A qualitative stakeholder analysis of beliefs, facilitators, and barriers for a feasible prehabilitation program before lung cancer surgery.

BACKGROUND: In order to develop a feasible prehabilitation program before surgery of NSCLC, this study aimed to gain insight into beliefs, facilitators, and barriers of (1) healthcare professionals to refer patients to a prehabilitation program, (2) patients to participate in and adhere to a prehabilitation program, and (3) informal caregivers to support their loved ones. METHODS: Semi-structured interviews were conducted with healthcare professionals, patients who underwent surgery for NSCLC, and their informal caregivers. The capability, opportunity, and motivation for behavior-model (COM-B) guided the development of the interview questions. Results were analyzed thematically. RESULTS: The interviews were conducted with twelve healthcare professionals, seventeen patients, and sixteen informal caregivers. Four main themes were identified: (1) content of prehabilitation and referral, (2) organizational factors, (3) personal factors for participation, and (4) environmental factors. Healthcare professionals mentioned that multiple professionals should facilitate the referral of patients to prehabilitation within primary and secondary healthcare involved in prehabilitation, considering the short preoperative period. Patients did not know that a better preoperative physical fitness and nutritional status would make a difference in the risk of postoperative complications. Patients indicated that they want to receive information about the aim and possibilities of prehabilitation. Most patients preferred a group-based physical exercise training program organized in their living context in primary care. Informal caregivers could support their loved one when prehabilitation takes place by doing exercises together. CONCLUSION: A prehabilitation program should be started as soon as possible after the diagnosis of lung cancer. Receiving information about the purpose and effects of prehabilitation in a consult with a physician seems crucial to patients and informal caregivers to be involved in prehabilitation. Support of loved ones in the patient's own living context is essential for adherence to a prehabilitation program.

Evidence base for exercise prehabilitation suggests favourable outcomes for patients undergoing surgery for non-small cell lung cancer despite being of low therapeutic quality: a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review was to evaluate whether exercise prehabilitation programs reduce postoperative complications, postoperative mortality, and length of hospital stay (LoS) in patients undergoing surgery for non-small cell lung cancer (NSCLC), thereby accounting for the quality of the physical exercise program. METHODS: Two reviewers independently selected randomized controlled trials (RCTs) and observational studies and assessed them for methodological quality and therapeutic quality of the exercise prehabilitation program (i-CONTENT tool). Eligible studies included patients with NSCLC performing exercise prehabilitation and reported the occurrence of 90-day postoperative complications, postoperative mortality, and LoS. Meta-analyses were performed and the certainty of the evidence was graded (Grading of Recommendations Assessment, Development and Evaluation (GRADE)) for each outcome. RESULTS: Sixteen studies, comprising 2,096 patients, were included. Pooled analyses of RCTs and observational studies showed that prehabilitation reduces postoperative pulmonary complications (OR 0.45), postoperative severe complications (OR 0.51), and LoS (mean difference -2.46 days), but not postoperative mortality (OR 1.11). The certainty of evidence was very low to moderate for all outcomes. Risk of ineffectiveness of the prehabilitation program was high in half of the studies due to an inadequate reporting of the dosage of the exercise program, inadequate type and timing of the outcome assessment, and low adherence. CONCLUSION: Although risk of ineffectiveness was high for half of the prehabilitation programs and certainty of evidence was very low to moderate, prehabilitation seems to result in a reduction of postoperative pulmonary and severe complications, as well as LoS in patients undergoing surgery for NSCLC.

Associations between pretreatment nutritional assessments and treatment complications in patients with stage I-III non-small cell lung cancer: A systematic review.

BACKGROUND: Patients with stage I-III non-small cell lung cancer (NSCLC) are often nutritionally depleted and therefore at high-risk for treatment complications. Identifying these patients before the start of treatment is important to initiate preventive interventions for better treatment outcomes. This study aimed to evaluate which outcome variables of pretreatment nutritional assessments are associated with posttreatment complications in patients with stage I-III NSCLC, as well as to identify cut-off values for clinical risk stratification. METHODS: In this systematic review, PubMed, Embase, and Cinahl databases were searched for eligible studies published up to March 2021. Studies describing the association between pretreatment nutritional assessment and treatment complications in patients with NSCLC were included. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale for cohort studies. RESULTS: A total of 23 studies were included, which merely focused on surgical treatment for NSCLC. Methodological quality was poor in thirteen studies (57%). Poor outcomes of body mass index, sarcopenia, serum albumin, controlling nutritional status, prognostic nutrition index, nutrition risk score, and (geriatric) nutrition risk index were associated with a higher risk for treatment complications. Cut-off values for pretreatment nutritional assessment were reported in a limited number of studies and were inconsistent. CONCLUSION: Poor outcomes of pretreatment nutritional assessments are associated with a higher risk for posttreatment complications. Further research is needed on the ability of easy-to-use pretreatment nutritional assessments to accurately identify patients who are at high risk for treatment complications, as high-risk patients may benefit from pretreatment interventions to improve their nutritional status.

Associations between pretreatment physical performance tests and treatment complications in patients with non-small cell lung cancer: A systematic review.

This systematic review evaluated which outcome variables and cut-off values of pretreatment exercise tests are associated with treatment complications in patients with stage I-III non-small cell lung cancer (NSCLC). PRISMA and Cochrane guidelines were followed. A total of 38 studies with adult patients undergoing treatment for stage I-III NSCLC who completed pretreatment exercise tests, and of whom treatment-related complications were recorded were included. A lower oxygen uptake at peak exercise amongst several other variables on the cardiopulmonary exercise test and a lower performance on field tests, such as the incremental shuttle walk test, stair-climb test, and 6-minute walk test, were associated with a higher risk for postoperative complications and/or postoperative mortality. Cut-off values were reported in a limited number of studies and were inconsistent. Due to the variety in outcomes, further research is needed to evaluate which outcomes and cut-off values of physical exercise tests are most clinically relevant.

[Hepatopulmonary syndrome. A consideration in patients with liver disease accompanied by dyspnoea and hypoxaemia]. / Het hepatopulmonaal syndroom.

BACKGROUND: Hepatopulmonary syndrome is a severe complication of liver disease, with greatly increased mortality. The syndrome is characterized by increased blood-flow, intrapulmonary vasodilatation and angiogenesis, leading to effects including the formation of shunts. This leads to a decrease in arterial oxygen pressure. Liver transplantation is the only effective treatment. CASE DESCRIPTION: A 74-year-old woman with cirrhosis of the liver attended the pulmonary outpatients' clinic with progressive dyspnoea, which worsened if she sat upright from a lying position (platypnoea). Contrast echocardiography confirmed the diagnosis 'hepatopulmonary syndrome'. The patient was not eligible for liver transplantation. She was given oxygen therapy and died from decompensated cirrhosis of the liver eighteen months later. CONCLUSION: Early recognition of hepatopulmonary syndrome is important, because patients may be given priority for liver transplantation. Contrast echocardiography is indicated in patients with liver disease and suffering from hypoxaemia for which there is no other explanation, to reveal the presence of intrapulmonary shunt.

EGFR mutated non-small cell lung cancer patients: more prone to development of bone and brain metastases?

OBJECTIVES: Both bone and brain are frequent sites of metastasis in non-small cell lung cancer (NSCLC). Conflicting data exist whether EGFR mutant (+) patients are more prone to develop brain metastases or have a better outcome with brain metastases compared to EGFR/KRAS wildtype (WT) or KRAS+ patients. For bone metastases this has not been studied. METHODS: In this retrospective case-control study all EGFR+ (exons 19 and 21) patients diagnosed at two pathology departments were selected (2004/2008 to 2012). For every EGFR+ patient a consecutive KRAS+ and WT patient with metastatic NSCLC (mNSCLC) was identified. Patients with another malignancy within 2 years of mNSCLC diagnosis were excluded. Data regarding age, gender, performance score, histology, treatment, bone/brain metastases diagnosis, skeletal related events (SRE) and subsequent survival were collected. RESULTS: 189 patients were included: 62 EGFR+, 65 KRAS+, 62 WT. 32%, 35% and 40%, respectively, had brain metastases (p=0.645). Mean time to brain metastases was 20.8 [± 12.0], 10.8 [± 9.8], 16.4 [± 10.2] months (EGFR+-KRAS+, p = 0.020, EGFR+-WT, p = 0.321). Median post brain metastases survival was 12.1 [5.0-19.1], 7.6 [1.2-14.0], 10.7 [1.5-19.8] months (p = 0.674). 60%, 52% and 50% had metastatic bone disease (p=0.528). Mean time to development of metastatic bone disease was 13.4 [± 10.6], 23.3 [± 19.4], 16.4 [± 9.6] months (p = 0.201). Median post metastatic bone disease survival was 15.0 [10.6-20.3], 9.0 [5.2-12.9], 3.2 [0.0-6.9] months (p = 0.010). Time to 1st SRE was not significantly different. CONCLUSIONS: Incidence of brain and bone metastases was not different between EGFR+, KRAS+ and WT patients. Post brain metastases survival, time from mNSCLC diagnosis to metastatic bone disease and 1st SRE did not differ either. Post metastatic bone disease survival was significantly longer in EGFR+ patients. Although prevention of SRE's is important for all patients, the latter finding calls for a separate study for SRE preventing agents in EGFR+ patients.

[A young man with rapidly progressing dyspnoea and a mediastinal mass]. / Een jonge man met snel progressieve dyspnoe en een mediastinale massa.

An 18-year-old male presented with a 2-week history of rapid progressive dyspnoea and dry cough due to a large mediastinal mass with compression of the trachea. Based on the raised serum values of the tumour markers chorionogonadotrophin and alphafoetoprotein the diagnosis of germ-cell tumour was made. Because of the severity of his symptoms chemotherapy with bleomycin, etoposide and cisplatin was begun on the same day and before the results of the histology investigations were known. The next day the symptoms were diminished and after completing four courses of chemotherapy there was complete remission. The differential diagnosis of a rapid progressive mediastinal mass is limited and mainly relates to malignant lymphoma and germ-cell tumours. In emergency situations if tumour markers are raised then anti-tumour therapy may be begun before any histological confirmation is available.

FDG-PET in staging lung cancer: how does it change the algorithm?

BACKGROUND: In patients with lung cancer, positron emission tomography (PET) using fluor-18-fluorodesoxyglucose (FDG) may be used both to detect extrathoracic metastases (ETM) and for mediastinal lymph node staging (MLS), potentially reducing the need for mediastinoscopy. We assessed the added value of FDG-PET in detecting ETM and focused on the reliability of FDG-PET and mediastinoscopy for MLS. PATIENTS AND METHODS: In 72 consecutive patients with non-small cell lung cancer, the impact of adding FDG-PET to full conventional clinical staging was prospectively analyzed. The predictive value of FDG-PET findings and tumor location for pathologic mediastinal lymph node status were assessed in a logistic regression analysis. RESULTS: Unexpected extrathoracic metastases were detected by FDG-PET in 15% of patients. In MLS overall negative and positive predictive values were 71 and 83% for FDG-PET, and 92 and 100% for mediastinoscopy. However, the negative predictive value of FDG-PET was only 17% in case of FDG-PET positive N1 nodes and/or a centrally located primary tumor, whereas it was 96% in case of FDG-PET negative N1 nodes and a non-centrally located primary tumor. CONCLUSION: By incorporating FDG-PET in clinical staging, 15% of patients with lung cancer are upstaged due to unexpected extrathoracic metastases. In case of a negative mediastinal FDG-PET, mediastinoscopy can only be omitted in the presence of a non-centrally located primary tumor and without FDG-PET positive N1 nodes.

[Surgical treatment of tumor metastases in the lungs, brain or liver]. / Chirurgische behandeling van tumormetastasen in longen, hersenen of lever.

Metastases are generally an expression of widespread disease and therefore warrant systemic treatment. However, clinical observations have revealed that local surgical treatment might be beneficial in the case of organ-confined metastatic disease. Randomised studies have revealed that in the case of brain metastases, metastasectomy followed by radiotherapy, has a favourable outcome with respect to both the quality of life and overall survival. Retrospective non-randomised studies in selected patient groups show prolonged post-treatment survival in the case of both lung and liver metastasectomy. The most important prognostic factors for metastasectomy are: disease control elsewhere in the body, tumour species, the patient's general condition, and the possibility of a total resection of the metastasis. These factors form the basis of the separate decision-making process for each individual patient.

[Bupropion: an effective new aid for smoking cessation]. / Bupropion: een effectief nieuw hulpmiddel bij het stoppen met roken.

Smoking is responsible for a substantial percentage of the total morbidity and mortality in western society. In the Netherlands 34% of the population smoke. A considerable part of the smokers tried to stop smoking, but did not succeed. Since December 1999 a new type of anti-smoke therapy is available; bupropion chloride (Zyban). With this treatment an improvement in success ratio in comparison with placebo is described of 11-15% after a year in a healthy population. Combined with nicotine patches this percentage was 20%. These percentages are higher than those of nicotine replacement therapy alone (3-13%). It is very important that effects of bupropion are tested in high-risk patients with asthma, chronic obstructive pulmonary disease (COPD) and cardiovascular diseases as these groups may benefit most from cessation of smoking. Especially in the COPD group cessation of smoking makes a more substantial contribution to improvement of the disease process than the medication now available. Therefore, it might be considered to prescribe bupropion under strict control in this group even now, before definitive research results are obtained.

Smoking cessation: which aids are worthwhile?

Smoking is a major preventable health risk in western society. In the Netherlands, it is held responsible for 86 and 36% of annual mortality from lung cancer and cardiovascular disease, respectively. Nevertheless about 33% of Dutch people smoke. Only 2% of smokers quit successfully after being advised to stop once by a physician. Although the medical profession should play a leading role in campaigns to stop smoking, general practitioners advise only 10% of their smokers to quit. An overview was made of the various aids that can be used to support attempts to quit smoking. Three aids: supportive schedules, nicotine replacement and bupropion chloride had proven long-term effectiveness in up to 5-10, 3-13 and 11-15% of the subjects, respectively. In conclusion, supportive counselling combined with nicotine substitutes or bupropion chloride is the most worthwhile intervention to support quitting attempts. Wider application of this strategy is expected to have major implications on morbidity (50% myocardial infarct risk reduction) and mortality in the Netherlands.

Effects of fluticasone propionate and beclomethasone dipropionate on parameters of inflammation in peripheral blood of patients with asthma.

Bronchial inflammation plays a central role in asthma. We investigated whether parameters of inflammation were increased in peripheral blood. Furthermore, we tested whether fluticasone propionate (FP), a new inhaled corticosteroid (ICS), and beclomethasone dipropionate (BDP) affected these parameters. FP 750 microg/day and BDP 1500 microg/day were compared in a randomized, crossover study consisting of two 6-week treatment periods, each preceded by a 3-week placebo period. Twenty-one patients with symptomatic asthma completed the study. The results were compared with those of six normal subjects (controls). Immunophenotyping of inflammatory cells was performed in whole blood, and serum eosinophil cationic protein (ECP) was measured. With regard to clinical efficacy, ICS increased PC20 histamine by more than 1.9 doubling doses and FEV1 by more than 0.34 l. The number of CD3/HLA-DR+ lymphocytes was significantly increased in asthmatics compared to the normal subjects, both after placebo (P<0.01) and after therapy (P<0.05). The CD3/HLA-DR+ lymphocytes decreased significantly after treatment with FP (P<0.05). Serum ECP was elevated in patients without ICS and decreased after treatment with BDP (P<0.001). In conclusion, the number of CD3/HLA-DR+ lymphocytes and serum ECP levels were raised in the peripheral blood of symptomatic asthmatics, and decreased by clinically effective doses of ICS. In this respect, FP 750 microg/day was at least as effective as BDP 1500 microg/day.

Sustained protection against distilled water provocation by a single dose of salmeterol in patients with asthma.

The long-acting beta2-agonist salmeterol inhibits in vitro the release of inflammatory mediators up to 20 h. These mediators are involved in ultrasonically nebulized distilled water (UNDW)-induced bronchoconstriction. We investigated whether salmeterol provides prolonged protection against UNDW provocation and whether this effect was paralleled by its bronchodilator effects. Nineteen asthmatic patients (mean forced expiratory volume in one second (FEV1) 84.8% predicted, mean provocative concentration of histamine producing a 20% decrease in FEV1 0.65 mg x mL(-1)) participated in this randomized, double-blind, placebo-controlled crossover trial. After measuring baseline FEV1, patients inhaled 50 microg salmeterol or placebo by metered-dose inhaler. FEV1 was measured after 20 and 40 min, and UNDW provocations and FEV1 measurements were performed after 10, 20 and 34 h. Compared to placebo, salmeterol caused marked bronchodilatation from 20 min up to 20 h after inhalation. Salmeterol also provided more than 20 h of protection against UNDW provocation (still more than one doubling dose). Protection beyond the period of bronchodilatation did not occur. Eleven subjects had a significant reduction in provocative dose of UNDW causing a 20% fall in FEV1 (PD20,UNDW) values between 10 and 20 h, at a time when there was still persistent bronchodilation. No correlation existed between changes in FEV1 and changes in PD20,UNDW. From the equations of regression lines between FEV1 and corresponding PD20,UNDW values, it was calculated that only approximately 25% of the afforded protection was explained by bronchodilatation. In conclusion, a single dose of salmeterol induces both bronchodilatation and protection independently of this bronchodilation against a physiological bronchoconstrictor stimulus for more than 20 h.

Effects of inhaled corticosteroids on bone.

Inhaled corticosteroids (ICS) are the most effective therapy for asthma currently available. The increasing use of ICS raises the issue of possible adverse systemic effects. Since one of the most important side-effects of oral corticosteroids (OCS) is osteoporosis, this article focuses on current knowledge of the effects of ICS on bone. Generally, doses higher than 1.0 mg/day cause a dose-dependent decrease in serum osteocalcin levels. Decreases in bone density have been suggested after treatment with ICS, but in most studies it is impossible to quantify the contribution of previous treatment with OCS and other confounding factors to bone loss. The clinical relevance of the observed changes in the long term is unknown. To date, no fracture data have been reported in patients. Beclomethasone dipropionate, budesonide and fluticasone propionate do not appear to be different per milligram ICS. In general, the lowest clinically efficacious dosage of ICS should be aimed at.