Clinical Oncology

[Targeted therapy: based upon the primary tumor or on its metastases?]

TÍMÁR József

SEPTEMBER 10, 2014

Clinical Oncology - 2014;1(03)

[Most of the primary tumors at various stages are resected or destroied by radiotherapy. Meanwhile, contemporary target therapies are administered in advanced stages, but the required molecular pathologic analysis is performed on the primary tumor supposing stable genetic profi ls durings at different stages of cancer progression. Advanced molecular technologies provided high resolution images on the clonal heterogeneity of the primary tumors and its role in cancer progression. Data indicate that in early and locoregional stages/recurrences the chance for genetic discordance is low while, in late visceral metastases this risk is increasingly higher. The clinical relevance of the genetically discordant metastatic tumors is proven by several retrospective studies. This is the basis of the recommendations that in case of progressing cancer molecular pathologic tests must be performed on metastatic tumors, especially when the primary tumor is resected. On the other hand, it is an unresolved issue what to do in case of discordance between the primary and the metastasis.]



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Clinical Oncology

[Pharmacological treatment of metastatic melanoma]

OLÁH Judit, GYULAI Rolland

[Malignant melanoma belongs to the group of relatively easily manageable tumors; if detected and removed early, it rarely metastasizes. Although the visible nature of the primary tumor provides opportunity for early diagnosis, there is a signifi cant portion of patients who receive proper management only with substantial delay. The fact that there are annually 300-400 patients with metastatic disease in Hungary, can be mostly attributed to public unawareness about melanoma, and consequent delay in seeking medical treatment. Metastatic melanoma remains - even today - an incurable disease. Molecular genetic research, however, resulted in revolutionary changes in melanoma management. Today, apart from the classic pathological prognostic factors, information regarding specifi c molecular modifi cations (such as in the expression of the BRAF, NRAS, c-KIT genes and proteins) are inevitable for the setting up of a personalized oncological treatment plan. By targeting members of the MAPK signal transmission pathway (using BRAF- and MEK-inhibitors), signifi cant improvement could be achieved in metastatic melanoma. Similarly, new drugs targeting specifi c immune checkpoint regulators (such as CTLA-4 and PD-1/PD-1L) provide previously unprecedented survival benefi t for melanoma patients. In this review the most recent developments in the fi eld of melanoma management are summarized.]

Clinical Oncology

[Treatment of hepatocellular carcinoma - today]


[The hepatocellular carcinoma (HCC) is one of the main causes of cancer-related death globally, and at the same time, it is the main event leading to death in cirrhotic patients. In the etiology of HCC, the non-alcoholic liver disease may be an important cause besides the viral cirrhosis. The HCC’s staging systems (Child-Pugh scores, Cancer of the Liver Italian Programme/CLIP, Barcelona Clinic Liver Cancer/ BCLC) play an important role in predicting the prognosis and determining the appropriate therapy. In Europe, the treatment strategy is based on the BCLC staging system. Screening of cirrhotic patient is also important because curative therapy is available only for the early-stage HCC. Several therapeutic options exist in the intermediate stage disease; among them the radiofrequency ablation (RFA), the transarterial chemoembolization (TACE) and the percutan ethanol injection (PEI) are most important. For the advanced disease, the only approved systemic therapy is sorafenib, which has been well-tolerated and yielded a substantially relative improvement in overall survival. For patient in end-stage disease with impaired liver function or a poor performance status, only supportive care is recommended.]

Clinical Oncology

[Pregnancy and cancer]

NAGY Zsuzsanna, SZILLER István, VALTINYI Dorottya, HORVÁTH Orsolya

[The joint appearance of pregnancy and cancer is rare. It is highly recommended that the tumorous pregnant should be managed by a multidisciplinary team. The early diagnosis is very important, but it is not easy, because the symptoms of pregnancy and cancer are rather similar. Imaging diagnosis has to avoid ionizing radiation (e.g. PET/CT). The same is true for chemotherapy in the fi rst trimester, due to the increased risk of developmental abnormalities. Consequently, radiation therapy is not allowded throughout the pregnancy, and the chemotherapy in the fi rst trimester is a strong indication for the interruption of pregnancy. Surgery, with good practice, usually can be performed without complications. Chemotherapy, given in the second and third trimester generally follows the standard protocols with a low frequency of developmental errors. Early delivery should not be encouraged, except the delay has a hazardous effect on the mother and/or on the child. The pregnant should be informed about all steps to be an active part of the fi nal decision.]

Clinical Oncology

[European examination for clinical oncologists]


[One of the major tasks of the European Examination Board is to harmonize the knowledge and practice of clinical oncologists throughout the world. The examination consits 100 questions and the positive result is aknowledged by a diploma. More and more countries replace the national exam by ESMO-exam. It is still a challenge how to evaluate the activity of clinical oncologists who are specialized in different area of oncology. The ESMO-exam is available mainly at the ESMO congresses.]

Clinical Oncology

[New aspects in cancer pain relief]


[Authors investigate the new advances in cancer pain relief among the long survival cancer patient, 25-30% of whom suffering from pain. The new molecular targets provide new druggable pain relief options. The changed strategy of pain-killing therapy enhance s the possibility for the long survival cancer patients to decrease problems of the side effects of opiod therapy. The lower doses of opioids in invasive theraputical techniques help patients to live in higher quality of life without the uncomfortable side effects of the drugs.]

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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

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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

Evaluation of the effectiveness of transforaminal epidural steroid injection in far lateral lumbar disc herniations

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Far lateral lumbar disc herniations (FLDH) consist approximately 0.7-12% of all lumbar disc herniations. Compared to the more common central and paramedian lumbar disc herniations, they cause more severe and persistent radicular pain due to direct compression of the nerve root and dorsal root ganglion. In patients who do not respond to conservative treatments such as medical treatment and physical therapy, and have not developed neurological deficits, it is difficult to decide on surgical treatment because of the nerve root damage and spinal instability risk due to disruption of facet joint integrity. In this study, we aimed to evaluate the effect of transforaminal epidural steroid injection (TFESI) on the improvement of both pain control and functional capacity in patients with FLDH. A total of 37 patients who had radicular pain caused by far lateral disc herniation which is visible in their lumbar magnetic resonance imaging (MRI) scan, had no neurological deficit and did not respond to conservative treatment, were included the study. TFESI was applied to patients by preganglionic approach. Pre-treatment Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores of the patients were compared with the 3rd week, 3rd month and 6th month scores after the procedure. The mean initial VAS score was 8.63 ± 0.55, while it was 3.84 ± 1.66, 5.09 ± 0.85, 4.56 ± 1.66 at the 3rd week, 3rd month and 6th month controls, respectively. This decrease in the VAS score was found statistically significant (p = 0.001). ODI score with baseline mean value of 52.38 ± 6.84 was found to be 18.56 ± 4.95 at the 3rd week, 37.41 ± 14.1 at the 3rd month and 34.88 ± 14.33 at the 6th month. This downtrend of pa­tient’s ODI scores was found statistically significant (p = 0.001). This study has demonstrated that TFESI is an effective method for gaining increased functional capacity and pain control in the treatment of patients who are not suitable for surgical treatment with radicular complaints due to far lateral lumbar disc hernia.

Clinical Neuroscience

Comparison of direct costs of percutaneous full-endoscopic interlaminar lumbar discectomy and microdiscectomy: Results from Turkey

ÜNSAL Ünlü Ülkün, ŞENTÜRK Salim

Microdiscectomy (MD) is a stan­dard technique for the surgical treatment of lumbar disc herniation (LDH). Uniportal percutaneous full-endoscopic in­terlaminar lumbar discectomy (PELD) is another surgical op­tion that has become popular owing to reports of shorter hos­pitalization and earlier functional recovery. There are very few articles analyzing the total costs of these two techniques. The purpose of this study was to compare total hospital costs among microdiscectomy (MD) and uniportal percutaneous full-endoscopic interlaminar lumbar discectomy (PELD). Forty patients aged between 22-70 years who underwent PELD or MD with different anesthesia techniques were divided into four groups: (i) PELD-local anesthesia (PELD-Local) (n=10), (ii) PELD-general anesthesia (PELD-General) (n=10), (iii) MD-spinal anesthesia (MD-Spinal) (n=10), (iv) MD-general anesthesia (MD-General) (n=10). Health care costs were defined as the sum of direct costs. Data were then analyzed based on anesthetic modality to produce a direct cost evaluation. Direct costs were compared statistically between MD and PELD groups. The sum of total costs was $1,249.50 in the PELD-Local group, $1,741.50 in the PELD-General group, $2,015.60 in the MD-Spinal group, and $2,348.70 in the MD-General group. The sum of total costs was higher in the MD-Spinal and MD-General groups than in the PELD-Local and PELD-General groups. The costs of surgical operation, surgical equipment, anesthesia (anesthetist’s costs), hospital stay, anesthetic drugs and materials, laboratory wor­kup, nur­sing care, and postoperative me­dication diffe­red significantly among the two main groups (PELD-MD) (p<0.01). This study demonstrated that PELD is less costly than MD.