| The incidence and mortality rate of lung cancer is the highest in all cancer field over all the world. According to the latest report from World Health Organization, the number of deaths from lung cancer is1.1million every year, accounting for17.8%of all cancer deaths. The Ministry of Health survey showed that Lung cancer has replaced liver cancer to become the first cause of death in our country in2008, and each year, about600,000people die from lung cancer. By2025, the number of cases of lung cancer will be more than1million every year, and China will become "the world’s first lung cancer country".Lung cancer is divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) due to the clinical and pathological features. SCLC accounts for about20-25%of the total lung cancer. With the deterioration of environmental pollution, the incidence of SCLC is becoming to increased. The main features of SCLC are rapid proliferation, widespread metastasis in early stage, chemotherapy and radiotherapy sensitive, easy to relapse and drug resistance after relapse. The median survival is7-12months, and two-year survival rate is only5%, and the five-year survival rate is less than2%. Radiotherapy and chemotherapy were normal treatment of small cell lung cancer. During the treatment, somatic symptoms and treatment can lead to discomfort on the patient’s emotional, mental status and behavioral responses, seriously impacting on the quality of life (quality of life) of patients and the survival time. Therefore, in many countries abroad the clinical oncologists and clinical psychologists have formed a consensus that the goal of treatment in patients with small cell lung cancer not only to control the physical symptoms, reduce adverse reactions and treatment of diseases caused, but also reduce the patient’s psychological and emotional distress, improve health-related quality (Health-related quality of life, HRQOL) of life of patients. HRQOL assessment has become one of the ultimate goal of cancer clinical evaluation.Usually, the majority of small cell lung cancer had non-specific symptoms, and when the patients got to the hospital, it was late for treatment. Many patients tend to lose confidence in the treatment, and the patients may be sadness and deep in a mood disorder. Patients more easily use denying that avoiding other negative coping style, resulting in worse psychological pressure, and suffering from psychological damage. Social support is seen as a protective factor for psychological stress, which would enhance the individual’s mental fitness. Social support and individual coping styles are also closely related. Therefore, mood disorders in cancer patients, coping style and social support and other psychological factors that gradually cause damage or protection has become a hot psychosocial oncology research.The most important characteristic of the Small cell lung cancer is early stage of a wide range of distant metastasis,60%～80%of patients at the time of diagnosis is extensive. Therefore, a clinical specimen associated with tumor invasion and metastasis markers may help in the early diagnosis of SCLC, which will be help to improve the five-year survival rate of patients. However, tumor invasion and metastasis were complex biological processes in which extracellular matrix (extracellular matrix, ECM) degradation is one of the hot research. A Disintegrin And Metalloprotease (ADAMs) family is involved in the hydrolysis of an important class of ECM proteolytic enzyme, it also can be hydrolyzed and shedding all kinds of protein molecules present in the cell membrane, thus regulating cell and cell-cell interactions with the extracellular matrix. Therefore, ADAMs played an important role in tumorigenesis, invasion and metastasis. Although previous studies have shown that ADAMs in many tumors have higher expression, but there was a lack of ADAMs expression levels in small cell lung cancer research. Therefore, it was very important to detect the expression levels of ADAMs family in small cell lung cancer, and to investigate the expression change.In summary, the assessment of health-related quality of life and mental health status and its influencing factors on patients with small cell lung cancer patients,and to explore the role of psychological and behavioral responses associated with quality of life, while looking for the diagnosis and to investigate early markers that SCLC molecular mechanism widely distant metastasis, were all important for improving the quality of life, effectively evaluating the therapeutic effect and improving patient five years survival.Part Ⅰ:Health related quality of life assessment on SCLC patientsIn the field of medical research, It was known that quality of life (Quality of Life, QOL) mainly refers to the state to assess the individual physical, psychological, social function. Quality of life of patients is an important indicator of the effectiveness of medical services they accepted. Health-related quality of life (Health-related quality of life, HRQOL) is an important part of quality of life. In cancer therapy and treatment evaluation process, research of health-related quality of life pay attention to the change of physical functional, psychological, and social function of life by objective measurements of subjective judgment and evaluationBecause of the difficulties occurred in the clinical work, the researches on health-related quality of life of cancer patients in our country were less than that of other countries. In this study we investigate the health-related quality of life(HRQOL) for patients with SCLC by using the authority of the HRQOL assessment scale. In this phase of study, hospitalized patients with small cell lung cancer, the same period of hospitalized patients with non-small cell lung cancer (NSCLC) and other unselect cancer patients were recruited. Based on the preliminary interviews, by using of European Cancer Research and Treatment health-related quality of Life Questionnaire organization (EORTC) developed (QLQ-C30) Chinese version, we assessed the HRQOL of SCLC patients.一、Results of QLQ-C30on SCLC patientsThe present study showed that compared with NSCLC group and other cancer group, the scores of the overall quality of life subscales of SCLC patients were lower, but not significantly (p>0.05), which indicated the worse of the overall health of SCLC patients.QLQ-C30function scales showed that the score of SCLC patients on emotional function subscale was significantly lower than non-small cell lung cancer and other tumor group score (p<0.05). The score of SCLC patients on social function subscale was significantly lower than NSCLC group (p<0.05) and other tumor group, but the difference was not statistically significant (p>0.05), which indicated that compared with other cancer patients, SCLC patients were facing with more emotional problems, and social functioning was significantly worse.Results of QLQ-C30symptom scales displayed that the score of SCLC patients, non-small cell lung cancer and other tumor group in fatigue, pain, nausea and vomiting were low, and the scores of SCLC patients were significantly lower than NSCLC on fatigue scale (p<0.05). The scores of SCLC patients scores were lower than other tumor group on pain scale, the difference was significant (p<0.05). These results displayed that physical fatigue and pain in SCLC patients were more obvious than other cancer patients.Individual Functioning Scale showed that the scores of SCLC patients in insomnia, loss of appetite, diarrhea, economic difficulties subscale scores, and insomnia scale scores were significantly lower than NSCLC and other tumor group (p <0.05). This result suggested that compared with other, SCLC patients showed more insomnia and other serious symptoms.二、Resunlts of QLQ-LC13on SCLC patientsLung cancer-specific module (QLQ-LC13) is used to detect the quality of life in patients with lung disease and specific symptoms. This scale was the effective complement of questionnaire QLQ-C30.The results of present study showed that SCLC patients and NSCLC patients all displayed worse symptoms on dyspnoea, coughing, chest pain, hemoptysis symptom subscale. Moreover, the scores of SCLC patients on dyspnoea, chest pain and pain in other parts subscales were obviously poorer than that of NSCLC patients (p<0.05), indicating that SCLC patients in these three areas showed more severe symptoms.三、Different age and gender of SCLC patients QLQ-C30assessment resultsThe results of the study showed that there was a significant difference on emotional function in patients of different ages, social function, dyspnea, insomnia, and financial difficulties five subscale scores (p<0.05). Different sex patients’ HRQOL assessment results show that There was no significant difference in the overall health and quality between female patients and male patients, but women exhibited lower functional scale scores and higher symptom scale scores. Among them, the role function in female patients, emotional function, cognitive function and social function subscale and insomnia, constipation symptom scale scores were significantly lower than in male patients (p<0.05); fatigue, nausea, vomiting, pain, dyspnea and diarrhea symptoms subscale and economic difficulties subscale scores were significantly higher than males, the difference was significant (p<0.05).四、QLQ-C30results in SCLC patients with different marital status of small-cell comparisonThe results of the study showed that there was a significant difference between.the functioning and symptoms subscale scores during the different marital status of patients, and the overall quality of life of patients was significantly higher than married divorced and single/widowed patients (p<0.05). The scores of emotional function in patients divorced, role function, cognitive function, pain, loss of appetite and economic difficulties subscale scores were significantly lower than married patients (p<0.05). Emotional function, role function, loss of appetite, pain, insomnia and economic difficulties scale score of single/widowed patients were lower than married patients, the difference was statistically significant (p<0.05)五、QLQ-C30results in SCLC patients with different levels of education relatively small cellsThe results of the study showed that there was no significant difference between the different educational levels of the overall health of patients with small cell lung cancer, but the role function, cognitive function, social function, insomnia, economic difficulties subscale scores showed significant differences (p<0.05).六、QLQ-C30results in SCLC patients with different payment methodsThe results showed that there were significant differences between the different payment methods in the HRQOL of patients with small cell lung cancer Self-pay patients the cost of cognitive function, emotional function, insomnia, breathing difficulties and economic difficulties subscale scores were significantly lower than patients with health insurance (p<0.05), but the patient’s own expense, role function, social function, fatigue, pain, loss of appetite subscale scores than patients with insurance, the difference was significant (p<0.05).七、QLQ-C30Results in different diagnosed time in SCLC patientsIt was detected that the HRQOL of SCLC patients with different diagnosed time showed significant differences were showed in patient with diagnosis time≤6months of and the patient with diagnosed time≥12months, and their overall health and physical function, cognitive function, emotional function, social function subscales scores were significantly lower than those diagnosed≥12months time patients (p<0.05). Between the two fatigue, difficulty breathing, loss of appetite and insomnia subscale scores showed significant differences (p<0.05).Part Ⅱ:Health related quality of life assessment on SCLC patient.The incidence of lung cancer is the results of the combined effects of multifactorial, multi-stage, multi-step, and psychosocial oncology (psycho-oncology) advanced that psychosocial factors have significant influence on the occurrence, development and prognosis of small cell lung cancer. Studies have shown that the frequency of negative life events that take place before disease, was associated with the occurrence of the psychological distress, and may have influence on the social support and coping styles.The higher malignant of small cell lung cancer was a greater threat to cancers’ lives, and the majority of SCLC patients were suffering from different emotional distress, such as anxiety, depression, fear and anger after diagnosis. Because of the different environment for the growth and life experience, patients will build different social support system, using different coping style and express diversity psychological behavior. In addition, pain, nausea, vomiting and other physical reactions that associated with the disease and treatment can also cause the occurrence of patient’s helplessness, depression, anger and other negative emotional response. Therefore, in the second phase of the study, we assessed the current situation of emotional distress, social support, coping style and mental health of SCLC patients. First, small-cell lung cancer patients and unselected other cancer patients were recruited. By using the Hospital Anxiety and Depression Scale (HADS), and Medical Outcomes Study Social support Survey (MOS-SSS-CM), we carried out research on the condition of emotional distress and social support. Meanwhile, we probed the relationship among health-related quality of life mood disorders and social support in SCLC patients. Second, by using90Symptom Check List (SCL-90), Life Event Scale (LES) and medical coping Questionnaire (MCMQ), we explore the mental health, life events and coping styles of SCLC patients. The results of this section are as follows.一、Anxiety and depression assessment of SCLC patientHospital Anxiety and Depression Scale is mainly used in general hospital patients, including anxiety and depression subscal. The results showed that11percent of SCLC patients had scores≥11on both anxiety and depression subscales,23percent had anxiety only and21percent had depression only (scores>11). Furthermore, forty-three percent and forty-seven percent had scores>8, which showed borderline anxiety and depression. Meanwhile, the scores of depression subscale between patients with SCLC and unselected cancer patients had presented significant different (p<0.05).二、Social support and relationship with HRQOL and mood disorderAccording to the results, there was no significant different between SCLC patients and compared group in social support. However, there was a positive correlation between the overall and subscales of the MOS-SSS-CM and HRQOL functioning score:physical, role, emotion, cognitive and social(p<0.01), which indicated that better social support partly predicted the better HRQOL. Meanwhile, there was a moderated negative correlation between social support and mood disorder, including both anxiety(p<0.05) and depression(p<0.01). Therefore, it may be claimed that as the social support increases, anxiety and depression decreases.三、Mental health assessment of SCLC patientSCL-90is an individual self-assessment questionnaire on the mental health, which containing nine factors:somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid and psychotic. SCL-90scores of SCLC patients in somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychotic scores were significantly higher than the healthy group (P<0.05).四、Investigation on life events of SCLC patientLife Event Scale (LES) is a self-rating scale, which contains three types of48common life events in our social life, family life, work and study, social interaction. By LES, we can evaluate the assessment on life events and its impact on the patients. The result of LES showed that there was significant different between SCLC patients and health people on the total amount of stimulation, negative life events, the total frequency of life event (P<0.05)五、Result of SCLC patient in MCMQMedical Coping Style Questionnaire (MCMQ) is a scale that is used to explore the patient’s coping style and has three subscales, acceptance, avoiding and yielding. Face is positive, mature coping, avoidance and yield is negative, pessimistic way. Positive response will help the cancer patients to reduce anxiety and to cooperate with treatment. Poor response has seriously effect on the survival and quality of life of patients. This study show that SCLC patients acceptance score was significantly higher than the norm group; There was illustrious difference in avoid and yield strategies between ED patients and LD patients on coping style (P<0.05.Part Ⅲ:The influensiong factor research on the reception of psychological intervention of SCLC patients.The aforementioned study showed the health-related quality of life and mental health of the small cell lung cancer patient were significantly lower averages. In response to this situation, effective mental health services may be one effective way to improve physical and mental health of small cell lung cancer patients. Mental health services are all kinds of mental patients, patients with psychosomatic diseases and problems of individual behavior to carry out effective psychological interventions to improve mental state, improve coping capacity, and promote the process of individual mental health. Objective tumor psychological intervention is that when cancer patients and their families facing the psychological and psychosomatic frustration functional changes, helping them to face difficulties through the crisis, and to improve their mood and inspire their confidence, thereby contributing to psychological rehabilitation, improve resistance cancer awareness.Currently, psychological interventions compared with previous cancer patients in China showed some development, but compared with the United States and Europe there is still a large gap, which not only was related with the level of development of psychological intervention, employing skills, but also with patients, family members of patients and clinicians level of awareness of psychological intervention.Therefore, this study was not blind at this stage to carry out psychological intervention. By using self-made questionnaire on patients with psychological intervention/acceptance of mental health services, and the patient does not accept conventional psychological crisis solution-depth research carried out, so as to effectively carry out psychological intervention in patients with small cell lung cancer, and to improve patient health-related quality of life and mental health to provide reference.一、Cognitive status of small cell lung cancer patients with psychological interventionThe survey showed that64%of small cell lung cancer patients knew nothing about the psychological intervention/mental health services, and only4%of the patients expressed a better understanding of psychological intervention. Although51%of SCLC patients thought that they need to receive psychological intervention, only13%of the patients expressed their willingness to accept mental health services.二、Effection on the receiving psychological intervention for SCLC patientsThe results of the study showed that different educational levels had impaction on the receiving of psychological intervention (p<0.05).81%of patients believe that the object of psychological intervention is mentally ill. Only7%patients thought that psychological intervention was helpful,19%patients thought that psychological intervention maybe helpful, and52%of the patients thought that there was no help.15%of patients considered psychiatrist as a silly thing. There were nine percent of patients believe that they will adjust their mentality.77%of patients received psychological intervention fear others will see themselves with strange eyes.95%of patients that received psychological intervention will increase the financial burden.三、Survey on the solve manner of SCLC patients on psychosomatic and emotional problemsThe survey shows that when face with the depression, anxiety, emotional responses,25%of patients choose to adjustments by theirself,33%of patients choose to seek help from physicians, and28%of patients choose to asked help from their relativest, no patients choose to seek psychological intervention.Part Ⅳ:The role of ADAM-12in proliferation, invasion and metastasis in SCLCThe tumor invasion and metastasis is a combined effect including multi-factor, multi-stage and multi-steps. The degradation of the extracellular matrix (ECM) has been the main focus of studies on the invasion and metastasis of SCLC. ECM is the natural barrier to prevent tumor cells into the blood circulation. The ECM degradation is the essential step for tumor invasion and metastasis. A disintegrin and metalloprotease (ADAMs) is a kind of protease containing disintergrin and metalloprotease domains. They can degrade ECM and shed the membrane-bound precursors that modulate cell-cell and cell-matrix interactions. So, ADAMs plays an important role in the carcinogenesis, invasion and metastasis of tumor. ADAMs and ADAMTS highly expressed in many tumors. Given the roles of ADAMs in regulating cellular proliferation and movement, and there is no paper reporting the relationship between ADAMs and SCLC, this study detected the expressions of ADAMs and evaluated the relationship between ADAMs and SCLC prognosis, and found out the effective marker to help diagnosis and assess prognosis. The main results are the following.一、The expressions of ADAMs in SCLC tissue samplesThe expressions of ADAM-8,-10,-11,-12and-17were detected by using immunohistochemistry in150SCLC tissue samples, and the results indicated that the positive expression of ADAM-8,-10,-11,-15and-17was31.33%(47/150),34.66%(52/150),19.33%(29/150),39.33%(59/150) and10%(15/150), respectively. The positive expression of ADAM-12was the highest at93.33%(140/150) and the strong positive expression of ADAM-12was significantly greater compared with the other ADAMs. This indicated that ADAM-12may be play an important role in the proliferation, invasion and metastasis in SCLC.二、The expression of ADAM-12as an independent prognosis factor was an negative correlation with SCLC prognosis.Univariate survival analysis showed that ADAM-8(P=0.903), ADAM-10(P=0.075), ADAM-11(P=0.317), ADAM-15(P=0.349) or ADAM-17(P=0.427) was no correlation with SCLC prognosis. However, ADAM-12(P=0.022) was a significant negative prognostic factor. Multivariate survival analysis was performed to assess the prognostic influence of various factors. The results were consistent with the univariate survival analysis. The level of ADAM-12expression (P=0.049, HR=0.443,95%CI:0.197to0.995) were significant independent prognostic factors and ADAM-12was closely associated with the clinical stage (P<0.001).三、Serum and urine ADAM-12levels in SCLC patientsSerum and urine from70SCLC patients and40healthy volunteers were collected, centrifuged and stored at-80℃. The ROC curves yielded a higher AUC of0.899(P<0.001,95%CI:0.842to0.956) for346pg/ml in serum ADAM-12level from SCLC patients than normal controls (a AUC of0.847for105pg/ml), and a higher AUC of0.979(P<0.001,95%CI:0.959to0.999) for258pg/ml in urine ADAM-12level from SCLC patients than normal controls (a AUC of0.869for92pg/ml). The serum ADAM-12level was significantly higher in SCLC patients than in healthy volunteers (502±234vs180±92pg/ml, P<0.001) and in those with extensive disease compared to those with limited disease (586±205vs317±185pg/ml). The urine ADAM12level was consistent with the serum level and was higher in SCLC patients than in healthy volunteers (404±247vs128±50pg/ml) and in patients with extensive disease compared to patients with limited disease (477±201vs303±152pg/ml). This indicates that ADAM-12levels in serum and urine are correlated with SCLC progression and that ADAM-12can be considered to be a diagnostic marker for SCLC disease since the expression of ADAM-12increased with the development and progression of disease.Part Ⅴ:Conclusion、innovation and defects一、Conclusion1、Small cell lung cancer patients showed poorer health-related quality of life, but there was no significant difference compared to other cancer patients in overall health. SCLC patients expressed seriouse emotional distress, pain, fatigue.2、Social support of SCLC patients presented no difference with the compared group. However, social support had significant effect on the HRQOL and depression or anxiety.3、Mental health of SCLC patients was significantly lower than the healthy group; the total frequency of SCLC patients in stressful life events was higher than the healthy control group, and SCLC patient tended to use passive strategies to deal with stress..4、DAM-12is highly expressed in SCLC patients’ tissue samples, blood and urine, and is closely related to the occurrence of the disease, development, and can be used as an indicator of SCLC clinical diagnosis and evaluation of prognosis二、Innovation and defects1、In this study, we assessed the condition of the health-related quality of life on SCLC patients and detected the relatiosnship of social support and HRQOL2、The present study, we investigated the mood disorders, social support and coping style in patients with small cell lung, and explore the relevant factors leading to psychological distress and HRQOL in SCLC patients.3、This study firstly reported the expressions of ADAMs in SCLC, and found that ADAM-12could be considered as the marker to help diagnosis and evulate the prognosis. These results had important clinical significance and value.4、The defects were following. (1) Difficulties for participants to well know the study content may have negative effects on the results of this study.(2) This study is only a preliminary status on the perception of psychological intervention in patients with small cell lung cancer, a more in-depth study and coping strategies will result in follow-up studies continue to follow up, so without making reports target. |
PDF Full Text Request