LAM KID

[A successful story of the science of bone metabolism in Hungary - Interview with István Marton, a founder of Hungarian Society of Osteoporosis and Osteoarthrology]

SZEKERES László

OCTOBER 20, 2011

LAM KID - 2011;1(02)

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LAM KID

[Inhibition of receptor activator of nuclear kappa-B ligand: pathophysiology and preclinical data]

LAKATOS Péter, NÁDASI Edit

[Bone remodeling is a lifelong process, in which the balanced functions of osteoclasts and osteoblasts have a key role. In certain conditions, for example during the dramatical hormonal changes in the postmenopausal period, the upset of this balance leads to a pathologically increased bone loss. Such conditions lead to an increased bone loss, which results in an increased risk of fractures. Bone resorption is primarily regulated by a member of the tumor necrosis factor family, receptor activator of nuclear factor κB ligand, which plays a central role in the development, function and survival of osteoclasts. Catabolic effects of this ligand is inhibited by another member of the tumor necrosis factor family, osteoprotegerin, which binds to the ligand and prevents its interaction with its receptor, the receptor activator of nuclear factor κB. Osteoclast activity is at least partly dependent on the relative balance of the ligand and osteoprotegerin. It has been shown in a number of animal models that inhibition of the ligand markedly decreases bone resorption and increases cortical and cancellous bone volume, density and strength, without having any significant effect on other organs. On the basis of these findings, inhibition of receptor activator of nuclear κB ligand is a promising therapy of conditions characterised by increased bone loss. In phase 3 clinical trials, denosumab therapy significantly increased bone mineral density at various regions of the skeleton and significantly decreased the levels of bone turnover markers compared with placebo and alendronate therapy, and significantly decreased the incidence of new vertebral, total hip and nonvertebral fractures compared with placebo. On the basis of these findings, denosumab therapy offers a novel, revolutionary solution for the treatment of postmenopausal osteoporosis.]

LAM KID

[Pain relief in metastatic bone disease]

BOÉR Katalin

[Metastatic bone disease is a hallmark of distant relapse of a number of solid tumours. The treatment of bone metastases is palliative, the main goal is to relieve pain, whereas it’s also important to reduce the risk of bone fractures, prolong survival and maintain the physical activity of patients. Pain is one of the most common symptoms of bone metastases, and state-of-the-art pain relief has an important role in maintaining the patients’ quality of life. Therapies to control pain include drug therapy, radiotherapy, surgery, systemic oncotherapy, such as chemotherapy and/or hormone therapy, multibone radioisotope therapy and administration of bisphosphonates. Regarding the relief of pain caused by malignant tumours, the guidelines developed by the World Health Organization should be followed. The algorithm of pain relief starts with assessment of the pain’s intensity and includes both pharmacological and nonpharmacological interventions. Analgesics used for pain relief include nonopioids, opioids and adjuvant agents. The pain can be efficiently relieved with the combined use of modern analgesics in the great majority of patients.]

LAM KID

[Pain relief in the neurologist’s view]

KOMOLY Sámuel

[Pain, on the basis of its anatomical origin, can be nociceptive (somatic, visceral) or neuropathic, that is, occuring as a direct consequence of a lesion or disease affecting the somatosensory system. The past few years’ epidemiological studies showed that chronic neuropathic pain affects 7-8% of the general population. Diagnosis of neuropathic pain can be established without instrumental examinations, with the help of validated tests that can be used by any physician. Neuropathic pain greatly deteriorates the patients’ quality of life, and the effect of traditional analgesics is insufficient for its treatment. Thus, it is important to know those treatment procedures and drugs that have been proved to be efficient for relieving neuropathic pain.]

LAM KID

[Pain management in rheumatology]

NAGY Katalin

[Pain is the most common symptom in rheumatology, which can be of mechanical or inflammatory origin, acute and chronic, nociceptive, neuropathic and psychogenic. Pain can be relieved by analgesics, nonsteroidal anti-inflammatory drugs, opioids, adjuvants and special drugs depending on the etiology, for example a gout attack can be stopped by colchicine. For pain relief, we use therapeutic guidelines of the World Health Organization (WHO), which recommends the use of analgesics, NSAIDs and adjuvants as the first step, weaker opioids as the second, and strong opioids as the third step. In rheumatology, the first step's drugs are generally used. If possible, NSAIDs should be administered briefly, potentially combined with analgesics and muscle relaxants. If pain management is insufficient, tramadol should be given. Pain relief in rheumatology also include the use of local and intraarticular injections, physiotherapy, TENS and balneotherapy. Complex therapies that combine the above mentioned methods is often more effective than the use of medications only.]

LAM KID

[Osteoid osteoma]

MAGYAR Péter, KOVÁCS Balázs

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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.

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