Esophagectomy,the surgical removal of all or part of the esophagus,is a surgical procedure that is associated with high morbidity and mortality.Pulmonary complications are an especially important postoperative problem...Esophagectomy,the surgical removal of all or part of the esophagus,is a surgical procedure that is associated with high morbidity and mortality.Pulmonary complications are an especially important postoperative problem.Therefore,many perioperative strategies to prevent pulmonary complications after esophagectomy have been investigated and introduced in daily clinical practice.Here,we review these strategies,including improvement of patient performance and technical advances such as minimally invasive surgery that have been implemented in recent years.Furthermore,interventions such as methylprednisolone,neutrophil elastase inhibitor and epidural analgesia,which have been shown to reduce pulmonary complications,are discussed.Benefits of the commonly applied routine nasogastric decompression,delay of oral intake and prophylactic mechanical ventilation are unclear,and many of these strategies are also evaluated here.Finally,we will discuss recent insights and new developments aimed to improve pulmonary outcomes after esophagectomy.展开更多
AIM:To develop a panel of blood-based diagnostic biomarkers consisting of circulating microRNAs for the detection of pancreatic cancer at an early stage.METHODS:Blood-based circulating microRNAs were profiled by high ...AIM:To develop a panel of blood-based diagnostic biomarkers consisting of circulating microRNAs for the detection of pancreatic cancer at an early stage.METHODS:Blood-based circulating microRNAs were profiled by high throughput screening using microarray analysis,comparing differential expression between early stage pancreatic cancer patients(n = 8) and healthy controls(n = 11).A panel of candidate microRNAs was generated based on the microarray signature profiling,including unsupervised clustering and statistical analysis of differential expression levels,and findings from the published literature.The selected candidate microRNAs were then confirmed using TaqMan real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR) to further narrow down to a three-microRNA diagnostic panel.The three-microRNA diagnostic panel was validated with independent experimental proce-dures and instrumentation of RT-qPCR at an independent venue with a new cohort of cancer patients(n = 11),healthy controls(n = 11),and a group of high risk controls(n = 11).Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of the three-microRNA panel.RESULTS:In the initial high throughput screening,1220 known human microRNAs were screened for differential expression in pancreatic cancer patients versus controls.A subset of 42 microRNAs was then generated based on this data analysis and current published literature.Eight microRNAs were selected from the list of 42 targets for confirmation study,and three-microRNAs,miR-642b,miR-885-5p,and miR-22,were confirmed to show consistent expression between microarray and RT-qPCR.These three microRNAs were then validated and evaluated as a diagnostic panel with a new cohort of patients and controls and found to yield high sensitivity(91%) and specificity(91%) with an area under the curve of 0.97(P < 0.001).Compared to the CA19-9 marker at 73%,the three-microRNA panel has higher sensitivity although CA19-9 has higher specificity of 100%.CONCLUSION展开更多
Early screening for colorectal cancer(CRC) holds the key to combat and control the increasing global burden of CRC morbidity and mortality. However, the current available screening modalities are severely inadequate b...Early screening for colorectal cancer(CRC) holds the key to combat and control the increasing global burden of CRC morbidity and mortality. However, the current available screening modalities are severely inadequate because of their high cost and cumbersome preparatory procedures that ultimately lead to a low participation rate. People simply do not like to have colonoscopies. It would be ideal, therefore, to develop an alternative modality based on blood biomarkers as the first line screening test. This will allow for the differentiation of the general population from high risk individuals. Colonoscopy would then become the secondary test, to further screen the high risk segment of the population. This will encourage participation and therefore help to reach the goal of early detection and thereby reduce the anticipated increasing global CRC incidence rate. A blood-based screening test is anappealing alternative as it is non-invasive and poses minimal risk to patients. It is easy to perform, can be repeated at shorter intervals, and therefore would likely lead to a much higher participation rate. This review surveys various blood-based test strategies currently under investigation, discusses the potency of what is available, and assesses how new technology may contribute to future test design.展开更多
Two-dimensional thermoelasticity analysis of functionally graded thick beams is presented using the state space method coupled with the technique of differential quadrature. Material properties vary continuously and s...Two-dimensional thermoelasticity analysis of functionally graded thick beams is presented using the state space method coupled with the technique of differential quadrature. Material properties vary continuously and smoothly through the beam thickness, leading to variable coefficients in the state equation derived from the elasticity equations. Approximate laminate model is employed to translate the state equation into the one with constant coefficients in each layer. To avoid numerical instability, joint coupling matrices are introduced according to the continuity conditions at interfaces in the approximate model. The differential quadrature procedure is applied to discretizing the beam in the axial direction to make easy the treatment of arbitrary end conditions. A simply-supported beam with exponentially varying material properties is considered to validate the present method. Numerical examples are performed to investigate the influences of relative parameters.展开更多
BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of health.This approach is especially relevant for patients with chronic disorders.Chroni...BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of health.This approach is especially relevant for patients with chronic disorders.Chronic gastrointestinal and hepatopancreatico-biliary(GI-HPB)disorders are among the top-6 of the most prevalent chronically affected organ systems.The impact of chronic GI-HPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIHPB disorders are often younger than persons with chronic diseases in other organ systems.AIM To describe and quantify the dimensions of PH in patients with chronic GI-HPB disorders.METHODS Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIHPB disorder attending the Outpatient Department of the Maastricht University Medical Center.Validated questionnaires and data from patient files were used to quantify the six dimensions of PH.Internal consistency was tested with McDonald’s Omega.Zero-order Pearson correlations and t-tests were used to assess associations and differences.A P value<0.05 was considered significant.RESULTS The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general population.Regarding quality of life,participation and daily functioning,GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-HPB disorders.Intercorrelation scores between the six dimensions were only very weak to weak,forcing us to quantify each domain separately.CONCLUSION All six dimensions of PH are impaired in the GI-HPB patients.Malnutrition and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.展开更多
Artemisinins tested against W-2 strains of malaria falciparum are investigated with molecular electrostatic potential (MEP), in an attempt to identify key features of the compounds that are necessary for their activit...Artemisinins tested against W-2 strains of malaria falciparum are investigated with molecular electrostatic potential (MEP), in an attempt to identify key features of the compounds that are necessary for their activities, as well as to investigate likely interactions with the receptor in a biological process and to use that information to propose new molecules. In order to discover the best geometry involving the ligand-receptor complexes (heme) studied and help in the proposition of the new derivatives, molecular simulations of interactions between the most negative charged region around the peroxide and heme locates (the ones around the Fe2+ ion) were carried out. In addition, PCA (principal components analysis), HCA (hierarchical cluster analysis), SDA (stepwise discriminant analysis), and KNN (K-nearest neighbor) multivariate models were employed to investigate which descriptors are responsible for the classification between the higher and lower antimalarial activity of the compounds, and also this information was used to propose new potentially active molecules. The information accumulated in studies of MEP, molecular docking, and multivariate analysis supported the proposal of new structures with potential antimalarial activities. The multivariate models constructed were applied to the new structures and indicated numbers 19 and 20 as the most prominent for syntheses and biological assays.展开更多
A study was conducted to compare the potential of natural farming versus conventional chemical farming to withstand adverse climate effects. The study investigated two cyclones, namely cyclone Pethai and cyclone Titli...A study was conducted to compare the potential of natural farming versus conventional chemical farming to withstand adverse climate effects. The study investigated two cyclones, namely cyclone Pethai and cyclone Titli of 2018, which caused significant damage to Andhra Pradesh’s coastal corridor. In addition, the impact of heavy rainfall in 2021 on two different farming systems was studied. The worst-affected Paddy crop regions where these cyclones caused severe damage were surveyed. Multiple linear regression was utilized to investigate predictors including crop damage, wind damage, submergence, and yield loss in these two agricultural systems during these two cyclonic and heavy rainfall events. The study indicated that natural farming practices were more resilient to climate variability than conventional chemical farming techniques. The study showed a statistically significant difference (p < 0.001) between these two farming systems in terms of damage caused due to climate variabilities.展开更多
Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PT...Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced sub- acute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the un- derestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotrans- ferase monitoring, at least during the first six months of therapy.展开更多
N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning m...N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning methods (PCA, HCA, KNN, SIMCA, and SDA). The optimization of molecular structures was performed using the B3LYP/6-31G* approach. MEP maps and ligand-receptor interactions were used to investigate key structural features required for biological activities and likely interactions between N-11-azaartemisinins and heme, respectively. The supervised machine learning methods allowed the separation of the investigated compounds into two classes: cha and cla, with the properties ε<sub>LUMO+1</sub> (one level above lowest unoccupied molecular orbital energy), d(C<sub>6</sub>-C<sub>5</sub>) (distance between C<sub>6</sub> and C<sub>5</sub> atoms in ligands), and TSA (total surface area) responsible for the classification. The insights extracted from the investigation developed and the chemical intuition enabled the design of sixteen new N-11-azaartemisinins (prediction set), moreover, models built with supervised machine learning methods were applied to this prediction set. The result of this application showed twelve new promising N-11-azaartemisinins for synthesis and biological evaluation.展开更多
AIM:To investigate the value of elevated drain amylase concentrations for detecting anastomotic leakage(AL) after minimally invasive Ivor-Lewis esophagectomy(MIILE).METHODS:This was a retrospective analysis of prospec...AIM:To investigate the value of elevated drain amylase concentrations for detecting anastomotic leakage(AL) after minimally invasive Ivor-Lewis esophagectomy(MIILE).METHODS:This was a retrospective analysis of prospectively collected data in two hospitals in the Netherlands. Consecutive patients undergoing MI-ILE were included. A Jackson-Pratt drain next to the dorsal side of the anastomosis and bilateral chest drains were placed at the end of the thoracoscopic procedure. Amylase levels in drain fluid were determined in all patients during at least the first four postoperative days. Contrast computed tomography scans and/or endoscopic imaging were performed in cases of a clinically suspected AL. Anastomotic leakage was defined as any sign of leakage of the esophago-gastric anastomosis on endoscopy,re-operation,radiographic investigations,post mortal examination or when gastro-intestinal contents were found in drain fluid. Receiver operator characteristic curves were used to determine the cut-off values. Sensitivity,specificity,positive predictive value,negative predictive value,risk ratio and overall test accuracy were calculated for elevated drain amylase concentrations.RESULTS:A t o t a l o f 8 9 p a t ie n t s w e re in c lu d e d between March 2013 and August 2014. No differences in group characteristics were observed between patients with and without AL,except for age. Patients with AL were older than were patients without AL(P = 0.01). One patient(1.1%) without AL died within 30 d after surgery due to pneumonia and acute respiratory distress syndrome. Anastomotic leakage that required any intervention occurred in 15 patients(16.9%). Patients with proven anastomotic leakage had higher drain amylase levels than patients without anastomotic leakage [median 384 IU/L(IQR 34-6263) vs median 37 IU/L(IQR 26-66),P = 0.003]. Optimal cut-off values on postoperative days 1,2,and 3 were 350 IU/L,200 IU/L and 160 IU/L,respectively. An elevated amylase level was found in 9 of the 15 patients with AL. Five of these 9 patie展开更多
BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures.Non-surgical treatment options like ...BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures.Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT)have been implemented.The trends in(non-)surgical treatment and its impact on overall survival(OS)in patients with proximal esophageal cancer are unclear,related to its rare disease status.To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study,patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry.The proximal esophagus consists of the cervical esophagus and the upper thoracic section,extending to 24 cm from the incisors.Trends in radiotherapy,chemotherapy,and surgery,and OS were assessed.Analyses were stratified by presence of distant metastasis.Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS,adjusted for patient,tumor,and treatment characteristics.RESULTS In total,2783 patients were included.Over the study period,the use of radiotherapy,resection,and CRT in non-metastatic disease changed from 53%,23%,and 1%in 1989-1994 to 21%,9%,and 49%in 2010-2014,respectively.In metastatic disease,the use of chemotherapy and radiotherapy increased over time.Median OS of the total population increased from 7.3 mo[95%confidence interval(CI):6.4-8.1]in 1989-1994 to 9.5 mo(95%CI:8.1-10.8)in 2010-2014(logrank P<0.001).In non-metastatic disease,5-year OS rates improved from 5%(95%CI:3%-7%)in 1989-1994 to 13%(95%CI:9%-17%)in 2010-2014(logrank P<0.001).Multivariable regression analysis demonstrated a significant treatment effect over time on survival.In metastatic disease,median OS was 3.8 mo(95%CI:2.展开更多
文摘Esophagectomy,the surgical removal of all or part of the esophagus,is a surgical procedure that is associated with high morbidity and mortality.Pulmonary complications are an especially important postoperative problem.Therefore,many perioperative strategies to prevent pulmonary complications after esophagectomy have been investigated and introduced in daily clinical practice.Here,we review these strategies,including improvement of patient performance and technical advances such as minimally invasive surgery that have been implemented in recent years.Furthermore,interventions such as methylprednisolone,neutrophil elastase inhibitor and epidural analgesia,which have been shown to reduce pulmonary complications,are discussed.Benefits of the commonly applied routine nasogastric decompression,delay of oral intake and prophylactic mechanical ventilation are unclear,and many of these strategies are also evaluated here.Finally,we will discuss recent insights and new developments aimed to improve pulmonary outcomes after esophagectomy.
基金Supported by The Valley Hospital Foundation Research Fund and private donations
文摘AIM:To develop a panel of blood-based diagnostic biomarkers consisting of circulating microRNAs for the detection of pancreatic cancer at an early stage.METHODS:Blood-based circulating microRNAs were profiled by high throughput screening using microarray analysis,comparing differential expression between early stage pancreatic cancer patients(n = 8) and healthy controls(n = 11).A panel of candidate microRNAs was generated based on the microarray signature profiling,including unsupervised clustering and statistical analysis of differential expression levels,and findings from the published literature.The selected candidate microRNAs were then confirmed using TaqMan real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR) to further narrow down to a three-microRNA diagnostic panel.The three-microRNA diagnostic panel was validated with independent experimental proce-dures and instrumentation of RT-qPCR at an independent venue with a new cohort of cancer patients(n = 11),healthy controls(n = 11),and a group of high risk controls(n = 11).Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of the three-microRNA panel.RESULTS:In the initial high throughput screening,1220 known human microRNAs were screened for differential expression in pancreatic cancer patients versus controls.A subset of 42 microRNAs was then generated based on this data analysis and current published literature.Eight microRNAs were selected from the list of 42 targets for confirmation study,and three-microRNAs,miR-642b,miR-885-5p,and miR-22,were confirmed to show consistent expression between microarray and RT-qPCR.These three microRNAs were then validated and evaluated as a diagnostic panel with a new cohort of patients and controls and found to yield high sensitivity(91%) and specificity(91%) with an area under the curve of 0.97(P < 0.001).Compared to the CA19-9 marker at 73%,the three-microRNA panel has higher sensitivity although CA19-9 has higher specificity of 100%.CONCLUSION
基金Supported by The Valley Hospital Foundation Research FundThe community of The Valley Hospital in Ridgewood,NJ,especially Ms.Audrey Meyers,CEO,Mr.Anastasios Kozaitis,president of the Valley Hospital Foundation
文摘Early screening for colorectal cancer(CRC) holds the key to combat and control the increasing global burden of CRC morbidity and mortality. However, the current available screening modalities are severely inadequate because of their high cost and cumbersome preparatory procedures that ultimately lead to a low participation rate. People simply do not like to have colonoscopies. It would be ideal, therefore, to develop an alternative modality based on blood biomarkers as the first line screening test. This will allow for the differentiation of the general population from high risk individuals. Colonoscopy would then become the secondary test, to further screen the high risk segment of the population. This will encourage participation and therefore help to reach the goal of early detection and thereby reduce the anticipated increasing global CRC incidence rate. A blood-based screening test is anappealing alternative as it is non-invasive and poses minimal risk to patients. It is easy to perform, can be repeated at shorter intervals, and therefore would likely lead to a much higher participation rate. This review surveys various blood-based test strategies currently under investigation, discusses the potency of what is available, and assesses how new technology may contribute to future test design.
基金This work was supported by the National Natural Science Foundation of China (Grant Nos. 10432030 and 10372088).
文摘Two-dimensional thermoelasticity analysis of functionally graded thick beams is presented using the state space method coupled with the technique of differential quadrature. Material properties vary continuously and smoothly through the beam thickness, leading to variable coefficients in the state equation derived from the elasticity equations. Approximate laminate model is employed to translate the state equation into the one with constant coefficients in each layer. To avoid numerical instability, joint coupling matrices are introduced according to the continuity conditions at interfaces in the approximate model. The differential quadrature procedure is applied to discretizing the beam in the axial direction to make easy the treatment of arbitrary end conditions. A simply-supported beam with exponentially varying material properties is considered to validate the present method. Numerical examples are performed to investigate the influences of relative parameters.
文摘BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of health.This approach is especially relevant for patients with chronic disorders.Chronic gastrointestinal and hepatopancreatico-biliary(GI-HPB)disorders are among the top-6 of the most prevalent chronically affected organ systems.The impact of chronic GI-HPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIHPB disorders are often younger than persons with chronic diseases in other organ systems.AIM To describe and quantify the dimensions of PH in patients with chronic GI-HPB disorders.METHODS Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIHPB disorder attending the Outpatient Department of the Maastricht University Medical Center.Validated questionnaires and data from patient files were used to quantify the six dimensions of PH.Internal consistency was tested with McDonald’s Omega.Zero-order Pearson correlations and t-tests were used to assess associations and differences.A P value<0.05 was considered significant.RESULTS The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general population.Regarding quality of life,participation and daily functioning,GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-HPB disorders.Intercorrelation scores between the six dimensions were only very weak to weak,forcing us to quantify each domain separately.CONCLUSION All six dimensions of PH are impaired in the GI-HPB patients.Malnutrition and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.
文摘Artemisinins tested against W-2 strains of malaria falciparum are investigated with molecular electrostatic potential (MEP), in an attempt to identify key features of the compounds that are necessary for their activities, as well as to investigate likely interactions with the receptor in a biological process and to use that information to propose new molecules. In order to discover the best geometry involving the ligand-receptor complexes (heme) studied and help in the proposition of the new derivatives, molecular simulations of interactions between the most negative charged region around the peroxide and heme locates (the ones around the Fe2+ ion) were carried out. In addition, PCA (principal components analysis), HCA (hierarchical cluster analysis), SDA (stepwise discriminant analysis), and KNN (K-nearest neighbor) multivariate models were employed to investigate which descriptors are responsible for the classification between the higher and lower antimalarial activity of the compounds, and also this information was used to propose new potentially active molecules. The information accumulated in studies of MEP, molecular docking, and multivariate analysis supported the proposal of new structures with potential antimalarial activities. The multivariate models constructed were applied to the new structures and indicated numbers 19 and 20 as the most prominent for syntheses and biological assays.
文摘A study was conducted to compare the potential of natural farming versus conventional chemical farming to withstand adverse climate effects. The study investigated two cyclones, namely cyclone Pethai and cyclone Titli of 2018, which caused significant damage to Andhra Pradesh’s coastal corridor. In addition, the impact of heavy rainfall in 2021 on two different farming systems was studied. The worst-affected Paddy crop regions where these cyclones caused severe damage were surveyed. Multiple linear regression was utilized to investigate predictors including crop damage, wind damage, submergence, and yield loss in these two agricultural systems during these two cyclonic and heavy rainfall events. The study indicated that natural farming practices were more resilient to climate variability than conventional chemical farming techniques. The study showed a statistically significant difference (p < 0.001) between these two farming systems in terms of damage caused due to climate variabilities.
文摘Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced sub- acute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the un- derestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotrans- ferase monitoring, at least during the first six months of therapy.
文摘N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning methods (PCA, HCA, KNN, SIMCA, and SDA). The optimization of molecular structures was performed using the B3LYP/6-31G* approach. MEP maps and ligand-receptor interactions were used to investigate key structural features required for biological activities and likely interactions between N-11-azaartemisinins and heme, respectively. The supervised machine learning methods allowed the separation of the investigated compounds into two classes: cha and cla, with the properties ε<sub>LUMO+1</sub> (one level above lowest unoccupied molecular orbital energy), d(C<sub>6</sub>-C<sub>5</sub>) (distance between C<sub>6</sub> and C<sub>5</sub> atoms in ligands), and TSA (total surface area) responsible for the classification. The insights extracted from the investigation developed and the chemical intuition enabled the design of sixteen new N-11-azaartemisinins (prediction set), moreover, models built with supervised machine learning methods were applied to this prediction set. The result of this application showed twelve new promising N-11-azaartemisinins for synthesis and biological evaluation.
文摘AIM:To investigate the value of elevated drain amylase concentrations for detecting anastomotic leakage(AL) after minimally invasive Ivor-Lewis esophagectomy(MIILE).METHODS:This was a retrospective analysis of prospectively collected data in two hospitals in the Netherlands. Consecutive patients undergoing MI-ILE were included. A Jackson-Pratt drain next to the dorsal side of the anastomosis and bilateral chest drains were placed at the end of the thoracoscopic procedure. Amylase levels in drain fluid were determined in all patients during at least the first four postoperative days. Contrast computed tomography scans and/or endoscopic imaging were performed in cases of a clinically suspected AL. Anastomotic leakage was defined as any sign of leakage of the esophago-gastric anastomosis on endoscopy,re-operation,radiographic investigations,post mortal examination or when gastro-intestinal contents were found in drain fluid. Receiver operator characteristic curves were used to determine the cut-off values. Sensitivity,specificity,positive predictive value,negative predictive value,risk ratio and overall test accuracy were calculated for elevated drain amylase concentrations.RESULTS:A t o t a l o f 8 9 p a t ie n t s w e re in c lu d e d between March 2013 and August 2014. No differences in group characteristics were observed between patients with and without AL,except for age. Patients with AL were older than were patients without AL(P = 0.01). One patient(1.1%) without AL died within 30 d after surgery due to pneumonia and acute respiratory distress syndrome. Anastomotic leakage that required any intervention occurred in 15 patients(16.9%). Patients with proven anastomotic leakage had higher drain amylase levels than patients without anastomotic leakage [median 384 IU/L(IQR 34-6263) vs median 37 IU/L(IQR 26-66),P = 0.003]. Optimal cut-off values on postoperative days 1,2,and 3 were 350 IU/L,200 IU/L and 160 IU/L,respectively. An elevated amylase level was found in 9 of the 15 patients with AL. Five of these 9 patie
文摘BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures.Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT)have been implemented.The trends in(non-)surgical treatment and its impact on overall survival(OS)in patients with proximal esophageal cancer are unclear,related to its rare disease status.To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study,patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry.The proximal esophagus consists of the cervical esophagus and the upper thoracic section,extending to 24 cm from the incisors.Trends in radiotherapy,chemotherapy,and surgery,and OS were assessed.Analyses were stratified by presence of distant metastasis.Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS,adjusted for patient,tumor,and treatment characteristics.RESULTS In total,2783 patients were included.Over the study period,the use of radiotherapy,resection,and CRT in non-metastatic disease changed from 53%,23%,and 1%in 1989-1994 to 21%,9%,and 49%in 2010-2014,respectively.In metastatic disease,the use of chemotherapy and radiotherapy increased over time.Median OS of the total population increased from 7.3 mo[95%confidence interval(CI):6.4-8.1]in 1989-1994 to 9.5 mo(95%CI:8.1-10.8)in 2010-2014(logrank P<0.001).In non-metastatic disease,5-year OS rates improved from 5%(95%CI:3%-7%)in 1989-1994 to 13%(95%CI:9%-17%)in 2010-2014(logrank P<0.001).Multivariable regression analysis demonstrated a significant treatment effect over time on survival.In metastatic disease,median OS was 3.8 mo(95%CI:2.