Quality of life in long-term survivors of oropharynx carcinoma

PURPOSE: To collect data on the health-related quality of life (QOL) of long-term survivors and to determine to what extent QOL might be an appropriate end point in the comparison of treatment options in oropharyngeal carcinoma. METHODS AND MATERIALS: All patients treated between 1992 and 1998, in two French comprehensive cancer centers, by brachytherapy (BT) +/- external beam radiotherapy (EBRT) or surgery plus RT, or exclusive EBRT for T1-T3 (International Union Against Cancer staging system) oropharynx squamous cell carcinoma, were included. QOL was measured once in disease-free patients at least 2 years after treatment initiation. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and the specific H&N35 module were self-administered by all participating patients. Sociodemographic data were collected using a questionnaire specifically designed for the study. The association between the QOL scores of the various treatment-, disease-, and patient-related variables was performed through bivariate analysis and then by multivariate analysis. The mean QOL scores of the EORTC QLQ-C30 questionnaire were compared with the mean scores in the general population. RESULTS: Of the 159 eligible patients, 113 agreed to participate (97 men and 16 women, median age 61 years, range 41-83). The initial treatment was EBRT plus BT in 49 patients, surgery plus RT in 27, and EBRT alone in 37. The median follow-up time was 62 months (range 24-110). Compared with the general population, the three scores indicating the most impaired QOL were emotional and social functioning and fatigue. The clinical significance of global QOL impairment was borderline. The physical functioning, role functioning, and pain scores did not significantly differ from those of the general population. In multivariate analysis, the initial treatment had no significant influence on any dimension of QOL, except global QOL and emotional functioning. Surprisingly, surgery plus RT, as the initial treatment, favorably influenced the emotional functioning score and EBRT plus BT negatively influenced the global QOL score. None of these treatment modalities influenced any symptom scales. Patient selection was, at least partially, responsible for these paradoxical results. CONCLUSION: The results of this study bring original and useful data about the QOL of long-term survivors of oropharynx carcinoma. In these patients, the QOL was significantly impaired, particularly in its psychosocial dimensions. The level of symptoms and functioning (except global QOL and emotional) was similar whatever the initial treatment. These results suggest the importance of coping processes. In a trial comparing treatment options from a long-term perspective, survival remains the most relevant end point, and a QOL evaluation should be a secondary end point. More prospective studies on QOL in head-and-neck cancer patients are needed to determine new strategies for rehabilitation management.     

Impact of briefly-assessed depression on secondary prevention outcomes after acute coronary syndrome: a one-year longitudinal survey

Background  

Patients with acute coronary syndromes (ACS) are at increased risk of further acute cardiac events. Secondary prevention aims to decrease morbidity and mortality post-ACS. Depression is related to increased risk in this population, and to poorer secondary prevention activities. However, lengthy depression assessment techniques preclude depression assessment in routine care. The present study investigated the relationship of briefly-assessed depression with secondary prevention outcomes one year post-ACS.     

Histopathologic consequences of hyperglycemic cerebral ischemia during hypothermic cardiopulmonary bypass in pigs

BACKGROUND: This study examined whether 34 degrees C or 31 degrees C hypothermia during global cerebral ischemia with hyperglycemic cardiopulmonary bypass (CPB) in surviving pigs improves electroencephalographic (EEG) recovery and histopathologic scores when compared with normothermic animals. METHODS: Anesthetized pigs were placed on CPB and randomly assigned to 37 degrees C (n = 9), 34 degrees C (n = 10), or 31 degrees C (n = 8) management. After increasing serum glucose to 300 mg/dL, animals underwent 15 minutes of global cerebral ischemia by temporarily occluding the innominate and left subclavian arteries. Following reperfusion, rewarming, and termination of CPB, animals were recovered for 24 (37 degrees C animals) or 72 hours (34 degrees C and 31 degrees C animals). Daily EEG signals were recorded, and brain histopathology from cortical, hippocampal, and cerebellar regions was graded by an independent observer. RESULTS: Before ischemia, serum glucose concentrations were similar in the 37 degrees C (307+/-9 mg/dL), 34 degrees C (311+/-14 mg/dL), and 31 degrees C (310+/-15) groups. By the first postoperative day, EEG scores in 31 degrees C animals (4.2+/-0.6) had returned to baseline and were greater than those in the 34 degrees C (3.4+/-0.5) and 37 degrees C (2.5+/-0.4) groups (p < 0.05, respectively, between groups). Cooling to 34 degrees C showed selective improvement over 37 degrees C in hippocampal, temporal cortical, and cerebellar regions, but the greatest improvement in all regions occurred with 31 degrees C. Cumulative neuropathology scores in 31 degrees C animals (13.5+/-2.2) exceeded 34 degrees C (6.8+/-2.2) and 37 degrees C (1.9+/-2.1) animals (p < 0.05, respectively, between groups). CONCLUSIONS: Hypothermia during CPB significantly reduced the morphologic consequences of severe, temporary cerebral ischemia under hyperglycemic conditions, with the greatest protection at 31 degrees C.     

Expression of inducible nitric oxide synthase and p53 in oral epithelial dysplasia

AIM: Nitric oxide (NO) has been studied in a variety of human cancers and is implicated in both tumor promotion and inhibition. Downregulation of the enzyme iNOS by wild-type p53 (but not mutant) protein has been shown to occur in normal cells and some tumors, but the relationship has not been reported in oral epithelial dysplasia. METHODS AND RESULTS: An immunohistochemical study was conducted with antibodies to iNOS and p53 (clone DO-7) in 36 cases of oral dysplasia of varying severity. Statistical analysis showed a significant correlation between iNOS staining and grade of dysplasia (P <.001) and between p53 and iNOS staining (P <.001). CONCLUSIONS: This preliminary study has shown that iNOS expression correlates with severity of dysplasia, and it is also increased in those cases showing positive staining for p53. Further research is required to fully establish the relationship between iNOS and p53 in both dysplasia and oral squamous cell carcinoma.     

Phase II study of sequential high-dose methotrexate (MTX) and 5-fluorouracil (F) alternated with epirubicin (E) and cisplatin (P) [FEMTX-P] in advanced gastric cancer

BACKGROUND:: FAMTX (5-fluorouracil, adriamycin, methotrexate) is one of themost effective drug combinations in gastric cancer. Therefore,modifications of FAMTX appear of interest and the FEMTX-P regimentwas conceived. PATIENTS AND METHODS:: Fifty patients with unresectable locally advanced and/or metastaticgastric carcinoma were treated with methotrexate 1500 mg/m²i.v. and 5-fluorouracil 1500 mg/m² i.v. on day 1; leucovorinrescue 15 mg/m² orally every 6 hours for 8 doses on days 2 and3; epirubicin 60 mg/ m² i.v. and cisplatin 50 mg/m² i.v. onday 15, q 4 weeks. RESULTS:: Of forty-seven patients evaluable for response, five (11%) achievedcomplete responses and seventeen (36%) partial responses (totalresponse rate 47%). The median duration of response was 8+ months(range: 5–25+ months). Four of 14 patients with locallyadvanced disease were successfully downstaged and subsequentlyresected. The median duration of survival of all patients was10 months (range: 1–25+ months). Leukopenia grade 4 occurredin 18% of patients and thrombocytopenia grade 4 and mucositisgrade 4 in 4% and 2%, respectively. Treatment postponement forhematologic toxicity was necessary in 54% of patients. CONCLUSIONS:: The FEMTX-P regimen is an active regimen in advanced gastriccarcinoma, with acceptable toxicity. chemotherapy, FEMTX-P, gastric cancer     

Metronidazole (Flagyl): characterization as a cytotoxic drug specific for hypoxic tumour cells.

The cytocidal properties of metronidazole against hypoxic mammalian cells are described. This chemotherapeutic action has been shown to be dependent on drug concentration and duration of exposure. The x-ray TCD50 for a murine anaplastic carcinoma was reduced from 6081 rad to 4643 rad when animals were given metronidazole orally for 36 h before radiation treatment. The effect is attributed to the direct killing of hypoxic tumour cells by a mechanism analogous to that proposed for the action of the drug on anaerobic micro-organisms. It is concluded that further work with metronidazole as a cytotoxin specific for hypoxic cells is warranted, particularly in view of the reported lack of toxicity associated with the preliminary clinical use of the drug as a radiosensitizer in man.     

Time Zone Transitions and Business Executives

Circadian (or 24 hour) rhthms in man are currently a very activefield for research. These rhythms have a number of applicationsin occupational medicicne; their implecations for business executivesmaking long East-West or West-East journeys across time zonesare of particluar interest.Examles of physiological and psychlogicaldisturbances in test subjects flying across time zones are descrbed.Replies form medical advisers to leading compaies concend withthe problem are commented on and a survey of 315 senior executivesin a number of major British and American companes detailed.Form the replies recevied, it emerged that 87.5 per cent ofthe exectives had sleep disturbaces following such journeysand that business negotiations were conducted by 50 per centbefor gaining a nitht's sleep even though less than 20 per centclamed to be fully fit when so doing. Comments and advice toexecutives making long East-West or West-East flights are suggested.