Postoperative Complications and Long-Term Quality of Life After Multimodality Treatment for Esophageal Cancer: An Analysis of the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP).

BACKGROUND: Esophagectomy has major effects on health-related quality of life (HR-QoL). Postoperative complications might contribute to a decreased HR-QOL. This population-based study aimed to investigate the difference in HR-QoL between patients with and without complications after esophagectomy for cancer. METHODS: A prospective comparative cohort study was performed with data from the Netherlands Cancer Registry (NCR) and Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP). All patients with esophageal and gastroesophageal junction (GEJ) cancer after esophagectomy in the period 2015-2018 were enrolled. The study investigated HR-QoL at baseline, then 3, 6, 9, 12, 18, and 24 months postoperatively, comparing patients with and without complications as well as with and without anastomotic leakage. RESULTS: The 486 enrolled patients comprised 270 patients with complications and 216 patients without complications. Significantly more patients with complications had comorbidities (69.6% vs 57.3%; p = 0.001). No significant difference in HR-QoL was found over time between the patients with and without complications. In both groups, a significant decline in short-term HR-QoL was found in various HR-QoL domains, which were restored to the baseline level during the 12-month follow-up period. No significant difference was found in HR-QoL between the patients with and without anastomotic leakage. The patients with grades 2 and 3 anastomotic leakage reported significantly more "choking when swallowing" at 6 months (ß = 14.5; 95% confidence interval [CI], - 24.833 to - 4.202; p = 0.049), 9 months (ß = 22.4, 95% CI, - 34.259 to - 10.591; p = 0.007), and 24 months (ß = 24.6; 95% CI, - 39.494 to - 9.727; p = 0.007) than the patients with grade 1 or no anastomotic leakage. CONCLUSION: In general, postoperative complications were not associated with decreased short- or long-term HR-QoL for patients after esophagectomy for esophageal or GEJ cancer. The temporary decrease in HR-QoL likely is related to the nature of esophagectomy and reconstruction itself.

Prognostic value of patient-reported quality of life for survival in oesophagogastric cancer: analysis from the population-based POCOP study.

BACKGROUND: Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer. However, real-world data are lacking. Moreover, differences in disease stages and tumour-specific symptoms are usually not taken into consideration. The aim of this population-based study was to assess the prognostic value of HRQoL, including tumour-specific scales, on OS in patients with potentially curable and advanced oesophagogastric cancer. METHODS: Data were derived from the Netherlands Cancer Registry and the patient reported outcome registry (POCOP). Patients included in POCOP between 2016 and 2018 were stratified for potentially curable (cT1-4aNallM0) or advanced (cT4b or cM1) disease. HRQoL was measured with the EORTC QLQ-C30 and the tumour-specific OG25 module. Cox proportional hazards models assessed the impact of HRQoL, sociodemographic and clinical factors (including treatment) on OS. RESULTS: In total, 924 patients were included. Median OS was 38.9 months in potentially curable patients (n = 795) and 10.6 months in patients with advanced disease (n = 129). Global Health Status was independently associated with OS in potentially curable patients (HR 0.89, 99%CI 0.82-0.97), together with several other HRQoL items: appetite loss, dysphagia, eating restrictions, odynophagia, and body image. In advanced disease, the Summary Score was the strongest independent prognostic factor (HR 0.75, 99%CI 0.59-0.94), followed by fatigue, pain, insomnia and role functioning. CONCLUSION: In a real-world setting, HRQoL was prognostic for OS in patients with potentially curable and advanced oesophagogastric cancer. Several HRQoL domains, including the Summary Score and several OG25 items, could be used to develop or update prognostic models.

Communicating treatment risks and benefits to cancer patients: a systematic review of communication methods.

PURPOSE: Cancer patients are increasingly involved in decision-making processes. Hence, clinicians need to inform patients about the risks and benefits of different treatment options in order for patients to make well informed decisions. The aim of this review is to determine the effects of methods of communicating prognostic information about (1) disease progression (survival, progression, recurrence and remission), (2) side effects and complications and (3) health-related quality of life (HRQL) on cognitive, affective and behavioral outcomes in cancer patients. METHODS: A literature search was performed to select articles that were published up to  November 2019 and that examined verbal and/or visual risk communication interventions in an oncological clinical setting. RESULTS: The search yielded 14,875 studies; 28 studies were ultimately included. For disease progression information, we found that framing affects treatment choice. Furthermore, limiting the amount of progression information in a graphical display could benefit patients' understanding of risks and benefits. For prognostic information about side effects and complications, precise and defined risk information was better understood than information presented in words. When displaying HRQL data, no consensus was found on which graph type to use. CONCLUSION: Great heterogeneity in the results and methodology and in the compared communication formats precluded us from drawing any further conclusions. Practical implications for clinicians are to consider the effects that different types of framing might have on the patient and to not rely exclusively on words to describe risks, but rather include at least some form of numbers or visualization.

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative.

BACKGROUND: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. MATERIAL AND METHODS: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. RESULTS: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. CONCLUSION: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting.

Spectral inputs and ocellar contributions to a pitch-sensitive descending neuron in the honeybee.

By measuring insect compensatory optomotor reflexes to visual motion, researchers have examined the computational mechanisms of the motion processing system. However, establishing the spectral sensitivity of the neural pathways that underlie this motion behavior has been difficult, and the contribution of the simple eyes (ocelli) has been rarely examined. In this study we investigate the spectral response properties and ocellar inputs of an anatomically identified descending neuron (DNII(2)) in the honeybee optomotor pathway. Using a panoramic stimulus, we show that it responds selectively to optic flow associated with pitch rotations. The neuron is also stimulated with a custom-built light-emitting diode array that presented moving bars that were either all-green (spectrum 500-600 nm, peak 530 nm) or all-short wavelength (spectrum 350-430 nm, peak 380 nm). Although the optomotor response is thought to be dominated by green-sensitive inputs, we show that DNII(2) is equally responsive to, and direction selective to, both green- and short-wavelength stimuli. The color of the background image also influences the spontaneous spiking behavior of the cell: a green background produces significantly higher spontaneous spiking rates. Stimulating the ocelli produces strong modulatory effects on DNII(2), significantly increasing the amplitude of its responses in the preferred motion direction and decreasing the response latency by adding a directional, short-latency response component. Our results suggest that the spectral sensitivity of the optomotor response in honeybees may be more complicated than previously thought and that ocelli play a significant role in shaping the timing of motion signals.

Visual response properties of neck motor neurons in the honeybee.

Recent behavioural studies have demonstrated that honeybees use visual feedback to stabilize their gaze. However, little is known about the neural circuits that perform the visual motor computations that underlie this ability. We investigated the motor neurons that innervate two neck muscles (m44 and m51), which produce stabilizing yaw movements of the head. Intracellular recordings were made from five (out of eight) identified neuron types in the first cervical nerve (IK1) of honeybees. Two motor neurons that innervate muscle 51 were found to be direction-selective, with a preference for horizontal image motion from the contralateral to the ipsilateral side of the head. Three neurons that innervate muscle 44 were tuned to detect motion in the opposite direction (from ipsilateral to contralateral). These cells were binocularly sensitive and responded optimally to frontal stimulation. By combining the directional tuning of the motor neurons in an opponent manner, the neck motor system would be able to mediate reflexive optomotor head turns in the direction of image motion, thus stabilising the retinal image. When the dorsal ocelli were covered, the spontaneous activity of neck motor neurons increased and visual responses were modified, suggesting an ocellar input in addition to that from the compound eyes.

External Validation of the Dutch SOURCE Survival Prediction Model in Belgian Metastatic Oesophageal and Gastric Cancer Patients.

The SOURCE prediction model predicts individualised survival conditional on various treatments for patients with metastatic oesophageal or gastric cancer. The aim of this study was to validate SOURCE in an external cohort from the Belgian Cancer Registry. Data of Belgian patients diagnosed with metastatic disease between 2004 and 2014 were extracted (n = 4097). Model calibration and discrimination (c-indices) were determined. A total of 2514 patients with oesophageal cancer and 1583 patients with gastric cancer with a median survival of 7.7 and 5.4 months, respectively, were included. The oesophageal cancer model showed poor calibration (intercept: 0.30, slope: 0.42) with an absolute mean prediction error of 14.6%. The mean difference between predicted and observed survival was -2.6%. The concordance index (c-index) of the oesophageal model was 0.64. The gastric cancer model showed good calibration (intercept: 0.02, slope: 0.91) with an absolute mean prediction error of 2.5%. The mean difference between predicted and observed survival was 2.0%. The c-index of the gastric cancer model was 0.66. The SOURCE gastric cancer model was well calibrated and had a similar performance in the Belgian cohort compared with the Dutch internal validation. However, the oesophageal cancer model had not. Our findings underscore the importance of evaluating the performance of prediction models in other populations.

Endovascular treatment of acute subclavian pseudo-aneurysm after fracture of the clavicle.

Pseudo-aneurysms of the subclavian artery remain a rare complication after fracture of the clavicle. Nerve compression has been described with delayed paralysis as a consequence. We report a case of delayed diagnosis of a subclavian pseudo-aneurysm after a closed fracture of the clavicle in a 93-year-old patient. Diagnosis was confirmed by ultrasound and multi-slice-Ct. Two attempts to treat the pseudo-aneurysm with percutaneous thrombin injection failed. Considering the age of the patient, it was decided to exclude the pseudo-aneurysm by endovascular approach. A Hemobahn endoprosthesis was inserted by the introduction of an 11F sheath after cutting down the brachial artery under local anaesthesia. Angiography revealed complete exclusion of the pseudo-aneurysm. Follow-up at 9 months by ultrasound confirmed exclusion of the pseudo-aneurysm. Plain X-ray of the endograft showed no stent fractures. Paresis of the arm had improved. This case illustrates that endovascular exclusion is a safe approach, with reduced morbidity, compared with open surgery. Concern about stent deformation and stent fractures has been expressed. With the introduction of highly flexible stents, one can hope that this complication is less likely to occur. Although follow-up is relatively short, we believe that endovascular exclusion of subclavian pseudo-aneurysms is preferable to a surgical approach.

Prediction models for patients with esophageal or gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Clinical prediction models are increasingly used to predict outcomes such as survival in cancer patients. The aim of this study was threefold. First, to perform a systematic review to identify available clinical prediction models for patients with esophageal and/or gastric cancer. Second, to evaluate sources of bias in the included studies. Third, to investigate the predictive performance of the prediction models using meta-analysis. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL, and The Cochrane Library were searched for publications from the year 2000 onwards. Studies describing models predicting survival, adverse events and/or health-related quality of life (HRQoL) for esophageal or gastric cancer patients were included. Potential sources of bias were assessed and a meta-analysis, pooled per prediction model, was performed on the discriminative abilities (c-indices). RESULTS: A total of 61 studies were included (45 development and 16 validation studies), describing 47 prediction models. Most models predicted survival after a curative resection. Nearly 75% of the studies exhibited bias in at least 3 areas and model calibration was rarely reported. The meta-analysis showed that the averaged c-index of the models is fair (0.75) and ranges from 0.65 to 0.85. CONCLUSION: Most available prediction models only focus on survival after a curative resection, which is only relevant to a limited patient population. Few models predicted adverse events after resection, and none focused on patient's HRQoL, despite its relevance. Generally, the quality of reporting is poor and external model validation is limited. We conclude that there is a need for prediction models that better meet patients' information needs, and provide information on both the benefits and harms of the various treatment options in terms of survival, adverse events and HRQoL.

Pharmacokinetics of lignocaine and bupivacaine in surgical patients following epidural administration. Simultaneous investigation of absorption and disposition kinetics using stable isotopes.

The pharmacokinetics of lignocaine (lidocaine) and bupivacaine following epidural administration were studied in 12 surgical patients using a stable isotope method. Shortly after epidural administration of the agent to be evaluated, a deuterium-labelled analogue was administered intravenously. Plasma concentrations of the unlabelled and the deuterium-labelled local anaesthetics were determined using gas chromatography and mass fragmentography. The pharmacokinetic behaviour of both agents was consistent with a 2-compartment open model and two parallel first-order absorption processes. The mean distribution and elimination half-lives were 12 minutes and 100 minutes for lignocaine, and 22 minutes and 143 minutes for bupivacaine. The mean volumes of the central compartment and the mean steady-state volumes of distribution were: lignocaine, 43L and 99L; bupivacaine, 33L and 68L. Total plasma clearances averaged 0.95 L/min (57 L/h) for lignocaine and 0.52 L/min (31.2 L/h) for bupivacaine. The half-lives, characterising the fast and slow absorption processes, were 9.3 and 82 minutes for lignocaine, and 7.0 minutes and 362 minutes for bupivacaine; the fractions of the doses absorbed in the fast and slow processes were lignocaine 0.38 and 0.58, bupivacaine 0.28 and 0.66, respectively. The results indicate that the local anaesthetics are completely absorbed from the epidural space into the general circulation. The initial absorption rates of both local anaesthetics appear to be similar, but, later, the absorption of bupivacaine proceeds much more slowly than the absorption of lignocaine.

Cognitive function after spinal or general anesthesia for transurethral prostatectomy in elderly men.

Cognitive functions in 53 elderly men who underwent a transurethral prostatectomy were assessed pre-operatively and 4 days and 3 months post-operatively. Thirteen patients had a preference for one particular type of anesthesia, and the remaining 40 were randomly allocated to receive either spinal or general anesthesia. Cognitive function was not different between the groups receiving different types of anesthesia at either time point and did not decrease post-operatively. No pre- or perioperative variable could distinguish the subgroup of patients who had a post-operative decrease of 2 points or more on the Mini-Mental State Examination. No difference in post-operative performance was found in the patient groups with pre-operative Mini-Mental State Examination scores above or under their age-specific norm. It is concluded that neither hospitalization nor the two forms of anesthesia investigated cause a decrease in cognitive function in elderly men.

The use of frequency diagrams in the survey of resistance to pesticides in ticks in Southern Africa.

A method whereby resistance data can be analysed by means of frequency distributions is described. This method established that Rhipicephalus appendiculatus and R. evertsi evertsi show either little or only developing resistance to the pesticides chlorfenvinphos and dioxathion. Boophilus spp., however, show more instances and higher levels of resistance to these 2 pesticides.

[Mediastinoscopy and bronchial carcinoma. Experience with 600 mediastinoscopies (author's transl)]. / Mediastinoscopie en longcarcinoom. Ervaring met 600 mediastinoscopieën

Of 600 mediastinoscopies carried out from 1966 to 1973, 479 were performed to assess the operability of a pulmonary carcinoma. Of these, (43%) were positive and (57%) negative. Of the 161 patients found positive during an initial period, 14 were considered candidates for operation. The tumour was irresectable in one patient, who died after 3.5 months; curative resection was possible in one and palliative resection in 12 patients. These 12 patients all died within a year. Of the 184 patients found negative during an initial period, 149 were treated by operation. The tumour proved irresectable in 5%, while curative resection was possible in 76% and palliative resection in 19%. Comparison with the period 1957-1963, when in the same hospital resection was performed after a negative Daniels biopsy, shows that the tumour was irresectable in 20%, while curative resection was possible in 35% and palliative resection in 45%. During a second period, patients with a positive mediastinoscopy were refused operation. Of 89 negative patients, 81 were treated by operation. No tumour was found to be irresectable; curative resection was possible in 78% and palliative resection in 22%. A survival study was made of 100 operated patients with a follow-up from a minimum of two years and four months to a maximum of four years and four months. The early mortality averaged 10%. The late mortality was 31% after curative lobectomy, 43% after curative pneumonectomy, and 100% after palliative resection. The survival was 49%

[The practice guideline 'Neuraxis blockade and anticoagulation']. / Richtlijn 'Neuraxisblokkade en antistolling'.

In a patient with a coagulation disorder, the administration of a local anaesthetic by means of a needle or via the insertion of a catheter into the epidural space or spinal cavity may lead to bleeding and haematoma formation, with a danger of pressure on the spinal cord or nerve roots. Employing the method of the Dutch Institute for Healthcare (CBO) for the development of practice guidelines, a working group of anaesthesiologists, a haematologist and a hospital chemist have drawn up recommendations for neuraxis blockade in combination with anticoagulant therapy. In patients with a clinically acquired tendency toward increased bleeding, the management is highly dependent on the cause of the bleeding tendency. If the patient uses acetylsalicylic acid or clopidogrel, the medication must be withdrawn at least 10 days before neuraxis blockade is started. Therapy with glycoprotein-IIb/IIIa-receptor antagonists is an absolute contra-indication for neuraxis blockade. In patients who are using coumarin derivatives, neuraxis blockade results in an increased risk of a neuraxial haematoma. The coumarin derivative should then be withdrawn and replaced by a different form of anticoagulation. The use of low-molecular-weight heparin at the usual prophylactic dosage is not a contra-indication for neuraxis blockade and the risk of a neuraxial haematoma following neuraxis blockade is also not increased significantly by the subcutaneous administration of unfractionated heparin.

[Postoperative pain control in The Netherlands]. / Postoperatieve pijnbestrijding in Nederland.

OBJECTIVE: To determine how postoperative analgesia care is managed in the Netherlands. DESIGN: Descriptive study (questionnaire). SETTING: Departments of anaesthesiology in all 168 Dutch hospitals. METHOD: Questionnaires were sent inquiring about postoperative pain therapies and their complications, the organisation and management of postoperative analgesic care, the importance of effective pain control, factors of influence on patient's assessment of pain and the management of the quality of postoperative analgesia. RESULTS: The questionnaires of 73% (n = 122) of the hospitals were suitable for analysis. Locoregional analgesic techniques are used, but intermittent intramuscular administration of an opioid is still the analgesic therapy of choice in the postoperative period. 89% of the interviewed anaesthesiologists assess the average intensity of postoperative pain as moderate or severe, and more than half of the interviewed anaesthesiologists answered that effective postoperative pain management is of substantial influence on the postoperative recovery of the patient. CONCLUSION: It is essential to improve postoperative pain control in the Netherlands. Frequent assessments and precise documentation of the intensity of pain and pain relief, on which further therapy can be based, might be a first step in improving postoperative pain control. Optimal postoperative pain management requires the input of equipment and staff.

[Surgical treatment of carpal tunnel syndrome: endoscopic or classical (open)? A prospective randomized trial]. / Operatieve behandeling wegens carpaletunnelsyndroom: endoscopisch of klassiek (open)? Een prospectief gerandomiseerd onderzoek.

OBJECTIVE: To compare the results of open with endoscopic release of the carpal tunnel in patients with the carpal tunnel syndrome. DESIGN: Randomised prospective study. SETTING: General hospital Zeeuws-Vlaanderen, Oostburg and Terneuzen, the Netherlands. METHOD: 178 patients were randomised for open or endoscopic release. The symptom severity score and functional status score were completed before and three months after the procedure. One week after the operation the patients' postoperative pain was measured on a 10-point visual analogue scale. Differences were analysed using the Chi-square test or the t-test. RESULTS: Randomisation failed in two patients; 85 patients had an endoscopic release and 91 patients had an open release. The postoperative pain was significantly less in the endoscopic group. Improvement in symptom severity score and functional status score was the same in both groups. There was no difference in absence from work. Two local complications occurred in the endoscopically treated group. Of the patients 25% were not or only slightly satisfied with the results. CONCLUSION: Endoscopic release of the carpal tunnel is as effective as the open release but it gives less postoperative pain. Because of the risk of complications and the additional costs, the endoscopic release is not the preferred method for treatment of the carpal tunnel syndrome, however.

[An abscess as an unexpected complication following epidural anesthesia]. / Een abces als onverwachte complicatie na epidurale anesthesie.

A 58-year-old man underwent surgery for an inguinal hernia. Surgery was performed under epidural anaesthesia. The patient afterwards developed increasing low back pain. Magnetic resonance imaging showed an epidural abscess, which was drained by laminectomy. The patient recovered without neurological sequelae.

A wearable wireless platform for visually stimulating small flying insects.

Linking neurons and muscles to their roles in behavior requires not only the ability to measure their response during unrestrained movement but also the ability to stimulate them and observe the behavioral results. Current wireless stimulation technologies can be carried by rodent-sized animals and very large insects. However, the mass and volume of these devices make them impractical for studying smaller animals like insects. Here we present a battery-powered electronics platform suitable to be carried on a flying locust (2.7 g). The device has an IR-based (infrared) receiver, can deliver optical or electrical stimulation, occupies a volume of 0.1 cm(3), and weighs ~280 mg. We show the device is capable of powering two white SMD light emitting diodes (LEDs) for ~4 min and can be recharged in ~20 min. We demonstrate that our system shows no crosstalk with an IR-based Vicon tracking system. The entire package is made from commercial off-the-shelf components and requires no microfabrication.

Phase sensitivity of complex cells in primary visual cortex.

Neurons in the primary visual cortex are often classified as either simple or complex based on the linearity (or otherwise) of their response to spatial luminance contrast. In practice, classification is typically based on Fourier analysis of a cell's response to an optimal drifting sine-wave grating. Simple cells are generally considered to be linear and produce responses modulated at the fundamental frequency of the stimulus grating. In contrast, complex cells exhibit significant nonlinearities that reduce the response at the fundamental frequency. Cells can therefore be easily and objectively classified based on the relative modulation of their responses - the ratio of the phase-sensitive response at the fundamental frequency of the stimulus (F1) to the phase-invariant sustained response (F0). Cells are classified as simple if F1/F0>1 and complex if F1/F0<1. This classification is broadly consistent with criteria based on the spatial organisation of cells' receptive fields and is accordingly presumed to reflect disparate functional roles of simple and complex cells in coding visual information. However, Fourier analysis of spiking responses is sensitive to the number of spikes available - F1/F0 increases as the number of spikes is reduced, even for phase-invariant complex cells. Moreover, many complex cells encountered in the laboratory exhibit some phase sensitivity, evident as modulation of their responses at the fundamental frequency. There currently exists no objective quantitative means of assessing the significance or otherwise of these modulations. Here we derive a statistical basis for objectively assessing whether the modulation of neuronal responses is reliable, thereby adding a level of statistical certainty to measures of phase sensitivity. We apply our statistical analysis to neuronal responses to moving sine-wave gratings recorded from 367 cells in cat primary visual cortex. We find that approximately 60% of complex cells exhibit statistically significant (α<0.01) modulation of their responses to optimal moving gratings. These complex cells are phase sensitive and reliably encode spatial phase.