Značaj FHIT i Bcl-2 u bolesnika s oralnim lihen planusom u usporedbi s zdravom oralnom sluznicom i oralnim karcinomom pločastih stanica

Background: Oral lichen planus (OLP) is a precancerous lesion which might progress into oral squamous cell cancer (OSCC) in 0-1.2 % of the affected patients. Albeit there are many published studies upon this topic, there are no universally accepted clinical and histopathological criteria which would suggest which patients will develop OSCC. Therefore, the aim of this study was to compare epithelial and sub epithelial FHIT and Bcl-2 expression between patients with OLP, OSCC and healthy oral mucosa.Materials and Methods: Fifty patients with OLP, 20 with OSCC who had histologically confi rmed diagnoses and 20 healthy controls were included in this study. Immuno-histochemical analysis was performed on primary monoclonal antibodies Bcl-2 (Dako, Finland) and FHIT (Zymed Laboratories Inc., USA) were used. Statistical analysis included Kolmogorov-Smirnoff test, χ2 test and Spearman’s correlation. All p values lower than p<0.05 were considered as significant. Results: Expression of FHIT in the OLP and OSCC epithelium is significantly decreased when compared to the healthy oral mucosa. However, no significant differences between FHIT expression between OLP and OSCC could be found. OLP and OSCC patients have signifi cantly increased expression values of Bcl-2 in the epithelium when compared to the epithelium of healthy participants. Furthermore, Bcl-2 expression is significantly increased in patients with OLP when compared to the patients with OSCC. Subepithelial infiltrate in OLP and OSCC reveals signifi cantly higher Bcl 2 expression when compared to the healthy controls. However, Bcl-2 expression in the infl ammatory infi ltrate is signifi cantly higher in OSCC patients when compared to the OLP patients. Conclusion: Loss of FHIT expression in the epithelium is not suffi cient for malignant transformation in OLP patients. It seems that other molecular changes are needed for OLP progression into OSCC. Bcl-2 expression in the infl ammatory infi ltrate is signifi cantly higher in OSCC patients when compared to the OLP patients and healthy controls, however bcl-2 expression in the epithelium does not correlate with precancerous (OLP) and OSCC lesions.Uvod: Oralni lihen planus (OLP) je prekancerozna lezija koji u 0-1,2 % oboljelih može progredirati u oralni karcinom pločastih stanica (OKPS). Premda su objavljeni brojni radovi na ovu temu, ne postoje opće prihvaćeni klinički i patohistološki kriteriji koji bi upućivali na to u kojih će se bolesnika razviti OKPS. Dakle, cilj je ovog istraživanja bio usporediti ekspresiju FHIT i Bcl-2 u epitelu i subepitelu pacijenata s OLP, OKPS te osoba sa zdravom oralnom sluznicom. Materijal i metode: U istraživanje je bilo uključeno pedeset pacijenata s histološki potvrđenom dijagnozom OLP, 20 pacijenata s histološki potvrđenom dijagnozom OKPS te 20 zdravih pacijenata kao kontrolna skupina. Korištene su imunohistokemijske analize na primarnim monoklonim protutijelima Bcl (Dako, Finska) i FHIT (Zymed Laboratories Inc., SAD). U statističkoj analizi korišteni su Kolmogorov-Smirnovljev test, hi kvadrat test i Spearmanov koefi cijent korelacije. P vrijednosti manje od 0.05 su smatrane značajnima. Rezultati: Ekspresija FHIT u epitelu zahvaćenom s OLP i OKPS je značajno smanjena u usporedbi sa zdravom oralnom sluznicom. Međutim, nije nađena značajna razlika u FHIT ekspresiji kod OLP i OKPS. Pacijenti oboljeli od OLP i OKPS imaju značajno pojačanu ekspresiju Bcl-2 u usporedbi s zdravim sudionicima. Nadalje, Bcl-2 ekspresija je značajno veća u pacijenata s OLP, nego u pacijenata s OKPS. Subepitelni infi ltrat u pacijenata s OLP i OKPS pokazuje značajno povećanje Bcl-2 ekspresije u odnosu na zdrave osobe iz kontrolne skupine. Međutim, Bcl-2 ekspresija u upalnom infiltratu je značajno viša u OKPS pacijenata nego li u OLP pacijenata. Zaključak: Gubitak FHIT ekspresije u epitelu sam po sebi nije dovoljan za zloćudnu transformaciju kod pacijenata koji boluju od OLP. Čini se da su za progresiju OLP u OKPS potrebne i druge molekularne promjene. Ekspresija Bcl-2 u upalnom infi ltrate je znakovito visa u bolesnika s OPKS u odnosu na bolesnicke s OLP i zdrave kontrole, ipak, ekspresija bcl-2 u epitelu ne korelira s prekanceroznim (OLP) odnosno lezijama OPKS

Uloga parametara kompletne krvne like u bolesnika s kolorektalnim karcinomom

Chronic inflammation has been linked with many cancers. It seems that easily available and usual blood inflammatory markers might serve as a prognostic factor for overall survival and disease-free survival in patients with various cancers. Preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as well as hemoglobinemia, thrombocytosis, elevated C-reactive protein values, neutropenia and leukocytosis have been shown to affect overall survival and disease-free survival in patients with colorectal cancer (CRC), however, with controversial results. Complete blood count, NLR and PLR were determined in 71 patients with CRC (stages 3 and 4) after neoadjuvant chemo-radiotherapy and before surgery, treated at Hospital for Tumors in Zagreb. Statistical analysis included Mann-Whitney U test, Student’s t-test, univariate and multivariate analysis. The results of Mann-Whitney U test and Student’s t-test showed that neutrophil count (p=0.024), NLR (p=0.003) and PLR (p=0.007) correlated significantly with overall survival. However, there was no significant correlation of age, leukocyte, lymphocyte and platelet counts and hemoglobin values with overall survival of patients. Furthermore, the same tests showed that leukocyte (p=0.04), neutrophil (p=0.0014) and platelet (p=0.006) counts, NLR (p=0.0006) and PLR (p=0.0015), as well as hemoglobin values (p=0.028) correlated significantly with disease-free survival. The results of univariate analysis showed that unlike PLR, NLR correlated with overall survival and disease-free survival (p=0.0002), although the correlation of PLR and disease-free survival almost reached significance (p=0.059). Furthermore, the results of univariate analysis showed significant correlation of advanced pathological TNM stage with overall survival. There was no correlation of patient age and gender, tumor stage and neoadjuvant chemo-radiotherapy with overall survival and disease-free survival. The results of multivariate analysis showed that NLR (cut-off value 3.27) and advanced pathological TNM stage significantly correlated with disease-free survival but not with overall survival. It seems that NLR might be an accurate marker for overall survival and disease-free survival in CRC patients after neoadjuvant chemo-radiotherapy and before surgery.Kronična upala je povezana s mnogim karcinomima. Čini se da lako dostupni i uobičajeni upalni biljezi u serumu mogu biti prognostički čimbenik za ukupno preživljenje i razdoblje bez bolesti u bolesnika s različitim karcinomima. Prijeoperacijski odnos neutrofila i limfocita (NLR) te trombocita i limfocita (TLR), kao i hemoglobinemija, trombocitoza, neutropenija i leukocitoza su povezani s ukupnim preživljenjem i razdobljem bez bolesti u bolesnika s kolorektalnim karcinomom (KRK), doduše, s proturječnim rezultatima. Kompletna krvna slika, NLR i TLR su određeni u 71 bolesnika s KRK (stadij 3 i 4) nakon neoadjuvantne kemoradioterapije i prije kirurškog zahvata, koji su liječeni na Klinici za tumore u Zagrebu. Statistička analiza je uključivala Mann-Whitneyev U test, Studentov t-test, univarijatnu i multivarijatnu analizu. Rezultati Mann-Whitneyeva U testa i Studentova t-testa su pokazali da su broj neutrofila (p=0,024), NLR (p=0,003) i TLR (p=0,007) značajno povezani s ukupnim preživljenjem. Ipak, nije bilo značajne povezanosti između dobi, broja leukocita, limfocita i trombocita te hemoglobina s ukupnim preživljenjem bolesnika. Nadalje, isti testovi su pokazali da su broj leukocita (p=0,04), neutrofila (p=0,0014) i trombocita (p=0,006), NLR (p=0,0006) i TLR (p=0,0015), kao i hemoglobin (p=0,028) značajno povezani s razdobljem bez bolesti. Rezultati univarijatne analize su pokazali da, za razliku od TLR, NLR korelira s ukupnim preživljenjem i preživljenjem bez bolesti, iako je korelacija zamalo postignuta između TLR i razdoblja bez bolesti (p=0,059). Nije bilo povezanosti između bolesnikove dobi i spola, stadija tumora i neoadjuvantne kemoradioterapije s ukupnim preživljenjem i razdobljem bez bolesti. Rezultati multivarijatne analize su pokazali kako NLR (granična vrijednost 3,27) i uznapredovali patološki stadij TNM značajno koreliraju s preživljenjem bez bolesti za razliku od ukupnog preživljenja. Čini se da je NLR pouzdan biljeg ukupnog preživljenja kao i preživljenja bez bolesti u bolesnika s KRK nakon neoadjuvantne kemoradioterapije i prije kirurškog zahvata

Portal triad obstruction and reperfusion in rats –the effect of BPC 157

To investigate effects of pentadecapeptide BPC 157 therapy in temporary portal triad obstruction – PTO (hepatic artery, portal vein, common bile duct, 30 min in rats), and in reperfusion period thereafter, during 15 min and 24 h. BPC 157 (10 μg/kg, 10 ng/kg), or saline (5 ml/kg) was applied as a bath at the hepatoduodenal ligament area immediately after portal triad clamping or at the same area at 1 min or at 24 h reperfusion time. A period of 30 min of PTO much like reperfusion during 15 min and 24 h regularly produced severe hemorrhagic congestion (scored 0-4) of the stomach, duodenum, jejunum, cecum, colon, and esophageal bleeding in all controls. Contrarily, given either in ischemia period or in reperfusion period, BPC 157 counteracts severe hemorrhagic congestion in all organs, counteracts esophageal bleeding and maintained grossly intact esophageal mucosa. BPC 157 promptly induced effective shunting (venography in portal vein below ligation, portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left iliac vein-inferior caval vein). BPC 157, since attenuates portal hypertension in PTO-period, and completely eliminates pre-existing portal hypertension in post-PTO-period resulting in the values much like in the normal rats. PTO induced esophageal bleeding and severe hemorrhagic congestion in stomach, duodenum, jejunum, cecum and colon. BPC 157 counteracts these complications along with portal hypertension. Pringle maneuver and its consequences may have BPC 157 application as a successful therapy

BPC 157 pentadecapepide attenuates acute renal ischemia injury, prevents ensuing hemodynamic disturbances, peaked and inverted p waves, and gastrointestinal lesions

We focused on the effects of BPC 157 on acute unilateral renal ischemia in rats, subsequent severe portal (PV) and inferior vena cava (IVC) hypertension and thrombosis, abdominal aorta (AA) hypotension, peaked or inverted P waves and gastrointestinal lesions. Medication (/kg) (BPC 157 (10 μg)(treated group) or saline (5 ml)(control group)) was applied as an abdominal bath immediately after the right renal artery was ligated. 10min, 1h, and 24h after ligation electrocardiography, USB microcamera recording, intravascular cannulation, and thrombi extraction was performed. Control rats exhibited PV and IVC hypertension, aortic hypotension (mmHg) (10min: 32±2 PV, 24±4 IVC, 75±2 AA; 1h: 43±4 PV, 46±3 IVC, 73±4 AA; 24h: 30±2 PV, 34±1 IVC, 86±3 AA) and thrombosis (thrombus weight, mg) (10min: 1.3±0.3 IVC, 3.5±0.4 PV; 1h: 15.1±0.5 IVC, 5.4±0.2 PV; 24h: 16.3±1.5 IVC, 6.1±0.9 PV). Treated group showed improved pressure values (10min: 4±1 PV, 8±1 IVC, 84±3 AA; 1h: 18±2 PV, 6±1 IVC, 92±3 AA; 24h: 5±1 PV, 10±1 IVC, 97±2 AA) and milder thrombosis (10min: no thrombi; 1h: 7.7±0.3 IVC, 2.3±0.2 PV; 24h: 11.6±0.5 IVC, 3.2±0.2 PV). Control rats exhibited peaked (10 min, 1h) or inverted (24h) P waves, gastric and intestinal lesions (24h) and complete renal infarction (24h), whereas the treated rats exhibited no P wave abnormalities, significantly mitigated gastrointestinal lesions (24h) and only partial renal infarction (24h). BPC 157 therapy reduces the severity of renal ischemia injury, counteracts hemodynamic disturbances, P wave abnormalities and gastrointestinal lesions that follow

Complications of portal triad obstruction and reperfusion in rats. pentadecapeptide BPC 157 counteracts venous and arterial thrombosis and arrhythmias

We wanted to explore effect of pentadecapeptide BPC 157 therapy in temporary portal triad obstruction (PTO) (hepatic artery (HA), portal vein (PV), bile duct occlusion for 30 min in rats), and in reperfusion period in post-PTO-period on the counteraction of the Pringle maneuver complications (cloth formation in the PV, superior mesenteric vein (SMV), lienal vein (LV), inferior caval vein (ICV) HA, peaked P wave and tachycardia). Medication (BPC 157 (10 μg/kg, 10 ng/kg), or saline (5 ml/kg) (controls)) was applied as a bath at the clamped area after portal triad clamping in rats with PTO or at the area that used to be clamped at 1 min or at 24 h reperfusion time. A period of 30 min of PTO produced thrombosis in the ICV, PV, SMV, LV and HA. In BPC 157 treated rats, the weights of the formed clots were smaller. PTO rats exhibited peaked P wave values and tachycardia which were absent in BPC 157-treated rats. Rats in post-PTO-period, during reperfusion exhibited peaked P wave values and tachycardia. Applications of BPC 157 (given at 1 min or at 24 h reperfusion time) resulted in the absence of the peaked P waves. Tachycardia was also affected; sinus rhythm appeared in a normal range of heart frequency. Confronted with Pringle maneuver and its consequences, BPC 157 therapy distinctively mitigates the whole syndrome, involving the counteraction of the course of the thrombosis in both veins and arteries, and ECG acute right ventricular overload

BPC 157 pentadecapepide attenuates acute renal ischemia injury, prevents ensuing hemodynamic disturbances, peaked and inverted p waves, and gastrointestinal lesions

We focused on the effects of BPC 157 on acute unilateral renal ischemia in rats, subsequent severe portal (PV) and inferior vena cava (IVC) hypertension and thrombosis, abdominal aorta (AA) hypotension, peaked or inverted P waves and gastrointestinal lesions. Medication (/kg) (BPC 157 (10 μg)(treated group) or saline (5 ml)(control group)) was applied as an abdominal bath immediately after the right renal artery was ligated. 10min, 1h, and 24h after ligation electrocardiography, USB microcamera recording, intravascular cannulation, and thrombi extraction was performed. Control rats exhibited PV and IVC hypertension, aortic hypotension (mmHg) (10min: 32±2 PV, 24±4 IVC, 75±2 AA; 1h: 43±4 PV, 46±3 IVC, 73±4 AA; 24h: 30±2 PV, 34±1 IVC, 86±3 AA) and thrombosis (thrombus weight, mg) (10min: 1.3±0.3 IVC, 3.5±0.4 PV; 1h: 15.1±0.5 IVC, 5.4±0.2 PV; 24h: 16.3±1.5 IVC, 6.1±0.9 PV). Treated group showed improved pressure values (10min: 4±1 PV, 8±1 IVC, 84±3 AA; 1h: 18±2 PV, 6±1 IVC, 92±3 AA; 24h: 5±1 PV, 10±1 IVC, 97±2 AA) and milder thrombosis (10min: no thrombi; 1h: 7.7±0.3 IVC, 2.3±0.2 PV; 24h: 11.6±0.5 IVC, 3.2±0.2 PV). Control rats exhibited peaked (10 min, 1h) or inverted (24h) P waves, gastric and intestinal lesions (24h) and complete renal infarction (24h), whereas the treated rats exhibited no P wave abnormalities, significantly mitigated gastrointestinal lesions (24h) and only partial renal infarction (24h). BPC 157 therapy reduces the severity of renal ischemia injury, counteracts hemodynamic disturbances, P wave abnormalities and gastrointestinal lesions that follow

Stable Gastric Pentadecapeptide BPC 157 Antagonized Local Anesthetic Effect of Lidocaine

Pentadecapeptide BPC 157 was previously shown as a cardioprotective compound in a model of arrhythmia induced by bupivacaine toxicity where it counteracts arrhythmias and prevents lethal outcome much like in other cardiotoxicity mainly related to potassium disturbances, both hyperkalemia and hypokalemia, in vivo and in vitro. We wanted to explore does BPC 157 antagonize effect of lidocai We used Wistar Albino male rats, underwent regional blocks with lidocaine (spinal intrathecal block (lidocaine 6 mg/kg, 0.1 ml/rat, 550 gb.w.) or axillary block (lidocaine 15 mg/kg, 0.3 ml/rat, 220 g b.w.). Rats received BPC 157 (10 μg, 10 ng, 10 pg/kg intraperitoneally or intragastrically) or an equivolume of saline (5 ml/kg), either immediately or at 10 min when local anesthesia was fully established. While lidocaine application produced a prolong function failure, all BPC 157 regimens significantly shortened time to full function recovery in the conditions of full local anesthesia. In other experiments, using a hot plate (55o C for 3 minutes) when rat hind paws were infiltrated with 2% lidocaine (0.1 ml/paw), a subsequent infiltration with BPC 157 (10 μg, 10 ng, 10 pg/kg) results in the faster feet lifting and much less edema. ECG recording documented that the regimens of BPC 157 counteracted the lidocaine-induced arrhythmias. Therefore, it may be possible that BPC 157 acts as the missing antidote to local anesthethics, and potentially deleterious and even life threatening adverse effects of toxic doses of local anesthethics would be markedly attenuated or even abolished

Kirurško liječenje kolorektalnog karcinoma

Surgery remains the only radical treatment for colorectal cancer. However, with introduction of multidisciplinary teams and availability and advancement in all modes of treatments (surgical technique, technology and perioperative care, sistemic therapy and radiotherapy protocols), in more advanced stages the better disease control is achieved. In this article we outline primarily indications and considerations in surgical treatment modeKirurško liječenje je jedini kurativni pristup liječenju kolorektalnog karcinoma. Ipak, uvođenjem multidisciplinarnih timova i napretkom i dostupnošću svih načina liječenja (kirurška tehnika i tehnologija kao i perioperativna skrb za pacijenta, te napredak u sistemskoj i radioterapiji) u poodmaklim stadijima, su omogućili uspješniju kontrolu bolesti. U ovom članku izosimo primarno indikacije i dileme kirurškog načina liječenj

Značaj rutinskih krvnih pretraga u bolesnika s karcinomima glave i vrata

More research suggest that parts of complete blood count might indicate disease-free and overall survival in patients with various cancers and therefore also in patients with head and neck cancer. Therefore, the aim of this paper was to review current knowledge upon signifi cance of complete blood count in head and neck cancers. PubMed was searched in the last 10 years in order to fi nd out references upon this topic and 19 articles were included. Leukocytosis and thrombocytosis negatively correlate with treatment outcome in patients with head and neck cancers, however not in all studies. High preoperative values of neutrophil and lymphocyte ratio suggest poorer disease outcome, i.e. shorter disease free period and overall survival in patients with head and neck cancer. It seems that published data provide an additional practical guidelines for evaluation of disease course in patients with head and neck cancer.Sve vise je istraživanja koja pokazuju kako elementi kompletne krvne slike mogu ukazati na period bez bolesti i ukupno preživljenje u bolesnika s raznim karcinomima. PubMed pregledom nađeno je 19 radova objavljenih zadnjih 10 godina o rutinskim laboratorijskim pretragama i karcinomima glave i vrata. Leukocitoza i trombocitoza su negativno povezane s ishodom liječenja u većini slučajeva bolesnika s orofaringealnim karcinomom, iako ne u svim istraživanjima. Visoke prijeoperacijske vrijednosti odnosa neutrofi la i limfocita ukazuju na lošiji ishod bolesti odnosno na kraći period bez bolesti i na lošije ukupno preživljenje u bolesnika s karcinomima glave i vrata. Čini se kako rezultati istraživanja omogućuju dodatne praktične vodiče u prognostici tijeka bolesti u bolesnika koji boluju od karcinoma glave i vrata

Complications of portal triad obstruction and reperfusion in rats. pentadecapeptide BPC 157 counteracts venous and arterial thrombosis and arrhythmias

We wanted to explore effect of pentadecapeptide BPC 157 therapy in temporary portal triad obstruction (PTO) (hepatic artery (HA), portal vein (PV), bile duct occlusion for 30 min in rats), and in reperfusion period in post-PTO-period on the counteraction of the Pringle maneuver complications (cloth formation in the PV, superior mesenteric vein (SMV), lienal vein (LV), inferior caval vein (ICV) HA, peaked P wave and tachycardia). Medication (BPC 157 (10 μg/kg, 10 ng/kg), or saline (5 ml/kg) (controls)) was applied as a bath at the clamped area after portal triad clamping in rats with PTO or at the area that used to be clamped at 1 min or at 24 h reperfusion time. A period of 30 min of PTO produced thrombosis in the ICV, PV, SMV, LV and HA. In BPC 157 treated rats, the weights of the formed clots were smaller. PTO rats exhibited peaked P wave values and tachycardia which were absent in BPC 157-treated rats. Rats in post-PTO-period, during reperfusion exhibited peaked P wave values and tachycardia. Applications of BPC 157 (given at 1 min or at 24 h reperfusion time) resulted in the absence of the peaked P waves. Tachycardia was also affected; sinus rhythm appeared in a normal range of heart frequency. Confronted with Pringle maneuver and its consequences, BPC 157 therapy distinctively mitigates the whole syndrome, involving the counteraction of the course of the thrombosis in both veins and arteries, and ECG acute right ventricular overload