Prevalence and Prognostic Significance of Extramural Venous Invasion in Patients with Locally Advanced Esophageal Cancer

BACKGROUND: Extramural venous invasion (EMVI) is a known adverse prognostic factor in patients with colorectal carcinoma. The prevalence and significance of EMVI in esophageal cancer (EC) patients is still unclear. METHODS: From a prospectively maintained database, we retrospectively reviewed the resection specimens of patients with pathologic locally advanced (pT3/T4/N0-3) EC who were treated with curative intent between 2000 and 2015. Patients with previous malignancies and gastroesophageal junction (type II/III) tumors were excluded. Included were 81 patients who underwent surgery alone and 37 patients who underwent neoadjuvant chemoradiotherapy (nCRT). EMVI was assessed on hematoxylin and eosin slides and confirmed or excluded by additional Elastica van Gieson staining. Survival was analyzed using a multivariable Cox regression. RESULTS: EMVI was present in 23.5% (n = 19) of patients in the surgery-alone group and 21.6% (n = 8) of patients in the nCRT group. The prevalence of EMVI after surgery alone was significantly high in squamous cell carcinomas and among tumors located in the mid-esophagus, as well as those with lymphovascular invasion (p  pT3/N0-3 EC patients, EMVI was present in 23.5% of patients in the surgery-alone group and in 21.6% of patients after nCRT. EMVI was an independent adverse prognostic factor in patients after surgery alone

Eating and feeding problems in children with cancer:Prevalence, related factors, and consequences

Background & aims: During treatment for cancer, children experience many side effects such as lack of appetite, nausea, and vomiting. As a result, ensuring adequate intake puts pressure on both the child and the parent. This study aims to determine the prevalence, causes and consequences of eating and feeding problems in children treated for cancer. Methods: Parents of 85 children with cancer completed the Behavioral Pediatrics Feeding Assessment Scale (BPFAS) and symptoms, BMI, energy intake, feeding style, and parental distress were measured at 0, 3, 6 and 12 months after diagnosis. Results: Parent-reports revealed that almost a quarter of the children experienced eating disorder: 15.7% experienced problems related to diminished intake and 8.6% related to excessive intake. Prevalence of feeding disorders related to parents’ behavior was 21.1%. In children <8 years prevalence of eating and feeding disorders was significantly higher: 31% and 36% for child and parent behavior respectively. Younger age, poor pre-illness eating behavior, increase in symptoms and a demanding feeding style were associated with more eating problems. Excessive eating resulted in higher energy intake, however, no association was found between eating problems and nutritional status. Food refusal resulted in more parental distress. Conclusions: Especially younger children with cancer are at risk for eating and feeding problems. In addition, poor pre-illness eating behavior, symptoms and a demanding feeding style aggravate eating problems. Therefore, interventions should focus at diminishing side effects of treatment and instructing parents to be less demanding regarding their child's eating behavior

Driving Pressure Is Associated With Outcome in Pediatric Acute Respiratory Failure

OBJECTIVES: Driving pressure (ratio of tidal volume over respiratory system compliance) is associated with mortality in acute respiratory distress syndrome. We sought to evaluate if such association could be identified in critically ill children. DESIGN: We studied the association between driving pressure on day 1 of mechanical ventilation and ventilator-free days at day 28 through secondary analyses of prospectively collected physiology data. SETTING: Medical-surgical university hospital PICU. PATIENTS: Children younger than 18 years (stratified by Pediatric Mechanical Ventilation Consensus Conference clinical phenotype definitions) without evidence of spontaneous respiration. INTERVENTIONS: Inspiratory hold maneuvers. MEASUREMENTS AND MAIN RESULTS: Data of 222 patients with median age 11 months (2-51 mo) were analyzed. Sixty-five patients (29.3%) met Pediatric Mechanical Ventilation Consensus Conference criteria for restrictive and 78 patients (35.1%) for mixed lung disease, and 10.4% of all patients had acute respiratory distress syndrome. Driving pressure calculated by the ratio of tidal volume over respiratory system compliance for the whole cohort was 16 cm H2O (12-21 cm H2O) and correlated with the static airway pressure gradient (plateau pressure minus positive end-expiratory pressure) (Spearman correlation coefficient = 0.797; p < 0.001). Bland-Altman analysis showed that the dynamic pressure gradient (peak inspiratory pressure minus positive end-expiratory pressure) overestimated driving pressure (levels of agreement -2.295 to 7.268). Rematching the cohort through a double stratification procedure (obtaining subgroups of patients with matched mean levels for one variable but different mean levels for another ranking variable) showed a reduction in ventilator-free days at day 28 with increasing driving pressure in patients ventilated for a direct pulmonary indication. Competing risk regression analysis showed that increasing driving pressure remained independently associated with increased time to extubation (p < 0.001) after adjusting for Pediatric Risk of Mortality III 24-hour score, presence of direct pulmonary indication jury, and oxygenation index. CONCLUSIONS: Higher driving pressure was independently associated with increased time to extubation in mechanically ventilated children. Dynamic assessments of driving pressure should be cautiously interpreted

The effect of pressure support on imposed work of breathing during paediatric extubation readiness testing

BACKGROUND: Paediatric critical care practitioners often make use of pressure support (PS) to overcome the perceived imposed work of breathing (WOBimp) during an extubation readiness test (ERT). However, no paediatric data are available that shows the necessity of adding of pressure support during such tests. We sought to measure the WOBimp during an ERT with and without added pressure support and to study its clinical correlate. This was a prospective study in spontaneously breathing ventilated children < 18 years undergoing ERT. Using tracheal manometry, WOBimp was calculated by integrating the difference between positive end-expiratory pressure (PEEP) and tracheal pressure (Ptrach) over the measured expiratory tidal volume (VTe) under two paired conditions: continuous positive airway pressure (CPAP) with and without PS. Patients with post-extubation upper airway obstruction were excluded. RESULTS: A total of 112 patients were studied. Median PS during the ERT was 10 cmH2O. WOBimp was significantly higher without PS (median 0.27, IQR 0.20-0.50 J/L) than with added PS (median 0.00, IQR 0.00-0.11 J/L). Although there were statistically significant changes in spontaneous breath rate [32 (23-42) vs. 37 (27-46) breaths/min, p < 0.001] and higher ET-CO2 [5.90 (5.38-6.65) vs. 6.23 (5.55-6.94) kPa, p < 0.001] and expiratory Vt decreased [7.72 (6.66-8.97) vs. 7.08 (5.82-8.08) mL/kg, p < 0.001] in the absence of PS, these changes appeared clinically irrelevant since the Comfort B score remained unaffected [12 (10-13) vs. 12 (10-13), P = 0.987]. Multivariable analysis showed that changes in WOBimp occurred independent of endotracheal tube size. CONCLUSIONS: Withholding PS during ERT does not lead to clinically relevant increases in WOBimp, irrespective of endotracheal tube size

Effect of Extending the Original Eligibility Criteria for the CROSS Neoadjuvant Chemoradiotherapy on Toxicity and Survival in Esophageal Cancer

Patients with curable esophageal cancer (EC) who proceed beyond the original Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect that extending the CROSS eligibility criteria for nCRT has on treatment-related toxicity and overall survival (OS) in EC. The study enrolled 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0) treated with the CROSS schedule followed by esophagectomy. Group 1 consisted of 89 patients who met the CROSS criteria, and group 2 consisted of 72 patients who met the extended eligibility criteria, i.e. a tumor length greater than 8 cm (n = 24), more than 10% weight loss (n = 35), more than 2-4 cm extension in the stomach (n = 21), celiac lymph node metastasis (n = 13), and/or age over 75 years (n = 2). The study assessed the differences in nCRT-associated toxicity [National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) grade3] and 90-day postoperative mortality. Moreover, the prognostic value for OS was assessed with multivariate Cox regression analysis. No difference was found in nCRT-associated toxicity (P = 0.117), postoperative complications (P = 0.783), and 90-day mortality (P = 0.492). The OS differed significantly (P = 0.004), with a median of 37.3 months [95% confidence interval (CI), 10.4-64.2 months] for group 1 and 17.2 months (95% CI 13.8-20.7 months) for group 2. Pathologic N stage (P = 0.023), pathologic T stage (P = 0.043), and group 2 (P = 0.008) were independent prognostic factors for OS. Extension of the CROSS study eligibility criteria for nCRT did not affect nCRT-associated toxicity, postoperative complications, and postoperative mortality, but was prognostic for OS

The long-term safety of chronic azithromycin use in adult patients with cystic fibrosis, evaluating biomarkers for renal function, hepatic function and electrical properties of the heart

Background: Azithromycin maintenance therapy is widely used in cystic fibrosis (CF), but little is known about its long-term safety. We investigated whether chronic azithromycin use is safe regarding renal function, hepatic cell toxicity and QTc-interval prolongation. Methods: Adult CF patients (72 patients using azithromycin for a cumulative period of 364.8 years and 19 controls, 108.8 years) from two CF-centers in the Netherlands with azithromycin (non)-use for at least three uninterrupted years were studied retrospectively. Results: There was no difference in mean decline of estimated glomerular filtration rate (eGFR), nor in occurrence of eGFR-events. No drug-induced liver injury could be attributed to azithromycin. Of the 39 azithromycin users of whom an ECG was available, 4/39 (10.3%) had borderline and 4/39 (10.3%) prolonged QTc-intervals, with 7/8 patients using other QTc-prolonging medication. Of the control patients 1/6 (16.7%) had a borderline QTc-interval, without using other QTc-prolonging medication. No cardiac arrhythmias were observed. Conclusion: We observed no renal or hepatic toxicity, nor cardiac arrythmias during azithromycin use in CF patients for a mean study duration of more than 5 years. One should be aware of possible QTc-interval prolongation, in particular in patients using other QTc-interval prolonging medication

Performance of acute respiratory distress syndrome definitions in a high acuity paediatric intensive care unit

BACKGROUND: For years, paediatric critical care practitioners used the adult American European Consensus Conference (AECC) and revised Berlin Definition (BD) for acute respiratory distress syndrome (ARDS) to study the epidemiology of paediatric ARDS (PARDS). In 2015, the paediatric specific definition, Paediatric Acute Lung Injury Consensus Conference (PALICC) was developed. The use of non-invasive metrics of oxygenation to stratify disease severity were introduced in this definition, although this potentially may lead to a confounding effect of disease severity since it is more common to place indwelling arterial lines in sicker patients. We tested the hypothesis that PALICC outperforms AECC/BD in our high acuity PICU, which employs a liberal use of indwelling arterial lines and high-frequency oscillatory ventilation (HFOV). METHODS: We retrospectively collected data from children < 18 years mechanically ventilated for at least 24 h in our tertiary care, university-affiliated paediatric intensive care unit. The primary endpoint was the difference in the number of PARDS cases between AECC/BD and PALICC. Secondary endpoints included mortality and ventilator free days. Performance was assessed by the area under the receiver operating characteristics curve (AUC-ROC). RESULTS: Data from 909 out of 2433 patients was eligible for analysis. AECC/BD identified 35 (1.4%) patients (mortality 25.7%), whereas PALICC identified 135 (5.5%) patients (mortality 14.1%). All but two patients meeting AECC/Berlin criteria were also identified by PALICC. Almost half of the cohort (45.2%) had mild, 33.3% moderate and 21.5% severe PALICC PARDS at onset. Highest mortality rates were seen in patients with AECC acute lung injury (ALI)/mild Berlin and severe PALICC PARDS. The AUC-ROC for Berlin was the highest 24 h (0.392 [0.124–0.659]) after onset. PALICC showed the highest AUC-ROC at the same moment however higher than Berlin (0.531 [0.345–0.716]). Mortality rates were significantly increased in patients with bilateral consolidations (9.3% unilateral vs 26.3% bilateral, p = 0.025). CONCLUSIONS: PALICC identified more new cases PARDS than the AECC/Berlin definition. However, both PALICC and Berlin performed poorly in terms of mortality risk stratification. The presence of bilateral consolidations was associated with a higher mortality rate. Our findings may be considered in future modifications of the PALICC criteria. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-021-01848-z

(18)F-FDG PET image biomarkers improve prediction of late radiation-induced xerostomia

BACKGROUND AND PURPOSE: Current prediction of radiation-induced xerostomia 12months after radiotherapy (Xer12m) is based on mean parotid gland dose and baseline xerostomia (Xerbaseline) scores. The hypothesis of this study was that prediction of Xer12m is improved with patient-specific characteristics extracted from (18)F-FDG PET images, quantified in PET image biomarkers (PET-IBMs). PATIENTS AND METHODS: Intensity and textural PET-IBMs of the parotid gland were collected from pre-treatment (18)F-FDG PET images of 161 head and neck cancer patients. Patient-rated toxicity was prospectively collected. Multivariable logistic regression models resulting from step-wise forward selection and Lasso regularisation were internally validated by bootstrapping. The reference model with parotid gland dose and Xerbaseline was compared with the resulting PET-IBM models. RESULTS: High values of the intensity PET-IBM (90th percentile (P90)) and textural PET-IBM (Long Run High Grey-level Emphasis 3 (LRHG3E)) were significantly associated with lower risk of Xer12m. Both PET-IBMs significantly added in the prediction of Xer12m to the reference model. The AUC increased from 0.73 (0.65-0.81) (reference model) to 0.77 (0.70-0.84) (P90) and 0.77 (0.69-0.84) (LRHG3E). CONCLUSION: Prediction of Xer12m was significantly improved with pre-treatment PET-IBMs, indicating that high metabolic parotid gland activity is associated with lower risk of developing late xerostomia. This study highlights the potential of incorporating patient-specific PET-derived functional characteristics into NTCP model development

Prognostic Value of the Circumferential Resection Margin in Esophageal Cancer Patients After Neoadjuvant Chemoradiotherapy

Background. Circumferential resection margins (CRM) for esophageal cancer (EC), defined by the College of American Pathologists (CAP; >0 mm) or the Royal College of Pathologists (RCP; >1 mm) as tumor-free (R0), are based on a surgery-alone approach. We evaluated the usefulness of both definitions in current practice with neoadjuvant chemoradiotherapy (nCRT). Methods. CRMs were measured in 209 patients (104 with nCRT) with locally advanced EC after transthoracic esophagectomy. Local recurrence and cancer related death were scored as events. Patients were followed for at least 2 years or until death. Prognostic factors (P <0.1 in univariate analyses) for 2-year disease-free survival (DFS) and local recurrence-free survival (LRFS) were incorporated in multivariate Cox regression analyses. Both CRM measurements were analyzed separately and prognostic cutoff values (0-1.0 mm) were assessed in both groups. Results. Independent prognostic factors (P <0.05) for 2-year DFS were tumor length, lymph node ratio, angioinvasion, and CAP R0 in the surgery-alone group and pN stage (P <0.01) in the nCRT group. Prognostic factors (P <0.05) for 2-year LRFS were CAP, lymph node ratio, and tumor length in the surgery-alone group, and CAP and grade in the nCRT group. Optimal CRM cutoff values between 0.0 and 0.2 mm were prognostic for 2-year DFS in the surgery-alone and at 0.3 mm for the nCRT group. Conclusions. nCRT affected the CRM cutoff values. After nCRT, the CRM R0 according to the CAP was only prognostic for 2-year LRFS. However, in the surgery-alone group, it was prognostic for both the 2-year DFS and LRFS