Pre-operative nutrition and the elective surgical patient: why, how and what?

Pre-operative nutrition therapy is increasingly recognised as an essential component of surgical care. The present review has been formatted using Simon Sinek's Golden Circle approach to explain 'why' avoiding pre-operative malnutrition and supporting protein anabolism are important goals for the elective surgical patient, 'how' peri-operative malnutrition develops leading in part to a requirement for pre-operative anabolic preparation, and 'what' can be done to avoid pre-operative malnutrition and support anabolism for optimal recovery.

Malnutrition modifies the response to multimodal prehabilitation: a pooled analysis of prehabilitation trials.

Patients with colorectal cancer are at risk of malnutrition before surgery. Multimodal prehabilitation (nutrition, exercise, stress reduction) readies patients physically and mentally for their operation. However, it is unclear whether extent of malnutrition influences prehabilitation outcomes. We conducted a pooled analysis from five 4-week multimodal prehabilitation trials in colorectal cancer surgery (prehabilitation: n = 195; control: n = 71). Each patient's nutritional status was evaluated at baseline using the Patient-Generated Subjective Global Assessment (PG-SGA; higher score, greater need for treatment of malnutrition). Functional walking capacity was measured with the 6-minute walk test distance (6MWD) at baseline and before surgery. A multivariable mixed effects logistic regression model evaluated the potential modifying effect of PG-SGA on a clinically meaningful change of ≥19 m in 6MWD before surgery. Multimodal prehabilitation increased the odds by 3.4 times that colorectal cancer patients improved their 6MWD before surgery as compared with control (95% confidence interval (CI): 1.6 to 7.3; P = 0.001, n = 220). Nutritional status significantly modified this outcome (P = 0.007): Neither those patients with PG-SGA ≥9 (adjusted odds ratio: 1.3; 95% CI: 0.23 to 7.2, P = 0.771, n = 39) nor PG-SGA <4 (adjusted odds ratio: 1.3; 95% CI: 0.5 to 3.8, P = 0.574, n = 87) improved in 6MWD with prehabilitation. In conclusion, baseline nutritional status modifies prehabilitation effectiveness before colorectal cancer surgery. Patients with a PG-SGA score 4-8 appear to benefit most (physically) from 4 weeks of multimodal prehabilitation. Novelty: Nutritional status is an effect modifier of prehabilitation physical function outcomes. Patients with a PG-SGA score 4-8 benefited physically from 4 weeks of multimodal prehabilitation.

Systematic development and feasibility testing of a multibehavioural digital prehabilitation intervention for patients approaching major surgery (iPREPWELL): A study protocol.

Improving outcomes for people undergoing major surgery, specifically reducing perioperative morbidity and mortality remains a global health challenge. Prehabilitation involves the active preparation of patients prior to surgery, including support to tackle risk behaviours that mediate and undermine physical and mental health and wellbeing. The majority of prehabilitation interventions are delivered in person, however many patients express a preference for remotely-delivered interventions that provide them with tailored support and the flexibility. Digital prehabilitation interventions offer scalability and have the potential to benefit perioperative healthcare systems, however there is a lack of robustly developed and evaluated digital programmes for use in routine clinical care. We aim to systematically develop and test the feasibility of an evidence and theory-informed multibehavioural digital prehabilitation intervention 'iPREPWELL' designed to prepare patients for major surgery. The intervention will be developed with reference to the Behaviour Change Wheel, COM-B model, and the Theoretical Domains Framework. Codesign methodology will be used to develop a patient intervention and accompanying training intervention for healthcare professionals. Training will be designed to enable healthcare professionals to promote, support and facilitate delivery of the intervention as part of routine clinical care. Patients preparing for major surgery and healthcare professionals involved with their clinical care from two UK National Health Service centres will be recruited to stage 1 (systematic development) and stage 2 (feasibility testing of the intervention). Participants recruited at stage 1 will be asked to complete a COM-B questionnaire and to take part in a qualitative interview study and co-design workshops. Participants recruited at stage 2 (up to twenty healthcare professionals and forty participants) will be asked to take part in a single group intervention study where the primary outcomes will include feasibility, acceptability, and fidelity of intervention delivery, receipt, and enactment. Healthcare professionals will be trained to promote and support use of the intervention by patients, and the training intervention will be evaluated qualitatively and quantitatively. The multifaceted and systematically developed intervention will be the first of its kind and will provide a foundation for further refinement prior to formal efficacy testing.

Gastroenterology Numbers in Canada: A Comparison of Human Resource Databases.

Several databases track gastroenterology (GI) human resource (HR) numbers in Canada. They differ in the data which they collect and, hence, in their estimates of GI HR. The two most likely to reflect current HR are the Canadian Institute of Health Research (CIHI) and Canadian Medical Association (CMA) databases. The estimates of GI's generated by each of the databases correlate closely with each other. Approximately 50 trainees enter the adult GI workforce per year, and approximately five enter the pediatric group. We estimate that Canada as a whole has between 782 and 848 GIs or 2.14 GIs per 100,000 population in 2016. Six of the 10 provinces have fewer than two GIs per 100,000 population. National GI numbers are increasing by 6% per year. Validation studies are required.

Axillary recurrence in breast cancer.

AIM: To determine whether axillary recurrence reflects inadequate axillary treatment or adverse pathological features. METHODS: The case-records were reviewed of 2122 women aged under 75 years, treated for invasive breast cancer during the time-period 1/1/86-31/12/91 in a geographically defined area. Data were abstracted on operations performed, pathological features, post-operative treatments and details of axillary recurrence. The risk of axillary recurrence was examined by pathological, treatment and patient factors. RESULTS: Axillary recurrence was more than twice as likely after inadequate compared to adequate treatment of the axilla (adequate staging or axillary radiotherapy or clearance). Delayed treatment of the axilla was not as successful as adequate primary treatment: multiple axillary recurrences were twice as common, one third of which were uncontrolled at time of death. Inadequate surgical treatment was associated with increased rates of recurrence despite endocrine therapy, chemotherapy or radiotherapy. Lymphoedema was twice as common if axillary radiotherapy was combined with any axillary surgical procedure. CONCLUSIONS: Axillary recurrence is more common in tumours with adverse pathology but may also result from inadequate axillary treatment. In order to minimise axillary recurrence, optimal treatment of the axilla entails adequate staging (sampling of four or more nodes) and treatment (axillary clearance or radiotherapy and endocrine therapy) in all women.

Quality of life: perception of lung cancer patients.

An investigation was carried out to examine what quality of life means to lung cancer patients. 200 patients with either lung cancer (108) or chronic respiratory disease (92) were interviewed using a short open-ended questionnaire. They were asked to define quality of life in general, identify what they considered to be a good quality of life for themselves and to rank the relative importance attached to each nominated item. A content analysis was carried out and patients' responses were categorised into eight items. These were: ability to do what one wants to do/work, enjoyment of life, family life, financial security, happiness, health, living longer and social life/leisure activities. Of these, health (42%), enjoyment of life (25%) and family life (24%) were the three most nominated items as definition of quality of life in general. Patients perceived a good quality of life for themselves differently. Family life (58%), health (51%) and social life (43%) were found to be the most nominated components of a good quality of life for the patients. Overall, patients ranked family life and health as the first or second most important factors. There were no significant differences between cases and controls. The study results are challenging and serve to remind us that the term quality of life is misused in many studies. Most existing measures do not encompass the wider aspects of quality of life identified here, but rather concentrate on the "health-related" aspects of quality of life. To achieve this, the research into the best ways of measuring and assessing quality of life must continue to seek individual values and preferences and how these can be applied in a simple way in clinical studies.

Cancer risk of hypertensive patients taking calcium antagonists.

OBJECTIVE: To measure rates of incident and fatal cancer in hypertensive patients taking calcium antagonists and to compare these with rates in three control groups. DESIGN: A retrospective analysis of cancer in patients of the Glasgow Blood Pressure Clinic prescribed either a calcium antagonist or other antihypertensive drugs (non-calcium antagonist group). Record linkage of the clinic with the West of Scotland Cancer Registry and with the Registrar General, Scotland provided information on incidence of cancer and on deaths and their causes. PATIENTS: 2297 patients were prescribed calcium antagonist and 2910 were prescribed antihypertensive drugs other than calcium antagonist. MAIN OUTCOME MEASURES: Relative risk of cancer, the ratio of observed to expected cancers in the calcium antagonist group, was estimated using expected values based on three control groups; namely the non-calcium antagonist group, a middle-aged population of Renfrew and Paisley and the West of Scotland population. RESULTS: There were 134 incident cancers in the calcium antagonist group, representing relative risks of 1.02 [95% confidence interval (CI) 0.82-1.271 compared with the non-calcium antagonist group, 1.01 (95% CI 0.84-1.18) compared with Renfrew-Paisley controls and 1.02 (95% CI 0.85-1.19) compared with West of Scotland controls. Findings for cancer mortality were similarly negative. Risks were no higher for older patients. CONCLUSIONS: Our study lends no support to the suggestion that calcium antagonists cause cancer.

The fate of biogenic monoamines in perfused rabbit lung.

1. Inactivation of beta-phenylethylamine and several of its derivatives was studied in a preparation of rabbit lung perfused with Krebs physiological medium at 37 degrees C. Inactivation or removal of these compounds was calculated as the difference between the concentration of each amine in the perfusion medium and the effluent, collected separately from each lung. The extent of amine metabolic degradation was also measured, by column chromatography, in lung effluent. 2. With this technique the magnitude of amine removal as a function of concentration was determined and an apparent Km and Vmax of removal were calculated for each amine. 3. Percentage removal was highest with phenylethylamine (95%), and decreased, apparently in relation to increasing phenyl- and side chain-hydroxylation (and therefore likely increased hydrophilicity), and 5-hydroxytryptamine (64%), tyramine (53%), octopamine (35%), dopamine (32%) and noradrenaline (23%). 4. Inactivation of each amine could be accounted for by metabolic degradation to deaminated products, which appeared in lung effluent within 90 s of beginning amine perfusion. 5. When intrapulmonary metabolism of phenylethylamine was inhibited by simultaneous perfusion with semicarbazide (10 mM) and pargyline (10 micronM), the removal rate was unaltered, establishing that uptake of the amine from the vascular space is not dependent on metabolism at least for 4 min infusions.

Effect of nafazatrom and indomethacin on pulmonary removal of prostaglandin E1 after endotoxin in rabbits.

1 We compared the effects of endotoxin on pulmonary prostaglandin E1 (PGE1) removal in groups of rabbits pretreated with the cyclo-oxygenase inhibitor, indomethacin, or nafazatrom (Bay g 6575), which has been shown to increase plasma prostacyclin concentrations. 2 In untreated animals, endotoxin transiently decreased pulmonary removal of [3H]-PGE1, caused pulmonary hypertension, systemic hypotension and increased plasma concentrations of PGE2 and 6-keto-PGF1 alpha. 3 Indomethacin pretreatment prevented the transient decrease in pulmonary removal of [3H]-PGE1 in response to endotoxin, prevented the haemodynamic effects and inhibited prostaglandin synthesis. Pretreatment with nafazatrom did not affect the decreased pulmonary removal of [3H]-PGE1, exacerbated the haemodynamic response, reduced survival and potentiated the increase in circulating 6-keto-PGF1 alpha. 4 We conclude that indomethacin acts to prevent the depression of pulmonary [3H]-PGE1 removal by eliminating surface area changes associated with endotoxin-induced pulmonary vasoconstriction. 5 These data suggest that nafazatrom treatment results in exacerbation of the endotoxin-induced systemic hypotension presumably due to its effect on increased plasma prostacyclin during the later phase of endotoxaemia.

Vascular effects of ginsenosides in vitro.

Ginsenosides (saponins extracted from Panax ginseng) elicit qualitatively and quantitatively different responses in isolated, contracted ring preparations of different blood vessels from rabbits, dogs and humans. Ginsenosides themselves did not affect the tone of 'resting' isolated blood vessels directly, but contracted slightly the renal vein of rabbits at the maximum concentration tested. The mixture caused relaxation of the noradrenaline (NA) or prostaglandin F2 alpha (PGF2 alpha)-induced contraction of the pulmonary artery and intrapulmonary artery of rabbits, and the PGF 2 alpha-induced contraction of the canine mesenteric vein. Ginsenosides potentiated, in a concentration-dependent manner, the contractile responses of renal veins of dogs and rabbits to PGF2 alpha The reason for such heterogeneous responses of different blood vessels to ginsenosides in unknown. It is suggested that either potentiation of contraction or relaxation of contracted blood vessels might be mediated by interaction with endogenous vasoactive substances. The potentiation of PGF2 alpha-induced contraction may be related to the reduction of renal blood flow observed in anaesthetized dogs. The simultaneous contraction and relaxation effects may explain its biphasic actions on blood pressure.

Effects of monocrotaline pretreatment of rats on removal of 5-hydroxytryptamine and noradrenaline by perfused lung.

1 The alkaloid, monocrotaline, causes significant pulmonary damage in many species, including the rat. We, therefore, determined whether the inactivation of biogenic amines by perfused lungs of rats was modified by prior treatment of the animals with monocrotaline.2 Young rats (45 to 50 g) treated for 21 days with monocrotaline (22 mug/ml) in their drinking water developed right ventricular hypertrophy. Treated animals gained weight more slowly and consumed less food and water than control rats that drank tap water. Lungs from monocrotaline-treated animals were heavier and had a higher protein content than control lungs.3 Isolated lungs from treated animals removed and metabolized 50% less perfused 5-hydroxytryptamine than did controls.4 The diminished 5-hydroxytryptamine metabolism was probably due to impaired delivery of substrate to intrapulmonary monoamine oxidase (MAO) since MAO activity in 600 g supernatant fractions of homogenates of lungs from monocrotaline-treated rats was not different from control values.5 Pulmonary removal of perfused noradrenaline was decreased about 60% by the 21-day treatment, suggesting that the effects of monocrotaline were somewhat nonspecific.6 These effects were not caused by monocrotaline directly, since perfusion of lungs from untreated animals with this drug did not alter removal of co-perfused 5-hydroxytryptamine.7 Reduced pulmonary removal of circulating biogenic amines following pretreatment with monocrotaline may reflect damage to capillary endothelium, which could also affect other metabolic functions of lung.

Panax ginseng pharmacology: a nitric oxide link?

Panax ginseng is used in traditional Chinese medicine to enhance stamina and capacity to cope with fatigue and physical stress. Major active components are the ginsenosides, which are mainly triterpenoid dammarane derivatives. The mechanisms of ginseng actions remain unclear, although there is an extensive literature that deals with effects on the CNS (memory, learning, and behavior), neuroendocrine function, carbohydrate and lipid metabolism, immune function, and the cardiovascular system. Reports are often contradictory, perhaps because the ginsenoside content of ginseng root or root extracts can differ, depending on the method of extraction, subsequent treatment, or even the season of its collection. Therefore, use of standardized, authentic ginseng root both in research and by the public is to be advocated. Several recent studies have suggested that the antioxidant and organ-protective actions of ginseng are linked to enhanced nitric oxide (NO) synthesis in endothelium of lung, heart, and kidney and in the corpus cavernosum. Enhanced NO synthesis thus could contribute to ginseng-associated vasodilatation and perhaps also to an aphrodisiac action of the root. Ginseng is sold in the U.S. as a food additive and thus need not meet specific safety and efficacy requirements of the Food and Drug Administration. Currently, such sales amount to over $300 million annually. As public use of ginseng continues to grow, it is important for this industry and Federal regulatory authorities to encourage efforts to study the efficacy of ginseng in humans by means of appropriately designed double-blind clinical studies.

In situ iodination of angiotensin-converting enzyme and other pulmonary endothelial membrane proteins.

Biochemical responses of endothelial cells in culture to pharmacological or physiological stimuli are often extrapolated to define the behavior of the vascular endothelium in vivo. However, culture conditions cannot recreate the environment of endothelial cells in vivo. To compare cell functions in vivo and in vitro, we iodinated endothelial membrane proteins of both the perfused rabbit lung and cultured rabbit lung endothelial cells. Endothelial cell protein 125I-labeling in the perfused intact lung was catalyzed by lactoperoxidase and glucose oxidase immobilized on 3-10 microns polyacrylamide beads (Enzymobeads, Bio-Rad). Changes in 5-hydroxytryptamine uptake, angiotensin converting enzyme activity and perfusion pressure made before, during and/or after iodination were small, suggesting that the procedure does not grossly injury the lung. As confirmed by tissue autoradiography, iodination was confined to the vascular space. A subcellular "membrane" fraction of the whole homogenate was enriched for several iodinated proteins. Lectin binding further purified a library of putative iodinated endothelial membranes proteins, one of which was angiotensin-converting enzyme as shown by immunoprecipitation with goat anti-rabbit antibody to angiotensin-converting enzyme. Iodinated proteins of similar molecular weights were also isolated from cultured rabbit lung endothelium iodinated under the same conditions, thus confirming the endothelial lineage of proteins iodinated in the intact lung. We conclude that this technique labels endothelial surface proteins in the intact lung without causing observable tissue injury and thus should be valuable in the study of the physiology and pathophysiology of the vascular lining in vivo.

Captopril removal by rabbit lung in vivo.

Removal of [14C]captopril by the lungs of anesthetized rabbits was measured by the multiple indicator dilution technique. After coinjection of indocyanine green (ICG) and [14C]captopril into the jugular vein of anesthetized rabbits, serial blood samples were collected from the carotid artery and each was analyzed for its content of both substances. Percent removal (R) of captopril after its initial injection of 10 nmoles captopril/kg (calculated at the peak of the ICG outflow curve) was 40.2 +/- 2.5 (S.E.M.) and was significantly greater than R after a second injection of 10 nmoles captopril/kg (20.1 +/- 2.4) 1 hr later. Removal of 70 nmoles captopril/kg (5.8 +/- 3.0 after first injection, 6.4 +/- 2.2 after second injection) was significantly lower than R of 10 nmoles captopril/kg. During a single pulmonary passage of either dose of captopril, R was inversely related to the calculated fractional concentration of intravascular captopril. Pulmonary metabolism of the angiotensin converting enzyme (ACE) substrate [3H]benzoyl-Phe-Ala-Pro [( 3H]BPAP) was 70.1 +/- 1.7% in the absence of captopril, and was reduced significantly to 27.4 +/- 2.4% by 10 nmoles captopril/kg and 7.6 +/- 0.2% by 6 mumoles BPAP/kg. BPAP (6.4 +/- 0.6 mumoles/kg) significantly reduced R of the first and second injections of 10 nmoles captopril/kg but this effect was selective, since BPAP did not reduce pulmonary removal of [14C]serotonin. These data indicate that pulmonary removal of captopril in vivo is saturable and may primarily reflect binding of the drug to pulmonary endothelial ACE.

Uptake and displacement of [3H]dihydroalprenolol, [3H]epinephrine and [3H]clonidine in isolated perfused rabbit lung.

Uptake and displacement of three adrenergic receptor ligands, [3H]dihydroalprenolol ([3H]DHA), [3H]epinephrine ([3H]EPI) and [3H]clonidine ([3H]CLON), were examined in isolated rabbit lungs by recirculating perfusion. Removal of [3H]DHA was the most extensive (85% uptake; 6.6 ml/min clearance), [3H]CLON removal was intermediate (50%; 3.8 ml/min), and [3H]EPI removal was the lowest (33%; 1.2 ml/min). Specific displacement of each radioligand from lung was attempted using several competing agents. Both (--)- and (+)-propranolol equally displaced [3H]DHA from lung. Phentolamine, (--)-phenylephrine and (--)-epinephrine were unable to displace 10 nM [3H]EPI from lung, although the latter two agents did produce concentration-dependent increases in perfusion pressure. High concentrations of (--)-epinephrine, which produced near maximal physiological responses, inconsistently displaced 30-4- nM [3H]EPI from lung. [3H]Clonidine was displaced by unlabeled clonidine at concentrations that caused increases in perfusion pressure. Pretreatment of lungs with either 10 microM phentolamine or phenoxybenzamine did not alter the total amount of [3H]CLON displaced by clonidine, suggesting that [3H]CLON was displaced predominantly from non-specific sites, perhaps preventing detection of [3H]CLON displacement from specific (receptor) sites. Alternatively, these results may be interpreted as inhibition of uptake of each radioligand. Thus, both (--)- and (+)-propranolol interfered with [3H]DHA removal, suggesting a common mechanism for uptake and/or retention for these two beta-adrenergic receptor antagonists. Inhibition of [3H]EPI removal was observed only at high concentrations of (--)-epinephrine which indicates that pulmonary removal of epinephrine occurs through a low affinity uptake system. [3H]Clonidine removal was effectively inhibited by the same (microM) concentrations of unlabeled clonidine that produced physiological responses. Neither phentolamine nor phenoxybenzamine was able to interfere with pulmonary removal of [3H]CLON. Therefore, uptake and displacement of these adrenergic receptor radioligands showed no correlation with pharmacological effects produced by these agents in isolated perfused rabbit lung. The results are more closely associated with inhibition of removal and/or non-specific retention of the radioligands examined.

Superoxide scavenging effect of Ginkgo biloba extract on serotonin-induced mitogenesis.

We have reported previously that serotonin (5-HT) stimulates the mitogenesis of bovine pulmonary artery smooth muscle cells (SMCs) through active transport of 5-HT and cellular signaling that includes elevation of superoxide (O2.-) and enhancement of protein tyrosine phosphorylation. Ginkgo biloba extract 501 (EGb 501), which has been demonstrated to act as an antioxidant, was found to block both the elevated O2.- and the proliferative and hypertrophic influences of 5-HT on SMCs, but not to directly inhibit the associated activation of NAD(P)H oxidase or the stimulation of phosphorylation of GTPase-activating protein (GAP). A similar effect of Ginkgo biloba extract 501 occurred on Chinese hamster lung fibroblasts (CCL-39), where 5-HT receptor, as opposed to transporter, action has been associated with mitogenesis. We conclude from these studies that Ginkgo biloba extract 501 quenches O2.- formation by 5-HT, thereby blocking its mitogenic effect. Stimulation of protein tyrosine phosphorylation of GAP by 5-HT appears to precede the elevation of O2.-.

Reduction of monocyte adhesion to xenogenic tissue by endothelialization: an adhesion molecule and time-dependent mechanism.

Great interest has been shown for the seeding of autologous endothelial cells on prosthetic materials. We investigated the inflammatory and immunogenic properties of xenogeneic tissue before and after seeding with cultured human great saphenous vein endothelial cells in vitro. Adhesion of monocytes to xenogeneic tissue with or without endothelium and the endothelial cell expression of E-selectin, intercellular adhesion molecule 1, vascular adhesion molecule 1, and major histocompatibility complex class II antigens were investigated 1, 3, and 7 days after seeding. Both monocyte adhesion and endothelial adhesion molecule expression were relatively high 1 day after seeding and were significantly lowered after 3 to 7 days. There was no difference between monocyte adhesion and adhesion molecule expression on viable or nonviable xenogeneic tissue. Monocyte adhesion and adhesion molecule expression increased after interleukin-1 beta or interferon-gamma stimulation of the endothelial cells. The results suggest that human endothelial cells exhibit an early proinflammatory and immunogenic activity immediately after seeding. Three and 7 days after seeding, the endothelialized surface is less adhesive for monocytes as compared with nonendothelialized tissue. These findings have implications when cultured or intraoperatively recruited endothelial cells are used clinically.

Rapid visualization of viable and nonviable endothelium on cardiovascular prosthetic surfaces by means of fluorescent dyes.

Increasing interest in endothelialization of synthetic and tissue cardiovascular prostheses in vitro emphasizes the need for simple and rapid methods to evaluate presence of endothelium on surfaces. Scanning electron microscopy is a commonly used method for this purpose. In this study we investigated alternative and more rapid staining methods. Human saphenous vein endothelial cells in culture and on cardiovascular prosthetic materials (pyrolytic carbon, cusps of bioprosthetic heart valves, pig aorta, and expanded polytetrafluoroethylene) were labeled by exposing them to medium containing 5-chloromethylfluorescein diacetate or 1,1-dioctadecyl-3,3,3',3'-tetramethylindo carbocyanine perchlorate. For comparison, specimens were also fixed and processed for scanning electron microscopy. A bright fluorescence of endothelial cells labeled with 5-chlormethylfluorescein diacetate or 1,1-deoctadecyl-3,3,3',3'-tetramethylindo carbocyanine perchlorate wre clearly visualized in culture, on pyrolytic carbon, and on expanded polytetrafluoroethylene. Unfixed, prelabeled cells could be visualized immediately and unlabeled cells could be investigated for viability within 1 hour. Cells seeded on biologic tissue specimens could be visualized within 15 minutes with a modified hematoxylin-eosin staining. We suggest the use of these methods for rapid visualization of endothelium present on surfaces of cardiovascular prosthetic materials where they can partly replace the use of scanning electron microscopy.

Quality of life in patients with lung cancer: a review of literature from 1970 to 1995.

A review of the literature was carried out covering the last 25 years (1970 to 1995) by searching through the MEDLINE and manually. The review consists of two companion parts. The first includes studies of quality of life in lung cancer patients in general, while the second part is restricted to defined samples of small and non-small cell lung cancer patients. Excluding non-English and review articles, in total 151 citations were identified and all have been reviewed. Over 50 instruments were used to measure quality of life in lung cancer studies. Of these, the European Organisation for Research and Treatment of Cancer Quality of Life Lung Cancer Questionnaire (EORTC QLQ-LC13) in conjunction with the core cancer questionnaire (QLQ-C30) was found to be the best developed instrument, although there were two other lung cancer-specific measures with good reliability and validity. Several topics in this chapter have been highlighted, including the importance of regularly measuring quality of life in lung cancer patients. Progress and achievements in areas such as performance status as a proxy of quality of life measure, psychological morbidity and symptom distress as predictive factors of quality of survival, and communication problems in quality of life studies of lung cancer patients have been emphasized and their implications in lung cancer care discussed. It is argued that palliation of symptoms, psychosocial interventions, and understanding patients' feelings and concerns all contribute to improving quality of life in lung cancer patients. It is concluded that the future challenge in treatment of lung cancer lies not only in improving the survival, but mainly the patients' quality of life regardless of cell type. Clinical trial and epidemiologic population-based outcome studies are recommended to provide this and to allow a better understanding of the contribution of the socioeconomic characteristics of the patients to their pretreatment and posttreatment quality of life.

Quality of life in lung cancer patients: as an important prognostic factor.

Given that lung cancer is one of the common cancers world-wide, the implications of focusing on quality of life as well as survival require to be understood. We have carried out a study of the relationship between survival and quality of life in patients with lung cancer comparing patients those who lived with those who died within 3 months. The design of the study allowed every patient in a defined geographical area with a potential diagnosis of lung cancer to be studied from first outpatient consultation till after a definitive treatment has been given. Quality of life was measured using three standard questionnaires: the Nottingham Health Profile (NHP), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its lung cancer supplementary questionnaire (QLQ-LC13) in addition to a study specific questionnaire collecting data on demographic, social, clinical and performance status. The contribution of quality of life in relation to survival adjusted for known prognostic factors was determined using Cox's proportional hazard model. In all 129 lung cancer patients were interviewed, and 96 patients were alive at 3-months follow-up. Only 90 of 96 patients alive at 3-months follow-up were assessable. Descriptive analyses showed that those who were dead had more perceived health problems, greater level of symptoms and significant lower physical and role functioning and global quality of life at presentation. On the other hand, univariate analyses showed that patients' aggregate scores on the NHP, the functioning scores, and global quality of life scores alone were significant predictors of survival (P<0.03, P<0.04, P<0.04, respectively ). The multivariate analyses showed that pre-diagnosis global quality of life was the most significant predictor of the length of survival even after adjusting for known prognostic factors (age, P<0.04; extent of disease, P<0.03; global quality of life, P<0.02), while performance status, sex and weight loss were not. This study confirmed that pre-diagnosis quality of life was a significant predictor of survival. Indeed, pre-diagnosis quality of life should be considered as a clinical status which has to be established by physicians before treatment starts as it is such an important predictor of survival.