Kirurško liječenje karcinoma prostate visokog rizika i oligometastatske bolesti

Prostate cancer is responsible for the largest number of cancer-related deaths in male population in many countries of the world. Aggressive forms of the disease are associated with an increased risk of local recurrence and death. Treatment of high-risk local prostate cancer most commonly involves radical prostatectomy (RP) or external beam radiation therapy (EBRT ) combined with androgen deprivation therapy (ADT ) with or without the addition of brachytherapy (BT). The use of surgery for high risk prostatic carcinoma (HR PC) is on the rise, because of its advantages including the possibility of cure with surgery alone without the risk of toxicities from prolonged ADT, accurate staging, and avoiding the influence of PSA originating from benign prostatic hyperplasia on future therapy. Oligometastatic prostate cancer may be considered as the last border of possibly curable disease. Radical prostatectomy in oligometastatic prostate cancer can significantly decrease the risk of local complications but only multimodal approach in selected group of patients may offer opportunities to eradicate tumor or delay its progression. Surgery for oligometastatic disease most commonly targets lymphatic disease with salvage pelvic lymph node dissection, whereas it rarely targets distant metastases. Further prospective, randomized studies are necessary to define the role and value of therapies in oligometastatic prostate cancer.Rak prostate ostaje najčešći uzrok smrtnosti od karcinoma u mnogim zemljama svijeta. Bolesnici s agresivnijom bolešću izloženi su većem riziku od neuspjeha lokalnog liječenja i smrti. Liječenje visoko rizične lokalne bolesti najčešće uključuje radikalnu prostatektomiju, radioterapiju (EBRT ) s androgenom deprivacijskom terapijom (ADT ) ili EBRT plus brahiterapiju (BT) i ADT . Kirurško liječenje karcinoma prostate visokog rizika (HR PC) je u porastu zbog svojih prednosti koje uključuju mogućnost izlječenja samo operacijom, točno određivanje stadija bolesti, uklanjanje dobroćudnog izvora PSA koji je čimbenik za određivanje buduće terapije, te mogućnost izbjegavanja toksičnosti dugotrajne primjene ADT-a. Čini se da je oligometastatska bolest posljednja barijera potencijalno izlječivog karcinoma prostate. Radikalna prostatektomija u oligometastatskom karcinomu prostate može značajno smanjiti rizik od lokalnih komplikacija, ali samo multimodalni pristup odabranoj skupini bolesnika može pružiti mogućnosti za potpuno uklanjanje tumora ili usporavanje njegovog napredovanja. Kirurško liječenje oligometastatske bolesti najčešće je usmjereno na limfogeno širenje s disekcijom zahvaćenih zdjeličnih limfnih čvorova, a rjeđe može biti usmjereno na udaljene metastaze. Potrebna su daljnja prospektivna, randomizirana istraživanja za definiranje uloge i vrijednosti terapije oligometastatskog karcinoma prostate

Isoflurane post-conditioning stimulates the proliferative phase of myocardial recovery in an ischemia-reperfusion model of heart injury in rats

Summary. The application of isoflurane in a postconditioning manner, during early reperfusion following a period of coronary occlusion, has numerous beneficial effects on the ischemic myocardium, including reduction of infarct size. It does so by stimulating a sequence of well studied anti-apoptotic pro-survival mechanisms in a similar manner to various ‘ischemic’ pre-/postconditioning approaches which achieve their cardio protective effects in both laboratory and clinical situations. Proliferation of newly formed blood vessels, resulting in formation of highly vascularized granulation tissue, is an essential stage of infarct healing. It can be evaluated by detecting various angiogenic factors, including vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) or by quantification of expression of vascular smooth muscle progenitors, such as Nestin. Expression of these three markers was used to evaluate the effect of early isoflurane post-conditioning in ischemia-reperfusion type cardiac injury. A large reduction in infarct size (59.3% of control), and marked increase of expression of VEGF (43.4%), PECAM1/CD31 (136%) and Nestin (77.9%) was found in experimental animals when compared to control animals that did not receive isoflurane treatment. Hence, based on our results, we can emphasize two morphologically detectable benefits of isoflurane post-conditioning: a marked reduction in infarct size and much better organization/vascularization of necrotic tissue

Designing Anatomy Program in Modern Medical Curriculum: Matter of Balance

Aim To evaluate the structure of the anatomy program in the first year medical curriculum of University of Split School of Medicine by comparing it with the recommendations by the Educational Affairs Committee of the American Association of Clinical Anatomists (AACA) and the Terminologia Anatomica (TA); we also quantitatively evaluated the organization of teaching material in contemporary topographical anatomy textbooks and matched them with the AACA recommendations, TA, and the curriculum of the anatomy course taught at Medical School in Split, Croatia. Methods TA, official recommendations of the AACA, 6 contemporary anatomy textbooks, and the structure of the anatomy course were analyzed for the proportion of the terms or text devoted to standard topographical regions of the body. The findings were correlated using Spearman ρ test. Results The curriculum outline correlated both with the AACA recommendations (Spearman ρ = 0.83, P = 0.015) and TA (Spearman ρ = 0.73, P = 0.046). Textbooks contained 8 distinct sections, 7 allocated to topographic anatomy regions and 1 to general anatomy concepts and principles. The structure of all textbooks correlated significantly with the course curriculum. However, 4 out of 6 textbooks did not correlate with TA and only a single textbook showed significant correlation with the AACA recommendations. Conclusion Anatomy textbooks vary in the amount of text dedicated to different parts of topographical anatomy and are not quite concordant with curriculum recommendations and standard anatomical terminology. Planning the structure of an anatomy course should not be based on a single book or recommendation but on evidence

Histological differences in healing following experimental transmural infarction in rats

Mechanisms of cardiac regeneration following transmural myocardial infarction were analysed in rat hearts using immunohistochemistry for α-SMA, caspase-3, Ki-67 and nestin markers. Seven weeks after experimental myocardial infarction, two different types of healing processes were revealed in rats with and without aneurysmatic bulging of the left ventricular wall. Besides thinning of the ventricular wall, three zones characterized both types of scars: the scar zone (divided into central and peripheral parts), the peri-infarct zone and the border zone. The main difference between the types of scars was the presence of a central necrotic zone inside the aneurysmatic wall, while connective tissue with myofibroblasts characterized the same zone in nonbulging wall. Apoptotic caspase-3 positive cells were found in the granulation tissue of the border zone in aneurysmatic scar, while in non-bulging scar they characterized all three zones. Proliferating Ki-67 positive cells displayed reverse expression pattern compared to apoptotic cells. Quantification of α-SMA positive cells revealed 60% α-SMA positive cells inside the central part of the aneurysmatic scar zone and 39% in invaginating areas, versus 19% in non-invaginating areas of the peripheral zone, but only 30% in the peripheral part of the non-bulging scar zone. Nestin positive cells were found in both types of scars, but with different distribution. These results suggest that even seven weeks after myocardial infarction, the healing processes in non-bulging scars are in chronic phase, while aneurysmatic scars are still in subacute phase. Histological differences in scar healing might be important for functional properties of the heart wall and for heart recovery prognosis

Daily Mini Quizzes as Means for Improving Student Performance in Anatomy Course

Aim To evaluate daily-written 10-question quizzes in a medical anatomy course as a way to integrate assessment into the course and to evaluate their effect on the course success. Methods Students answering correctly 8/10 or more questions were awarded 0.5 points per quiz. There were 34 quizzes with a maximum point score 17. Measurable outcomes of academic progress in anatomy course (pass rates on 4 examination terms, total pass rate, and average marks) were calculated, and 2007/08 academic year was compared with the previous academic year in which daily written quizzes were not a part of the course. The relationship between cumulative points on daily quizzes and 3 components of the final examination (written, practical, and oral) for 2007/08 academic year was assessed by nonparametric correlation testing. Results Individual scores on quizzes ranged from 1.5 to 13.5 points. There was a positive correlation between scores on quizzes and grades on 3 components of the final examination: written (Spearman ρ = 0.784, P < 0.001, n = 79), practical (Spearman ρ = 0.342, P < 0.002, n = 79), and oral (Spearman ρ = 0.683, P < 0.001, n = 79) part. Compared with students in the previous academic year, students attending the course with daily quizzes significantly improved their academic achievement, expressed as the pass rate at the first examination term (39% vs 62%, respectively, χ2 test, P = 0.006, ) and the average course grade (2.71 ± 1.08 vs 3.38 ± 1.26, respectively; t test, P < 0.001). Conclusion Despite their frequency and possible associated stress, daily quizzes were associated with better academic success in the anatomy course

New Paradigm in Training of Undergraduate Clinical Skills: the NEPTUNE-CS project at the Split University School of Medicine

Clinical skills’ training is arguably the weakest point in medical schools’ curriculum. This study briefly describes how we at the Split University School of Medicine cope with this problem. We consider that, over the last decades, a considerable advancement in teaching methodologies, tools, and assessment of students has been made. However, there are many unresolved issues, most notably: (i) the institutional value system, impeding the motivation of the teaching staff; (ii) lack of a strong mentoring system; (iii) organization, timing, and placement of training in the curriculum; (iv) lack of publications pertinent to training; and (v) unwillingness of patients to participate in student training. To improve the existing training models we suggest increased institutional awareness of obstacles, as well as willingness to develop mechanisms for increasing the motivation of faculty. It is necessary to introduce changes in the structure and timing of training and to complement it with a catalog, practicum, and portfolio of clinical skills. At Split University School of Medicine, we developed a new paradigm aimed to improve the teaching of clinical skills called “Neptune-CSS,” which stands for New Paradigm in Training of Undergraduate Clinical Skills in Split

Subpopulations of white blood cells.

<p>Subpopulations of white blood cells.</p

Historic, Demographic, and Genetic Evidence for Increased Population Frequencies of CCR5Δ32 Mutation in Croatian Island Isolates after Lethal 15th Century Epidemics

AIM: To assess the frequency of 32 base pair deletion in CCR5 (CCR5Delta32), which has been shown to confer resistance to HIV infection in a homozygous form, in 10 isolated island communities of Dalmatia, Croatia, with different histories of exposure to epidemics during and since the medieval period. ----- METHODS: In 2002, DNA analysis of 100 randomly selected individuals from each of the 10 isolated communities of 5 Croatian islands (Susak, Rab, Vis, Lastovo, and Mljet) showed high levels of 3-generational endogamy, indicating limited gene flow. Five of the communities were decimated by epidemics of unknown cause between 1449-1456, while the other 5 villages remained unaffected. Genotyping of the CCR5 gene was performed using the polymerase chain reaction method with primers flanking the region containing 32-bp deletion. ----- RESULTS: The frequency of CCR5Delta32 in the 5 villages affected by the epidemic was 6.1-10.0%, and 1.0-3.8% in the 5 unaffected villages. The Delta32 mutation was found in 71 of 916 alleles among the individuals from the affected villages (7.5%), and in 24 of 968 alleles in unaffected villages (2.5%, chi(2)=27.3, P<10-6). A previous study in 303 random Croatian blood donors showed the frequency of the CCR5 Delta32 of 7.1% in the general population. The difference remained significant after correcting for population structure using both STRAT and STRUCTURE software and the genomic control test, to ensure results do not arise from the background genetic differences. ----- CONCLUSION: Our results and historical evidence, suggest that the mid-15th century epidemic could have acted as a selection pressure for the CCR5Delta32 mutation