Caries assessment and restorative treatment thresholds reported by Swedish dentists.

The aim was to study any variability in approximal and occlusal caries diagnoses and restorative treatment decisions among Swedish dentists. The material consisted of a pre-coded questionnaire sent to a random sample of 923 dentists with 4 items concerning approximal and occlusal caries diagnosis and restorative treatment decisions. Responses were received from 651 (70.5%) dentists. In an adolescent with low caries activity and good oral hygiene, more than 90% of the dentists stated that they would not automatically restore a primary approximal caries lesion if its radiographic appearance did not show obvious progression in the outer 1/3 to 1/2 of the dentin. Moreover, 67% of the dentists would only consider immediate restorative treatment of an occlusal surface if obvious cavitation and/or radiographic signs of dentin caries could be observed. When diagnosing questionable occlusal caries, the dentists largely relied on the radiographic appearance. Concerning both approximal and occlusal caries, the threshold for restorative treatment differed between the metropolitan regions in Sweden, and younger more often than older dentists would postpone restorative treatment of approximal caries until the lesion had reached a relatively advanced stage of progression. The responses also showed that dentists in private practice would restore approximal caries at an earlier stage of progression than the dentists in the Public Dental Health Service.     

Irinotecan combined with bolus 5-fluorouracil and folinic acid Nordic schedule as first-line therapy in advanced colorectal cancer.

BACKGROUND: This multicentre phase II study evaluated the efficacy and safety of irinotecan combined with the Nordic schedule of 5-fluorouracil (5-FU) and folinic acid (FA) as first-line therapy in patients with advanced colorectal cancer. PATIENTS AND METHODS: Seventy-four patients with measurable disease and a WHO performance status of 2 or less were treated with irinotecan 210 mg/m(2) as a 30-90 min intravenous infusion on day 1, followed by 5-FU 500 mg/m(2) and FA 60 mg/m(2) bolus on days 1 and 2, every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was the objective response rate. RESULTS: Twenty-nine out of 68 evaluable patients achieved a complete (n = 7) or partial (n = 22) response, leading to an overall response rate of 43% [95% confidence interval (CI) 31% to 55%]. The median duration of response was 10 months. The estimated median time to progression and survival were 6.4 months (95% CI 5.4-9.0) and 15.6 months (95% CI 13.3-19.0), respectively, in the intention-to-treat population. A total of 860 cycles were administered to 74 patients. Neutropenia was the main adverse event with grade 3-4 toxicity in 66% of patients and 17.5% of cycles. Grade 3-4 non-haematological toxicities were infrequent and included diarrhoea in 16% of patients and 2% of cycles and nausea/vomiting in 10% of patients and 1% of cycles. CONCLUSIONS: Irinotecan combined with the bolus Nordic schedule of 5-FU/FA is active in advanced colorectal cancer with an easily managed safety profile which ensures good schedule compliance. The low incidence of grade 3-4 non-haematological toxicity justifies the further evaluation of this combination in the context of randomised clinical trials.     

Expression of cyclin D1a and D1b as predictive factors for treatment response in colorectal cancer

Background:

The aim of this study was to investigate the value of the cyclin D1 isoforms D1a and D1b as prognostic factors and their relevance as predictors of response to adjuvant chemotherapy with 5-fluorouracil and levamisole (5-FU/LEV) in colorectal cancer (CRC).

Methods:

Protein expression of nuclear cyclin D1a and D1b was assessed by immunohistochemistry in 335 CRC patients treated with surgery alone or with adjuvant therapy using 5-FU/LEV. The prognostic and predictive value of these two molecular markers and clinicopathological factors were evaluated statistically in univariate and multivariate survival analyses.

Results:

Neither cyclin D1a nor D1b showed any prognostic value in CRC or colon cancer patients. However, high cyclin D1a predicted benefit from adjuvant therapy measured in 5-year relapse-free survival (RFS) and CRC-specific survival (CSS) compared to surgery alone in colon cancer (P=0.012 and P=0.038, respectively) and especially in colon cancer stage III patients (P=0.005 and P=0.019, respectively) in univariate analyses. An interaction between treatment group and cyclin D1a could be shown for RFS (P=0.004) and CSS (P=0.025) in multivariate analysis.

Conclusion:

Our study identifies high cyclin D1a protein expression as a positive predictive factor for the benefit of adjuvant 5-FU/LEV treatment in colon cancer, particularly in stage III colon cancer.     

Swedish dentists' decisions on preparation techniques and restorative materials

This study aimed at mapping the preparation techniques and restorative materials that Swedish dentists are using for primary approximal and occlusal carious lesions. It involved sending a pre-coded questionnaire to a random sample of 923 dentists, with eight items concerning approximal and occlusal restorative preparation techniques and dental materials. Responses were received from 651 (70.5%) dentists. To restore a primary approximal carious lesion in an adolescent with low caries activity and good oral hygiene, the tunnel preparation was chosen by 48% of the dentists, the saucer-shaped preparation by 32%, and the traditional Class II preparation by 20%. The most common preparation technique for restoring an occlusal carious lesion was removal of the carious part only, which was chosen by 74% of the dentists. For a lower second molar with a minor occlusal caries lesion combined with a suspected dentin lesion as judged radiographically, about half of the dentists chose to restore the carious part only and 27% would seal the rest of the fissure system in addition. For a similar lesion with no obvious radiolucency in the dentin, about 1/3 chose the 'no treatment' alternative, 1/3 fluoride treatment, and the rest fissure sealing or other techniques. Composite was used most often and amalgam least often for both approximal and occlusal carious lesions.     

Biochemical signs of impaired cobalamin status during and after radiotherapy for rectal cancer

PURPOSE: The aim of the study was to investigate whether pelvic radiotherapy for rectal cancer had a negative impact on cobalamin status. METHODS AND MATERIALS: Consecutive patients receiving pelvic radiotherapy (50 Gy) for rectal cancer were evaluated prospectively (n = 54). Serum cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine (tHcy) were measured at start and end of radiotherapy, at follow-up 4-6 weeks and 1 year (n = 23) after radiotherapy. RESULTS: Mean serum cobalamin decreased from 306 pmol/L before treatment to 267 pmol/L at the end of radiotherapy (p < 0.001), 247 pmol/L 4-6 weeks after radiotherapy (p < 0.001), and 249 pmol/L 1 year after radiotherapy (p = 0.02). Mean serum MMA was 0.16 micromol/L pretreatment, 0.17 micromol/L at the end of radiotherapy (n.s.), and increased to 0.19 micromol/L after 4-6 weeks (p = 0.007), and to 0.21 micromol/L after 1 year (p < 0.001). There was no change in serum tHcy. Mean serum holoTC was reduced from 111 pmol/L pretreatment to 93 pmol/L 4-6 weeks after radiotherapy (p = 0.002). CONCLUSIONS: The data suggest rapid and persistent decrease in cobalamin status after radiotherapy for rectal cancer, as reflected by reduced serum cobalamin combined with increased serum MMA. This observation, though modest, may motivate routine monitoring of cobalamin status at follow-up after radiotherapy.     

Constant denaturant gel electrophoresis (CDGE) in BRCA1 mutation screening

Screening for mutations in the breast and ovarian cancer susceptibility gene, BRCA1, is complicated by the wide spectrum of mutations found in this large gene. In the present study a constant denaturant gel electrophoresis (CDGE) mutation screening strategy was established for ˜80% of the genomic coding sequence (exons 2, 11, 13–16, 20, 24). This strategy was applied to screen genomic DNA from 50 familial breast and/or ovarian cancer patients who had previously been examined for BRCA1 mutations by SSCP. A total of 14 carriers of 12 distinct disease-associated mutations and 7 carriers of 6 distinct rare substitutions leading to amino acid substitutions were identified. The SSCP failed to detect 40% of the different deletions/insertions (4/10) and 75% (6/8) of the different base substitutions leading to terminating codons or rare amino acid changes. SSCP did, however, identify one rare base substitution that could not be detected in the CDGE screening. To evaluate the CDGE mutation screening strategy further, 25 unrelated patients from Norwegian breast and/or ovarian cancer families were examined for BRCA1 mutations using a combined genomic DNA/cDNA approach covering the entire coding sequence of the gene. A total of six mutation carriers were detected, all of whom had cases of ovarian cancer in their families. Three patients from independent families carried an 1135insA mutation in exon 11, two others had a Gly484ter and an 1675delA mutation, respectively, and the sixth carried a splice mutation (5194-2 a→c) causing deletion of exon 18. CDGE may become an efficient tool in diagnostic and population based screening for BRCA1 mutations. Hum Mutat 11:166–174, 1998. © 1998 Wiley-Liss, Inc.     

Type 1 protein tyrosine kinases in benign and malignant breast lesions

Aims : To determine their significance, we examined the expression pattern of the four epidermal growth factor receptor (EGFR) family members as well as the phosphotyrosine kinase activity in breast tumour tissues.  

Methods and results

Fifty-three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% (9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 proteins was found in the benign tumours. Contrary to previous reports, we observed c-erbB-4 receptor protein to be less expressed in the malignant breast tumours. The 'normal' breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c-erbB-4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c-erbB-4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found.  

Conclusion

Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2, c-erbB-3 and phosphotyrosine are largely in line with what has been reported, we found the c-erbB-4 protein expression to be decreased in the malignant tumours.     

Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas.

Fifty-nine primary breast carcinomas and 11 metastases were examined to identify genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours), 13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59 in 29%, and NM23HI in 26% of the primary tumours). Loss of all the markers except p144D6 was observed even more frequently in the metastases. Pairwise comparisons for concordance of allele losses on 17p indicated that there might be two genes on 17p implicated in breast cancer development; the TP53 gene and a gene located close to the p144D6 and pYNZ22.1 markers. LOH of the RBI gene was associated with LOH of pYNZ22.1 and p144D6, but not with LOH of TP53. LOH of RBI and TP53 was associated with occurrence of ductal carcinomas, RBI and p144D6 losses with tumour size, and p144D6 losses with positive node status as well. LOH of TP53 and the three 17q markers NM23HI, pTHH59, and pRMU3 was most frequently observed in tumours from postmenopausal women. p144D6 losses occurred most frequently in progesterone receptor-negative tumours, whereas pTHH59 losses occurred most frequently in oestrogen receptor-negative tumours. LOH of the investigated loci was not associated with ERBB2 protooncogene amplification, with positive family history of breast cancer, or with survival.     

Colony forming ability of human breast carcinomas: lack of prognostic significance

To study whether colony growth in vitro reflects the prognosis of breast cancer patients, specimens from a total number of 138 patients with primary breast carcinomas were cultivated in the Courtenay-Mills soft agar method. The plating efficiency (PE) values were related to various clinical and histopathological parameters. No significant correlation was found between colony forming ability and menopausal status, histopathology, TNM-status or steroid hormone receptor status. The crude survival of the patients was not significantly correlated to the in vitro growth of the tumours; neither was there any difference in relapse-free survival between patients whose tumours failed to grow in vitro and those having growing tumours (PE greater than 0). A multivariate survival analysis of 115 patients with primary tumours without distant metastases revealed that the PE was not a significant independent prognostic indicator, as it gave no additional prognostic information above that of node and ER status. It is concluded that routine measurement of colony formation in vitro is not warranted in the management of breast cancer.