Adnan Aydiner

Quality of life, symptom experience and distress of lung cancer patients undergoing chemotherapy

UNLABELLED The diagnosis of lung cancer in the advanced stage of illness, the poor prognosis associated with the disease, and the side effects of chemotherapy all have an impact on various dimensions of quality of life (QoL). THE PURPOSE OF THE RESEARCH The current study was designed to describe the QoL and symptom distress of lung cancer patients undergoing chemotherapy and to explore the relationships between demographic/treatment-related characteristics and QoL. METHODS AND SAMPLE The sample consisted of 154 lung cancer patients undergoing chemotherapy. The symptom experiences and QoL of lung cancer patients undergoing chemotherapy were evaluated using the Memorial Symptom Assessment Scale and Quality of Life Index - Cancer Version. RESULTS The lung cancer patients had low QoL scores. The scores on the Health and Functioning subscale were the lowest (20.33 ± 5.59), while those of the Family subscale were the highest (27.66 ± 2.77). The most common physical symptoms experienced by lung cancer patients were lack of energy, coughing, pain, lack of appetite, and nausea, while the psychological symptoms were feeling nervous, difficulty sleeping, feeling sad, and worrying. There was a negative relationship between the symptom distress and quality of life scores (r=-0.45; p<0.000). Females and those with low income levels and performance status experienced greater symptom distress. CONCLUSIONS Lung cancer patients receiving chemotherapy suffer many limitations due to the symptoms and disruptions to their QoL, arising from both the disease process and its treatment. Lung cancer patients need to be assessed regularly and supported.

Prognostic factors in pancreatic carcinoma: Serum LDH levels predict survival in metastatic disease

In this study, our aim was to investigate the impact of various prognostic factors on survival in patients with pancreatic carcinoma. The group consisted of 127 cases with adenocarcinoma histologically. The patients had a median age of 58 years, and 81 (64%) were male. The median survival time of the whole group was 7 months, and the 4-year survival rate was 18%. The median survival duration of the patients without metastases was 8 months, and the survival rate at 1 year was 37.5% and 7.2% at 5 years. It was associated with improved survival compared with the cases with metastatic disease (p < 0.0001). In univariate analysis, decreased performance status (p = 0.0009) and unresectability of tumor (p < 0.0001) were associated with poor outcome. However, only surgery was found to be a statistically significant parameter in multivariate analysis (p = 0.002). The median survival duration of patients with metastases was 5 months, and the 1-year survival rate was 10%. Age younger than 60 years (p = 0.04), decreased serum hemoglobin levels (p = 0.04), and elevated lactic dehydrogenase (LDH) levels (p = 0.0001) were associated with a significantly shorter survival rate. In the Cox model, a high serum LDH level was the only independent unfavorable prognostic factor (p = 0.001). In conclusion, surgical intervention in the group without metastases and serum LDH levels in the group with metastases were the most important prognostic factors influencing survival. Pretreatment serum LDH determinations may provide a useful means of stratifying patient populations when comparing treatment programs for advanced pancreatic cancer.

Anemia in oncology practice: relation to diseases and their therapies.

Anemia is common in patients with cancer and is a frequent complication of myelosuppressive chemotherapy. In this study, we investigated the incidence and severity of chemotherapy-induced anemia caused by the most common chemotherapy regimens, including the new generation of chemotherapeutic agents, used in the treatment of the major nonmyeloid malignancies in adults. Five hundred fifty-two patients with histologically proven carcinoma originating from breast (n = 165), lung (n = 128), colon (n = 75), ovary (n = 84), and malignant lymphoma (n = 100) were included in this study. Hemoglobin levels for each patient were measured with an automatic counter during both pretreatment and before each chemotherapy cycle during therapy. To document the incidence of anemia, the National Cancer Institute grading system was used. Before chemotherapy, 44% of patients with breast carcinoma had anemia. There was a 16% increase in the incidence of anemia after chemotherapy. Severe anemia was observed in less than 1% of patients. No difference was found in the incidence of anemia between the fluorouracil, doxorubicin, cyclophosphamide (FAC) and cyclophosphamide, methotrexate, fluorouracil (CMF) regimens used in the adjuvant setting. However, single-agent chemotherapy with newer generation caused more anemia when compared with the FAC regimen (p < 0.005). Chemotherapy resulted in a significant decrease in hemoglobin levels when compared with pretreatment values in patients with lung cancer (p < 0.001). During treatment, the increase in the incidence of grade II anemia was associated with a parallel decrease in the incidence of grade I anemia. The incidence of severe anemia did not exceed 15%. The incidence of anemia was equivalent in both patients with small-cell lung cancer and those with non–small-cell lung cancer treated with the etoposide and cisplatin (EP) combination. Seventy-one percent of patients with colon cancer had anemia before initiation of chemotherapy. No difference was observed in posttreatment hemoglobin values compared with pretreatment values. Patients treated with irinotecan and fluorouracil and leucovorin (FUFA) combination showed similar rates of anemia. Incidence of anemia in patients with ovarian cancer at admission was 68%. Chemotherapy resulted in a prominent increase in incidence of anemia, which increased to 91.5%. There was an increase in grade II anemia, which corresponded to the decrease in grade I anemia. Less than 10% of patients developed severe anemia. No difference in the incidence of anemia was observed in patients with ovarian cancer treated with either cisplatin and cyclophosphamide or cisplatin combination. Showing a high incidence of anemia (82%) at presentation, hemoglobin levels in patients with malignant lymphoma were unaltered with chemotherapy. Severe anemia occurred in less than 3% of patients. There was a higher incidence of anemia in patients with non-Hodgkin’s lymphoma receiving the cyclophosphamide, epirubicin, vincristine, prednisone (CEOP) regimen in contrast to patients with Hodgkin’s lymphoma treated with the doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) combination. There was a prominent decline in the hemoglobin levels with cisplatin-based combinations in contrast to combinations including noncisplatin agents (p < 0.001). In this study, we have observed equivalent rates of treatment-related anemia when compared with previous data in patients with specific tumor types. The incidence of pretreatment anemia was high in various malignancies. The mechanisms underlying the propensity for a higher risk of pretreatment anemia in patients with malignant disorders and its influence on the outcome has to be elucidated by further population-based and molecular studies.

Serum levels of leptin and proinflammatory cytokines in advanced-stage non-small cell lung cancer

In this study, we aimed to investigate the diagnostic and prognostic roles and the effects of chemotherapy of serum proinflammatory cytokines consisting of IL-6, TNF-α, CRP, and leptin levels in patients with advanced-stage non-small cell lung cancer. Twenty-eight patients newly diagnosed of non-surgical advanced non-small cell lung cancer and 15 healthy controls were included. All patients with good performance status were treated with combination therapy consisting of cisplatin plus vinorelbine chemotherapy. Blood samples were obtained in fasting conditions before chemotherapy first and after two cycles of chemotherapy. IL-6 and TNF-α immunoassays employ the quantitative sandwich enzyme immunoassay technique. Leptin (Sandwich) ELISA is a solid-phase enzyme-linked immunosorbent assay based on the sandwich principle. CRP is a photometric immunoturbidimetric test. Most of the patients were elderly, male predominance, good performance status, and no or less than 10% weight loss. Higher serum TNF-α (p<0.001) and CRP (p<0.001), and lower leptin (p=0.021) levels in patients than in controls. Serum IL-6 cytokine (p=0.693) levels were not significantly different. No statistically significant relationships between investigated serum parameters and various characteristics of patient and disease. Likewise, serum levels of leptin, IL-6, TNF-α, and CRP were all similar in lung cancer patients independently from severity of weight loss (p>0.05). A direct relationship was found between serum IL-6 and TNF-α levels (r=0.530, p=0.004). We found that both serum leptin (p=0.046) and IL-6 (p=0.002) levels were decreased owing to the chemotherapy effect independently from chemotherapy response. However, serum TNF-α and CRP levels were not changed by the chemotherapy effect. The stage of the disease, serum LDH levels, performance status, and responsiveness to chemotherapy yielded prognostic value. Only serum IL-6 levels out of the parameters showed a trend (p=0.06) related to a worse prognosis.

Multiple primary neoplasms at a single institution: differences between synchronous and metachronous neoplasms.

During the 10-year period (1987-1996) of our study, 26,255 patients with cancer were admitted to our clinic and, of these, 271 (1%) patients had multiple primary malignant tumors. Ninety-two (34%) patients had synchronous tumors (synchronous group), and 179 (66%) patients had metachronous tumors (metachronous group). The mean age at first diagnosis was higher in the former group. The ratio of men to women was 1.36 in the synchronous group and 0.74 in the metachronous group (p = 0.018). Smokers and drinkers were more common in the synchronous group. Breast cancer and lung cancer were most prevalent, and associations between head/neck and lung cancer and between breast and breast cancer were the most frequent associations in both the synchronous and the metachronous group. The frequency of aerodigestive tumors was higher and that of mesenchymal tumors was lower in the synchronous group than in the metachronous group. Localization in the medial region and in the head/neck was more frequent in the synchronous group than in the case of metachronous secondary tumors.

Serum lactate dehydrogenase levels at presentation predict outcome of patients with limited-stage small-cell lung cancer.

&NA; Serum lactate dehydrogenase (LDH) is a biochemical parameter that is elevated in the majority of extensive‐stage small‐cell lung cancer (SCLC). In this study, distribution and prognostic importance of serum LDH in limited‐disease SCLC were investigated. Serum concentrations of LDH were measured in 184 patients at initial examination. These results were compared with prospectively recorded clinicopathologic characteristics and patient outcome data. Significant positive association was found between LDH levels and weight loss, performance status, response to chemotherapy, and albumin but not between age, gender, and hemoglobin values. Patients with high concentrations of LDH had a significantly worse prognosis than did patients with normal levels. The probability of overall survival at 1 year was 60.2% in patients with normal serum LDH levels and 33.1% in patients with higher values (p = 0.0017). Also, the prognostic value of LDH on overall survival was shown in multivariate analysis (p = 0.05). At the time of diagnosis, serum levels of LDH appear to have a significant relation to outcome in patients with limited‐stage SCLC.

Granulosa cell tumor of the ovary: retrospective analysis of 45 cases.

Adult granulosa cell tumors of the ovary are rare neoplasms, accounting for less than 5% of all ovarian malignancies. In addition to the tumor stage, residual disease, patient age, tumor size, extent of surgery, and also some histologic factors have been reported to be of prognostic importance. Tumor registries were screened for all patients treated between 1979 and 1998 for ovarian tumors at the University of Istanbul. There were 952 ovarian carcinomas, of which 47 were granulosa cell tumors. All charts were reviewed, and the clinical data were extracted. Prognostic factors and treatment results were evaluated retrospectively. The median follow-up was 84 (range: 6–141 months) months. According to univariate analysis, there were only two significant factors for overall survival (OS): stage and presence of residual disease. The OS of the 23 patients with early stage (mean, 122 months; median, unreached) was significantly (p = 0.0001) better than the OS of the 22 patients with advanced stage (mean, 34 months; median, 21 months). A significant difference (p = 0.0004) in OS was also observed between patients with residual (mean, 42 months; median, 21 months) and nonresidual (mean, 108 months; median, unreached) disease. In a multivariate analysis, only stage remained statistically significant (p = 0.0001). The overall 5-year survival rate was 55% and median survival after recurrence was 21 months. Despite the small number of patients, the study showed that stage and macroscopic residual disease are significant prognostic factors. The benefit of chemotherapy and radiotherapy remains controversial.

Autophagy and Nuclear Changes in FM3A Breast Tumor Cells after Epirubicin, Medroxyprogesterone and Tamoxifen Treatment in vitro

Objective: Autophagy is a form of physiological programmed cell death which is observable after hormonal withdrawal. In this study, the FM3A murine breast tumor cell line was treated with epirubicin alone and with medroxyprogesterone acetate (MPA) or tamoxifen, to determine if structural and kinetic signs of autophagy may also occur in an enhanced manner during epirubicin sensitization via hormonal agents. Methods: One-week soft agar colony growth, 96-hour values of plating and pulse thymidine labeling and electron microscopical examinations were performed following treatment with MPA and tamoxifen alone or with epirubicin. Results: Tamoxifen induced signs of autophagy, which was enhanced when it was combined with MPA. Epirubicin also induced autophagy of secretory granules, which coalesced to form an intracytoplasmic lumen. Combining MPA with epirubicin enhanced the formation of apoptotic blebs and chromatin fragmentation. When epirubicin was combined with tamoxifen, peculiar nuclear structures were formed. Conclusions: Hormonal agents may modulate anthracycline activity towards specific patterns in eliciting cell death, via autophagy and/or as yet unknown nucleolus-specific interactions.

Stevens-Johnson syndrome in a patient receiving anticonvulsant therapy during cranial irradiation.

&NA; A 28‐year‐old female patient with a recent history of breast carcinoma was referred to our clinic with generalized necrotic skin eruptions and severe mucosal erosions, which developed right after the completion of cranial radiotherapy for brain metastases. She had been receiving prophylactic diphenylhydantoin treatment 100 mg three times daily during radiation therapy. The extensive involvement of the oral mucosa with conjunctivitis and synechiae of the eyelids, facial swelling, and extension of the rash over the trunk and shoulders with bullous detachment of less than 10% of the total body surface strongly suggested Stevens‐Johnson syndrome caused by phenytoin treatment in our patient. There has been conflicting evidence on the role of radiotherapy in the increased risk of severe drug reactions. Although various authors have emphasized the augmented rate of severe mucocutaneous reactions caused by anticonvulsants given during radiotherapy and suggested discontinuing the prophylactic use of such drugs in patients with no history of seizures, others have argued in favor of prophylactic anticonvulsants. Given the high risk of seizures, reaching 20% in patients with brain tumors, and the low incidence of drug reactions, the suggestion of refraining from prophylactic anticonvulsants in the setting of primary or metastatic brain tumors is controversial.

Angiogenesis and p53 protein expression in breast cancer: prognostic roles and interrelationships.

The authors have analyzed, on the one hand, the prognostic impact of microvessel density (MVD) and p53 protein expression in patients with breast cancer, and on the other hand, the correlation between the microvascular pattern and the p53 protein expression. Tumors from 120 patients whose paraffin-embedded tissue blocks were available were analyzed using the immunohistochemical method. MVD and p53 protein expression were correlated with histologic grade and tumor size, respectively. The patients with highly vascularized tumor (high MVD) had decreased overall survival (p = 0.04), whereas overexpressed p53 patients did not. In multivariate analysis, axillary lymph node status (p = 0.007), tumor size (p = 0.01), and MVD (p = 0.02) showed important prognostic influence on overall survival. When the simultaneous influence of MVD and p53 protein expression on survival were analyzed, no interrelationship was detected. The results demonstrate the prognostic impact of MVD on overall survival in breast cancer and no association between MVD and p53 protein expression.