Bengt Magnusson

Initial versus deferred melphalan‐prednisone therapy for asymptomatic multiple myeloma stage I — A randomized study

Abstract:  From October 1983 until December 1988, 50 patients with asymptomatic multiple myeloma stage I were included in a prospective randomized multi‐centre study comparing melphalan‐prednisone (MP) therapy started at the time of diagnosis with deferred therapy where MP was started at the time of disease progression. Twenty‐five patients were randomized to each group. The median time from diagnosis to start of therapy in the group with deferred therapy was 12 months. The reasons for starting therapy were increasing M‐protein in 8 cases, symptomatic bone disease in 9 and anaemia in 5. In 2 cases, disease progression was complicated by vertebral fractures necessitating radiotherapy. Two patients in the group in which MP was started at the time of diagnosis developed acute leukaemia. No differences in response rate, response duration or survival were observed between the treatment groups. We conclude that in asymptomatic myeloma deferral of chemotherapy is feasible in well‐informed and well‐controlled patients but conveys no advantage in survival. In clinical practice the benefits of treatment deferral are to some extent outweighed by disease progression before start of treatment.

Accuracy of Proximal Caries Depth Measurements: Comparison between Limited Cone Beam Computed Tomography, Storage Phosphor and Film Radiography

The aim of this study was to compare the accuracy of limited cone beam computed tomography (LCBCT), an image plate system and F-speed film in assessing the depth of proximal carious lesions. Radiographs of a dry mandible with sound and carious teeth were obtained with all three methods. In 41 molar and premolar proximal surfaces, 2 observers independently measured lesion depth on the images from the three modalities. The correlation of measurements was assessed with Pearson’s correlation analysis. Results from imaging modalities and histological sectioning (gold standard) were compared using Bland-Altman plots. Overall comparison of the depth measurements from the imaging modalities and the gold standard was done using repeated-measures ANOVA. Pairwise comparisons of systems were done by the Bonferroni t test. The correlation between the measurements of the two observers was 0.977 for film, 0.997 for image plate system and 0.998 for LCBCT. Bland-Altman plots revealed that LCBCT agreed very closely with the gold standard while the agreement between the latter and the image plate – or film – images was moderate. The mean difference and 95% limits of agreement between LCBCT and the gold standard were smaller than those between either image plate or F-speed film and the gold standard. The LCBCT method appears as a promising tool for detection and monitoring of proximal carious lesions.

Karyotypic evolution in Ph-positive chronic myeloid leukemia in relation to management and disease progression

In a prospective study of 32 patients with chronic myeloid leukemia the frequency of chromosome abnormalities in addition to the Philadelphia chromosome (Ph) increased when the disease progressed. Before metamorphosis, 10 patients (31%) had developed additional abnormalities. Such abnormalities were present in three of them at the time of diagnosis; in the other seven, they were detected late in the chronic phase. New clonal abnormalities heralded or accompanied a more malignant phase of the disorder, usually a blastic leukemia. During metamorphosis, 78% of the patients had additional abnormalities, which in 68% of these cases comprised at least one of +8, +22q- or i(17q). Clones with additional abnormalities disappeared in eight cases, either spontaneously or in association with cytostatic therapy during the chronic or blastic phase. Involvement of chromosome #8, usually in the form of a trisomy, was found in 7 of 12 patients treated with busulfan, but was not found in any of the 10 hydroxyurea-treated patients, of whom 8 were splenectomized early during the chronic phase. Cells from the spleen, obtained by fine needle aspiration or splenectomy were cytogenetically examined in 18 cases during the chronic phase, but abnormalities in addition to the Ph were noted in only one patient, who was examined in the late chronic phase. The same abnormalities were present in bone marrow cells of this patient.

Inhibition studies of alkaline phosphatase in hard tissue-forming cells.

The effects of the alkaline phosphatase inhibitors levamisole and R 8231 on p-nitro-phenylphosphatase, inorganic pyrophosphatase and adenosine triphosphatase (ATPase) activities in dentingenically active odontoblasts were studied. The p-nitrophenylphosphatase and inorganic pyrophosphatase activities were inhibited, while 40% of the ATP-splitting enzyme activity remained under the assay condition used. This finding, togeather with earlier studies, indicates that at least two different phosphatase are active at alkaline pH in hard tissue-forming cells; on nonspecific alkaline phosphatase and one specific ATPase. The ATPase activity is uninfluenced by ouabain and ruthenium red and is activated by Ca-2+ ions.

The lateral periodontal cyst a histopathological and radiographic study of 32 cases

The lateral periodontal cyst is a developmental odontogenic cyst usually found in the premolar area of the lower jaw. The clinical, radiographic and histopathological features of 32 previously unreported lateral periodontal cysts were reviewed. In four cases the follow-up, which extended over several years, was also studied. Different theories of pathogenesis are discussed.

Initial treatment in multiple myeloma: no advantage of multidrug chemotherapy over melphalan‐prednisone

From October 1983 until December 1986, 164 patients with multiple myeloma stage II–III were included in a prospective randomized multi‐centre study comparing melphalan‐prednisone (MP) with multidrug chemotherapy (MDC). The patients comprised 77% of all newly diagnosed myeloma stage II–III cases reported from 18 hospitals covering the entire Health Care Region of Western Sweden (1.5 million inhabitants). Patients randomized to MP (29 stage II and 55 stage III patients) were given oral melphalan and prednisone every 6 weeks. For patients randomized to MDC, stage II patients (n= 25) were given VMCP every 4 weeks and stage III patients (n= 53) VBAP and VMCP alternately every 4 weeks.

Squamous cell carcinoma in a patient with oral lichen planus treated with topical application of tacrolimus

Oral lichen planus (OLP) is a chronic mucosal disorder of unclear etiology. The mainstay of therapy is topical use of steroids but other immuno-modulating therapies have also been tried. One such example is topical application of tacrolimus. Tacrolimus was in 2000 approved for treatment of atopic dermatitis, but in 2005 a boxed warning was included because of a potential risk of cancer development and for lack of long-term studies of the safety of the drug. The present study describes a patient who in 2003 was diagnosed with OLP and where treatment has included an intermittent use of tacrolimus. Five years after diagnosis, the patient developed a squamous cell carcinoma in the region where tacrolimus had been applied. The possible relationship between the use of tacrolimus and cancer development and rationale to include tacrolimus in OLP treatment is discussed.

The giant cell fibroma A review of 103 cases with immunohistochemical findings

This article reports a series of 103 cases of giant cell fibromas occurring in the oral mucosa. The commonest location was the gingiva, followed by the tongue and the buccal mucosa. The mean age of the patients was 27.7 years, and the median age 21 years. Microscopically, the tumors were characterized by the presence of large stellate or angular cells, which occasionally contained several nuclei. Immunohistochemical stains showed that the cells were vimentin-positive but negative for S-100 protein, cytokeratin, leukocyte common antigen, and neurofilament.

Mutations of the p53 gene in oral squamous-cell carcinomas from sudanese dippers of nitrosamine-rich toombak and non-snuff-dippers from the Sudan and Scandinavia

Using PCR‐SSCP/DNA sequencing methods, we analyzed 14 oral squamous‐cell carcinomas (OSCCs) and 8 pre‐malignant oral lesions from different Sudanese patients for prevalence of mutations in exons 5 to 9 of the p53 gene in relation to toombak‐dipping status. OSCCs (14 from Sudan, 28 from Scandinavia), and 3 pre‐malignant oral lesions from Sudanese non‐dippers were used as controls. A statistically significant increased incidence in mutations of the p53 gene was found in OSCCs from toombak dippers (93%; 13/14), as compared with those from non‐dippers in Sudan (57%; 8/14) and in Scandinavia (61%; 17/28) respectively. In OSCCs from dippers, mutations were found in exons 5 to 9, while in those from non‐dippers they were found in exons 5, 7, 8, 9, and no mutations were found in exon 8 in any of the OSCCs from Sudan. Certain types of mutations, however, were similar with respect to exposure to toombak. OSCCs from dippers showed 15 transversions, 9 transitions, 3 insertions and one deletion, compared with 7 transversions, 2 transitions and one deletion found in OSCCs from Sudanese non‐dippers, and 9 transversions, 17 transitions and 2 insertions found in those from non‐dippers in Scandinavia. No mutations were found in any of the non‐malignant oral lesions in relation to dipping or non‐dipping status. These findings suggest that (i) the use of toombak plays a significant role in induction of increased p53 gene mutations, (ii) mutations observed were similar to those induced by tobacco‐specific N‐nitrosamines (TSNAs) in experimental animal models and those already reported in toombak dippers, (iii) types of mutations associated with TSNAs were similar in the exposed and the control groups, (iv) a novel mutation in exon 6 was found in the OSCCs from toombak dippers, (v) the p53 exons 5 (codon 130), 6 (codons 190, 216) and 7 (codons 229, 249, 252) mutations are probable hot spots for toombak‐related OSCCs. Further studies are necessary to validate the increased incidence and exon locations of the p53‐gene mutations as a biomarker of malignant transformation in populations in which the oral use of tobacco is habitual. Int. J. Cancer 81:527–534, 1999.

The immunohistochemical expression of DNA-PKcs and Ku (p70/p80) in head and neck cancers: relationships with radiosensitivity

PURPOSE The DNA-PK complex is one of the major pathways by which mammalian cells respond to DNA double-strand breaks induced by ionizing radiation. This study evaluated the relationship between the immunohistochemical expression of the individual components of DNA-PK and cellular radiosensitivity in head and neck cancers. METHODS AND MATERIALS Biopsies from patients with previously untreated squamous cell carcinomas of the head and neck were assessed for inherent tumor radiosensitivity measured as the surviving fraction at 2 Gy (SF2) using a soft agar clonogenic assay. Paraffin-embedded tumor material from 64 successfully grown specimens was immunohistochemically stained for expression of DNA-PKcs and Ku (p70/p80). The same tumor material was previously analyzed for the immunohistochemical expression of p53. RESULTS A significant correlation was found between the degree of expression of DNA-PKcs and Ku (p70/p80) (r = 0.55, p<0.001). There were no overall significant differences in the levels of expression of DNA-PKcs and Ku (p70/p80) in tumors from patients of either sex, different sites, histologies, and stages. No relationship was found between SF2 and the expression of either DNA-PKcs (r = 0.22, p = 0.081) or Ku (p70/p80) (r = 0.064, p = 0.62). Comparison with previous immunohistochemical characterization showed no significant correlations between the expression levels of p53 and either DNA-PKcs (r = 0.093, p = 0.46) or Ku (p70/p80) (r = -0.17, p = 0.17). CONCLUSIONS This study suggests that determining the immunohistochemical expression of DNA-PK in head and neck cancers from multiple sites does not have a role as a predictive assay of tumor in vitro radiosensitivity.