Lege Artis Medicinae

[ACTINOMYCOSIS MIMICKING LUNG CANCER]

CSERNI Gábor, BORI Rita, BOROSS Gábor, FRANK Emil, LÓRÁND Katalin, SERÉNYI Péter, LENGYEL Mária, KOVÁCS Károly, HALÁSZ Mátyás

JULY 20, 2006

Lege Artis Medicinae - 2006;16(07)

[INTRODUCTION - The mortality of lung cancer is high, but with early diagnosis the disease can often be cured. The differential diagnosis of pulmonary carcinoma is widely diverse. CASE REPORT - In a 53-year-old male patient, who had been successfully treated for pneumonia complicated with thoracic empyema, both a CT scan and bronchoscopy raised the suspicion of a malignant tumour. Brush cytology was inconclusive; it raised the possibility of malignancy but was not felt diagnostic of a malignant process, whereas biopsy revealed only inflammatory changes. After right lower lobectomy, actinomycosis was diagnosed by histology. This case is used in the paper as an opportunity to discuss the pseudotumorous presentation of thoracic actinomycosis. CONCLUSION - Pulmonary and thoracic actinomycosis is rare, but due to its ability to simulate tumours, it is an important disease to consider in the differential diagnosis of lung cancer.]

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Lege Artis Medicinae

[NONINVASIVE MECHANICAL VENTILATION IN CHRONIC OBSTRUCTIVE LUNG DISEASES WITH ACUTE OR CHRONIC RESPIRATORY FAILURE]

BALIKÓ Zoltán

[Over the past decade, the use of noninvasive ventilation in the setting of acute exacerbations of chronic obstructive pulmonary disease (COPD) has gained popularity, and is recommended by evidence-based guidelines. The evidence that it should be effective in chronic COPD is much weaker, and large, prospective, randomised, controlled studies that would also provide a guide for the selection of the best candidates, are still lacking. It has bee established, however, that home mechanical ventilation is certainly beneficial for a well-defined subgroup of patients. This includes the so called “blue bloater” patients (with hypercapnia and polyglobulia), other cases with increased hypercapnia, and patients with "overlapping" syndrome (COPD accompanied by sleep apnoe). Also, for patients with acute respiratory failure who refuse intratracheal intubation noninvasive mechanical ventilation remains the only choice. The past years have unequivocally proved the superiority of the positive pressure ventilation mode for either short term or long term use.]

Lege Artis Medicinae

[Interdisciplinary forum of MOTESZ - Budapest, 23-25th March, 2006.]

KRAMER Imre

Lege Artis Medicinae

[THE POTENTIAL ROLE OF THE SEMICARBAZIDESENSITIVE AMINE OXIDASE ACTIVITY IN THE DEVELOPMENT OF DIABETIC RETINOPATHY]

DURA Eszter

[Recent data suggest that the copper-containing semicarbazide-sensitive amine oxidase enzyme (SSAO) may play a role in vascular endothelial damage through conversion of certain endogenous monoamines, such as methylamine, into cytotoxic aldehydes, hydrogen peroxide and ammonia. SSAO is present in various human tissues and in the serum. Elevated SSAO activities have been reported in patients with both types of diabetes mellitus. We have demonstrated that the activity of serum SSAO is significantly higher in type 2 diabetic patients with high-risk proliferative diabetic retinopathy compared to those without retinopathy. Our clinical results support the hypothesis that elevated SSAO activity may be involved in the pathogenesis of microvascular diabetic late complications, such as retinopathy. The enzymatic conversion of the endogenous monoamines (e.g. methylamine, aminoacetone) into toxic aldehydes and hydrogenperoxide may be one of the possible mechanisms of the development of microangiopathy. Also, the vascular adhesion protein-1 (VAP-1) function of the molecule can cause leukostasis and leukocyte activation through increased leukocyte adhesion, resulting in worsening of the capillary circulation and hypoxia. Further prospective, larger studies are needed to elucidate the role of the possible association between serum SSAO activity and highrisk proliferative retinopathy in patients with type 2 diabetes. The pharmacological manipulation of SSAO activity might be an interesting new concept for prevention and treatment of diabetic retinopathy.]

Lege Artis Medicinae

[In the focus: periferal vascular diseases - Readers’ questions answered by dr. Éva Meskó]

MESKÓ Éva

Lege Artis Medicinae

[POSSIBLE TERATOGENICITY OF VAGINAL METRONIDAZOLE TREATMENT AND ITS EFFECT ON GESTATIONAL AGE AND PREVALENCE OF PRETERM BIRTH - CASE-CONTROL STUDY]

KAZY Zoltán, PUHÓ Erzsébet, CZEIZEL Endre

[INTRODUCTION - The primary aim of the study was to investigate the possibility of a teratogenic effect of vaginal metronidazole treatment during pregnancy. MATERIALS AND METHODS - Various congenital abnormalities and all (1-3) their matched controls were analysed in the population-based database of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. The study group comprised 38 151 pregnant women who had newborns without any congenital abnormalities (control group) and 22 843 pregnant women who had newborns or fetuses with congenital abnormalities. Main outcome measures were analysed in 22 congenital abnormalities groups. The use of metronidazole during the second and third trimesters being common, the secondary objective of the study was to analyse the effect of vaginal metronidazole treatment (500 mg of Klion) on gestational age and birth weight in the control group without congenital abnormalities. RESULTS - The prevalence of vaginal metronidazole treatment during pregnancy was 1.7% in the case group (n=388) and 1.5% in the control group (n=570) (odds ratio (OR), 1.1, 95% confidence interval (CI): 1.0-1.3). Comparisons of cases and their matched controls showed an association between vaginal metronidazole treatment during the second and third months of gestation and congenital hydrocephaly (adjusted OR with 95% CI, 10.7, 1.1-104.5), but this was only based on five cases. The analysis of metronidazole treatment reported by the physicians did not confirm this association. After metronidazole use the mean gestational age was slightly shorter (by 0.1 week) and the mean birth weight was also slightly lower (by 40g) in the treated group. CONCLUSION - This finding should only be regarded as an indication for a possible association between vaginal treatment with metronidazole during pregnancy and congenital hydrocephalus. The results showed that vaginal metronidazole treatment alone was not able to prevent a possible vaginal infection that is associated with preterm birth, and that the prevalence of low birth weight was higher among treated women. The protective effect of metronidazole on preterm birth and low birth weight was not confirmed.]

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Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

Possible genotype-phenotype correlations in Niemann-Pick type C patients and miglustat treatment

ÇAKAR Emel Nafiye, ÖNAL Hasan

Niemann-Pick type C is a rare lysosomal storage disease caused by impaired intracellular cholesterol transport. The autosomal recessive disease is caused by mutations in NPC1 or NPC2 genes. Clinical-laboratory features, genotype-phenotype correlation and miglustat treatment response of our patients diagnosed with early infantile Niemann-Pick type C were evaluated. In this article, four Niemann-Pick type C patients diagnosed in the early infantile period are presented. Common features of our patients were hepatomegaly, splenomegaly, cholestasis and retardation in motor development. Patients 1 and 2 are twins, with homozygous mutation c.2776G>A p.(Ala926Thr) in NPC1 gene and severe lung involvement. Lung involvement, which is mostly associated with NPC2 gene mutation in the literature, was severe in our patients and they died early. In patients 3 and 4, there were respectively c.2972del p.(Gln991Argfs*6) mutation in NPC1 gene and c.133C>T p.(Gln45*) homozygous mutation in NPC2 gene. In these two patients, improvement in neurological findings were observed with treatment of miglustat. In our twin patients, severe lung involvement was observed. Two of our four early infantile Niemann-Pick type C patients exhibited neurological gains with miglustat treatment.

Clinical Neuroscience

Life threatening rare lymphomas presenting as longitudinally extensive transverse myelitis: a diagnostic challenge

TOLVAJ Balázs, HAHN Katalin, NAGY Zsuzsanna, VADVÁRI Árpád, CSOMOR Judit, GELPI Ellen, ILLÉS Zsolt, GARZULY Ferenc

Background and aims – Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports – Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion – Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.

Lege Artis Medicinae

[Chronic obstructive pulmonary disease and recommendations for treatment]

LOSONCZY György

[Chronic obstructive pulmonary disease (COPD) is prognosticated to become the 3rd most prevalent cause of early lethality. It’s main etiology is long-term smoking which induces chronic inflammation and obstruction of the airways as well as elastolysis of the pulmonary interstitium which lead to emphysema. Increased resistance of the intrathoracic airways and emphysema induce hyperinflation of the lung and chest which increases the work-load of the respi­ratory muscles. COPD patients are typically hypoxaemic and normocapnic. Finally, fatigue of the respiratory muscles cause the development of global respiratory failure (hypercapnia and severe hypoxaemia). Most effective intervention is smoking cessation. Maintanance treatment includes inhalational long-acting bronchodilators with or without inhalational corticosteroids. Acute exacerbation is treated with O2 supplementation, inhalational bronchodilators, systemic steroids and/or antiobiotics. Frequency and severity of acute exacerbations prognosticate shorter survival. In chronic respiratory failure long-term home O2 therapy can be provided.]

Clinical Neuroscience

Evaluation of ischemic stroke patients with systemic cancer

UFUK Emre, TASKIN Gunes, IREM Pinar, FURUZAN Kokturk, ESENGUL Liman, ORHAN Yağiz

Purpose - In cancer patients, an ischemic stroke can be seen as both a direct effect of cancer and a complication of treatment. This condition can negatively affect the follow-up and treatment of these patients. For this research, we aimed to evaluate the clinical features, stroke types and etiological features of ischemic stroke patients with histories of cancer or found to have cancer during the aetiological investigation. Materials and methods - We retrospectively evaluated 100 patients (57 males, 43 females) who were hospitalized with acute stroke and determined to have the presence of cancer or a cancer history during the aetiological investigation between 2011 and 2016. All the demographic features, stroke types and localizations, National Institutes of Health Stroke Scale (NIHSS) scores, Rankin Scale scores, durations of cancer and cancer treatments were recorded. Results - The mean age of the patients was 67.07 ± 10.9 years old, the median NIHSS score was 5, and the median Rankin Scale score was 4. While 79% of patients had ischemic stroke risk factors, 21% did not. Atherosclerotic stroke was the most common stroke type (49%, n=49) and cryptogenic strokes were detected in 21% (n=21). In addition, 63% of the patients had chronic cancer (later than 6 months), 31% of the patients had recent cancer histories (less than 6 months), and 29% of the patients had metastases. Among all the malignancies, lung cancer (n=23), gastrointestinal cancer (n=20) and gynaecological-breast cancer (n=16) were the three most common. Moreover, 37% of the patients underwent chemotherapy, 29% underwent radiotherapy, and 88% of the patients had Carotid/Vertebral Doppler USG abnormalities. Conclusion - Similar to what is stated in the literature, an atherosclerotic stroke was the most common type of stroke in the cancer patients. Stroke risk factors were not detected in 21% of the patients, and in the majority of the patients, atherosclerotic changes in the carotid artery were observed in the Doppler examinations. In the aetiology and prognosis of ischemic stroke, it is important to keep in mind the existence of cancer in addition to the classical stroke risk factors.