(PERATECS)

Ältere Patienten mit einem bösartigen Tumorleiden profitieren von einem „Comprehensive Geriatric Assessment“ (CGA) zur präoperativen Risikoeinschätzung. Ein komplettes CGA ist zeitaufwendig. Um Ressourcen adäquat zu allozieren, können einfache Screening-Verfahren vorgeschaltet werden, wenn sie eine prognostische Wertigkeit bezüglich Kurz- und Langzeitergebnissen aufweisen. Zusätzlich sollten Patienten motiviert werden, um nachhaltig ihre Behandlungsqualität zu verbessern. Die Daten für diese Dissertation wurden im Rahmen zweier Studien mit dem Titel „Patienten Empowerment und risiko-adaptierte Behandlung zur Verbesserung des Outcomes älterer Patienten nach gastrointestinalen, thorakalen und urogenitalen Operationen bei malignen Erkrankungen (PERATECS)“ erhoben. Drei Manuskripte wurden dazu veröffentlicht, in denen erstens präoperative Risikofaktoren geriatrischer Krebspatienten als prognostische Indikatoren identifiziert wurden und zweitens relevantes Outcome der Krebspatienten durch zwei Empowerment-Instrumente analysiert wurde. In der ersten Publikation wurde eine klinische, monozentrische Beobachtungsstudie „PERATECS“ (DRKS00005150) veröffentlicht, in der der Zusammenhang zwischen präoperativer gesundheitsbezogener Lebensqualität und Mortalität in einer Kohorte (N=126) von älteren Krebspatienten (>65 Jahre) mit gastrointestinalen, thorakalen und urogenitalen bösartigen Tumoren untersucht wurde. Es konnte gezeigt werden, dass Subskalen der gesundheitsbezogenen Lebensqualität wie die subjektive kognitive Dysfunktion, Appetitlosigkeit und zusätzlich eine eingeschränkte objektive kognitive Dysfunktion und die Operationsschwere prädiktiv in Bezug auf die 1-Jahres-Mortalität bei älteren Krebspatienten war. Der Status der Lebensqualität zwölf Monate nach dem Eingriff war vergleichbar mit dem präoperativen. In der zweiten Publikation wurde eine offene, randomisiert kontrollierte Interventionsstudie „PERATECS“ (NCT01278537) in einer Kohorte (N=652) von älteren Krebspatienten (>65 Jahre) ausgewertet. Dabei wurde der Einfluss von Empowerment-Instrumenten, wie einem Patiententagebuch und einer Informationsbroschüre, auf die globale gesundheitsbezogene Lebensqualität im ersten postoperativen Jahr sowie auf die Krankenhausverweildauer (primäre Endziele) überprüft. Es konnte zwischen den Studiengruppen kein Unterschied in Bezug auf die primären Endziele festgestellt werden. Die Patienten in der Interventionsgruppe wiesen jedoch signifikant weniger postoperative Schmerzen auf. Um den möglichen Einfluss relevanter Parameter des CGA, insbesondere verschiedener Mangelernährungsmarker (Serumalbumin, Body-Mass-Index [BMI], Gewichtsverlust in den letzten 3 Monaten und Mini Nutritional Assessment [MNA®]) auf das sekundäre Endziel „schwerwiegende 30-Tages-Komplikationen“ zu überprüfen, wurde für eine weitere Publikation eine Post-Hoc-Analyse der Interventionsstudie in einer Subkohorte (N=517) vorgenommen. Diese Ergebnisse legen nahe, dass Serumalbumin, Timed "Up and Go"-Test (TUG), American Society of Anesthesiologists (ASA)-Status und BMI für die Entwicklung schwerwiegender Komplikationen nach Krebsoperationen wichtige präoperative Parameter sind. Zusammenfassend konnten Erkenntnisse hinsichtlich des prognostischen Stellenwerts einfacher, unabhängiger geriatrischer Screening-Parameter hinsichtlich kurz- und langfristiger klinischer Endpunkte gezeigt werden. Die Behandlungsqualität bei postoperativen Schmerzen als Kurzzeit-Outcome konnte durch Empowerment verbessert werden. Folgestudien zum präoperativen CGA können zur Validierung der Parameter konzipiert werden.Older patients with a malignant tumor benefit from a Comprehensive Geriatric Assessment (CGA) for pre-operative risk assessment. In order to allocate resources adequately, simple screening procedures with short- and long-term prognostic value should be used. In addition, patients should be "empowered" to sustainably improve their quality of treatment. Data for this dissertation were collected in two studies titled "Patient empowerment and risk assessed treatment to improve outcome in the elderly after gastrointestinal, thoracic or urogenital cancer surgery (PERATECS)”. The first publication examined the link between preoperative health related quality of life and mortality in a cohort (N=126) of elderly cancer patients (≥ 65 years) with abdominal malignancies, who were enrolled in the monocentric, observational clinical study “PERATECS” (DRKS00005150). Subscales of quality of life, such as subjective cognitive dysfunction as well as loss of appetite, and additionally limited objective cognitive dysfunction and the operative severity were predictive with respect to 1-year mortality in elderly cancer patients. The status of global quality of life twelve months after the procedure was comparable to the preoperative status. In the second publication, a cohort (N=652) of older cancer patients (>65 years) was evaluated in an open, randomized controlled intervention study "PERATECS" (NCT018537). The impact of patient empowerment on the global health-related quality of life in the first post-operative year as well as on hospital length of stay (primary objectives) was investigated. No difference between the study groups, in terms of primary objectives could be revealed. However, the patients in the intervention group had significantly less post-operative pain in the empowerment group. A post-hoc analysis of the intervention study in a sub-cohort (N=517) was carried out for a third publication. The possible influence of relevant parameters of the CGA, in particular various malnutrition parameters (serum albumin, body mass index [BMI], weight loss in the last 3 months, and Mini Nutritional Assessment [MNA®]) on the secondary objective "severity of 30-day complications” was investigated. Serum albumin, Timed up and go –Test (TUG), American Society of Anesthesiologists (ASA)-Physical Status Classification System and BMI were independent pre-operative parameters for the development of relevant 30-day complications following cancer surgery. In summary, the prognostic value of simple geriatric screening parameters for both short- and long-term clinical outcomes was evaluated in geriatric cancer patients. The quality of post-operative pain treatment as a short-term outcome could be improved by empowerment. Follow-up studies to the preoperative CGA can be designed to validate these parameters

Frequency distribution in intraoperative stimulation-evoked EMG responses during selective dorsal rhizotomy in children with cerebral palsy—part 2: gender differences and left-biased asymmetry

Introduction: Spinal reflexes reorganize in cerebral palsy (CP), producing hyperreflexia and spasticity. CP is more common among male infants, and gender might also influence brain and spinal-cord reorganization. This retrospective study investigated the frequency of higher-graded EMG responses elicited by electrical nerve-root stimulation during selective dorsal rhizotomy (SDR), prior to partial nerve- root deafferentation, considering not only segmental level and body side, but also gender. Methods: Intraoperative neuromonitoring (IOM) was used in SDR to pinpoint the rootlets most responsible for exacerbated stimulation-evoked EMG patterns recorded from lower-limb muscle groups. Responses were graded according to an objective response-classification system, ranging from no abnormalities (grade 0) to highly abnormal (grade 4+), based on ipsilateral spread and contralateral involvement. Non-parametric analysis of data with repeated measures was primarily used in investigating the frequency distribution of these various EMG response grades. Over 7000 rootlets were stimulated, and the results for 65 girls and 81 boys were evaluated, taking changes in the composition of patient groups into account when considering GMFCS levels. Results: The distribution of graded EMG responses varied according to gender, laterality, and level. Higher-graded EMG responses were markedly more frequent in the boys and at lower segmental levels (L5, S1). Left-biased asymmetry in higher-graded rootlets was also more noticeable in the boys and in patients with GMFCS level I. A close link was observed between higher-grade assessments and left-biased asymmetry. Conclusions: Detailed insight into the patient's initial spinal-neurofunctional state prior to deafferentation suggests that differences in asymmetrical spinal reorganization might be attributable to a hemispheric imbalance

Prediction of long-term mortality by preoperative health-related quality-of-life in elderly onco-surgical patients.

OBJECTIVE: Aim of this study was to evaluate the association between preoperative health-related quality of life (HRQoL) and mortality in a cohort of elderly patients (>65 years) with gastrointestinal, gynecological and genitourinary carcinomas. DESIGN: Prospective cohort pilot study. SETTING: Tertiary university hospital in Germany. PATIENTS: Between June 2008 and July 2010 and after ethical committee approval and written informed consent, 126 patients scheduled for onco-surgery were included. Prior to surgery as well as 3 and 12 months postoperatively all participants completed the EORTC-QLQ-C30 questionnaire (measuring self-reported health-related quality of life). Additionally, demographic and clinical data including the Mini Mental State Examination (MMSE) were collected. Surgery and anesthesia were conducted according to the standard operating procedures. Primary endpoint was the cumulative mortality rate over 12 months after one year. Changes in Quality of life were considered as secondary outcome. RESULTS: Mortality after one year was 28%. In univariable and multivariable logistic regression analysis baseline HRQoL self-reported cognitive function (OR per point: 0.98; CI 95% 0.96-0.99; p = 0.024) and higher symptom burden for appetite loss (per point: OR 1.02; CI 95% 1.00-1.03; p = 0.014) were predictive for long-term mortality. Additionally the MMSE as an objective measure of cognitive impairment (per point: OR 0.69; CI 95% 0.51-0.96; p = 0.026) as well as severity of surgery (OR 0.31; CI 95% 0.11-0.93; p = 0.036) were predictive for long-term mortality. Global health status 12 months after surgery was comparable to the baseline levels in survivors despite moderate impairments in other domains. CONCLUSION: This study showed that objective and self-reported cognitive functioning together with appetite loss were prognostic for mortality in elderly cancer patients. In addition, impaired cognitive dysfunction and severity of surgery were predictive for one-year mortality whereas in this selected population scheduled for surgery age, gender, cancer site and metastases were not

Patient Empowerment Improved Perioperative Quality of Care in Cancer Patients Aged ≥ 65 Years - A Randomized Controlled Trial.

This randomized controlled, clinical prospective interventional trial was aimed at exploring the effect of patient empowerment on short- and long-term outcomes after major oncologic surgery in elderly cancer patients.This trial was performed from February 2011 to January 2014 at two tertiary medical centers in Germany. The study included patients aged 65 years and older undergoing elective surgery for gastro-intestinal, genitourinary, and thoracic cancer. The patients were randomly assigned to the intervention group, i.e. patient empowerment through information booklet and diary keeping, or to the control group, which received standard care. Randomization was done by block randomization in blocks of four in order of enrollment. The primary outcome were 1,postoperative length of hospital stay (LOS) and 2. long-term global health-related quality of life (HRQoL) one year postoperatively. HRQoL was assessed using the EORTC QLQ C30 questionnaire. Secondary outcomes encompassed postoperative stress and complications. Further objectives were the identification of predictors of LOS, and HRQoL at 12 months.Overall 652 patients were included. The mean age was 72 ± 4.9 years, and the majority of patients were male (68.6%, n = 447). The ^median of postoperative length of stay was 9 days (IQR 7-14 day). There were no significant differences between the intervention and the control groups in postoperative LOS (p = 0.99) or global HRQoL after one year (women: p = 0.54, men: p = 0.94). While overall complications and major complications occurred in 74% and 24% of the cases, respectively, frequency and severity of complications did not differ significantly between the groups. Patients in the intervention group reported significantly less postoperative pain (p = 0.03) than the control group. Independent predictors for LOS were identified as severity of surgery, length of anesthesia, major postoperative complications, nutritional state, and pre-operative physical functional capacity measured by the Timed Up and Go-test by multiple robust regressions.Patient empowerment through information booklet and diary keeping did not shorten the postoperative LOS in elderly onco-surgical patients, but improved quality of care regarding postoperative pain. Postoperative length of stay is influenced by pre-operative nutritional state, pre-operative functional impairment, severity of surgery, and length of anesthesia.Clinicaltrials.gov. Identifier NCT01278537

Univariable logistic regression analyses of long-term mortality for sociodemographic, clinical, and Health-related Quality of Life Data (HRQOL) Data.

<p>OR = Odds ratio; CI = Confidence interval; p = p-value; ASA = American Society of Anesthesiologists.</p>**<p>Measured by the Physiological and Operative Severity Scoring system for enUmeration of Mortality and morbidity (POSSUM) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085456#pone.0085456-Copeland1" target="_blank">[28]</a>.</p>***<p>EORTC QLQ-C30 Questionnaire; Continuous range;</p><p>³High scores represent better function;</p>4<p>High score represent worse symptoms.</p

Changing of symptom related Health Related Quality of life–domains from preoperative baseline to 12 months follow up.

<p>The mean scores of the EORTC QLQ-C30 symptoms domains for survivors, non-survivors (data baseline and follow up after 3 months) and the reference values for women and men for the same-aged German population are shown. Higher scores represent higher symptom burden. The burden of appetite loss in the baseline was significant higher in non-survivors (p = 0.008) whereas the remaining symptom scales were not significant different between both groups in baseline assessment. The symptom burden increased in all domains 3 months after surgery. In survivors, one year after surgery, appetite loss and nausea and vomiting were similar to baseline levels, whereas fatigue (p<0.001), pain (p = 0.015), dyspnea (p<0.001), and financial difficulties (p = 0.001) were worse compared to baseline but improved in comparison to the 3 months follow up. The increase in symptom burden was moderate (10–20 points increase).</p

Flow chart of the study population.

<p>Flow chart of the study population.</p

Patients characteristic – Sociodemographic and clinical variables, stratified for Non-Survivors/Survivors.

<p>²Mann – Whitney –U-Test,</p><p>³Χ² test,</p>4<p>Cochran-Armitage trend test;</p>**<p>Measured by the Physiological and Operative Severity Scoring system for enUmeration of Mortality and morbidity (POSSUM) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085456#pone.0085456-Copeland1" target="_blank">[28]</a>.</p><p>SD: standard deviation, IQR: interquartile range, BMI: body mass index, GDS: geriatric depression scale; GI: Gastrointestinal, ASA: American Society of Anesthesiologists.</p

Study flow diagram.

<p>Study flow diagram.</p

Short-term postoperative outcomes.

<p>OR: operating room, LOS: length of hospital stay, cardiopulmonary: respiratory insufficiency, angina, myocardial infarction, arrhythmia, lung edema, pulmonary embolism; excluded: pneumonia; SD: standard deviation, IQR: interquartile range.</p><p>#: χ2-Test</p><p>Short-term postoperative outcomes.</p