Rectal cancer therapy: decision making on basis of quality of life?

BACKGROUND: As colorectal malignancies are relatively well treatable and show acceptable survival rates, the quality of life indicators are very important in this group of patients. PATIENTS AND METHODS: 372 patients with rectal cancer were included on a voluntary basis in this prospective study. The patient material consisted of two groups, those who underwent sphincter saving operation (64.51 %), and those who underwent Miles operation (35.49 %). The patients answered a colorectal cancer specific questionnaire on quality of life (CRC_QoL) 1 year after surgery. A CRC_QoL was prepared to analyze the correlation between the characteristics of the colorectal cancer and its treatment versus the physical and psychological state, somatic sensations and social connections of the patients. Our QoL questionnaire consists of 62 questions. Internal consistency of each factor was assessed by calculating Cronbach alpha values and was found satisfactory. For the test-retest reliability analysis the questionnaires were re-assessed. Correlation analysis showed that the answers were consistent (p < 0.01 in all cases). Discriminative validity analysis of the factors showed a significant difference in all cases. In self made score system higher numbers mean (9) worse, the smaller mean (0) better quality of life. The scale can also be seen as a percent distribution, where - in turn - the best quality is 100. The CRC_QoL questionnaire, scoring system, and score-to-percent transformation were done in this study. The results were evaluated by question and by patient group too. RESULTS: Our indicator did not show poor QoL for ostomates. Physical function was quite good in both groups: non-ostomates 87.69 +/- 20.85, ostomates: 96.46 +/- 8.25, p = 0.05 respectively. The cumulated converted percentile value for general state was significantly better (p = 0.03) for the ostomates (86.18 +/- 13.43) compared to non-ostomates (69.80 +/- 31.37). The cumulative gastrointestinal problem score did not reveal any significant difference (non-ostomates: 90.19 +/- 12.50, ostomates: 95.62 +/- 9.04, p = 0.11). Non-ostomates and ostomates did not differ regarding the cumulative score of stool-related questions: 83.75 +/- 20.53 versus 89.85 +/- 10.01 respectively, p = 0.14. The score for the peristomal problems was as high as 90.00 +/- 16.12. There was no difference in the cumulative gender specific indicators for both sexes, which showed the value 72.50 +/- 44.35 at non-ostomates and 63.64 +/- 50.45 at ostomates (p = 0.31). None of the patients regarded the chemotherapy problem as a factor diminishing the quality of their life. After calculating the total of all above mentioned functional parameters the score for non-ostomates results 82.50 +/- 19.83, and that of ostomates results 88.60 +/- 8.48, what is about the same, p = 0.12. The cumulative score of the two groups concerning emotional indicators did not really differ (non ostomates 78.69 +/- 24.19, ostomates 84.95 +/- 12.08, p = 0.11). The total cumulative scores among the groups did not show significant difference (non-ostomates 81.67 +/- 31.48, ostomates 87.12 +/- 16.40, p = 0.27). The global QoL was high in both groups with no significant difference among non-ostomates and ostomates (82.00 +/- 24.86 versus 88.60 +/- 8.48, respectively, p = 0.12). CONCLUSION: The quality of life of all patients was poorer than it was prior to the onset of the disease, but most of them could return to their prior way of living with not too many compromises. This process can be well monitored with our score system.

Role of the basement membrane in tumor cell dormancy and cytotoxic resistance.

OBJECTIVES AND METHODS: Tumor dormancy and resistance to cytotoxic agents are key limiting events in the treatment of malignant diseases. To determine whether both are influenced by the extracellular milieu in which tumors reside, HT1080 human fibrosarcoma, MCF-7 breast carcinoma and OSCORT osteosarcoma cell proliferation, viability, apoptosis and cytoreductive-treatment-induced death were investigated in the presence or absence of extracellular matrix (ECM). RESULTS: ECM-adherent, but not plastic-adherent HT1080 cells formed a multicellular network accompanied by reduced proliferation and lowered DNA synthetic capacity. The number of cells in S-phase was dramatically reduced. Viable cells entered a state of dormancy reminiscent of that observed in the step of metastasis after extravasation, i.e. prior to the initiation of progressive growth. Such ECM-induced dormancy could be reversed by plating cells on plastic, but only after a 48-hour lag period. No difference was indicated in clonogenicity of HT1080 cells originated from plastic or ECM gel. However, the cells released from ECM gel showed significantly reduced migration ability. The resistance of anchored cells against cytotoxic damage was increased by ECM gel. Examination of cytoreductive treatment revealed that ECM adherence at the time of injury is partially protective, a property which was also moderately apparent when injured cells were transferred to the basement membrane. CONCLUSIONS: Taken together, these results suggest that the ECM plays a key role in tumor dormancy and cytotoxic resistance, both explorable at the molecular level using our in vitro model system.