Disease severity and outcome in thymoma myasthenia gravis: a long-term observation study.

Thymomas occurring in myasthenia gravis (MG) are usually of the cortical subtype and are usually treated by thymectomy. However, the factors that influence MG outcome in thymoma MG patients are not known. In a long-term study, MG severity and treatment was observed in 24 thymoma and 24 non-thymoma MG patients for up to 30 years, and the occurrence of muscle autoantibodies was assayed. The rate of complete stable remission was low and did not differ between the two groups. There was no significant difference in MG severity between thymoma and non-thymoma MG patients at any time during the study. Titin and ryanodine receptor (RyR) antibody occurrence was significantly higher in thymoma MG patients. Four thymoma (all titin and RyR antibody positive) and two non-thymoma (both titin and one RyR antibody positive) MG patients died from MG-related respiratory insufficiency. Seventy percent of thymoma and 75% of non-thymoma MG patients were treated with immunosuppressive drugs. The number of patients who received plasmapheresis did not differ in those who were treated because of acute MG deterioration, irrespective of planned surgery.This study shows equal MG severity and outcome in thymoma and non-thymoma MG, but the presence of RyR antibodies in thymoma MG and titin/RyR in non-thymoma MG indicates a less favorable prognosis.

Thymectomy in nonthymoma early-onset myasthenia gravis in correlation with disease severity and muscle autoantibodies.

OBJECTIVE: To study the clinical effect of thymectomy in a well-defined early-onset MG subgroup and to correlate it to MG severity, the presence of circulating muscle autoantibodies, and the need for pharmacological treatment in a long-term setting. METHODS: Fifty-two consecutive AChR antibody-positive early-onset MG patients (34 thymectomized and 18 nonthymectomized) were included. Severity was assessed and the pharmacological treatment monitored on a yearly basis, starting from the year of MG onset, for 5, 10, 15, and 20 consecutive years; AChR, titin, and RyR antibodies were assayed. RESULTS: In the four follow-up groups, MG severity was significantly higher in nonthymectomized compared to thymectomized MG patients. The postthymectomy MG improvement was significant and persistent. There were 21/34 remissions in thymectomized patients and only 4/18 in the nonthymectomized group. Patients with initially high or low AChR antibody concentration had a similar thymectomy outcome. Only 6 patients had titin antibodies, and none had RyR antibodies. CONCLUSION: The present study indicates a benefit of thymectomy in early-onset MG. The muscle autoantibody concentration does not influence the outcome of thymectomy in early-onset MG.

Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis.

Thymectomy is still widely carried out in myasthenia gravis (MG) patients, but its role, especially in late-onset MG patients, is not established. These patients are immunologically heterogeneous, some with thymoma-like and others with early onset-like features. We evaluated whether any therapeutic effects of thymectomy correlate with the presence of non-acetylcholine receptor (AChR) muscle antibodies. The severity of MG, and titin and ryanodine receptor (RyR) antibodies, were assessed yearly starting from MG onset in 21 thymectomized and 22 non-thymectomized AChR antibody positive late-onset MG patients, who were followed for 2, 3 and 5 years. Clinical or pharmacological remission were seen in six of 11 titin antibody negative but none of the 10 titin antibody positive thymectomized patients, however, the non-thymectomized cases showed an opposite trend. The three MG-related deaths were all in patients with titin antibodies. There was no significant difference in MG severity between thymectomized and non-thymectomized patients; 2 years after MG onset, both groups were significantly improved. This study showed no dramatic benefit from thymectomy in late-onset MG in general. Any limited improvement appeared less likely in cases with titin and/or RyR antibodies.

p53 mutations in defined structural and functional domains are related to poor clinical outcome in non-small cell lung cancer patients.

The prognostic value of p53 status in non-small cell lung cancer has been investigated in 148 patients with clinical stage I-IIIB disease. Tumor tissues were examined for mutations in exons 4-9, with emphasis on defined structural and functional domains. Eighty-four mutations were detected in 83 (54%) of the patients. Eighty-eight percent of the mutations were within exons 5-8, and 12% of the mutations were within exons 4 and 9. Missense mutations occurred in 67% of the tumors, and 30% were null mutations (10% stop mutations, 15% frameshift mutations, and 5% splice site mutations). Patients with mutations in p53 had a significantly higher risk for lung cancer-related death and for death from all causes than those with wild-type p53 [hazard ratio (HR) = 2.09 and 95% confidence interval (CI) = 1.20-3.64 and HR = 1.69 and 95% CI = 1.06-2.70, respectively]. Mutations in p53 related to even still poorer lung cancer-related prognosis were found at the following locations: (a) exon 8 (HR = 3.5; 95% CI, 1.59-7.71)]; (b) the structural domains L2 + L3 (HR = 2.36; 95% CI, 1.18-4.74), and (c) codons involved in zinc binding (HR = 11.7; 95% CI, 3.56-38.69). Together, the biologically functional group of severe flexible mutants (codons 172, 173, 175, 176, 179, 181, 238, 245, and 267) and severe contact mutants (248, 282) were significantly related to shorter lung cancer-related survival (HR = 4.16; 95% CI, 1.93-8.97). Squamous cell carcinoma was the dominant histological type in tumors involved in poor prognosis in exon 8 (HR = 3.19; 95% CI, 1.07-9.45). These results indicate that mutations in defined structural and functional domains of p53 may be useful molecular biological markers for prognosis and treatment strategy in non-small cell lung cancer patients.

Dieulafoy's vascular malformation: role of endoscopic ultrasonography in therapeutic decision-making.

BACKGROUND: Dieulafoy's vascular malformation may cause severe, potentially life-threatening gastrointestinal bleeding. Endoscopic diagnosis may be difficult because of minute mucosal lesions, and additional intramural abnormalities are usually not encountered. Endoluminal high-frequency ultrasonography is a new modality for imaging intramural and perivisceral structures. METHODS: We report two cases of recurrent severe gastric bleeding in which different endosonographic modalities were used in the diagnosis of Dieulafoy's malformation, and the impact of endosonography on therapeutic strategy is discussed. In the first case a radial-scanning 7.5/12-MHz echoendoscope and a linear 20-MHz miniature probe were applied for B-mode imaging in a stable-state patient who had undergone previous endoscopic sclerotherapy, and arterial flow signals from the small intramural lesion were recorded using a 10-MHz transendoscopic pulsed Doppler probe. In the other case urgent endosonography was performed shortly after a bleeding episode, disclosing an aberrant large-calibre artery entering the gastric wall with a long submucosal branch. RESULTS: Both patients were successfully operated on with a transabdominal approach. CONCLUSION: Endosonography is a quick and safe diagnostic method and should be considered when vascular malformations are suspected as the cause of gastric bleeding.

Chronic cold agglutinin disease of the "idiopathic" type is a premalignant or low-grade malignant lymphoproliferative disease.

We investigated the clinical, pathological, and immunological features of "idiopathic" cold agglutinin disease (CAD) in a population-based study. Fourteen patients were studied, giving a prevalence of about 14 per million with a mean age of 75 years. Haemolysis was present in all cases, but only eight patients had clinical symptoms of peripheral haemagglutination. Serum electrophoresis, immunofixation, morphological bone marrow evaluation, and flow cytometric immunophenotyping were used to detect any monoclonal lymphoproliferative disorder. Flow cytometry seemed to be a sensitive way to demonstrate a clonal B-cell proliferation. Some evidence of clonality was found in 13 patients, and a clonal lymphoproliferative disease was documented by flow cytometry or biopsy in 10 out of 11 patients. We conclude that CAD is a symptom-producing monoclonal lymphoproliferative disorder in nearly all patients.

[Pulmonary changes as primary manifestations in Waldenström macroglobulinemia]. / Lungeforandringer som primaer manifestasjon av Waldenströms makroglobulinemi.

We describe a patient with a 19-year history of lymphocytic lung infiltrations. A diagnosis of lymphocytic interstitial pneumonitis was made in 1982 after an open lung biopsy, but in 1995 a comprehensive re-evaluation led to the diagnosis of Waldenström's macroglobulinaemia with primary bronchopulmonary involvement. It could also be demonstrated by polymerase chain reaction and immunological techniques that this disease had been present since before 1982. In 1995 it was still difficult to demonstrate bone marrow involvement, even with new and sensitive methods. We discuss some diagnostic problems of organ manifestations of uncommon systemic diseases. Pulmonary manifestations of Waldenström's macroglobulinaemia or other diseases of the immune system should be considered in patients with atypical lung disorders.

Renal effects of maintenance low-dose cyclosporin A treatment in psoriasis.

The renal effects of low-dose cyclosporin A (CsA) treatment in severe psoriasis was investigated in 10 patients treated with a mean CsA dose of 3.23 (range 1.94-4.10) mg/kg/day for 12 months. The psoriasis area and severity index was reduced by 63-76%. Ambulatory GFR (iothalamate-125I), ERPF (hippuran-131I), RVR and MAP were examined at 3-months intervals. A control renal biopsy was performed shortly before treatment start and a second biopsy was taken after 12 months of therapy. GFR was slightly but significantly reduced after 6 and 9 months; after 12 months the decrease was not significant (121.0 +/- 7.6 versus 115.2 +/- 7.8 ml/min/1.73M2, P > 0.10). After 12 months serum creatinine increased from 82 +/- 4 to 94 +/- 7 mumol/litre (P < 0.05), while an insignificant increase of ERPF was seen and FF decreased from 0.29 +/- 0.01 to 0.26 +/- 0.01 (P < 0.05). MAP remained unchanged. GFR and serum creatinine correlated significantly within each 3-month interval. A slight de novo interstitial fibrosis was seen in the second biopsy in 4 of 10 patients receiving a mean CsA dose of 3.2-4.1 mg/kg/day. In three of these patients a concomitant rise in serum creatinine was seen. In conclusion, low-dose CsA was associated with reversible fall in GFR and potentially progressive structural changes not always accompanied by corresponding functional alterations. One should consider reducing the daily dose of CsA to 3.0 mg/kg bodyweight or less in CsA therapy up to 1 year.

Prognostic impact of EGF-receptor in papillary thyroid carcinoma.

In this study of papillary thyroid carcinomas, immunopositivity for EGF-receptor was present in a majority of the cases (96%), although different staining patterns were observed. A distinct membraneous reaction was found in 46%, whereas cytoplasmatic positivity of various degrees was present in 90% of the cases. Strong cytoplasmic EGF-receptor staining was significantly associated with extra-thyroidal growth of the primary tumour (P = 0.009), and it was furthermore related to decreased recurrence free survival (P = 0.006). Membraneous EGF-receptor staining was not associated with recurrence free survival or patient survival. Multivariate Cox analysis showed that lymph node metastases (P = 0.0009) and cytoplasmic EGF-receptor staining (P = 0.0048) was independent indicators of tumour recurrences in this group of surgically treated papillary thyroid carcinomas.

Serum vitamin D metabolites and calcitriol receptor concentration in parathyroid tissue in primary hyperparathyroidism.

Vitamin D metabolites in serum and calcitriol receptor concentration in parathyroid tissue were examined in 52 patients operated on for primary hyperparathyroidism. The calcitriol receptor levels were not different in parathyroid adenomas (mean 224 fmol/mg of protein, range 29-509, N = 43), normal parathyroid tissue (mean 245, range 31-690, N = 20), and primary parathyroid hyperplasia (mean 172, range 46-477, N = 9). Preoperative serum levels of calcitriol concentration correlated inversely to the calcitriol receptor in normal parathyroid tissue in patients with adenoma (r = -0.57, N = 17, p = 0.017), but no such correlation was found in the corresponding adenomas (r = 0.14, p = 0.59). In 31 patients in whom both pre- and postoperative vitamin D metabolite analyses were carried out, 23 had lower calcitriol postoperative concentrations compared to preoperative values (p = 0.012, sign test). No change was found in the other vitamin D metabolites postoperatively. By multiple regression analysis calcitriol concentration in serum was inversely correlated to the serum concentration of urea and phosphate (p = 0.003). We conclude that calcitriol may influence calcitriol receptor expression in normal parathyroid tissue, but not in adenomatous parathyroid gland. Furthermore, serum calcitriol was correlated to the renal function, and phosphate level, and in most patients the calcitriol concentration was lower after the operation.

Is Lauren's histopathological classification of importance in patients with stomach cancer? A national experience. Norwegian Stomach Cancer Trial.

This study was performed to investigate the association between Lauren's histopathological classification system and different clinico-pathological characteristics in patients with gastric carcinoma. We revealed that the percentage of intestinal type tumour (ITT) increased with advancing age (52% in patients less than 60 years compared to 73% of octogenarians (P less than 0.001)). The male:female ratio was 1.7 for ITT versus 1.3 for diffuse type tumour (DTT (P = 0.12)). ITT was more common in proximally (fundus) localized tumours than in distal lesions (77% vs 65%; P less than 0.05). The proportion of patients with ITT decreased with advancing stages of the disease (70% in stage I and II vs 52% in stage IV (P less than 0.0001)). More patients with DTT had tumour infiltration in the resection margin (21% vs 9%; P less than 0.001). Intestinal metaplasia was found in 48% of those with ITT compared with 28% of those with DTT (P less than 0.001). No association was found between Lauren's classification and the ABO blood group or between the tumour types and infiltration in lymphatic or blood vessels. We conclude that gastric adenocarcinoma occurs in at least two different biological forms and that differentiation between the two is of relevance for treatment.

Prognostic importance of various clinicopathological features in papillary thyroid carcinoma.

The influence of various pathological features on tumour recurrences and cancer deaths has been studied in 173 consecutive cases of surgically treated papillary thyroid carcinoma recorded in 1971-1985. During the follow-up (median 7.3 years), 18.6% of the 161 radically treated patients had recurrent disease, and 8.7% died of thyroid cancer. In the univariate life-table analysis, recurrence-free survival was significantly related to age, pTNM category, tumour size, presence of certain growth patterns, tumour necrosis, tumour infiltration in surrounding thyroid tissue and thyroid gland capsule, lymph node metastases, presence of extra-nodal tumour growth and number of positive lymph nodes, whereas only tumour diameter, thyroid gland capsular infiltration and presence of extra-nodal tumour growth remained as significant prognostic factors in the multivariate analysis. Regarding thyroid cancer deaths, sex, age, pTNM category, radicality of surgical treatment, tumour diameter, macroscopic appearance, cellular atypia, tumour necrosis, thyroid gland capsular infiltration, vascular invasion, extra-thyroidal extension and lymph node metastases were all significant variables in the univariate analysis. However, only sex, age, radicality of surgical treatment and vascular invasion were found to be significant predictors of thyroid cancer deaths in the final multivariate Cox model, whereas cellular atypia and necrosis showed a borderline significance. Our study thus documents the independent importance of certain histological features for morbidity and mortality in surgically treated cases of papillary thyroid cancer.

Differentiated thyroid carcinomas: the relevance of various pathological features for tumour classification and prediction of tumour progress.

In this series of 263 surgically treated cases of thyroid cancer, 12% were finally classified as benign lesions after histopathological review. Difficulty in the assessment of tumour capsule invasion in follicular neoplasms was the most frequent cause of diagnostic error. Squamous metaplasia, clusters of ground glass nuclei and psammoma bodies were found to be the most specific discriminators between papillary and follicular carcinomas. Among papillary carcinomas, tumour diameter above 30 mm, thyroid capsular invasion and regional lymph node metastases were found to be significant prognostic factors according to survival analyses. Of additional practical importance, our results indicate that tumour infiltration in the thyroid capsule should be reported as a marker of early extra-thyroidal extension.

[Necrotizing sialometaplasia of the hard palate]. / Nekrotiserende sialometaplasi i den harde gane.

Necrotizing sialometaplasia is a benign, self-healing disease of salivary gland tissue and is usually confined to the minor salivary glands of the hard palate. It has clinical and histological features that simulate malignancies such as mucoepidermoid and squamous cell carcinomas. Wrong diagnosis has led to unnecessary mutilating surgical procedures. The etiology of the disease is unknown, but an ischaemic process is considered most likely. We describe two patients with necrotizing sialometaplasia, one with midline and one with bilateral symmetrical affection of the hard palate.

Increased content of chromium and nickel in lung tissues from patients with bronchial carcinoma.

Epidemiological studies have shown that occupational exposure to certain chromium and nickel compounds is followed by an increased lung cancer incidence. However, few data exist on the content of these metals in lung cancer patients in general. In the present study, central and peripheral lung tissue, bronchial tissue and hilar lymph nodes were collected from 20 patients with bronchial carcinoma and 21 control individuals, and the tissue concentration of chromium and nickel was measured by use of atomic absorption analysis. Increased levels of both metals were found in cancer patients as compared to controls. Lung tissue concentration of chromium was two-fold increased, while the bronchial wall content of nickel was three times the level in control individuals. Smokers showed a dose-related increase in the deposition of both chromium and nickel. Furthermore, in cancer patients an inverse relationship between smoking and the tissue level of chromium in regional lymph nodes was found, possibly indicating a depressive effect on pulmonary clearance mechanisms. Our results emphasize the possible role of small amounts of chromium and nickel as agents in bronchial carcinogenesis, unrelated to occupation and probably related to tobacco smoking.

[Fine needle aspiration cytology of the breast. A simple method?]. / Finnålsaspirasjonscytologi fra mamma. En enkel metode?

During the period 1981-85, 3,743 fine-needle aspiration cytologies of breast tissue from 3,188 patients were reported by the Gade Institute, Department of pathology. Subsequent histologic examination was performed in the case of 798 patients. Among 421 histologically proven carcinomas after previous fine-needle aspiration, there were no false positive and 13 false negative cytological diagnoses. The specificity was 100% and, depending on the criteria used, the sensitivity 77.9 or 96.4%. Altogether 223 doctors performed the aspirations. This high number was probably the main reason for an unacceptably high proportion of inadequate smears. In experienced hands the proportion of inadequate smears was less than 4-7% in patients with carcinomas.

Balloon cell melanoma mimicking clear cell carcinoma.

Balloon cells may occur in both benign nevi and malignant melanomas. Sometimes they dominate the histological appearance and cause difficulties in biopsy interpretation. There are no specific clinical characteristics. We report a metastatic balloon cell melanoma where the primary tumour was not identified and the histological appearance mimicked that of a clear cell renal carcinoma.

[Smoking prevention. Courses on smoking prevention conducted at a regional hospital]. / Røykeavvenning. Røykeavvenningskurs ved et regionsykehus.

We present the results of four smoking cessation courses conducted during the period 1986 to 1988 and including 105 persons. 68 women and 37 men participated in weekly lessons, three prior to and two after a predetermined quit-smoking day. Physicians presented information and smoking cessation techniques, the latter based on cognitive behavioural modification. At one year follow-up 27% of the participants had stopped smoking and 49% had reduced smoking consumption. More intensive follow-up and pharmacological treatment might reduce the relapse rate further.

Analyses of chromium and nickel in human pulmonary tissue. Investigations in lung cancer patients and a control population under special consideration of medical expertise aspects.

After inhalative occupational exposure to certain compounds containing nickel and chromium (mostly over many years), an accumulation of these metals may occur in the lung tissue. This is of particular importance, both from a toxicological point of view and with regard to expert reports, since certain nickel and chromium compounds may induce lung cancers. In the context of this study, samples of pulmonary tissue from 34 deceased persons from the Bergen area (Norway) were analysed by atomic absorption spectrometry with regard to their content of chromium and nickel. The deceased comprised 21 men and 13 women. In 15 cases, death resulted from lung cancer; in the other 19 deceased, there was no indication of a malignant disease of the airways. The concentrations of nickel found in the lung tissue do not differ between patients with lung cancer and patients with healthy lungs. On the other hand, the concentration of chromium in the pulmonary tissue in the patients who had died of lung cancer and who had all been inhalative smokers, are higher (statistically significant) than in the nonsmokers or in those with healthy lungs. An accumulation of these two metals in the tumor matrix could not be detected. Both the average nickel and the average chromium concentrations were higher in the persons who had probably been exposed occupationally. Considering the present state of scientific knowledge, the aspects relevant to expert reports which result from the analyses of metals in the pulmonary tissue are discussed.

Large intramuscular spindle-cell lipoma. With review of the literature. A case report.

A case of a large spindle-cell lipoma in an intramuscular (subfascial) localization is reported. The tumour occurred in a 58-year-old male patient and was localized subfascially in his left deltoid muscle. The tumour measured 20 X 8 X 8 cm; its weight was 780 grams. After initial biopsy, the tumour was extirpated. Microscopically, the tumour tissue consisted of mature fat cells and spindle-cell areas in varying amounts, constituting a typical appearance of a spindle-cell lipoma. There were no histological signs of malignancy. Especially, no areas of liposarcoma differentiation were detected. The patient is well, with no signs of recurrence, one and a half years after the operation. We have reviewed the literature on spindle-cell lipoma, and we believe this is the first example of this neoplasm to be reported in an intramuscular (subfascial) localization.