Helmer Søgaard

Methotrexate induced liver cirrhosis Studies including serial liver biopsies during continued treatment

Seven hundred and sixty‐four liver biopsies were performed in 328 psoriatics on treatment with methotrexate or being considered for systemic treatment either with methotrexate or with psoralens and long‐wave ultraviolet light. The diagnosis of cirrhosis was established histologically in twenty‐one patients. Two patients had cirrhosis in their premethotrexate biopsy and were not given methotrexate. The remainder all showed no signs of cirrhosis or fibrosis in their premethotrexate biopsy. The difference between the methotrexate treated psoriatics and the premethotrexate group was highly significant. Among thirty‐nine patients treated for more than 5 years, ten developed cirrhosis (25.6%). Almost all patients were on a divided dose intermittent oral dosage schedule. The cumulative dose of methotrexate, when cirrhosis was first found, ranged from 590 to 8105 mg, with an average dosage of 2200 mg. Other factors contributing to cirrhosis in this study seem to be previous treatment with arsenic, a previous intake of alcohol, and lowered renal function.

Improvement of psoriasis by a topical vitamin D3 analogue (MC 903) in a double-blind study

The effect of the non‐calciotropic vitamin D3 analogue MC 903 on psoriasis vulgaris was assessed in a double‐blind, placebo controlled trial in 30 patients. Lesions on one side of the body were treated for 6 weeks with a cream containing 10 μ/g, 33 μg//g or 100 μg/g MC 903 and lesions on the other side were treated with the cream base alone, according to a randomized design. Nine of the 10 patients in each treatment group completed the study. MC 903 cream gave a statistically significant decrease in erythema, thickness and scaling of the lesions, compared with the control. Overall assessment of psoriasis after 6 weeks showed moderate or excellent improvement in two of nine patients treated with 10 μg/g, in five of nine patients treated with 33 μ/g, and in seven of nine patients treated with 100 μ/g MC 903. Placebo treatment showed a moderate improvement in only one of the 27 patients. The histopathological picture of the psoriatic lesions corresponded with the clinical changes. The patients reported no adverse reactions, and laboratory tests did not show any significant changes; in particular there was no change in serum calcium levels. These results suggest that the vitamin D3 analogue MC 903 is an effective and safe topical treattnent for psoriasis.

Cancer of the nasal cavity and paranasal sinuses. A clinico-pathological study of 277 patients.

In the period 1963-1991, a total of 277 consecutive patients with malignant tumours of the nasal cavity and paranasal sinuses were treated at Aarhus University Hospital. The major histological types included squamous cell carcinoma (46%), lymphoma (14%), adenocarcinoma (13%), and malignant melanoma (9%). Kaplan-Meier estimates of 5-year corrected survival (death from cancer) showed the best prognosis for adenoid cystic carcinoma (87%), adenocarcinoma (65%) and lymphoma (56%), and the poorest prognosis for undifferentiated carcinoma (17%) and malignant melanoma (24%). The 5-year corrected survival for squamous cell carcinoma was 35%. Of the 180 patients with treatment failure, the vast majority occurred locally (n = 166); a minor proportion was regional (n = 23) or distant (n = 30). For the 195 patients with carcinoma, the following parameters were of statistical prognostic significance (5-year corrected survival): histological differentiation (moderate-well 65% vs. poor 22%), primary T-site (nasal cavity 56% vs. maxillary antrum 39% vs. other sinuses 24%), tumour stage (T2 68% vs. T3 37% vs. T4 29%), nodal stage (N0 48% vs. N1-3 21%), treatment (radiotherapy + surgery 56% vs. radiation alone 35%).

The value of amino-terminal propeptide of type III procollagen in routine screening for methotrexate-induced liver fibrosis: a 10-year follow-up.

Background  Methotrexate (MTX) ‐induced liver damage is an important complication in patients treated with this drug for skin disease. Reliable non‐invasive monitoring tests would have considerable importance.

Malignant parotid tumors in 110 consecutive patients: Treatment results and prognosis

The UICC 1987 classification system was used to retrospectively analyze the treatment results and prognostic factors in 110 consecutive patients. All of the patients had malignant parotid tumors which had been diagnosed and treated during the period from 1970 to 1986. Treatment consisted of surgery, radiotherapy, or a combination. Malignant mixed tumors were seen in 28% of the patients, mucoepidermoid tumors in 18%, adenoid cystic tumors in 15%, acinic tumors in 13%, undifferentiated tumors in 11%, adenocarcinomas in 10%, and other types in 5%. Ten‐year corrected survival rate was 52%, and significant differences of survival were found between: 1. patients with disease stages I through IV (I: 85%; II: 69%; III: 43%; IV: 14%); 2. those with local tumor extension (34%) and without local tumor extension (79%); 3. patients with facial nerve palsy (0%) and without facial nerve palsy (57%); and 4. those with low‐ or intermediate‐grade malignant tumors (69% combined) and those with high‐grade malignant tumors (30%). After primary treatment, 45% of the patients were cured, and, additionally, 22% were salvaged after local or neck node recurrences.

Treatment of mycosis fungoides with recombinant interferon‐αza2 alone and in combination with etretinate

Eleven patients with mycosis fungoides (MF) were treated with recombinant alpha‐intcrfcron (rIFN‐α2a2) in combination with etretinate (seven patients) or alone. One patient, who also received etretinate, went into complete remission and remained without signs of MF after 18 months. Six patients experienced partial remission; one of these was treated with rIFN‐α2a alone and was clinically in complete remission, but had still a pteomorphic skin infiltrate. Two patients were non‐evaluable, and two stopped therapy due to progressive disease. Five patients discontinued therapy due to side‐effects although three had partial remission of their disease. Only four patients received 12 months therapy. The study shows that rIFN‐α2a in combination with etretinate or alone can induce remission of MF.

Epidermoid carcinoma of the larynx. VI. Histologic grading in the clinical evaluation.

A multifactorial microscopic grading of malignancy was performed on a clinically well examined series of 129 patients with laryngeal carcinoma. The microscopic score was statistically significantly correlated to the frequency or regional lymph-node metastases and to the death rate. It afforded important supplementary information for the T-classification and for the prognosis. Microscopic grading is an essential supplement to the clinical evaluation of risk groups.

Methotrexate-induced liver cirrhosis: a follow-up

Studies on serial liver biopsies from 25 patients with methotrexate-induced liver cirrhosis, taken from 1 to 13 years after cirrhosis was established, confirm that this type is not of aggressive nature. When evaluated blind no progression was found in most of the later biopsies. Alcohol and previous use of hepatotoxic drugs such as the combination of arsenics and vitamin A seem to have been contributing factors to cirrhosis formation.

Histopathologic, stereologic, epidemiologic, and clinical parameters in the prognostic evaluation of squamous cell carcinoma of the oral cavity.

Prognostic indicators that could assist in a more precise selection of patients with oral cancer for differentiated therapy would be clinically valuable.

Methotrexate-lnduced Liver Cirrhosis

Background : Methotrexate (MTX) may induce liver damage, which in some psoriatics will lead to fibrosis or cirrhosis. Studies performed 10 years ago on 25 patients with MTX-induced l