Lege Artis Medicinae

[Systemic adjuvant pharmacotherapy of colorectal cancer]

BODOKY György

DECEMBER 10, 2009

Lege Artis Medicinae - 2009;19(12)

[Colorectal cancer is one of the most frequent cancer in the postindustrial world; its most common form is adenocarcinoma. In Hungary, colorectal cancer has the second highest mortality among tumours. If diagnosed early, it might be successfully treated by surgery, however, chemotherapy is necessary to prevent tumor relapse and development of metastases and achieve adequate palliation. In the past few years, adjuvant treatment of colorectal cancer has improved substantially. Many new drugs have been developed, which are also being used in combination with previously known agents. This article will discuss the novelties in the field of adjuvant chemotherapy for colorectal cancer and the main guidelines of adjuvant treatment.]

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[Insulin analogues and pregnancy]

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[Near-normoglycaemic metabolic control in pregnant women with diabetes - started before conception in pregestational diabetes - decreases the frequency of maternal and foetal complications. Such control can be achieved by using optimalised systems of insulin therapy. A number of (ultra)rapid and long-acting insulin analogues became available during the last decade, which - on the basis of theoretical considerations - might be used to maintain normoglycaemia. Summarising the data available today, the use of rapid insulin analogues (lispro, aspart) seem to be effective and safe during pregnancy. Some questions arise, however, about their modes of application. The use of long-acting insulin analogues in pregnancy is currently not indicated. Further trials are needed to prove their efficacy and safety in diabetic pregnancy.]

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[Resistant hypertension - differential diagnosis and therapy]

TISLÉR András

[Hypertension is considered resistant to therapy if the target blood pressure is not achieved despite treatment with three different types of antihypertensive drugs, including a diuretic. Causes of therapy resistance may be grouped into three broad categories: Pseudoresistance can be the result of inadequate blood pressure measurement technique, the “white-coat” effect or the patients’ noncompliance with pharmacological and nonpharmacological medical advices. Evaluation of the measurement technique - including the size of the cuff used - and blood pressure monitoring at home can help identify the causes of pseudoresistance. Secondary resistance comprises drug interactions and concomitant medical conditions that elevate blood pressure or antagonize antihypertensive therapy. In addition, secondary resistance can result from disorders associated with secondary hypertension, among which appropriate screening for hyperaldosteronism as well as for renoparenchymal and renovascular hypertension need special emphasis. Suboptimal therapy is frequently related to subclinical volume overload and the use of inappropriate type or dosing of diuretics. Furthermore, when choosing the optimal drug combination, care should be taken to inhibit the various systems that regulate blood pressure as much as possible. In addition to combining the most frequently used antihypertensive drugs, the use of aldosterone antagonists, vasodilators, nitrates or drugs affecting the central nervous system might help to optimise treatment.]

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[The relevancy of measuring the level of D-dimer test in clinical practice]

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[Plasma levels of D-dimer may rise in a number of pathological conditions, which might be relevant for diagnosis as well as for prognosis. Its concentration increases with age, perhaps because of the wide-spread co-morbidity. In this article we demonstrate the diagnostic role of Ddimer in the well-known thromboembolic diseases. Beyond that, we highlight the importance of measuring D-dimer levels in other, lesser-known conditions, about which important findings have been published, such as cardiovascular, inflammatory or malignant diseases. It seems that in these disorders - provided that appropriate clinical conditions are available -, measuring D-dimer levels might have a role not only in diagnosis but in the prognosis as well. Furthermore, our aim was to discourage inappropriate clinical practice. Ignoring to measure the D-dimer levels (for fear of it being high) might lead to diagnostic errors. On the other hand, routinely performing the D-dimer test without clinical consideration (in the hope of it being negative) might cause diagnostic confusion in case of unexpected positivity and - mostly because of false interpretation - lead to further, unnecessary examinations.]

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[Rituximab therapy in rheumatoid arthritis]

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[In recent years, immune checkpoint inhibitors have been shown to be effective in treating manifold types of cancer but less robust in colorectal cancer (CRC). While, the subgroup of CRC with microsatellite instability (MSI; also termed as mismatch repair defi cient) showed a moderate response to Pembrolizumab in a single arm phase II clinical trial, microsatellite stable (MSS) cancers were unresponsive. Possible mechanisms that affect immune response in colorectal cancer will be reviewed in this article. We will also propose that histone deacetylase (HDAC) inhibition may reverse the immune editing commonly seen in advanced CRC and render them sensitive to immune checkpoint blockade.]

Lege Artis Medicinae

[POSSIBILITES AND DIFFICULTIES OF COLORECTAL CANCER SCREENING IN HUNGARY]

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[The frequency of colorectal cancer is increasing all over the world. It is the second most frequent oncological disease leading to death in both sexes in Hungary. The main part of colorectal cancer develope after the age of 50. In case of patients having higher risk we have to calculate with the earlier appearance of the tumour and detectable molecular genetic disorders. The development of colorectal cancer needs a long time. Before the appearance of the cancer, precancerous processes (adenomas, polyps) can be detected in the large intestine. The development of colorectal cancer can be prevented by the removal of the adenomas (polypectomy). There are many different and efficient methods to detect the precancerous and early disorders. For increasing the compliance to screening programs the common efforts of the society, the National Health Care Services and medical doctors are necessary. The education of the population and the medical services would also be helpful. The colorectal cancer screening programs are costeffective and supported by the different health services independently from the type of the insurance. Screening the patients having higher risk is one of most important task. In these cases the use of colonoscopy is the most frequent method for the screening and follow up as well.]

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[How the molecular informations infl uence the therapeutic strategy against colorectal cancer?]

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[Colorectal cancer is not a homogenous disease, but it has different subgroups based on their molecular characteristics. NCCN and ESMO guidelines emphasize the importance of the determination of RAS and BRAF mutations in those patients who are intended to treat with targeted therapy. The increase in knowledge on the molecular changes will help to design and start a new generation of clinical trials, which will be designed not on their randomization of large groups of unselected patients, but rather on the consideration of the molecular subgroups determined before introducing therapy.]

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[Multidisciplinary medical oncological treatment of colorectal cancer]

LÁNG István

[All stage III. patients and some high risk patients with stage II. colorectal cancer (CRC) should be treated with bolus 5-fluorouracilfolinic acid adjuvant chemotherapy. The usual adjuvant/neoadjuvant treatment for rectal cancer is chemo-radiotherapy. In stage IV. CRC various combinations of 5-fluorouracil, folinic acid, irinotecan or raltitrexed can be used. Patients should be treated in specialised multidisciplinary oncological centers - and, if possible, as participants of clinical trials.]

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[Experience with bevacizumab in non-small cell lung cancer]

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[INTRODUCTION - Bevacizumab, a recombinant anti-vascular endothelial growth factor antibody, is the antiangiogenic drug used at advanced stage of non-small cell lung cancer. It is the only antiangiogenic therapy up till know available with reimbursement in Hungary. It is indicated in the first-line, platinum-based treatment of advanced stage non-squamous nonsmall cell lung cancer, and used together with chemotherapy. CASE REPORT - In this case report we present the case of a patient with advanced stage pulmonary adenocarcinoma, with a progressionfree survival of more than one year with bevacizumab- docetaxel-cisplatine therapy. CONCLUSION - Bevacizumab given together with combination chemotherapy is effective in advanced lung adenocarcinoma.]