Csilla András

Cancer-associated myositis: clinical features and prognostic signs.

Abstract: Idiopathic inflammatory myositis is characterized by progressive weakness of the proximal muscles. There is a higher risk of malignancy than in the normal population. The aim of this study was to evaluate the frequency of malignancy among 251 myositis patients. We also compared clinical and immunological characteristics of cancer‐associated myositis with primary myositis. There were no malignancies among polymyositis, overlap, or juvenile myositis patients. Twenty‐two of ninety dermatomyositis patients also had a malignant disease. Patients with cancer‐associated dermatomyositis were significantly older than primary myositis patients and had more severe cutaneous and muscle symptoms. Dysphagia and diaphragmatic involvement were more frequent among cancer‐associated patients, while extramuscular features were less frequent. After successful treatment of the malignancy, we were able to manage myositis symptoms. One‐year survival rate was significantly better in primary dermatomyositis patients. The subset of cancer‐associated myositis differs from primary myositis in many aspects of its clinical and immunological features. Prognosis and life expectancy in cancer‐associated myositis patients is determined by the underlying malignant disease. Therefore, age‐ and sex‐specific examinations for detection of an underlying malignancy are important in the management of patients with dermatomyositis.

Paraneoplastic rheumatic syndromes

Paraneoplastic symptoms caused by a malignancy but not directly related to tumour invasion are the result of a wide variety of tumour-derived biologic mediators, such as hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Recognition of paraneoplastic syndromes is important, as it may lead to an early diagnosis of cancer. On the other hand, the clinical severity of the symptoms can be used as a guide to the extent of response to underlying tumour therapy. The quality of life of the patient is affected, therefore the palliative treatment of paraneoplasia is very important.

Hypothyroidism and thyroiditis after therapy for Hodgkin's disease

During the follow-up of thyroid function of 151 patients with Hodgkin’s disease in complete remission for at least 1 year, 26 cases of subclinical, 12 cases of manifest clinical hypothyroidism and 2 cases of hyperthyroidism (Graves-Basedow disease) were confirmed. Thyroid dysfunction was more frequent in patients who had undergone mantle or neck radiotherapy. Hypothyroidism was most often revealed from the 6th year on following radiotherapy. Thyroid autoantibody positivity was found to be more frequent in patients with thyroid dysfunction, and conversely, thyroid dysfunction was more frequent among the 28 patients with autoantibody positivity. Ultrasound examination and fine needle aspiration cytology of the thyroid confirmed thyroiditis in 96% of the patients with antibody positivity. No relationship was found between thyroiditis and the form of treatment for Hodgkin’s disease. We have found that both neck irradiation and thyroiditis may play a role in the increased number of thyroid dysfunction in patients treated for Hodgkin’s disease. Thyroiditis is not caused by neck radiotherapy but may be the result of immune regulation disorders in Hodgkin’s disease. For substitution or isohormone therapy, levothyroxine is suggested for use. We suggest that examination of the thyroid should be performed at least once a year during the follow-up of Hodgkin’s disease patients.

Investigation of β-catenin and E-cadherin expression in dukes B2 stage colorectal cancer with tissue microarray method. Is it a marker of metastatic potential in rectal cancer?

Abstractβ-catenin and E cadherin are both membrane-associated proteins which are essential regulators and providers of cellular adhesion. In the metastatic cascade of malignant tumours, detachment of tumour cells from each other is a very important step. It has been shown in several tumour types, that reduced expression of these proteins is important. The aim of our study was to clarify the expression profile of these proteins, and correlate the findings with the metastasizing potential of early stage colon and rectal cancers. Formalin fixed and paraffin embedded samples from 79 Dukes B2 stage colorectal cancer were examined using a tissue microarray approach. The expression of β-catenin and E-cadherin proteins was determined immunohistochemically. Our findings indicated that there is a tendency for metastatic spread in cases when membranous expression of β-catenin is lost (p = 0.062). Similarly metastases in negative cases developed more rapidly, than in positive ones (p = 0.05). Survival rate was worse in the negative cases. The risk of metastasis in rectal cancer was significantly higher in the β-catenin membranously negative than positive groups (p = 0.024) and in case of β-catenin nuclear expression the risk was also higher (p = 0.047). Reduced E-cadherin expression also correlated with development of metastatic disease, but this association was statistically not significant. The immunohistochemical analysis of 79 cases shows that in Dukes B2 stage colorectal tumours clarification of β-catenin and E-cadherin expression patterns is reliable for predicting the metastatic potential of early stage rectal cancer and hence the method may have relevant implications in the therapeutic management of these cancers.

Prostate cancer underlying acute, definitive dermatomyositis: successful treatment with radical perineal prostatectomy

The idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by chronic inflammation leading to progressive weakness of the proximal muscles. In 7–66% of cases of adult dermatomyositis different malignant tumours can promote the difficult cascade mechanisms at the cell level, leading to rapid weakness of skeletal muscles [1]. We report on a patient with all characteristic signs of acute, severe dermatomyositis associated with a low-grade, low-stage prostate cancer cured by radical perineal prostatectomy.

The effect of metoprolol alone and combined metoprolol–felodipin on the digital microcirculation of patients with primary Raynaud's syndrome

OBJECTIVES Calcium channel inhibitors have beneficial impact on microcirculation, but beta-blocker effect is controversial. Clinicians still do not agree on beta-blocker combination with other treatments in the management of impaired microcirculation. The aim of the present study was to describe the effects of beta-blocker metoprolol monotherapy and combined with calcium channel inhibitor felodipin on digital microcirculation in primary Raynauds syndrome. METHODS We enrolled in this study 46 patients suffering from both hypertension and primary Raynauds syndrome. Fifteen patients were treated with beta-blocker monotherapy (metoprolol), 13 received combined beta-blocker and calcium channel blocker therapy (felodipin and metoprolol), while 18 patients without any medications served as controls. Measurement of digital microcirculation was carried out with laser Doppler scanner. RESULTS AND CONCLUSIONS Our investigation concludes that the concurrent administration of beta-blockers with calcium channel inhibitors positively reduces symptoms in patients suffering from Raynauds syndrome.

Increased mean platelet volume in primary Raynaud's phenomenon

We hypothesized that mean platelet volume (MPV), a reliable marker of platelet activation, might be elevated in primary Raynauds phenomenon (PRP) even if there was no thrombotic complication in our subjects. In this retrospective-cohort study, we examined the clinical value of MPV in 200 patients with PRP and 116 clinical controls, and measured MPV and platelet P-selectin (CD62P) in all study participants. We also evaluated the effect of age, gender, and disease duration on these platelet activation markers in PRP. MPV and CD62 positivities were significantly (p < 0.001) elevated in patients with PRP compared with controls. These differences retained when patients and controls were analyzed according to age, gender, and the disease duration. In logistic regression analysis, MPV (OR: 15.8, 95% CI: 8.14–30.64, p < 0.001) and CD62P (OR: 11.3, 95% CI: 4.85–26.12, p < 0.001) were found to be independently associated with PRP. In conclusion, increased MPV is independently related to PRP, and its level was not influenced by age, gender, and the duration of PRP.

A new mutation in Muir-Torre syndrome associated with familiar transmission of different gastrointestinal adenocarcinomas

Hereditary Nonpolyposis Colorectal Carcinoma (HNPCC) is the most frequent inherited disease which can lead to the development of tumors in the colon and other locations. Its genetic basis is related to the germline mutation of the Mismatch Repair (MMR) genes. Muir-Torre syndrome is considered one of the subtypes of this disease, in which the HNPCC tumor spectrum is frequently associated with sebaceous carcinoma of the skin or keratoacanthoma. A 57 years old male patient is presented with a mucinous carcinoma of the caecum and an adenocarcinoma of the pancreas head. A malignant sebaceous carcinoma was removed from his left neck area. His family history was significant for two cases of colon carcinoma, two cases of stomach cancer and a case of metacron endometrial and skin tumor as well. Both the colon carcinoma and the skin tumor proved to be microsatellite unstable. An Arg>Pro switch missense mutation was found in codon 265 of the hMLH1 gene. This error was found in 4 other members of his family. The detected genetic alteration was considered pathogenic and was not published yet in English literature. The significance of this particular case is the rare tumor association in a patient with Muir-Torre syndrome (MTS). In cases of sebaceous skin lesions, evaluation of family history is of utmost importance in the early detection of HNPCC and in the follow up care of family members with the particular mutation.

Correlations between clinicopathological parameters and molecular signatures of primary tumors for patients with stage T3n0 colorectal adenocarcinomas: a single center retrospective study on 100 cases.

BACKGROUND/AIMS To examine the clinical and protein expression characteristics of tumor tissues for prediction of prognosis in colorectal cancer (CRC). METHODOLOGY We retrospectively analyzed the clinicopathological data of patients with stage T3N0 CRC, operated between 1997-2003 and the surgical materials for the relation between disease prognosis and p53, p21, p16, β-catenin, E-cadherin, EGFR, hMLH1, hMSH2 and TS protein expressions. RESULTS A significantly shorter 3-year disease free survival was observed in patients under the age of 50. The worst 5-year overall survival (OS) observed for patients over 70. Tumor localization and number of processed lymph nodes significantly affected prognosis. The EGFR, hMSH2 and TS expressions and the 5-fluorouracyl treatment were not found to be of prognostic value; p53 and p21 positivity had significantly worse survival. When β-catenin membrane expression disappeared on tumor cells, the 5-year OS rate decreased and time to metastasis shortened significantly. Membrane β-catenin expression, processed lymph nodes number and age were detected as independent prognostic markers. CONCLUSIONS These results suggest that the evaluation of a clinicopathological profile, based on age, tumor localization, number of examined lymph nodes, p53, p21 and E-cadherin β-catenin expression appears to be useful in identifying high risk patients.

Polymorphism of clotting factors in Hungarian patients with Raynaud's phenomenon

Patients with primary Raynauds phenomenon may have a genetically determined risk for clotting factors that predispose them to aberrant microvascular thrombosis. We investigated the prevalence of factor V substitution of G to A at position 1691 (FVLeiden), prothrombin G20210A, and methyltetrahydrofolate reductase C677T mutations in these patients. Two hundred (158 women, 42 men, mean age of 42.4 ± 13.7 years) consecutive patients with primary Raynauds phenomenon and 200 age-sex-matched healthy controls of Hungarian origin were included in a case–control study. The prevalence of methyltetrahydrofolate reductase C677T homozygous among patients was significantly lower than in the control group (odds ratio 0.4, 95% confidence interval 0.2–0.9, P < 0.05). The prevalence of other thrombosis-associated alleles did not differ between patients with primary Raynauds phenomenon and control subjects. FVLeiden, prothrombin G20210A, and polymorphism, prothrombin G20210A mutations have no apparent effect on the etiology of primary Raynauds phenomenon.