Attitudes towards euthanasia among physicians, nurses and the general public in Finland.

The object of this study was to investigate the attitudes of physicians, nurses and the general public to physician-assisted suicide (PAS), active voluntary euthanasia (AVE) and passive euthanasia (PE) in Finland. Respondents received a postal questionnaire to evaluate the acceptability of euthanasia in five scenarios, which were imaginary patient cases. Age, severity of pain and prognosis of the disease were presented as background factors in these scenarios. This work was carried out in Finland in 1998. The respondents include a random selection of 814 physicians (506 responded, 62%), 800 nurses (582 responded, 68%) and 1000 representatives of the general public (587 responded, 59%).Thirty-four percent of the physicians, 46% of the nurses and 50% of the general public agreed that euthanasia would be acceptable in some situations. Of the scenarios, PE was most often considered acceptable in cases of severe dementia (physicians 88%, nurses 79% and general public 64%). In the same scenario, 8% of physicians, 23% of nurses and 48% of general public accepted AVE. In the scenario of an incurable cancer, 20% of the physicians, 34% of the nurses and 42% of the general public accepted PAS. All forms of euthanasia were generally more acceptable in older, than in younger, scenario patients. This paper conclude that PE was largely accepted among Finnish medical professionals and the general public. Only a minority favored AVE and PAS.

Reduced expression of CD44v3 variant isoform is associated with unfavorable outcome in non-small cell lung carcinoma.

The expression of CD44 standard form (CD44s) and variant isoforms v3 and v6 was analyzed in 233 resected non-small cell lung carcinoma (NSCLC) specimens by immunohistochemistry (IHC), and the mRNA status of CD44v3 and CD44v6 in a cohort of samples was determined by in situ hybridization (ISH) and further confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of CD44s, CD44v3, and CD44v6 was correlated with clinicopathologic variables and survival. The expression of CD44v3 and v6 was reduced in 97% and 90% of the adenocarcinomas and in 86% and 74% of the large cell/anaplastic carcinomas, respectively, as compared with squamous cell carcinomas, where they were reduced in 53% and 51% of the cases (P = .0001 and P = .004 for v3 and v6). The corresponding values for CD44s were 92%, 70%, and 51%, respectively (P = .011). The reduced CD44s and CD44v6 expression was associated with lymph node metastases (P = .03 and P = .005, respectively) and the reduced expression of CD44s also with advanced stage (P = .04). Recurrences during the follow-up were more often found within the tumors showing reduced expression of CD44v3 (P = .04). Combining ISH and IHC results showed that CD44v3 and v6 mRNA were not always processed into protein, suggesting a regulation disturbance posttranscriptionally since malignant transformation of cells has occurred. In survival analyses, the reduced expression of CD44s and CD44v3 was associated with a shortened disease-free survival (P = .04 and P = .01, respectively). In multivariate analysis, CD44v3 retained its independent prognostic value (P = .03). These results emphasize the value of CD44, and especially the v3 variant isoform in the behavior of NSCLC.

Phase II study of vinorelbine and gemcitabine for inoperable stage IIIB-IV non-small-cell lung cancer.

PURPOSE: To evaluate the efficacy of the combination of vinorelbine and gemcitabine as a non-platinum chemotherapy regimen in patients with inoperable locally-advanced or metastatic non-small-cell lung cancer (NSCLC). Efficacy was assessed primarily in terms of response rate, and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Patients with cytologically- or histologically-proven stage IIIB-IV NSCLC, bi-dimensionally measurable lesions, adequate haematological, hepatic and renal function, WHO performance status < or = 2 and no previous chemotherapy or radiotherapy were eligible. The first 12 patients were entered in a pilot study and received vinorelbine (VNR) 30 mg/m2 on days 1, 8, 15 and 22, and gemcitabine (GEM) 1000 mg/m2 on days 1, 8 and 15, of a 28-day cycle. Subsequently, patients were entered in a phase II trial of VNR 35 mg/m2 and GEM 1200 mg/m2 on days 1 and 15 of each 28-day cycle. Treatment consisted of three cycles of the chemotherapy, with a further three cycles for those patients who achieved stable disease or a complete or partial response (CR/PR) to the first three cycles. Patients who had achieved CR or PR after six cycles continued with the treatment until relapse. RESULTS: The dosage and scheduling of VNR and GEM in the pilot study resulted in neutropenia necessitating reductions or delays in treatment, and consequently low dose intensity. The schedule was thus modified to VNR 35 mg/m2 and GEM 1200 mg/m2 on days 1 and 15 of each 28-day cycle for the phase II trial. Thirty-three patients were enrolled in the phase II trial, and 28 were evaluable for response. The overall intent-to-treat response rate of all 45 patients was 40% (18 of 45), comprising 4 CR (9%) and 14 PR (31%). For the 28 evaluable patients who received the fortnightly chemotherapy the response rate was 46% (13 of 28), CR 11% (3 of 28) and PR 36% (10 of 28). Seven patients (25%) had stable disease. The one-year cumulative survival rate for the 33 patients receiving the fortnightly chemotherapy was 24% and median time-to-progression 4 months (range 1-16 months). Median survival for these patients was eight months. Nine out of twelve patients in the pilot study (75%) suffered grade 3-4 neutropenia. There was one toxic death, attributed to neutropenic fever and sepsis, and two cases of pulmonary embolism. One patient suffered Grade 4 thrombocytopenia. Only eight patients (24%) on the fortnightly schedule suffered grade 3-4 neutropenia, resulting in dose reductions or delays for three of them (9%). None of the patients on the fortnightly schedule suffered thrombocytopenia or anaemia. CONCLUSIONS: The fortnightly schedule of gemcitabine and vinorelbine was a well-tolerated out-patient regimen, producing response and survival rates comparable to those of cisplatin combination regimens, but with a more favourable toxicity profile. Gemcitabine and vinorelbine should now be tested in a triplet combination with a taxane as the third drug, or against a platinum-containing regimen in a phase III study.

Expression of hyaluronan in normal and dysplastic bronchial epithelium and in squamous cell carcinoma of the lung.

A series of 85 lung/bronchial tissue samples from 76 patients consisting of normal, metaplastic and dysplastic epithelium and different types of lung carcinomas were analyzed for the distribution of hyaluronan (HA), using a biotinylated hyaluronan binding complex as an HA-specific probe. The normal pseudo-stratified columnar bronchial epithelium was either negative for HA or displayed a weak staining around the basal cells. The epithelia of serous and mucous bronchial glands were HA negative whereas the submucosal connective tissue was strongly positive. In metaplastic, dysplastic and carcinoma in situ lesions the whole epithelium from basal to uppermost cells expressed HA on plasma membranes. Epithelial HA was also found in squamous cell carcinomas, but not in adenocarcinomas, carcinoid tumors or small cell carcinomas of the lung. Whereas epithelial HA was present in all lesions of the squamous cell type, the staining intensity displayed great local variability in 50% of the cases with severe dysplasia, carcinoma in situ and squamous cell carcinomas. In squamous cell carcinomas, such an irregular staining pattern was significantly associated with poor differentiation. Our results indicate that the expression of HA in different bronchial lesions and lung tumors is restricted to those showing squamous cell differentiation, being absent from other types of lung carcinomas. The increase of HA depleted areas in poorly differentiated squamous cell carcinomas emphasizes the important role of HA in tumor differentiation. HA on carcinoma cell surface may influence tumor growth and metastatic behavior.

Flow cytometric analysis of tumor DNA profile related to response to treatment and survival in small-cell lung cancer.

Flow cytometric (FCM) analysis of tumor DNA ploidy and S-phase fraction (SPF) has been widely used to predict prognosis and treatment response in many malignant tumors, but rarely in small-cell lung cancer (SCLC). In the present study, tumor DNA ploidy and SPF were measured from paraffin-embedded tumor biopsy samples of 36 small-cell lung cancer patients treated with combination chemotherapy and radiotherapy. Aneuploidy was detected in 69% of the tumors. There was a statistically non-significant trend towards more aneuploidy among extensive disease (ED) patients as compared to patients with limited disease (LD): 80% versus 65%, respectively (p = 0.69). The mean SPF was 21.3% (+/-7.6) in patients with LD and 29.0% (+/-5.3) in patients with ED, the difference (7.6%) being statistically significant (p = 0.008, 95% CI for the difference 2.2-13.1). No significant differences was detected in the survival of aneuploid and diploid patients or patients with low (< or = 24.9%) and high (> 24.9%) SPF. Similarly, no significant difference was observed between aneuploid and diploid cases in relation to response to treatment or response duration. It is concluded that the difference detected in the SPF with LD and ED of SCLC may indicate the biological aggressiveness of extensive SCLC.

Carboplatin and etoposide in extensive small cell lung cancer.

The combination of carboplatin and etoposide was evaluated in 61 previously untreated patients with extensive small cell lung cancer. Treatment was given at four-week intervals with 450 mg/m2 of carboplatin intravenously (i.v.) on day 1 and etoposide 100 mg/m2 i.v. on days 1-3. The response was complete in 5 (9%) and partial in 28 (50%) of the 56 evaluable patients (overall response rate 59%). The median time to progression after response as well as the median survival time in all evaluable patients was 4.6 months. WHO grade 3 and 4 leukopenia and thrombocytopenia occurred in 8% and 11% of the courses respectively. Two treatment-related deaths were registered. The combination of carboplatin and etoposide used in the present study produced acceptable response rate and toxicity, but duration of response and median survival were shorter than expected from earlier studies.

Carboplatin and etoposide (CarE) combined with radiotherapy and vincristine, doxorubicin and cyclophosphamide (VAC) in limited small cell lung cancer. A phase II study.

Sixty-eight patients with limited small cell lung cancer were treated between April 1988 and October 1990 with combination carboplatin 450 mg/m2 i.v. on day 1 and etoposide 100 mg/m2 i.v. on days 1-3 (CarE) for two courses, followed by thoracic radiotherapy (TRT) 50 Gy, and then vincristine 1 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 750 mg/m2 on day one (VAC) for four courses. Prophylactic cranial irradiation (30 Gy) was given to patients with CR after completion of chemotherapy. Sixty patients (89%) achieved an objective response (40% complete responses). The median time to progression was 8.5 months and median survival time 12.1 months. Predicted one- and two-year survival was 50% and 12% respectively. Myelosuppression was the main toxicity, with WHO grade 3 and 4 leukopenia occurring in 32% of VAC courses. There were 5 (7%) treatment-related deaths, all of them during VAC. We conclude that the present combination is active in terms of response rate, but it did not demonstrate any superiority in survival. The frequency of haematological toxicity was substantial during VAC courses.

Operative finding, treatment, and prognosis of carcinoma of the pancreas: an analysis of 267 cases.

Two hundred sixty-seven laparotomized patients with pancreatic cancer during the period 1947 to 1980 were retrospectively analyzed. In 199 histologically confirmed cases of pancreatic carcinoma the tumor was only local with no invasion to neighboring tissues or distant metastases in 15% of the cases at the primary laparotomy and diagnosis stages, and the survival rates after 1, 3, and 5 years were 22%, 3% and 1%, respectively. The prognosis was a little better if a patient was over 70 years old, duration of symptoms was more than one year, the reason for laparotomy was cholecystopathy, the tumor was stage I, the treatment was a combination therapy of pancreatic resection and postoperative irradiation (with a depth dose of greater than or equal to 4,000 rad). We concluded that, excluding the extremely rare cases of pancreatic carcinoma which are cured with pancreatic resection, the survival of patients after primary operation is correlated nearly in the same way with the given treatment and the stage of the disease. It seems that at present the only possibility of improving the results of treatment in pancreatic carcinoma is to develop the combined treatment of surgery, irradiation, and chemotherapy.