 12 US trainees (35.29%) do not think they have had adequate robotics training (p < 0.00001). Surgical trainees in the USA have had significantly more exposure to training in robotic surgery than their UK and Irish counterparts.
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Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Estados Unidos , Irlanda , Procedimentos Cirúrgicos Robóticos/métodos , Competência Clínica , Reino Unido , Robótica/educação , CurrículoRESUMO
BACKGROUND AND AIMS: Esophageal adenocarcinoma (EAC) is associated with visceral obesity (VO). Non-alcoholic fatty liver disease (NAFLD) is common within this phenotype; however, its incidence and clinical significance in EAC have not been studied. STUDY DESIGN: A total of 559 patients with hepatic stetatosis (HS) defined by unenhanced CT were enrolled. In a sub-study, in 140 consecutive patients a liver biopsy was taken intraoperatively to study HS and non-alcoholic steatohepatitis (NASH). Postoperative complications were defined as per the Esophageal Complications Consensus Group (ECCG). Liver biochemistry was measured peri-operatively, with an ALT > 5 defined as acute liver injury (ALI). Mann-Whitney U test or Fisher's exact test was utilized and the Kaplan-Meier method for survival. RESULTS: 42% (n = 234/559) of patients had CT-defined HS. HS was associated with VO in 56% of cases, metabolic syndrome (Met S) in 37% and type 2 diabetes in 25%, compared with 44, 21, and 15% in non-HS patients (p < 0.01). Pathologic HS was present in 32% (45/140) and graded as mild, moderate, and severe in 73, 24, and 3%, respectively, with NASH reported in 16% and indefinite/borderline NASH in 42% of HS cases. Postoperative ALI was similar (p = 0.88) in both HS (10%) and non-HS cohorts (11%). Operative complication severity was similar in both cohorts. 5-yr survival was 53% (HS) vs 50% (p = 0.890). CONCLUSION: This study establishes for the first time the incidence and clinical impact of NAFLD in EAC patients undergoing surgery and highlights no major impact on oncologic outcomes, nor in the severity of complications.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologiaRESUMO
OBJECTIVE: To determine the impact of surveillance on recurrence pattern, treatment, survival and health-related quality-of-life (HRQL) following curative-intent resection for esophageal cancer. SUMMARY BACKGROUND DATA: Although therapies for recurrent esophageal cancer may impact survival and HRQL, surveillance protocols after primary curative treatment are varied and inconsistent, reflecting a lack of evidence. METHODS: European iNvestigation of SUrveillance after Resection for Esophageal cancer was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers (2009-2015) across 20 centers (NCT03461341). Intensive surveillance (IS) was defined as annual computed tomography for 3 years postoperatively. The primary outcome measure was overall survival (OS), secondary outcomes included treatment, disease-specific survival, recurrence pattern, and HRQL. Multivariable linear, logistic, and Cox proportional hazards regression analyses were performed. RESULTS: Four thousand six hundred eighty-two patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy, 45.5% IS). At median followup 60 months, 47.5% developed recurrence, oligometastatic in 39%. IS was associated with reduced symptomatic recurrence (OR 0.17 [0.12-0.25]) and increased tumor-directed therapy (OR 2.09 [1.58-2.77]). After adjusting for confounders, no OS benefit was observed among all patients (HR 1.01 [0.89-1.13]), but OS was improved following IS for those who underwent surgery alone (HR 0.60 [0.47-0.78]) and those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58-0.89]). IS was associated with greater anxiety ( P =0.016), but similar overall HRQL. CONCLUSIONS: IS was associated with improved oncologic outcome in select cohorts, specifically patients with early-stage disease at presentation or favorable pathological stage post neoadjuvant therapy. This may inform guideline development, and enhance shared decision-making, at a time when therapeutic options for recurrence are expanding.
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Neoplasias Esofágicas , Qualidade de Vida , Humanos , Recidiva Local de Neoplasia/epidemiologia , Terapia Neoadjuvante/métodos , Tomografia Computadorizada por Raios XRESUMO
The attenuation of diabetic kidney disease (DKD) by metabolic surgery is enhanced by pharmacotherapy promoting renal fatty acid oxidation (FAO). Using the Zucker Diabetic Fatty and Zucker Diabetic Sprague Dawley rat models of DKD, we conducted studies to determine if these effects could be replicated with a non-invasive bariatric mimetic intervention. Metabolic control and renal injury were compared in rats undergoing a dietary restriction plus medical therapy protocol (DMT; fenofibrate, liraglutide, metformin, ramipril, and rosuvastatin) and ad libitum-fed controls. The global renal cortical transcriptome and urinary 1H-NMR metabolomic profiles were also compared. Kidney cell type-specific and medication-specific transcriptomic responses were explored through in silico deconvolution. Transcriptomic and metabolomic correlates of improvements in kidney structure were defined using a molecular morphometric approach. The DMT protocol led to â¼20% weight loss, normalized metabolic parameters and was associated with reductions in indices of glomerular and proximal tubular injury. The transcriptomic response to DMT was dominated by changes in fenofibrate- and peroxisome proliferator-activated receptor-α (PPARα)-governed peroxisomal and mitochondrial FAO transcripts localizing to the proximal tubule. DMT induced urinary excretion of PPARα-regulated metabolites involved in nicotinamide metabolism and reversed DKD-associated changes in the urinary excretion of tricarboxylic acid (TCA) cycle intermediates. FAO transcripts and urinary nicotinamide and TCA cycle metabolites were moderately to strongly correlated with improvements in glomerular and proximal tubular injury. Weight loss plus pharmacological PPARα agonism is a promising means of attenuating DKD.
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Diabetes Mellitus , Nefropatias Diabéticas , Fenofibrato , Ratos , Masculino , Animais , PPAR alfa/genética , PPAR alfa/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Fenofibrato/farmacologia , Fenofibrato/metabolismo , Ratos Zucker , Ratos Sprague-Dawley , Rim/metabolismo , Redução de Peso , Niacinamida , Diabetes Mellitus/metabolismoRESUMO
Modification of gut-islet secretions after Roux-En-Y gastric bypass (RYBG) surgery contributes to its metabolic and anti-diabetic benefits. However, there is limited knowledge on tissue-specific hormone distribution post-RYGB surgery and how this compares with best medical treatment (BMT). In the present study, pancreatic and ileal tissues were excised from male Zucker-Diabetic Sprague Dawley (ZDSD) rats 8-weeks after RYGB, BMT (daily oral dosing with metformin 300mg/kg, fenofibrate 100mg/kg, ramipril 1mg/kg, rosuvastatin 10mg/kg and subcutaneous liraglutide 0.2mg/kg) or sham operation (laparotomy). Insulin, glucagon, somatostatin, PYY, GLP-1 and GIP expression patterns were assessed using immunocytochemistry and analyzed using ImageJ. After RYGB and BMT, body weight and plasma glucose were decreased. Intestinal morphometry was unaltered by RYGB, but crypt depth was decreased by BMT. Intestinal PYY cells were increased by both interventions. GLP-1- and GIP-cell counts were unchanged by RYGB but BMT increased ileal GLP-1-cells and decreased those expressing GIP. The intestinal contents of PYY and GLP-1 were significantly enhanced by RYGB, whereas BMT decreased ileal GLP-1. No changes of islet and beta-cell area or proliferation were observed, but the extent of beta-cell apoptosis and islet integrity calculated using circularity index were improved by both treatments. Significantly decreased islet alpha-cell areas were observed in both groups, while beta- and PYY-cell areas were unchanged. RYGB also induced a decrease in islet delta-cell area. PYY and GLP-1 colocalization with glucagon in islets was significantly decreased in both groups, while co-staining of PYY with glucagon was decreased and that with somatostatin increased. These data characterize significant cellular islet and intestinal adaptations following RYGB and BMT associated with amelioration of obesity-diabetes in ZDSD rats. The differential responses observed and particularly those within islets, may provide important clues to the unique ability of RYGB to cause diabetes remission.
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Diabetes Mellitus , Fenofibrato , Derivação Gástrica , Metformina , Animais , Glicemia/metabolismo , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Insulina/metabolismo , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Masculino , Obesidade/cirurgia , Ramipril , Ratos , Ratos Sprague-Dawley , Ratos Zucker , Rosuvastatina Cálcica , Somatostatina/uso terapêuticoRESUMO
Visceral obesity (VO) and metabolic syndrome (MetS) are risk factors for esophageal adenocarcinoma (EAC); however, their impact on operative and oncological outcomes is unclear. The aim of this study was to determine the incidence of VO and MetS among patients with EAC, and to assess their independent impact on operative and oncological outcomes. A total of 454 consecutive patients undergoing treatment with curative intent were studied. Total, subcutaneous, visceral fat area (VFA), and lean body mass (LBM) were measured by computed tomography pretreatment, with VO defined as VFA >163.8cm2 for men and 80.1cm2 for women. MetS was defined per the ATPIII definition. Multivariable logistic and Cox proportional hazards regression were utilized to determine independent predictors of oncologic and operative outcomes. A total of 227 patients (50.0%) had VO. A total of 134 (30%) overall had MetS, 44% in the VO cohort. VO was associated with Barrett's esophagus (P = 0.002) and lower cT (P = 0.006) and cN stage (P = 0.011), and improved disease-specific (P = 0.021) and overall survival (P = 0.012). No survival benefit existed for patients with VO who also had MetS. For operative complications, neither VO nor MetS increased the severity of complications, or mortality. However, VO was significantly (P = 0.035) associated with anastomotic leak and pneumonia (P = 0.037). MetS alone did not increase complication risk. VO increases specific major operative complications with no increase in mortality. VO improved survival, mainly relating to earlier stage disease; however, co-existent MetS abrogated this benefit. These seemingly paradoxical outcomes highlight manageable and potentially targetable perioperative challenges in the context of an overall favorable oncologic vista.
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Adenocarcinoma , Neoplasias Esofágicas , Síndrome Metabólica , Adenocarcinoma/complicações , Adenocarcinoma/epidemiologia , Adenocarcinoma/terapia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/terapia , Feminino , Humanos , Incidência , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de RiscoRESUMO
OBJECTIVE: To identify the most prevalent symptoms and those with greatest impact upon health-related quality of life (HRQOL) among esophageal cancer survivors. BACKGROUND: Long-term symptom burden after esophagectomy, and associations with HRQOL, are poorly understood. PATIENTS AND METHODS: Between 2010 and 2016, patients from 20 European Centers who underwent esophageal cancer surgery, and were disease-free at least 1 year postoperatively were asked to complete LASER, EORTC-QLQ-C30, and QLQ-OG25 questionnaires. Specific symptom questionnaire items that were associated with poor HRQOL as identified by EORTC QLQ-C30 and QLQ-OG25 were identified by multivariable regression analysis and combined to form a tool. RESULTS: A total of 876 of 1081 invited patients responded to the questionnaire, giving a response rate of 81%. Of these, 66.9% stated in the last 6 months they had symptoms associated with their esophagectomy. Ongoing weight loss was reported by 10.4% of patients, and only 13.8% returned to work with the same activities.Three LASER symptoms were correlated with poor HRQOL on multivariable analysis; pain on scars on chest (odds ratio (OR) 1.27; 95% CI 0.97-1.65), low mood (OR 1.42; 95% CI 1.15-1.77) and reduced energy or activity tolerance (OR 1.37; 95% CI 1.18-1.59). The areas under the curves for the development and validation datasets were 0.81â±â0.02 and 0.82â±â0.09 respectively. CONCLUSION: Two-thirds of patients experience significant symptoms more than 1 year after surgery. The 3 key symptoms associated with poor HRQOL identified in this study should be further validated, and could be used in clinical practice to identify patients who require increased support.
Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Idoso , Estudos Transversais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Avaliação de SintomasRESUMO
BACKGROUND: Sarcopenia, myosteatosis and obesity in cancer may confer negative clinical outcomes, but their prevalence and impact among patients with retroperitoneal and trunk soft tissue sarcoma have not been systematically studied. The aim of this study was to determine body composition among patients with retroperitoneal and trunk sarcoma, and assess impact on operative and oncologic outcomes. METHODS: Consecutive patients undergoing treatment with curative intent from 2009 to 2019 were studied. Subcutaneous fat area and visceral fat areas, intramuscular adipose, lean body mass and fat mass were determined at diagnosis by CT at L3. Univariable and multivariable linear, logistic and Cox proportional hazards regression were performed. RESULTS: 95 patients (43.2% retroperitoneal, 48.4% trunk, 46.3% multivisceral resection) were studied. Visceral obesity was evident in 47.4%. Postoperative morbidity occurred in 25.9%, with preoperative radiotherapy (OR10.53 [95% CI 1.08-102.39], P = 0.042) and fat mass (OR1.41 [1.12-1.79], P = 0.004) independently predictive on multivariable analysis, while intramuscular adipose independently predicted inpatient LOS (P < 0.001), wound infection (P = 0.024, OR1.20 [1.02-1.40]) and major postoperative morbidity (P = 0.027, OR1.15 [1.02-1.31]). Increasing fat mass, subcutaneous fat area and intramuscular adipose were associated with greater tumor size (all P < 0.01), while intramuscular adipose predicted disease progression during neoadjuvant therapy (P = 0.024), and independently predicted disease specific survival (DSS) (P = 0.005, HR1.11 [1.03-1.20]) and overall survival (OS) on multivariable analysis (P < 0.001, HR1.19 [1.08-1.31]). CONCLUSION: Visceral obesity is common in retroperitoneal and trunk sarcoma, and measures of adiposity are associated with adverse operative, but not oncologic outcomes. Myosteatosis is independently associated with postoperative morbidity and adverse oncologic outcomes. Body composition may represent a marker of risk among patients with retroperitoneal and trunk sarcoma.
Assuntos
Sarcoma , Sarcopenia , Neoplasias de Tecidos Moles , Composição Corporal , Humanos , Obesidade/complicações , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Prognóstico , Estudos Retrospectivos , Sarcoma/cirurgia , Sarcopenia/complicaçõesRESUMO
OBJECTIVE: To determine the incidence, risk factors, and consequences of AKI in patients undergoing surgery for esophageal cancer. SUMMARY OF BACKGROUND DATA: Esophageal cancer surgery is an exemplar of major operative trauma, with well-defined risks of respiratory, cardiac, anastomotic, and septic complications. However, there is a paucity of literature regarding AKI. METHODS: consecutive patients undergoing curative-intent surgery for esophageal cancer from 2011 to 2017 in 3 high-volume centers were studied. AKI was defined according to the AKI Network criteria. AKI occurred if, within 48âhours postoperatively, serum creatinine rose by 50% or by 0.3âmg/dL (26.5âµmol/L) from preoperative baseline. Complications were recorded prospectively. Multivariable logistic regression determined factors independently predictive of AKI. RESULTS: A total of 1135 patients (24.7%:75.3% female:male, with a mean age of 64, a baseline BMI of 27âkgâm-2, and dyslipidemia in 10.2%), underwent esophageal cancer surgery, 85% having an open thoracotomy. Overall in-hospital mortality was 2.1%. Postoperative AKI was observed in 208 (18.3%) patients, with AKI Network 1, 2, and 3 in 173 (15.2%), 28 (2.5%), and 7 (0.6%), respectively. Of these, 70.3% experienced improved renal function within 48âhours. Preoperative factors independently predictive of AKI were age [P = 0.027, odds ratio (OR) 1.02 (1.00-1.04)], male sex [P = 0.015, OR 1.77 (1.10-2.81)], BMI at diagnosis [P < 0.001, OR 1.10 (1.07-1.14)], and dyslipidemia [P = 0.002, OR 2.14 (1.34-3.44)]. Postoperatively, AKI was associated with atrial fibrillation (P = 0.013) and pneumonia (P = 0.005). Postoperative AKI did not impact survival outcomes. CONCLUSION: AKI is common but mostly self-limiting after esophageal cancer surgery. It is associated with age, male sex, increased BMI, dyslipidemia, and postoperative morbidity.