The outcome of surgical treatment for pancreatic head carcinoma in relation to the extent of lymphadenectomy

Uvod. Ideja ekstenzivne limfadenektomije je zasnovana na ideji da limfni nodusi izvan polja standardne disekcije mogu sadržati metastaze. Studije japanskih autora Ishikawe-a i Manabe-a iz 1988. i 1989. pokazale su značajno duže višegodišnje preživljavanje pacijenata kojima je rađena duodenopankreatektomija (DP) sa radikalnom limfadenektomijom u odnosu na one kod kojih je rađena standardna limfadenektomija. Od tada, benefit od radikalne limfadenektomije bio je predmet brojnih retrospektivnih studija u Japanu i na Zapadu. Višegodišnje preživljavanje u ovim studijama nije bilo značajno duže ali su stope postoperativnih komplikacija bile u nekim studijama značajno veće. Prva randomizirana kontrolisana studija (RCT) koja je poredila rezultate nakon standardne odnosno radikalne limfadenektomije kod DP bila je studija Pedrazzoli-ja. U ovoj studiji pacijenti sa radikalnom limfadenektomijom su imali značajno duže višegodišnje preživljavanje ali se ovo odnosilo samo na podgrupu pacijenata sa metastazama u limfnim nodusima (N1-status). Sledeće tri randomizirane kontrolisane studije nisu uspele da ponove rezultate Pedrazzoli-jeve studije odnosno nisu pokazale benefit u višegodišnjem preživljavanju nakon radikalne limfadenektomije. Ostali rezultati u smisli mortaliteta, morbiditeta i kvaliteta života bili su slični ili lošiji kod pacijenata sa radikalnom disekcijom limfnih nodusa. Ciljevi istraživanja. Primarni cilj istraživanja bio je analiza uticaja vrste hirurške procedure, standardne odnosno radikalne limfadenektomije na dugoročno preživljavanje pacijenata kojima je urađena DP zbog karcinoma glave pankreasa. Drugi ciljevi uključivali su analizu uticaja vrste hirurške procedure, standardne odnosno radikalne limfadenektomije na stope perioperativnog mortaliteta, postoperativnog morbiditeta i analizu prediktora mortaliteta. Materijal i metode. Istraživanje je dizajnirano po tipu prospektivne kohortne studije. U studiju su uključeni pacijenti mlađi od 80 godina sa potencijalno resektabilnim adenokarcinomom glave pankreasa bez pacijenata sa mucinoznim cistadenokarcinomima i intraduktalnim papilarnim mucinoznim karcinomima. Drugi kriterijumi isključenja iz studije bili su udaljenje visceralne metastaze, R2 resekcija, ASA (American Society of Anesthesiologists) skor veći od 3 i adjuvantna terapija. Studija je odobrena od strane etičkog odbora a svi pacijenti su potpisali pristanak za učešće u studiji. Od januara 2007. do decembra 2010., 103 pacijenta sa potencijalno resektabilnim karcinomom glave pankreasa su operisani pilorus-preserving duodenopankreatektomijom (PPDP) na Klinici za digestivnu hirurgiju, Klinički Centar Srbije. Pacijenti su podeljeni u dve grupe. Prva grupa (S=53) je operisana PPDP sa standardnom limfadenektomijom. Druga grupa (R=50) je operisana PPDP sa radikalnom limfadenektomijom. Pacijenti su praćeni na mesec dana prvih 6 meseci, potom na 3 meseca do navršene prve godine od operacije i na 6 meseci nakon toga...Introduction. The idea of extended lymphadenectomy was based on the fact that lymph nodes outside the field of dissection can harbour micrometastases. In the studies by Japanese authors Ishikawa and Manabe from 1988 and 1989, long-term survival was significantly improved in patients who underwent pancreaticoduodenectomy (PD) with extended lymphadenectomy comparing to those with standard lymphadenectomy. Since then, the benefit of extended lymphadenectomy has been evaluated in retrospective studies in Japan and also in Western countries. Long-term survival did not differ significantly in patients with extended lymphadenectomy compared to those with standard lymphadenectomy but some studies showed significantly higher rates of postoperative complications in patients who underwent PD with extended lymphadenectomy. The first RCT (randomized controlled trial) to compare the results of standard versus extended lymphadenectomy in PD, was reported by Pedrazzoli et al. In this trial patients who underwent PD with extended lymphadenectomy had a significantly better long-term survival but this regards only to patients with lymph node metastasis (N1). Three other RCTs failed to repeat Pedrazzoli's results and did not prove benefit in long-term survival in patients who underwent extended lymphadenectomy for pancreatic head carcinoma. Other results concerning mortality, morbidity and quality of life were similar between groups or even worse in patients with extended pancreatoduodenectomy. Aims and objectives. The primary aim of this study was to evaluate the benefit of extended lymphadenectomy in PD and to estimate its impact on long-term survival in patients with pancreatic head carcinoma. Secondary end-points included perioperative mortality, postoperative morbidity and predictors of mortality (survival) in patients undergoing standard versus extended lymphadenectomy for pancreatic head carcinoma. Material and methods. The study was designed as a prospective cohort study. For this trial we enrolled patients younger than 80 years of age with potentially resectable adenocarcinoma of the pancreatic head, excluding mucinous cystadenocarcinoma and intraductal papillary mucinous carcinoma. Other exclusion criteria included distant visceral metastases, R2 resection, ASA (American Society of Anesthesiologists) score higher than 3 and any adjuvant therapy previously received. This study was approved by institutional ethical review board and all patients gave their written consent before they were enrolled in the study. From January 2007 to December 2010, 103 patients with potentially resectable pancreatic head carcinoma were enrolled and resected using pilorus-preserving pancreaticoduodenectomy (PPPD) at Clinic for Digestive Surgery, Clinical Center of Serbia. Patients were divided into two groups. First group (S=53) underwent PPPD with standard lymphadenectomy. Second group (R=50) was operated with PPPD with extended lymphadenectomy. Mortality was defined as any death related to surgery. The patients were followed monthly during first 6 months, every 3 months until one year from surgery and every 6 months since. Minimum follow-up period for each patient was 5 years..

Antioxidative defense

Free radicals occur constantly during metabolism and take part in numerous physiological processes, such as: intra-cellular and inter-cellular signalization, gene expression, removal of damaged or senescent cells, and control of the tone of blood vessels. However, there is an increased quantity of free radicals in situations of so-called oxidative stress, when they cause serious damage to cellular membranes (peroxidation of their lipids, damage of membrane proteins, and similar), to interior cellular protein molecules, as well as DNA molecules and carbohydrates. This is precisely why the organism has developed numerous mechanisms for removing free radicals and/or preventing their production. Some of these are enzyme-related and include superoxide-dismutase, catalase, glutathione-peroxidase, and others. Other, non-enzyme mechanisms, imply antioxidative activities of vitamins E and C, provitamin A, coenzyme Q, reduced glutation, and others. Since free radicals can leave the cell that has produced them and become dispersed throughout the body, in addition to antioxidative defense that functions within cellular structures, antioxidant extra-cellular defense has also been developed. This is comprised by: transferrin, lactoferrin, haptoglobin, hemopexin, ceruloplasmin, albumins, extra-cellular isoform SOD, extracellular glutathione-peroxidase, glucose, bilirubin, urates, and many other molecules

Physiology of free radicals

Free radicals imply that every atom, molecule, ion, group of atoms, or molecules with one or several non-paired electrons in outer orbital. Among these are: nitrogenoxide (NO•), superoxide-anion-radical (O2•-), hydroxyl radical (OH•), peroxyl radical (ROO•), alcoxyl radical (RO•) and hydroperoxyl radical (HO2•). However, reactive oxygen species also include components without non-paired electrons in outer orbital (so-called reactive non-radical agents), such as: singlet oxygen (1O2), peroxynitrite (ONOO-), hydrogen-peroxide (H2O2), hypochloric acid (eg. HOCl) and ozone (O3). High concentrations of free radicals lead to the development of oxidative stress which is a precondition for numerous pathological effects. However, low and moderate concentrations of these matter, which occur quite normally during cell metabolic activity, play multiple significant roles in many reactions. Some of these are: regulation of signal pathways within the cell and between cells, the role of chemoattractors and leukocyte activators, the role in phagocytosis, participation in maintaining, changes in the position and shape of the cell, assisting the cell during adaption and recovery from damage (e.g.caused by physical effort), the role in normal cell growth, programmed cell death (apoptosis) and cell ageing, in the synthesis of essential biological compounds and energy production, as well as the contribution to the regulation of the vascular tone, actually, tissue vascularization

Antioksidativna odbrana

Free radicals occur constantly during metabolism and take part in numerous physiological processes, such as: intra-cellular and inter-cellular signalization, gene expression, removal of damaged or senescent cells, and control of the tone of blood vessels. However, there is an increased quantity of free radicals in situations of so-called oxidative stress, when they cause serious damage to cellular membranes (peroxidation of their lipids, damage of membrane proteins, and similar), to interior cellular protein molecules, as well as DNA molecules and carbohydrates. This is precisely why the organism has developed numerous mechanisms for removing free radicals and/or preventing their production. Some of these are enzyme-related and include superoxide-dismutase, catalase, glutathione-peroxidase, and others. Other, non-enzyme mechanisms, imply antioxidative activities of vitamins E and C, provitamin A, coenzyme Q, reduced glutation, and others. Since free radicals can leave the cell that has produced them and become dispersed throughout the body, in addition to antioxidative defense that functions within cellular structures, antioxidant extra-cellular defense has also been developed. This is comprised by: transferrin, lactoferrin, haptoglobin, hemopexin, ceruloplasmin, albumins, extra-cellular isoform SOD, extracellular glutathione-peroxidase, glucose, bilirubin, urates, and many other molecules.Slobodni radikali neprekidno nastaju tokom metabolizma i učestvuju u brojnim fiziološkim procesima, kao što su: unutarćelijska i međućelijska signalizacija, genska ekspresija, uklanjanje oštećenih i ostarelih ćelija i kontrola tonusa krvnih sudova. Međutim, količina slobodnih radikala je pojačana u stanju tzv. oksidativnog stresa, kada izazivaju ozbiljna oštećenja ćelijskih membrana (peroksidaciju njihovih lipida, oštećenje membranskih proteina i sl.), unutarćelijskih proteinskih molekula, kao i molekula DNA i ugljenih hidrata. Upravo zbog toga, organizam ima razvijene brojne mehanizme za uklanjanje slobodnih radikala i/ili sprečavanje njihove proizvodnje. Neki od njih su enzimski a obuhvataju superoksid-dismutazu, katalazu, glutation-peroksidaze i sl. Drugi, neenzimski mehanizmi, podrazumevaju antioksidativno delovanje vitamina E i C, provitamina A, koenzima Q, redukovanog glutationa i dr. S obzirom da slobodni radikali mogu da napuste ćeliju koja ih je proizvela i raznesu se po telu, osim antioksidativne odbrane koja funkcioniše unutar ćelijskih struktura razvila se i vanćelijska odbrana antioksidanasa. Nju obavljaju: transferin, lakroferin, haptoglobin, hemopeksin, ceruloplazmin, albumini, ekstracelularna izoforma SOD, ekstracelularna glutation-peroksidaza, glukoza, bilirubin, urati i mnogi drugi molekuli

Sinteza hidroksiapatita supstituisanog srebrom metodom precipitacije

Hidroksiapatit, HAp, Ca10(PO4)6(OH)2, je materijal koji se, zahvaljujući svojoj biokompatibilnosti, često koristi u regeneraciji koštanog tkiva. Usled česte pojave infekcije, koja može nastati njegovom ugradnjom, primenjuje se hidroksiapatit supstituisan srebrom, koji ima dokazane antibakterijske osobine. Cilj ovog rada je sinteza HAp-a, čija struktura sadrži atome srebra, metodom precipitacije u vodenom rastvoru. Karakterizacija materijala je vršena ispitivanjem faznog sastava XRD analizom, ispitivanje morfologije čestica metodom SEM-a, hemijskog sastava ICP analizom i merenjem raspodele veličina čestica. Rendgenska difrakcija na polikristalnim uzorcima HAp-a sa manjim sadržajima srebra (0,5; 1; 2 at %) potvrdila je monofazni karakter sintetisanih prahova. Međutim, povećanje sadržaja Ag+ jona u kristalnim prahovima HAp-a uslovljava pojavu novih refleksija na difraktogramima, koje odgovaraju srebro-fosfatu

Fiziologija slobodnih radikala

Free radicals imply that every atom, molecule, ion, group of atoms, or molecules with one or several non-paired electrons in outer orbital. Among these are: nitrogenoxide (NO•), superoxide-anion-radical (O2•-), hydroxyl radical (OH•), peroxyl radical (ROO•), alcoxyl radical (RO•) and hydroperoxyl radical (HO2•). However, reactive oxygen species also include components without non-paired electrons in outer orbital (so-called reactive non-radical agents), such as: singlet oxygen (1O2), peroxynitrite (ONOO-), hydrogen-peroxide (H2O2), hypochloric acid (eg. HOCl) and ozone (O3). High concentrations of free radicals lead to the development of oxidative stress which is a precondition for numerous pathological effects. However, low and moderate concentrations of these matter, which occur quite normally during cell metabolic activity, play multiple significant roles in many reactions. Some of these are: regulation of signal pathways within the cell and between cells, the role of chemoattractors and leukocyte activators, the role in phagocytosis, participation in maintaining, changes in the position and shape of the cell, assisting the cell during adaption and recovery from damage (e.g.caused by physical effort), the role in normal cell growth, programmed cell death (apoptosis) and cell ageing, in the synthesis of essential biological compounds and energy production, as well as the contribution to the regulation of the vascular tone, actually, tissue vascularization.Slobodni radikali podrazumevaju svaki atom, molekul, jon, grupu atoma ili molekula sa jednim ili više nesparenih elektrona u spoljašnjoj orbtali. U njih spadaju: azot-oksid (NO•), superoksid anjon radikal (O2•-), hidroksilni radikal (OH•), peroksilni radikal (ROO•), alkoksilni radikal (RO•) i hidroperoksilni radikal (HO2•-). Međutim, u reaktivne kiseonične vrste ubrajamo i komponente bez nesparenih elektrona u spoljašnjoj orbitali (tzv. reaktivni neradikalski agensi), kao što su: singlet kiseonik (1O2), peroksinitrit (ONOO-), vodonik-peroksid (H2O2), hipohlorasta kiselina (npr. HOCl) i ozon (O3). Visoke koncentracije slobodnih radikala izazivaju oksidativni stres koji je preduslov mnogobrojnih patoloških efekata. Međutim, niske i umerene koncentracije ovih materija, koje nastaju sasvim normalno tokom metaboličke aktivnosti ćelije, igraju višestuke značajne uloge u mnogim reakcijama. Neke od njih su: regulacija signalnih puteva unutar ćelije i među ćelijama, uloga hemoatraktanata i aktivatora leukocita, uloga u fagocitozi, učešće u održavanju, promeni položaja i oblika ćelije, pomoć ćeliji tokom adaptacije i oporavka od oštećenja (npr. izazvanih fizičkim radom), uloga u normalnom ćelijskom rastu, programiranoj ćelijskoj smrti (apoptozi) i ćelijskom starenju, u sintezi esencijalnih bioloških jedinjenja i proizvodnji energije, kao i doprinos regulaciji vaskularnog tonusa, odnosno vaskularizacije tkiva

Gastric adenomyoma

Bacground. Gastric adenomyoma is a rare, hamartomatous tumor localized most frequently in the gastric antrum. Review of the available literature shows only sporadic reports or smaller series. Case reports. We presented a 72-year-old woman admitted due to epigastric pain with dyspeptic difficulties. Biochemical parameters and tumor markers were within the referential limits. Diagnostic procedures (upper endoscopy, endoscopic ultrasonography and computerized tomography) revealed an intramural tumor prominence with intact mucosa on the posterior wall of gastric antrum, not accessible for biopsy. Surgical treatment was performed with total extirpation of the tumor. Histopathological examination verified adenomyoma with focal low grade epithelial dysplasia. Cytologic immunophenotype was consistent with smooth muscle stromal and epithelial tumor (CK7 and CK20 ++ immunophenotype). Stromal component revealed low proliferative index (Ki-67 protein immunoexpression level 3%), and p53 less than 0.1% in both epithelial and stromal components. Following the operation, the patient remained in good condition. Conclusion. Uncertain malignant potential of the gastric adenomyoma in the presented case indicates that timely diagnostics with adequate surgical treatment is crucial for an adequate treatment

Uticaj oksidativnog stresa na razvoj bolesti

There is ever increasing data indicating the vmast contribution of oxidative stress to the pathogenesis of numerous diseases (atherosclerosis, hypertension, heart failure, diabetes mellitus, stroke, rheumatoid arthritis, and others). Thus, in the pathogenesis of atherosclerosis the primary role is held by reactive oxygen species that are synthetized by endothelial cells of arterial blood vessels, leukocytes and macrophages. Furthermore, native particles of lipoproteins of small density become atherogenic through oxidation caused by reactive oxygen species. The oxidation of small-density lipoproteins stimulates the inflammatory process, and it in turn steps up adhesion and the inflow of monocytes and affects the synthesis and release of numerous proinflammatory cytokines involved in the further course of the process. One of the reasons for the development of arterial hypertension is the simultaneous activation of NAD(P)H oxidase and 12/15-lipoxygenase, since it results in the stepped up production of reactive oxygen species. These stimulate the production of matrix metalloproteinase 2, which lead to vascular remodelling and to increased apoptosis of heart muscle cells. Stepped up apoptosis is linked with myocardial infarction, cardiomyopathies and the development of heart failure. The sensitivity of β-cells of the endocrine part of the pancreas to reactive oxygen species favor the naturally low concentrations of the collectors of free radicals in them, as well as an increase in the concentration of proinflammatory cytokines, glucosis and lipids that induce a reduction in the mass and function of β-cells. Hyperglycemia in diabetes mellitus causes tissue damage through non-enzyme glycosylation of intracellular and extracellular proteins, which results in: reduced enzyme activity, damaged nucleic acid, disrupted natural decomposition of proteins, and activation of cytotoxic pathways. These processes are the basis of the pathogenesis of numerous complications of diabetes mellitus. Since inducible nitrogen-oxide synthesis launches processes that stimulate apoptosis of cerebral endothelial cells, and superoxide-anion radicals, hypochloric acid and hydrogen peroxide damage the parenchyma of an ischemic brain and biomacromolecules (causing lipid peroxidation, oxidation of proteins and deoxyribonucleic acid), brain damage occurs during cerebral ischemia and reperfusion.Sve više podataka ukazuje na veliki doprinos oksidativnog stresa patogenezi brojnih bolesti (aterosklerozi, hipertenziji, srčanoj insuficijenciji, šećernoj bolesti, moždanom udaru, reumatoidnom artritisu i dr.). Tako, u patogenezi ateroskleroze primarno mesto zauzimaju reaktivne kiseonične vrste koje sintetišu endotelne ćelije arterijskih krvnih sudova, leukociti i makrofagi. Uz to, nativne čestice lipoproteina male gustine postaju aterogene, oksidacijom izazvanom reaktivnim kiseoničnim vrstama. Oksidacija lipoproteina male gustine stimuliše zapaljenjski proces, a on pojačava adheziju i dotok monocita i utiče na sintezu i oslobađanje brojnih proinflamatornih citokina uključenih u dalji tok procesa. Jedan od razloga za razvoj arterijske hipertenzije je istovremena aktivacija NAD(P)H oksidaza i 12/15-lipoksigenaze, jer rezultira pojačanom proizvodnjom reaktivnih kiseoničnih vrsta. One podstiču proizvodnju metaloproteinaza-2 matriksa, koje dovode do vaskularnog remodeliranja i do pojačane apoptoze srčanih mišićnih ćelija. Pojačana apoptoza je povezana sa infarktom miokarda, kardiomiopatijama i razvojem srčane insuficijencije. Osetljivosti β-ćelija endokrinog dela pankreasa na reaktivne kiseonične vrste pogoduju prirodno niske koncentracije skupljača slobodnih radikala u njima, kao i porast koncentracije proinflamatornih citokina, glukoze i lipida koji indukuju smanjenje mase i funkcije β-ćelija. Hiperglikemija kod šećerne bolesti izaziva oštećenja tkiva neenzimskim glikozilovanjem intracelularnih i ekstracelularnih proteina, usled čega se smanjuje enzimska aktivnost, oštećuju nukleinske kiseline, re meti prirodna razgradnja proteina i aktiviraju citotoksični putevi. Ovi procesi su i osnova patogeneze mnogih komplikacija šećerne bolesti. S obzirom na to da inducibilna azot-oksid sintaza pokreće procese koji podstiču apoptozu cerebralnih endotelnih ćelija, a superoksid-anjon radikal, hipohlorna kiselina i vodonik-peroksid oštećuju parenhim ishemičnog mozga i biomakromolekule (izazivaju peroksidaciju lipida, oksidaciju proteina i dezoksiribonukleinske kiseline), tokom cerebralne ishemije i reperfuzije nastaju oštećenja mozga

Sodium Reduction by Partial and Total Replacement of NaCl with KCl in Serbian White Brined Cheese

Cheese has been listed as one of four priority food groups intended for salt reduction reformulation. The present study aimed to investigate the possibility of producing Serbian white brined cheese (Homoljski Sir) with half of NaCl, three quarters of NaCl and all NaCl replaced with KCl (Na50, Na25 and Na0, respectively). Basic composition, proteolysis and texture profile parameters were monitored during 60 days of ripening. At the end of ripening, an acceptance test was conducted by untrained consumers (N = 46). According to the cluster analysis based on hedonic scores, three clusters emerged: male consumers (47.8%), agreeable consumers (30.4%) and highly educated female consumers (21.8%). Both partial and a total salt replacement had no effect on the course of proteolytical changes, the texture and basic composition during ripening. Female consumers did not accept any level of salt substitution, while male consumers showed dislike only for the Na0 cheese. Almost 80% of all consumers liked moderately-to-very-much the Na25 cheese variant. It implies that it is worth considering the production of cheese with 50–75% of NaCl replaced with KCl. The addition of natural flavoring and clear labeling of the sodium reduction should accompany the salt replacement strategy

Tracking of Energy Performance Indicators in Residential Building Stocks – Different Approaches and Common Results - EPISCOPE Synthesis Report No. 4

A central task of IEE EPISCOPE project was to carry out energy balance calculations and scenario analysis for national, regional or local residential building stocks against the background of energy saving and climate protection targets. The EPISCOPE Synthesis Report No. 4 documents the individual approaches of collecting information for the investigated residential building stocks as a foundation for building stock models and scenario calculations. Issues related to the availability of data and data quality are discussed, and concepts for a continuous monitoring (a regular data collection) are presented as a basis for a future tracking of energy performance in the observed building stocks