Burhan Savas

“Do not tell”: what factors affect relatives’ attitudes to honest disclosure of diagnosis to cancer patients?

Disclosure of the diagnosis of cancer to patients is a difficult task for physicians in developing countries. Family members often oppose truth telling. The aim of this study was to evaluate the incidence of the “do not tell” attitude in a general population of cancer patients and to explore the factors affecting the attitude of cancer patients’ relatives about honest disclosure. Using a questionnaire, relatives of 150 patients with recently diagnosed cancer were interviewed. Of the relatives, 66% did not want the diagnosis to be disclosed. Male gender of the patient, a diagnosis of a non-breast cancer malignancy, the presence of stage IV disease, no previous request for disclosure by the patient, insufficient knowledge of the relative about cancer in general, and stronger religious belief of the relative were associated with greater likelihood of the relative having a “do not tell” attitude in univariate analyses (P=0.032, P=0.000, P=0.051, P=0.021, P=0.128, and P=0.058, respectively). In a multivariate analysis, the diagnosis of a non-breast cancer malignancy, and insufficient knowledge of the relative about cancer in general retained their significance (exp(B)=14.77, P=0.000; exp(B)=3.04, P=0.01, respectively). Differences among different countries and cultures are discussed.

Multidrug Resistance-Associated Protein 1 (MRP1) mediated vincristine resistance: effects of N-acetylcysteine and Buthionine Sulfoximine

BackgroundMultidrug resistance mediated by the multidrug resistance-associated protein 1 (MRP1) decreases cellular drug accumulation. The exact mechanism of MRP1 involved multidrug resistance has not been clarified yet, though glutathione (GSH) is likely to have a role for the resistance to occur. N-acetylcysteine (NAC) is a pro-glutathione drug. DL-Buthionine (S,R)-sulfoximine (BSO) is an inhibitor of GSH synthesis. The aim of our study was to investigate the effect of NAC and BSO on MRP1-mediated vincristine resistance in Human Embryonic Kidney (HEK293) and its MRP1 transfected 293MRP cells. Human Embryonic Kidney (HEK293) cells were transfected with a plasmid encoding whole MRP1 gene. Both cells were incubated with vincristine in the presence or absence of NAC and/or BSO. The viability of both cells was determined under different incubation conditions. GSH, Glutathione S-Transferase (GST) and glutathione peroxidase (GPx) levels were measured in the cell extracts obtained from both cells incubated with different drugs.ResultsN-acetylcysteine increased the resistance of both cells against vincristine and BSO decreased NAC-enhanced MRP1-mediated vincristine resistance, indicating that induction of MRP1-mediated vincristine resistance depends on GSH. Vincristine decreased cellular GSH concentration and increased GPx activity. Glutathione S-Transferase activity was decreased by NAC.ConclusionOur results demonstrate that NAC and BSO have opposite effects in MRP1 mediated vincristine resistance and BSO seems a promising chemotherapy improving agent in MRP1 overexpressing tumor cells.

Does awareness of diagnosis make any difference to quality of life? Determinants of emotional functioning in a group of cancer patients in Turkey.

Abstract. The object of this study was to investigate how the information status with regard to diagnosis, in addition to social and clinical factors, influenced emotional functioning and quality of life in a group of cancer patients in Turkey. A consecutive sample of 100 cancer patients being treated for different diagnoses in a tertiary care centre were prospectively evaluated. Data on patient disease and social characteristics, clinical factors, and scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were analysed by logistic regression models. A significant proportion (44%) of the patients did not know of their diagnosis of cancer. The scores on functional and symptom scales and global health status/quality of life according to QLQ-C30 did not differ according to the information given or not given on diagnosis. However, the independently significant determinants of good emotional functioning were male gender (P=0.002), low serum alanine transferase levels (P=0.025), good social functioning (P=0.002), and the absence of constipation (P=0.005). In Turkey, it is still common for cancer patients not to be informed of their diagnosis, and there is a great need to improve this situation. Honest disclosure of the truth does not worsen any dimension of quality of life in general or emotional functioning in particular. On the contrary, those with hepatic dysfunction, female gender, poor social functioning and constipation are the ones at increased risk of poor emotional functioning, and these patients may benefit from psychological screening.

Does maintenance/consolidation chemotherapy have a role in the management of small cell lung cancer (SCLC)? : A metaanalysis of the published randomized controlled trials

The role of maintenance/consolidation chemotherapy was assessed in the management of small cell lung cancer (SCLC) via a metaanalytic approach.

Predictors of distant metastasis at presentation in breast cancer: a study also evaluating associations among common biological indicators

AbstractBackground. To investigate the correlation among some of the commonly used clinical, pathological factors and newer biological indicators, and to identify the independent predictors of distant metastasis at presentation in patients with breast cancer. Methods. The pathological specimens from 73 patients with breast cancer were retrospectively evaluated by immunohistochemistry. Data on 13 biological indicators; ER, PR, P53, c-erbB-2, PCNA, CEA, Ki-67, Vimentin, Ulex, Nm23, Cathepsin D, Factor VIII, PS2 together with clinical and pathological factors were collected. Results. A number of highly significant correlations were found among the biological indicators studied. By logistic regression analysis, the predictors of distant metastasis at presentation in univariate tests were tumor diameter, number of lymph nodes involved, P53, c-erbB-2 and grade. In multivariate analysis, tumor diameter (P=0.042, HR: 1.88(1.02–3.44)), c-erbB-2 expression (P=0.035, HR: 18.20 (1.23–268.66)) and grade (P=0.010, HR: 8.05(1.66–39.00)) retained their significance. Conclusion. Our findings show that inactivation of suppressor genes, expression of oncogenes, loss of differentiation, augmentation of proliferative activity, metastatic potential, angiogenesis and hormone receptor status are all interrelated facets of breast cancer pathogenesis. Patients with tumors overexpressing c-erbB-2 or with bigger or higher-grade tumors probably need to be more carefully evaluated for the presence of distant metastasis, thus be better staged, at presentation. This may be a new reason to test c-erbB-2 routinely in all patients with breast cancer in addition to its well-known prognostic and predictive uses.

Increased serum sTRAIL levels were correlated with survival in bevacizumab-treated metastatic colon cancer

BackgroundColorectal cancer is the third most common cancer and the third leading cause of cancer-related death. Bevacizumab is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF) for the treatment of metastatic cancer. The parameters of RECIST (Response Evaluation Criteria for Solid Tumors) are not adequate to detect important treatment effects and response. Our goal was to evaluate the possibility of using sTRAIL (serum-soluble TNF-related apoptosis-inducing ligand) and VEGF as markers of treatment efficacy and prognosis in patients with metastatic colon cancer.MethodssTRAIL and VEGF levels were measured by ELISA in the sera of 16 bevacizumab-treated metastatic colon cancer patients and 10 presumably healthy age-matched controls. The measurements were taken before and after treatment for comparison purposes.ResultsElevated levels of sTRAIL were found in seven out of 16 patients after bevacizumab treatment. Although these patients had a median survival time of 20.6 months, the remaining bevacizumab-treated patients who did not show an increase in sTRAIL had a median survival time of 9.4 months. As expected, serum VEGF levels were decreased in all patients who received bevacizumab therapy and showed no correlation between serum VEGF levels and patient survival (data not shown).ConclusionsSerum sTRAIL levels might be a useful predictor of prognosis in metastatic colon cancer, in the early evaluation stages following bevacizumab treatment.

Quality of Life in Patients With Advanced Non-small Cell Lung Cancer

Quality of life (QOL) has been shown to improve with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), but the determinants of this improvement have not been thoroughly explored. Fifty consecutive NSCLC patients starting chemotherapy with measurable disease and with an Eastern Co-operative Oncology Group (ECOG) performance status of ≤2 were evaluated for change in QOL by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). The status of global QOL before chemotherapy influenced the degree of change in physical functioning (F = 8.71, P =.001), global QOL (F = 23.82, P <.001), and fatigue (F = 7.92, P =.001), whereas age of the patient was again linked with the change in global QOL (F = 4.68, P =.014), and type of chemotherapy administration (1st vs. 2nd line) was associated with the change in fatigue (F = 7.82, P =.001). Our findings show that patient age and baseline QOL assessed by EORTC-QLQ-C30, but not ECOG performance status, may help predict the amount of improvement in certain aspects of QOL in patients with advanced NSCLC undergoing chemotherapy. Conversely, in this cohort, patients who are likely to have deteriorating QOL on chemotherapy may benefit from closer follow-up and nursing care to optimize supportive measures.

N‐acetylcysteine enhances multidrug resistance‐associated protein 1 mediated doxorubicin resistance

Background  Resistance of cancer cells against anticancer agents is caused partly by multidrug resistance‐associated protein 1 (MRP1). The exact mechanism of MRP1‐involved multidrug resistance has not yet been clarified, although glutathione (GSH) is likely to have a role for the resistance to occur. N‐acetylcysteine (NAC) is a pro‐glutathione drug. DL‐buthionine (S,R)‐sulfoximine (BSO) inhibits GSH synthesis. The aim of our study was to investigate the effect of NAC and BSO on MRP1‐mediated doxorubicin resistance in human embryonic kidney (HEK293) and its MRP1‐transfected 293MRP cells.

Epithelioid leiomyosarcoma with rhabdoid features

ZusammenfassungUterine Sarkome gehören zu den seltener auftretenden malignen Neoplasien, wobei die Leiomyosarkome (LMS) die am häufigsten vorkommenden Weichteilsarkome repräsentieren. Die meisten Leiomyosarkome besitzen die für sie typischen histologischen Charakteristika. Nur außerordentlich seltene Varianten beinhalten Riesenzellen, epitheloide und myxoide Zellen. Heterologe mesenchymale Komponenten (skelettartiger Muskel, Fettgewebe, Gefäße) können ebenfalls in diesen Tumoren vorkommen. Das Auftreten von rhabdoiden Zellen wurde in verschiedenen Arten maligner Neoplasien berichtet. Es wurde festgestellt, dass das Vorkommen dieser Zellen das Verhalten von Neoplasien ins Maligne beeinflussen kann. Wir berichten über einen Fall eines epitheloiden Leiyomyosarkoms mit rhabdoiden Eigenschaften bei einer 56-jährigen Patientin – eine bislang nur selten beschriebene Kombination.SummaryLeiomyosarcomas (LMS) are the most common type of uterine sarcoma. Most LMS have typical histologic features, and variants such as epithelioid LMS, myxoid LMS, LMS with osteoclast-like giant cells and LMS with rhabdoid features occur only rarely. Rhabdoid cells were first described in rhabdoid tumor, a distinctive renal neoplasm of infancy. Such tumors are composed of diffuse proliferation of rhabdoid cells that are round or polygonal in shape with eccentric nuclei, prominent nucleoli and glassy eosinophilic cytoplasm containing hyaline-like inclusion bodies. In the literature, extrarenal localizations of malign rhabdoid tumors have been described in a variety of primary sites such as the central nervous system, liver, skin and soft tissues. These characteristic rhabdoid cells have been reported in sarcomas and carcinomas of various types and in a few cases of uterine sarcomas. The presence of rhabdoid cells in tumors is considered to be a predictor of aggressive tumor behavior. Our case is that of a 56-year-old woman who was admitted to the state hospital with left inguinal mass. Microscopically the tumor was admixed of three different types of cell with spindle, epithelioid or rhabdoid features. Immunopositive cytoplasmic staining for myoglobulin and desmin was seen in rhabdoid cells, and cytokeratin immunopositivity was observed in epithelioid and some rhabdoid cells. Epithelioid cells and spindle cells were also SMA positive. The histopathologic and immunohistochemical findings support the diagnosis of epithelioid LMS with rhabdoid features. We report this very uncommon LMS variant; to the best of our knowledge there are only a few cases in the English literature.

Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrug resistance protein-1 dependent way : An in vitro study

We have explored the action of zoledronic acid, which has an apoptotic effect and is used as an agent for treating skeletal metastases and osteoporosis, in the presence of vinblastine, and whether this effect is associated with MRP‐1 (multidrug resistance protein‐1) expression. HEK (human embryonic kidney) 293 cells were transfected to form the multidrug resistant cell line designated 293MRP (MRP‐1 expressing HEK293 cells). Both lines were treated with varying concentrations of vinblastine and zoledronic acid. Apoptosis was determined by the TUNEL (deoxyuridine triphosphate nick end‐labeling) method.