Lege Artis Medicinae

[Misleading tumor markers in pulmonary carcinomas]

CIFRA János, BOGNER Barna, HELF László, SZÉKELYI Katalin, KÁLMÁN Endre, SÁPI Zoltán

DECEMBER 20, 2010

Lege Artis Medicinae - 2010;20(12)

[Lung cancers are the leading cause of tumorous mortality and the most frequent tumor in the 40- 70 years age range. The chance for cure in lung cancers is much higher in the early stage of disease so the early diagnosis has a paramount importance. Although many tumor markers are used in the diagnosis of malignant tumors, their specificity raise some doubts. The increased level of hCG is traditionally connected with choriocarcinomas and the CA 19-9 antigen is connected with gastrointestinal carcinomas. The production of hCG and CA19-9 is extremely rare but well established fenomenon in pulmonary carcinomas. In some cases of pulmonary cancers various tumor markers are produced, causing differential diagnostic difficulties. Through our cases and literature review we wanted to draw the attention of the organ unspecificity of these tumor markers.]

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Lege Artis Medicinae

[Lecturis Salutem! Greetings to the Reader!]

KAPÓCS Gábor

Lege Artis Medicinae

[Members of the editorial and advisory board and the redaction of the LAM, 1990-2010]

Lege Artis Medicinae

[Farewell to rosiglitazone: where to go?]

TAMÁS GYULA, KERÉNYI ZSUZSA

[The European Medicines Agency concluded that the marketing authorisation for all rosiglitazonecontaining medicines (Avandia, Avandamet, Avaglim) should be suspended across the European Union. The National Health Insurance Fund Administration in Hungary in a circular letter called the attention of GP’s to the necessity in getting the medical proposal (of an internist, endocrinologist or diabetologist) for substituting rosiglitazone to arrange a smooth modification of their treatment regimen. The review taking into account updated recommendations of the ADA-EASD and the Hungarian Diabetes Association summarises the potential drugs. The first line therapy of choice has to be starting with insulin. Pioglitazone might also be administered, with all known side effects of the glitazone family, e.g. congestive heart failure and bone fractures. Further alternatives are choosing the newer drugs of the incretin principle: the incretin mimetics (exenatid, liraglutid) and the incretin enhancers (sitagliptin, vildagliptin, saxagliptin). Beside their favourable profile of effect they do not have longterm follow up outcome studies and evidences for cardiovascular safety.]

Lege Artis Medicinae

[On rivaroxaban’s mechanism of effect]

BODA Zoltán

[A new era of anticoagulant therapy is approaching. No new oral anticoagulants have been introduced for seventy years. However, two large groups of anticoagulants (molecules with anti-FXa and anti-FIIa acitivity) are currently at advanced stages of clinical trials. This publication summarises the most important information on the mechanism of effect of the anti-FXa drug rivaroxaban. The possible advantages of the “direct” effect and the anti-FXa effect are emphasized. The most significant drug interactions of the new anticoagulant are also presented.]

Lege Artis Medicinae

[Pancreatology in practice: acute pancreatitis]

TAKÁCS Tamás

[Acute pancreatitis requires various diagnostic and treatment procedures. The clinical picture of acute pancreatitis is diverse, ranging from mild abdominal pain or dyspepsia to severe, lifethreatening multiorgan failure or sepsis. Most cases of pancreatitis result in a mild/edematous inflammation of the pancreas, whereas the remaining 15-20 percent results in severe necrotising pancreatitis with a mortality rate as high as 10-30 percent, although imaging diagnostics, operative endoscopy and intensive internal and surgical therapy have improved significantly in the past few years. Quick and accurate diagnosis of the disease is required for early therapeutic intervention. For example, we know that in cases of biliary acute pancreatitis an early (within 24-48 hours following the onset of symptoms) endoscopic sphincterotomy and stone extraction significantly improve the prognosis of the disaese. It is also important to introduce an adequate perfusion/rehydration therapy and a simultaneous enteral feeding introduced as soon as possible to avoid the superinfection of the pancreatic necrosis. Therefore, when reviewing the epidemiological characteristics, pathophysiology, up-to-date diagnostic and therapeutic approaches of the disease, we emphasise early interventions. We also highlight the importance of patient care and follow-up checks after an incident of acute pancreatitis.]

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Clinical Neuroscience

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

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.

Clinical Neuroscience

Isolated hypoglossal nerve palsy due to a jugular foramen schwannoma

ÖZTOP-CAKMAK Özgür, VANLI-YAVUZ Ebru, AYGÜN Serhat, BASTAN Birgül, EGEMEN Emrah, SOLAROGLU Ihsan, GURSOY-OZDEMIR Yesemin

Introduction – Although the involvement of the hypoglossal nerve together with other cranial nerves is common in several pathological conditions of the brain, particularly the brainstem, isolated hypoglossal nerve palsy is a rare condition and a diagnostic challenge. Case presentation – The presented patient arrived to the hospital with a history of slurred speech and an uncomfortable sensation on his tongue. Neurological examination showed left-sided hemiatrophy of the tongue with fasciculations and deviation towards the left side during protrusion. Based on the clinical and MRI findings, a diagnosis of hypoglossal nerve schwannoma was made. Discussion – Hypoglossal nerve palsy may arise from multiple causes such as trauma, infections, neoplasms, and endocrine, autoimmune and vascular pathologies. In our case, the isolated involvement of the hypoglossal nerve was at the skull base segment, where the damage to the hypoglossal nerve may occur mostly due to metastasis, nasopharyngeal carcinomas, nerve sheath tumors and glomus tumors. Conclusion – Because of the complexity of the region’s anatomy, the patient diagnosed with hypoglossal nerve schwannoma was referred for gamma knife radiosurgery.

Clinical Neuroscience

Symptom profiles and parental bonding in homicidal versus non-violent male schizophrenia patients

HALMAI Tamás, TÉNYI Tamás, GONDA Xénia

Objective - To compare the intensity and the profile of psychotic symptoms and the characteristics of parental bonding of male schizophrenia patients with a history of homicide and those without a history of violent behaviour. Clinical question - We hypothesized more intense psychotic symptoms, especially positive symptoms as signs of a more severe psychopathology in the background of homicidal behaviour. We also hypothesized a more negatively perceived pattern (less Care more Overprotection) of parental bonding in the case of homicidal schizophrenia patients than in non-violent patients and non-violent healthy controls. Method and subjects - Symptom severity and symptom profiles were assessed with the Positive and Negative Syndrome Scale in a group of male schizophrenia patients (n=22) with the history of committed or attempted homicide, and another group (n=19) of male schizophrenia patients without a history of violent behaviour. Care- and Overprotection were assessed using the Parental Bonding Instrument (PBI) in a third group of non-violent healthy controls (n=20), too. Results - Positive, negative and general psychopathology symptoms in the homicidal schizophrenia group were significantly (p<0.005) more severe than in the non-violent schizophrenia group. Non-violent schizophrenia patients scored lower on Care and higher on Overprotection than violent patients and healthy controls. Homicidal schizophrenia patients showed a pattern similar to the one in the healthy control group. Conclusions - It seems imperative to register intense positive psychotic symptoms as predictive markers for later violent behaviour. In the subgroup of male homicidal schizophrenia patients negatively experienced parental bonding does not appear to be major contributing factor to later homicidal behaviour.

Clinical Oncology

[Complications of infusion treatment with emphasis on extravasation of cytostatics]

HARISI Revekka

[The extravasation of cytostatics is the most signifi cant complication of infusion therapy in cancer treatment. Extravasation refers to the inadvertent infi ltration of cytostatic drugs into subcutaneous or subdermal tissues surrounding the intravenous or intraarterial administration site. According to literature data incidence estimates between 0,01-7%. Extravasated drugs are classifi ed according to their potential for causing damage as vesicant, irritant and nonvesicant. Knowledge of risk factors, the patientrelated and treatment-related ones is important to minimize the occurrence of extravasation. In order to reduce the risk of extravasation, the staff involved in the tumor infusion therapy must be specially trained to implement several preventive and therapeutical protocols. In 2012, ESMO-EONS has put together a new comprehensive treatment protocol on the topic of cytostatics extravasation. Protocol recommended that every oncological department, who administers chemotherapy have to have extravasation trained team and a standby extravasation kit. According to the new ESMO-EONS guideline subcutaneous corticoids are not recommended, anymore. In case of mechloretamine extravasation the recommendation is immediate subcutaneous injection of sodium thiosulfate. After extravasation of anthracyclines, mitomycin C and platin salts the best treatment opportunity is subcutan dimethyl sulfoxide administration. In case of anthracyclines’ extravasation intravenous dexrazoxane treatment is also effective. Hyaluronidase, injected into or under the skin, facilitates absorption of extravasated drugs because of increases connective tissue permeability, promotes the spreading and reduces the local concentration of the extravasated citostatic agents. Hyaluronidase might be effi cacious in preventing skin necrosis by extravasation due to vinca alkaloids. The treatment of unresolved tissue necrosis or pain lasting more than 10 days is surgical debridement. Because of the medical and juristic importance of the extravasation event, it is necessary to establish uniform guidelines for treatment of extravasation, in all Hungarian Oncological Centers.]