Laparoskopska parcijalna pericistektomija ehinokokne ciste slezene – prikaz bolesnice [Laparoscopic partial pericystectomy of splenic hydatid cyst - a case report]

Echinococcal cyst of the spleen is usually a result of infection with the parasite Echinococcus granulosus. The spleen is the third most frequent localization of echinococcus after liver and lungs. Partial laparoscopic pericystectomy can be done without the loss of blood and scattering of scolexes with spleen preservation and conservation of its immune function. We present the patient with a large (1 8 x 16 x 12 cm) echinococcal cyst of the spleen that compressed the surrounding organs (stomach, transverse colon, pancreas and left kidney), and prevented normal passage causing vomiting after every meal. In this patient, PAIR procedure (puncture, aspiration, injection, reaspiration) and conservative treatment was attempted on several occasions without success. Finally, laparoscopic partial pericystectomy was performed, evacuating the contents of the cyst. The surgery lasted 120 minutes. Postoperatively the patient was without complications. Hospitalization lasted five days. Six months later, the patient is without problems. These echinococcus cysts of the spleen cannot be solved using PAIR technique and conservative treatment. Laparoscopic partial pericystectomy is a better solution than open surgery due to less trauma to the patient, especially in elderly people

LAPAROSCOPIC PARTIAL PERICYSTECTOMY OF SPLENIC HYDATID CYST – A CASE REPORT

Ehinokokna cista slezene redovito je posljedica infekcije parazitom Echinococcus granulosus. Slezena je treća najčešća lokalizacija ehinokoka, nakon jetre i pluća. Parcijalna laparoskopska pericistektomija može se učiniti bez gubitka krvi i rasapa skoleksa s prezervacijom slezene i očuvanjem njezine imunosne funkcije. Prikazana je pacijentica s velikom (18 × 16 × 12 cm) ehinokoknom cistom slezene koja je pritiskala okolne organe (želudac, poprečni kolon, pankreas i lijevi bubreg), onemogućavajući normalnu pasažu i izazivajući povraćanje nakon svakog obroka. Kod bolesnice su u nekoliko navrata neuspješno pokušani postupak PAIR (punkcija, aspiracija, injekcija, reaspiracija) i konzervativno liječenje te je naposljetku učinjena laparoskopska parcijalna pericistektomija s evakuacijom sadržaja ciste. Zahvat je trajao 120 minuta. Postoperacijski tijek protekao je bez komplikacija. Hospitalizacija je trajala 5 dana. Šest mjeseci kasnije bolesnica je bez tegoba. Ovakve ehinokokne ciste slezene nije moguće ukloniti tehnikom PAIR i konzervativnim liječenjem. Laparoskopska parcijalna pericistektomija bolje je rješenje od otvorene operacije zbog manje traume za organizam, osobito kod starijih ljudi.Echinococcal cyst of the spleen is usually a result of infection with the parasite Echinococcus granulosus. The spleen is the third most frequent localization of echinococcus after liver and lungs. Partial laparoscopic pericystectomy can be done without the loss of blood and scattering of scolexes with spleen preservation and conservation of its immune function. We present the patient with a large (18×16×12 cm) echinococcal cyst of the spleen that compressed the surrounding organs (stomach, transverse colon, pancreas and left kidney), and prevented normal passage causing vomiting after every meal. In this patient, PAIR procedure (puncture, aspiration, injection, reaspiration) and conservative treatment was ­attempted on several occasions without success. Finally, laparoscopic partial pericystectomy was performed, evacuating the contents of the cyst. The surgery lasted 120 minutes. Postoperatively the patient was without complications. Hospi­talization lasted five days. Six months later, the patient is without problems. These echinococcus cysts of the spleen cannot be solved using PAIR technique and conservative treatment. Laparoscopic partial pericystectomy is a better solution than open surgery due to less trauma to the patient, especially in elderly people

LAPAROSCOPIC PARTIAL PERICYSTECTOMY OF SPLENIC HYDATID CYST – A CASE REPORT

Ehinokokna cista slezene redovito je posljedica infekcije parazitom Echinococcus granulosus. Slezena je treća najčešća lokalizacija ehinokoka, nakon jetre i pluća. Parcijalna laparoskopska pericistektomija može se učiniti bez gubitka krvi i rasapa skoleksa s prezervacijom slezene i očuvanjem njezine imunosne funkcije. Prikazana je pacijentica s velikom (18 × 16 × 12 cm) ehinokoknom cistom slezene koja je pritiskala okolne organe (želudac, poprečni kolon, pankreas i lijevi bubreg), onemogućavajući normalnu pasažu i izazivajući povraćanje nakon svakog obroka. Kod bolesnice su u nekoliko navrata neuspješno pokušani postupak PAIR (punkcija, aspiracija, injekcija, reaspiracija) i konzervativno liječenje te je naposljetku učinjena laparoskopska parcijalna pericistektomija s evakuacijom sadržaja ciste. Zahvat je trajao 120 minuta. Postoperacijski tijek protekao je bez komplikacija. Hospitalizacija je trajala 5 dana. Šest mjeseci kasnije bolesnica je bez tegoba. Ovakve ehinokokne ciste slezene nije moguće ukloniti tehnikom PAIR i konzervativnim liječenjem. Laparoskopska parcijalna pericistektomija bolje je rješenje od otvorene operacije zbog manje traume za organizam, osobito kod starijih ljudi.Echinococcal cyst of the spleen is usually a result of infection with the parasite Echinococcus granulosus. The spleen is the third most frequent localization of echinococcus after liver and lungs. Partial laparoscopic pericystectomy can be done without the loss of blood and scattering of scolexes with spleen preservation and conservation of its immune function. We present the patient with a large (18×16×12 cm) echinococcal cyst of the spleen that compressed the surrounding organs (stomach, transverse colon, pancreas and left kidney), and prevented normal passage causing vomiting after every meal. In this patient, PAIR procedure (puncture, aspiration, injection, reaspiration) and conservative treatment was ­attempted on several occasions without success. Finally, laparoscopic partial pericystectomy was performed, evacuating the contents of the cyst. The surgery lasted 120 minutes. Postoperatively the patient was without complications. Hospi­talization lasted five days. Six months later, the patient is without problems. These echinococcus cysts of the spleen cannot be solved using PAIR technique and conservative treatment. Laparoscopic partial pericystectomy is a better solution than open surgery due to less trauma to the patient, especially in elderly people

INFLUENCE OF PENTADECAPEPTIDE BPC 157 ON HEALING OF COLONCOLONIC ANASTOMOSIS UNDER VENOUS CONGESTION CONDITIONS IN RATS

Venska kongestija debelog crijeva je stanje zastoja venske cirkulacije debelog crijeva koje uzrokuje edem stijenke i smanjenje arterijske irigacije crijeva. U takvim je uvjetima cijeljenje kolokolične anastomoze rizično pa se na kongestiranom crijevu obično ne radi primarna anastomoza nego kolostoma. Pentadekapeptid BPC 157 je sintetski oblik aktivnog terminalnog dijela ljudskog želučanog proteina koji se u dosadašnjim istraživanjima pokazao kao važan promotor cijeljenja različitih tkiva, uključujući i različite dijelove probavne cijevi, te kao snažan aktivator kolateralne cirkulacije. U procesu cijeljenja stimulira stvaranje granulacijskog tkiva i organizaciju kolagena, smanjuje edem i stimulira angiogenezu. U ovom istraživanju je ispitano djelovanje pentadekapeptida BPC 157 na cijeljenje kolokolične anastomoze u uvjetima venske kongestije debelog crijeva izazvane podvezivanjem kaudalne mezenterične vene u štakora. Pokus je izveden na 105 mužjaka laboratorijskih životinja soja Wistar, tjelesne mase 200-220 g, u dobi 8-10 tjedana. Životinje su bile podijeljene u 15 skupina i 5 vremenskih intervala (3, 5, 7, 15 i 30 dana), a svaka se skupina sastojela od 7 životinja. Nakon postizanja kongestije silaznog dijela debelog crijeva učinjena je transekcija debelog crijeva i pripadajućeg mezokolona, a zatim je kreirana terminoterminalna kolokolična anastomoza. Tretirane životinje su nakon kreiranja anastomoze intraperitonealno dobile jednokratno pentadekapeptid BPC 157 u dozi 10 µg/kg ili 10 ng/kg, a kontrolne životinje su na isti način dobile fiziološke otopinu u dozi 5 mL/kg. U postoperacijskom periodu tretirane životinje su primale pentadekapeptid BPC 157 u dozi 10 µg/kg/dan ili 10 ng/kg/dan peroralno. Popuštanje kolokolične anastomoze je evidentirano kod 31,42 % kontrolnih životinja (11/35) i kod 2,85 % tretiranih životinja (2/70). Priraslice i smetnje pasaže su bile značajno manje izražene kod tretiranih životinja. Volumen venskih arkada debelog crijeva i broj venskih kolaterala između dviju susjednih venskih arkada uz oralnu i aboralnu stranu anastomoze su bili značajno veći kod tretiranih skupina. Edem i nekroza su bili značajno manje izraženi kod tretiranih životinja. Granulacijsko tkivo se javilo ranije kod tretiranih skupina uz vidljivu organizaciju kolagenih i retikulinskih vlakana dok kontrolne skupine životinja nisu imale organizaciju cijeljenja. Epitelizacija anastomoze se javila ranije i na kraju pokusa je bila značajno veća kod tretiranih životinja. Testiranjem anastomoze pokazana je veća čvrstoća anastomoze tretiranih životinja. Nije bilo statistički značajne razlike između skupina koje su dobivale pentadekapeptid BPC 157 10 µg/kg i skupina koje su dobivale pentadekapeptid BPC 157 10 ng/kg. Rezultati upućuju na značajno bolje cijeljenje kolokolične anastomoze kod tretiranih životinja, potvrđuju rezultate dosadašnjih istraživanja i sugeriraju mogućnost primjene pentadekapeptida BPC 157 u abdominalnoj kirurgiji.Background and objectives: Although great progress in colorectal surgery was achieved during the last few decades, the problem of colorectal anastomosis dehiscence, with resulting morbidity and mortality, remains to this day. Colonic anastomosis creation is an everyday procedure in abdominal surgery and basically does not differ from any other anastomosis creation. A particular type of colonic anastomosis is a colorectal-coloanal anastomosis, special due to rectum vascularization, absence of the serosa in the subperitoneal part of the rectum, and difficulty with the surgical procedure due to narrow space in the true pelvis. Thus, literature that focuses on colonic anastomoses usually refers to the colorectal anastomosis. Intestinal anastomosis healing is a complicated process that depends on the patient's general state, intestine state, technical conditions, and surgeon's knowledge and experience. Among many factors that affect the process of anastomosis healing, one of the most important is adequate arterial and venous circulation of the intestines. Colonic congestion is defined as colonic venous circulation stasis that causes intestinal wall edema and reduction of arterial irrigation, which is often observed in patients that suffer from colonic obstruction ileus caused by malignant tumors. Although ischemia and congestion both lead to tissue hypoxia, intestinal congestion is considered a more serious and complicated condition. By comparing ischemic and venous congestion intestinal injury, destruction of the intestinal mucosa induced by venous congestion arises earlier and is slower to normalize after etiological factor removal, which makes intestinal congestionreperfusion injury much more severe than ischemic-reperfusion injury. Colonic congestion is usually found in patients suffering from ileus caused by malignant tumors located in the colon, and in those cases, a colostomy is preferred over anastomosis creation. In case of venous congestion, meaning compromised venous circulation, primary anastomosis is usually not performed because congested intestinal anastomosishealing is risky and burdened with a high possibility of anastomosis dehiscence with accompanying peritonitis or intraabdominal abscess. Thus, colostomy is usually performed in those cases. Pentadecapeptide body protective compound 157 (BPC 157) is a terminal part of the BPC protein crucial for its activity. Pentadecapeptide BPC was isolated from human gastric juice and is found to need no additional carriers for absorption and to be stable in human gastric juice. The synthetic form of BPC 157 has been examined in great detail and scope via experimental research that has shown its positive effects on burn healing, gastric and duodenal ulcer healing, different fistula of the gastrointestinal tract, and intestinal anastomosis healing. The effectiveness of pentadecapeptide BPC 157 in healing promotion has been investigated in different animal models, proving its effect on connective tissue and blood vessels. In a burn animal model, it was shown that BPC 157 attenuates the inflammatory response, lessens the edema and necrosis of the burnt skin, and enhances collagen organization, angiogenesis, and tissue epithelization. In an animal model of esophagogastric anastomosis and colon-colonic anastomosis in cysteamine colitis caused by rectal cysteamine enema, greater mortality and anastomosis dehiscence was found in control groups, in contrast to treated groups. Pentadecapeptide BPC 157 helps the healing process by stimulating granulation tissue creation and collagen organization, as well as reducing the edema and stimulating angiogenesis. Recent studies have shown that pentadecapeptide BPC 157 activates anatomically present collateral circulation in arterial or venous obstruction conditions and thus lessens the negative impact of vascular obstruction.The exact mechanism of action of pentadecapeptide BPC 157 is still not clarified in full, but its effects on different tissues and organs are explained through many different interacting systems, the most important one being the NO system. It has been proven that pentadecapeptide BPC 157 induces NO formation and interferes with agonists (L-arginine, NO substrate) and antagonists (L-NAME) of the NO system. By inducing NO synthesis, pentadecapeptide BPC 157 stimulates vasodilatation in the early stages of the healing process. Additionaly, in early stages of the healing process, pentadecapeptide BPC 157 stimulates the production of EGR1, crucial for activation of genes that code for various cytokines and growth factors, thus stimulating collagen production and organization. It has been established that pentadecapeptide BPC 157 stimulates expression of EGR-1mRNA 15 minutes after application, and 30 minutes after application, BPC 157 stimulates NAB2 mRNA expression, which is a corepressor of EGR-1. Hsieh et al. have demonstrated that pentadecapeptide BPC 157 affects aortic tone via NO synthesis stimulation through the Src-Cav-1-eNOS signal pathway. The angiogenesis-modulating potential of pentadecapeptide BPC 157 manifests through stimulation of VEGF and VEGFR2 expression, which was examined in an animal model of limb ischemia. Pentadecapeptide BPC 157 increased VEGFR2 expression in blood vessel endothelium and thus enabled quick reestablishment of the circulation through the ischemic extremity. Angiomodulatory effects of pentadecapeptide BPC 157 were also examined in an animal model of duodenal lesions caused by ligation of superior anterior pancreaticoduodenal vein that revealed that pentadecapeptide BPC 157 causes collateral circulation activation through the NO system, and thus attenuates the congestion and duodenal mucosal lesions development. To this day, pentadecapeptide BPC 157 was administered in various different doses (µg/kg, ng/kg, or pg/kg) and applied in various different modes of drug delivery (locally: baths, cremes, eyedrops; systemically: intraperitoneally, intragastrically, perorally). Additionally, to this day no serious toxicity of pentadecapeptide BPC 157 has been noted. Based on described effects of pentadecapeptide BPC 157, we hypothesized that pentadecapeptide BPC 157 may have positive effects on colon-colonic anastomosis healing under venous congestion conditions. The aim of this study is to examine the effect of pentadecapeptide BPC 157 on colon-colonic anastomosis healing under venous congestion conditions caused by ligation of the caudal mesenteric vein in rats. Material and methods: The experiment was performed using 105 male albino Wistar rats, bodyweight 200-220 g, aged 8-10 weeks, divided into 15 groups and 5 time intervals (3, 5, 7, 15, or 30 days). Each group included 7 animals. For each time interval, there was one control group, one treated group that received pentadecapeptide BPC 157 dose of 10µg/ kg, and the second treated group that pentadecapeptide BPC 157 dose of 10 ng/kg. Two different doses of BPC 157 were used to examine the dosedependent effect of BPC 157. Animals were anesthetized via intraperitoneal injection containing diazepam 5 mg/kg (Apaurin, Krka, Slovenia), thiopental 50 mg/kg (Thiopental Injection BP, Rotexmedica, Germany), and buprenorphine 1 mg/kg (Bupredine Multidose, Dechra, Great Britain).In deeply anesthetized rats, median laparotomy was performed and caudal mesenteric vein (CMV) was ligated to achieve venous congestion in the descending colon. After venous congestion was achieved, transection of the colon descendens and adjacent mesocolon was done, after which terminoterminal colon-colonic anastomosis was created. After anastomosis creation, treated animals received pentadecapeptide BPC 157 intraperitoneally in doses 10 µg/ kg or 10 ng/kg and control animals were given 1 mL saline, also intraperitoneally. At each time interval (3, 5, 7, 15 or 30 days postoperatively) animals were again deeply anesthetized and relaparatomised to examine macroscopic changes: anastomosis dehiscence, adhesions, anastomosis passability, and venous arcade (vasa recta) presentation on the ventral and dorsal side of the colon, orally and aborally from the anastomosis. The anastomosis was tested as follows: intestinal clamps were used to occlude the descending colon 2.5 cm orally and 2.5 cm aborally from the anastomosis site and saline wasapplied intraluminally until volume that caused anastomosis leakage was reached. The colonic segment containing the anastomosis was explanted from euthanized animals (2 cm orally and 2 cm aborally from the anastomosis site). Surrounding mesocolon was removed from the resected part of the colon, the resected part was then rinsed in saline, placed over a styrofoam panel, and submerged into 4% formaldehyde solution for histopathological analysis. Mentioned analysis was performed by two independent pathologists who had no previous knowledge of tissue specimens. 5 fields of view were analyzed using 200x magnification. The morphological analysis included epithelisation, necrosis, edema, and granulation tissue formation evaluation. Histochemical coloring methods included hemalaun-eosine, Gommori for reticulin fibers and Masson for collagen fibers, and immunohistochemical coloring SMA for new smooth muscle cells visualization. All stages of the experiment were recorded using a Veho Discovery VMS-004 Deluxe USB camera with a microscope (Veho, Dayton, OH, SAD). Recordings took place before CMV ligation, after CMV ligation, after anastomosis creation and pentadecapeptide BPC 157 application, and at 3, 5, 7, 15 and 30 days postoperatively. Thus obtained films images were then saved as digital photographs to enable comparison between treated and control animals. Using digital photographs, two venous arcades (vasa recta) were analyzed on the ventral and dorsal side of the colon, orally and aborally from the anastomosis, as well as communicating branches between mentioned venous arcades.Program STATISTICA 12.1. (StatSoft, Inc, Tulsa, USA) was used for statistical processing. For the data distribution assessment, the Kolmogorov-Smirnoff test was used. Results are expressed as mean +/- standard deviation (SD) and as minimum/median/maximum. For parametric data, one way ANOVA test with NewmanKeuls post hoc test was used, and for nonparametric data Kruskal-Wallis test with Mann-Whitney post hoc test was used. Qualitative data in control and treated groups were analyzed using the Fisher test. p<0,05 was considered statistically significant. Results: Anastomosis dehiscence was evidenced in 11 of 35 control animals (31.42%) and 2 of 70 treated animals (2.85%). There was no evidence of diffuse peritonitis or intraabdominal abscess. Adhesions and intestinal obstruction of the anastomosis were significantly mitigated in treated groups at all time intervals. Better presentation of the blood vessels, meaning higher volume of venous arcades orally and aborally from the anastomosis and greater number of communicating branches between mentioned venous arcades, was found in treated animals. Anastomosis testing revealed better anastomosis solidity in treated animals. Histopathological analysis showed less edema and necrosis in treated animals. Granulation tissue was present at an earlier time interval in treated animals, with the visible organization of collagen and reticulin fibers. In control animals, no healing organization was found. Immunohistochemical staining showed smooth muscle cell bundles organization in treated animals, which was absent in control animals. Additionally, epithelization developed earlier in treated animals. At the end of the experiment, treated animals exhibited 80%nanastomosis epithelization, in contrast, control animals exhibited only 10% anastomosis epithelization. There was no statistically significant difference in any of the observed parameters between groups that received the pentadecapeptide BPC 157 dose of 10 µg /kg and 10 ng/kg. Conclusions: Pentadecapeptide BPC 157 enhances colon-colonic anastomosis healing under venous congestion conditions, which is observable at both macroscopic and microscopic levels. The enhancing effect of pentadecapeptide BPC 157 on coloncolonic anastomosis healing under venous congestion conditions was present in 10 µg/kg and 10 ng/kg doses without statistically significant differences between the doses. This experiment confirmes already established role of pentadecapeptide 157 in healingpromotion and opens the possibility of pentadecapeptide BPC 157 use in abdominal surgery

INFLUENCE OF PENTADECAPEPTIDE BPC 157 ON HEALING OF COLONCOLONIC ANASTOMOSIS UNDER VENOUS CONGESTION CONDITIONS IN RATS

Venska kongestija debelog crijeva je stanje zastoja venske cirkulacije debelog crijeva koje uzrokuje edem stijenke i smanjenje arterijske irigacije crijeva. U takvim je uvjetima cijeljenje kolokolične anastomoze rizično pa se na kongestiranom crijevu obično ne radi primarna anastomoza nego kolostoma. Pentadekapeptid BPC 157 je sintetski oblik aktivnog terminalnog dijela ljudskog želučanog proteina koji se u dosadašnjim istraživanjima pokazao kao važan promotor cijeljenja različitih tkiva, uključujući i različite dijelove probavne cijevi, te kao snažan aktivator kolateralne cirkulacije. U procesu cijeljenja stimulira stvaranje granulacijskog tkiva i organizaciju kolagena, smanjuje edem i stimulira angiogenezu. U ovom istraživanju je ispitano djelovanje pentadekapeptida BPC 157 na cijeljenje kolokolične anastomoze u uvjetima venske kongestije debelog crijeva izazvane podvezivanjem kaudalne mezenterične vene u štakora. Pokus je izveden na 105 mužjaka laboratorijskih životinja soja Wistar, tjelesne mase 200-220 g, u dobi 8-10 tjedana. Životinje su bile podijeljene u 15 skupina i 5 vremenskih intervala (3, 5, 7, 15 i 30 dana), a svaka se skupina sastojela od 7 životinja. Nakon postizanja kongestije silaznog dijela debelog crijeva učinjena je transekcija debelog crijeva i pripadajućeg mezokolona, a zatim je kreirana terminoterminalna kolokolična anastomoza. Tretirane životinje su nakon kreiranja anastomoze intraperitonealno dobile jednokratno pentadekapeptid BPC 157 u dozi 10 µg/kg ili 10 ng/kg, a kontrolne životinje su na isti način dobile fiziološke otopinu u dozi 5 mL/kg. U postoperacijskom periodu tretirane životinje su primale pentadekapeptid BPC 157 u dozi 10 µg/kg/dan ili 10 ng/kg/dan peroralno. Popuštanje kolokolične anastomoze je evidentirano kod 31,42 % kontrolnih životinja (11/35) i kod 2,85 % tretiranih životinja (2/70). Priraslice i smetnje pasaže su bile značajno manje izražene kod tretiranih životinja. Volumen venskih arkada debelog crijeva i broj venskih kolaterala između dviju susjednih venskih arkada uz oralnu i aboralnu stranu anastomoze su bili značajno veći kod tretiranih skupina. Edem i nekroza su bili značajno manje izraženi kod tretiranih životinja. Granulacijsko tkivo se javilo ranije kod tretiranih skupina uz vidljivu organizaciju kolagenih i retikulinskih vlakana dok kontrolne skupine životinja nisu imale organizaciju cijeljenja. Epitelizacija anastomoze se javila ranije i na kraju pokusa je bila značajno veća kod tretiranih životinja. Testiranjem anastomoze pokazana je veća čvrstoća anastomoze tretiranih životinja. Nije bilo statistički značajne razlike između skupina koje su dobivale pentadekapeptid BPC 157 10 µg/kg i skupina koje su dobivale pentadekapeptid BPC 157 10 ng/kg. Rezultati upućuju na značajno bolje cijeljenje kolokolične anastomoze kod tretiranih životinja, potvrđuju rezultate dosadašnjih istraživanja i sugeriraju mogućnost primjene pentadekapeptida BPC 157 u abdominalnoj kirurgiji.Background and objectives: Although great progress in colorectal surgery was achieved during the last few decades, the problem of colorectal anastomosis dehiscence, with resulting morbidity and mortality, remains to this day. Colonic anastomosis creation is an everyday procedure in abdominal surgery and basically does not differ from any other anastomosis creation. A particular type of colonic anastomosis is a colorectal-coloanal anastomosis, special due to rectum vascularization, absence of the serosa in the subperitoneal part of the rectum, and difficulty with the surgical procedure due to narrow space in the true pelvis. Thus, literature that focuses on colonic anastomoses usually refers to the colorectal anastomosis. Intestinal anastomosis healing is a complicated process that depends on the patient's general state, intestine state, technical conditions, and surgeon's knowledge and experience. Among many factors that affect the process of anastomosis healing, one of the most important is adequate arterial and venous circulation of the intestines. Colonic congestion is defined as colonic venous circulation stasis that causes intestinal wall edema and reduction of arterial irrigation, which is often observed in patients that suffer from colonic obstruction ileus caused by malignant tumors. Although ischemia and congestion both lead to tissue hypoxia, intestinal congestion is considered a more serious and complicated condition. By comparing ischemic and venous congestion intestinal injury, destruction of the intestinal mucosa induced by venous congestion arises earlier and is slower to normalize after etiological factor removal, which makes intestinal congestionreperfusion injury much more severe than ischemic-reperfusion injury. Colonic congestion is usually found in patients suffering from ileus caused by malignant tumors located in the colon, and in those cases, a colostomy is preferred over anastomosis creation. In case of venous congestion, meaning compromised venous circulation, primary anastomosis is usually not performed because congested intestinal anastomosishealing is risky and burdened with a high possibility of anastomosis dehiscence with accompanying peritonitis or intraabdominal abscess. Thus, colostomy is usually performed in those cases. Pentadecapeptide body protective compound 157 (BPC 157) is a terminal part of the BPC protein crucial for its activity. Pentadecapeptide BPC was isolated from human gastric juice and is found to need no additional carriers for absorption and to be stable in human gastric juice. The synthetic form of BPC 157 has been examined in great detail and scope via experimental research that has shown its positive effects on burn healing, gastric and duodenal ulcer healing, different fistula of the gastrointestinal tract, and intestinal anastomosis healing. The effectiveness of pentadecapeptide BPC 157 in healing promotion has been investigated in different animal models, proving its effect on connective tissue and blood vessels. In a burn animal model, it was shown that BPC 157 attenuates the inflammatory response, lessens the edema and necrosis of the burnt skin, and enhances collagen organization, angiogenesis, and tissue epithelization. In an animal model of esophagogastric anastomosis and colon-colonic anastomosis in cysteamine colitis caused by rectal cysteamine enema, greater mortality and anastomosis dehiscence was found in control groups, in contrast to treated groups. Pentadecapeptide BPC 157 helps the healing process by stimulating granulation tissue creation and collagen organization, as well as reducing the edema and stimulating angiogenesis. Recent studies have shown that pentadecapeptide BPC 157 activates anatomically present collateral circulation in arterial or venous obstruction conditions and thus lessens the negative impact of vascular obstruction.The exact mechanism of action of pentadecapeptide BPC 157 is still not clarified in full, but its effects on different tissues and organs are explained through many different interacting systems, the most important one being the NO system. It has been proven that pentadecapeptide BPC 157 induces NO formation and interferes with agonists (L-arginine, NO substrate) and antagonists (L-NAME) of the NO system. By inducing NO synthesis, pentadecapeptide BPC 157 stimulates vasodilatation in the early stages of the healing process. Additionaly, in early stages of the healing process, pentadecapeptide BPC 157 stimulates the production of EGR1, crucial for activation of genes that code for various cytokines and growth factors, thus stimulating collagen production and organization. It has been established that pentadecapeptide BPC 157 stimulates expression of EGR-1mRNA 15 minutes after application, and 30 minutes after application, BPC 157 stimulates NAB2 mRNA expression, which is a corepressor of EGR-1. Hsieh et al. have demonstrated that pentadecapeptide BPC 157 affects aortic tone via NO synthesis stimulation through the Src-Cav-1-eNOS signal pathway. The angiogenesis-modulating potential of pentadecapeptide BPC 157 manifests through stimulation of VEGF and VEGFR2 expression, which was examined in an animal model of limb ischemia. Pentadecapeptide BPC 157 increased VEGFR2 expression in blood vessel endothelium and thus enabled quick reestablishment of the circulation through the ischemic extremity. Angiomodulatory effects of pentadecapeptide BPC 157 were also examined in an animal model of duodenal lesions caused by ligation of superior anterior pancreaticoduodenal vein that revealed that pentadecapeptide BPC 157 causes collateral circulation activation through the NO system, and thus attenuates the congestion and duodenal mucosal lesions development. To this day, pentadecapeptide BPC 157 was administered in various different doses (µg/kg, ng/kg, or pg/kg) and applied in various different modes of drug delivery (locally: baths, cremes, eyedrops; systemically: intraperitoneally, intragastrically, perorally). Additionally, to this day no serious toxicity of pentadecapeptide BPC 157 has been noted. Based on described effects of pentadecapeptide BPC 157, we hypothesized that pentadecapeptide BPC 157 may have positive effects on colon-colonic anastomosis healing under venous congestion conditions. The aim of this study is to examine the effect of pentadecapeptide BPC 157 on colon-colonic anastomosis healing under venous congestion conditions caused by ligation of the caudal mesenteric vein in rats. Material and methods: The experiment was performed using 105 male albino Wistar rats, bodyweight 200-220 g, aged 8-10 weeks, divided into 15 groups and 5 time intervals (3, 5, 7, 15, or 30 days). Each group included 7 animals. For each time interval, there was one control group, one treated group that received pentadecapeptide BPC 157 dose of 10µg/ kg, and the second treated group that pentadecapeptide BPC 157 dose of 10 ng/kg. Two different doses of BPC 157 were used to examine the dosedependent effect of BPC 157. Animals were anesthetized via intraperitoneal injection containing diazepam 5 mg/kg (Apaurin, Krka, Slovenia), thiopental 50 mg/kg (Thiopental Injection BP, Rotexmedica, Germany), and buprenorphine 1 mg/kg (Bupredine Multidose, Dechra, Great Britain).In deeply anesthetized rats, median laparotomy was performed and caudal mesenteric vein (CMV) was ligated to achieve venous congestion in the descending colon. After venous congestion was achieved, transection of the colon descendens and adjacent mesocolon was done, after which terminoterminal colon-colonic anastomosis was created. After anastomosis creation, treated animals received pentadecapeptide BPC 157 intraperitoneally in doses 10 µg/ kg or 10 ng/kg and control animals were given 1 mL saline, also intraperitoneally. At each time interval (3, 5, 7, 15 or 30 days postoperatively) animals were again deeply anesthetized and relaparatomised to examine macroscopic changes: anastomosis dehiscence, adhesions, anastomosis passability, and venous arcade (vasa recta) presentation on the ventral and dorsal side of the colon, orally and aborally from the anastomosis. The anastomosis was tested as follows: intestinal clamps were used to occlude the descending colon 2.5 cm orally and 2.5 cm aborally from the anastomosis site and saline wasapplied intraluminally until volume that caused anastomosis leakage was reached. The colonic segment containing the anastomosis was explanted from euthanized animals (2 cm orally and 2 cm aborally from the anastomosis site). Surrounding mesocolon was removed from the resected part of the colon, the resected part was then rinsed in saline, placed over a styrofoam panel, and submerged into 4% formaldehyde solution for histopathological analysis. Mentioned analysis was performed by two independent pathologists who had no previous knowledge of tissue specimens. 5 fields of view were analyzed using 200x magnification. The morphological analysis included epithelisation, necrosis, edema, and granulation tissue formation evaluation. Histochemical coloring methods included hemalaun-eosine, Gommori for reticulin fibers and Masson for collagen fibers, and immunohistochemical coloring SMA for new smooth muscle cells visualization. All stages of the experiment were recorded using a Veho Discovery VMS-004 Deluxe USB camera with a microscope (Veho, Dayton, OH, SAD). Recordings took place before CMV ligation, after CMV ligation, after anastomosis creation and pentadecapeptide BPC 157 application, and at 3, 5, 7, 15 and 30 days postoperatively. Thus obtained films images were then saved as digital photographs to enable comparison between treated and control animals. Using digital photographs, two venous arcades (vasa recta) were analyzed on the ventral and dorsal side of the colon, orally and aborally from the anastomosis, as well as communicating branches between mentioned venous arcades.Program STATISTICA 12.1. (StatSoft, Inc, Tulsa, USA) was used for statistical processing. For the data distribution assessment, the Kolmogorov-Smirnoff test was used. Results are expressed as mean +/- standard deviation (SD) and as minimum/median/maximum. For parametric data, one way ANOVA test with NewmanKeuls post hoc test was used, and for nonparametric data Kruskal-Wallis test with Mann-Whitney post hoc test was used. Qualitative data in control and treated groups were analyzed using the Fisher test. p<0,05 was considered statistically significant. Results: Anastomosis dehiscence was evidenced in 11 of 35 control animals (31.42%) and 2 of 70 treated animals (2.85%). There was no evidence of diffuse peritonitis or intraabdominal abscess. Adhesions and intestinal obstruction of the anastomosis were significantly mitigated in treated groups at all time intervals. Better presentation of the blood vessels, meaning higher volume of venous arcades orally and aborally from the anastomosis and greater number of communicating branches between mentioned venous arcades, was found in treated animals. Anastomosis testing revealed better anastomosis solidity in treated animals. Histopathological analysis showed less edema and necrosis in treated animals. Granulation tissue was present at an earlier time interval in treated animals, with the visible organization of collagen and reticulin fibers. In control animals, no healing organization was found. Immunohistochemical staining showed smooth muscle cell bundles organization in treated animals, which was absent in control animals. Additionally, epithelization developed earlier in treated animals. At the end of the experiment, treated animals exhibited 80%nanastomosis epithelization, in contrast, control animals exhibited only 10% anastomosis epithelization. There was no statistically significant difference in any of the observed parameters between groups that received the pentadecapeptide BPC 157 dose of 10 µg /kg and 10 ng/kg. Conclusions: Pentadecapeptide BPC 157 enhances colon-colonic anastomosis healing under venous congestion conditions, which is observable at both macroscopic and microscopic levels. The enhancing effect of pentadecapeptide BPC 157 on coloncolonic anastomosis healing under venous congestion conditions was present in 10 µg/kg and 10 ng/kg doses without statistically significant differences between the doses. This experiment confirmes already established role of pentadecapeptide 157 in healingpromotion and opens the possibility of pentadecapeptide BPC 157 use in abdominal surgery

The laparoscopic liver resections-an initial experience and the literature review

The laparoscopic liver resection (LLR) represents a new pathway in hepatic surgery. Several studies have reported its application in both malignant and benign liver diseases. The most common liver resections performed laparoscopically are wedge, segmental resections and metastasectomy; although in large centers the laparoscopic right and left hepatectomies have begun to perform more frequently. We report the initial experience in LLRs at our department including a case of the first laparoscopic left lateral liver bisegmentectomy performed in patient with follicular nodular hyperplasia and the 15 cases of wedge laparoscopic resections of echinococcic liver cysts. According to literature the mortality rate in LLRs is up to 0.3% and morbidity rate up to 10.5%. The most common cause of the death is liver failure, while the most frequent complication is the bile leakage. Advantages for patients include smaller incisions, less blood loss, and shorter lengths of hospital stay. The LLRs in experienced hands were shown to be safe with acceptable morbidity and mortality for both minor and major hepatic resections in benign and malignant diseases

The surgical treatment of patients with colorectal cancer and liver metastases in the setting of the "liver first" approach

A surgical resection is the only curative method in the therapy of colorectal carcinoma and liver metastases. Along with the development of interventional radiological techniques the indications for surgery widen. The number of metastases and patients age should not present a contraindication for surgical resection. However, there are still some doubts concerns what to resect first in cases of synchronous colorectal carcinoma and liver metastases and how to ensure the proper remnant liver volume in order to avoid postoperative liver failure and achieve the best results. Through this review the surgical therapy of colorectal carcinoma and liver metastases was revised in the setting of "liver-first" approach and the problem of ensuring of remnant liver volume

Stable Gastric Pentadecapeptide BPC 157 Heals Established Vesicovaginal Fistula and Counteracts Stone Formation in Rats

With the stable gastric pentadecapeptide BPC 157 therapy known to heal various both external and internal rat fistulas, we attempt to approach vesicovaginal fistula, continuous urine leaking through vagina, bladder stones, and a possible therapy solution among rats with well-formed 2 week-fistulas (vaginal/vesical 4 mm large defects) started with delayed therapy. Subsequent control fistula course (the subsequent 1, 2, 4, and 6 weeks) since beginning revealed the failed healing, fistula leaking, adhesions, urinary leaking through vagina, failed epithelization, collagenization, granulation tissue and neovascularization, increased inflammation, and necrosis. Thereby, the later intervals revealed the persistent inability to sustain even minimal volume, vesical, and vaginal defects and stone formation at the end of the experiment (fistula-time day 56). BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once time daily or perorally in drinking water until sacrifice) was initiated with a considerable delay (at 2 weeks after fistula formation). Already within 1 week therapy, all BPC 157 regimens stopped urinary leaking through vagina, reversed the otherwise resistant poor healing course to the increased epithelization, collagenization, granulation tissue and neovascularization, decreased inflammation, and decreased necrosis. Thereby, at later intervals, all BPC 157 rats exhibited a five times larger volume that can be sustained before leaking as in healthy, vesical, and vaginal defects completely closed and no stone formation. Thus, macro/microscopic and functional recovery, and counteracted stone formation. Concluding, BPC 157 therapy’s beneficial effects resulted in healing and no stone formation, with µg- and ng-regimens, either given daily perorally in drinking water or intraperitoneally

Pentadecapeptide BPC 157 resolves suprahepatic occlusion of the inferior caval vein, Budd-Chiari syndrome model in rats

Background: Recently, as a possible therapy resolving solution, pentadecapeptide BPC 157 therapy, has been used in alleviating various vascular occlusion disturbances. BPC 157 was previously reviewed as novel mediator of Robert cytoprotection and endothelium protection in the stomach, and gut-brain axis, beneficial therapy in gastrointestinal tract, with particular reference to vascular recruitment, ulcerative colitis and tumor cachexia, and other tissues healing. Here we raised new hypothesis about BPC 157 therapy in the Budd-Chiari syndrome in rats, rapid bypassing of the suprahepatic inferior caval vein occlusion, and rats recovery with the active and effective pharmacotherapy treatment. ----- Aim: To investigate Budd-Chiari syndrome model (inferior caval vein suprahepatic occlusion) resolution, since BPC 157 resolves various rat vascular occlusion. ----- Methods: We assessed the activated bypassing pathways between the inferior and superior caval veins and portocaval shunt, counteracted caval/portal hypertension, aortal hypotension, venous/arterial thrombosis, electrocardiogram disturbances, liver and gastrointestinal lesions (i.e., stomach and duodenum hemorrhages, in particular, congestion). Rats with suprahepatic occlusion of the inferior vena cava by ligation were medicated at 1 min, 15 min, 24 h, or 48 h post-ligation. Medication consisted of 10 µg/kg BPC 157, 10 ng BPC 157 or 5 mL/kg saline, administered once as an abdominal bath or intragastric application. Gross and microscopic observations were made, in addition to assessments of electrical activity of the heart (electrocardiogram), portal and caval hypertension, aortal hypotension, thrombosis, hepatomegaly, splenomegaly and venography. Furthermore, levels of nitric oxide, malondialdehyde in the liver and serum enzymes were determined. ----- Results: BPC 157 counteracted increased P wave amplitude, tachycardia and ST-elevation, i.e., right heart failure from acute thrombotic coronary occlusion. The bypassing pathway of the inferior vena cava-azygos (hemiazygos) vein-superior vena cava and portocaval shunt occurred rapidly. Even with severe caval ˃ portal hypertension, BPC 157 antagonized portal and caval hypertension and aortal hypotension, and also reduced refractory ascites. Thrombosis of portal vein tributaries, inferior vena cava, and hepatic and coronary arteries was attenuated. In addition, there was reduced pathology of the lungs (severe capillary congestion) and liver (dilated central veins and terminal portal venules), decreased intestine hemorrhagic lesions (substantial capillary congestion, submucosal edema and architecture loss), and increased liver and spleen weight. During the period of ligation, nitric oxide- and malondialdehyde-levels in the liver remained within normal healthy values, and increases in serum enzymes were markedly reduced. ----- Conclusion: BPC 157 counteracts Budd Chiari syndrome in rats

Pentadecapeptide BPC 157 resolves Pringle maneuver in rats, both ischemia and reperfusion

Background: The Pringle maneuver [portal triad obstruction(PTO)] provides huge disturbances during ischemia and even more thereafter in reperfusion. Contrarily, a possible solution may be stable gastric pentadecapeptide BPC 157, with already documented beneficial effects in ischemia/reperfusion conditions. Recently, BPC 157, as a cytoprotective agent, successfully resolved vessel occlusions in rats (ischemic colitis; deep vein thrombosis, superior anterior pancreaticoduodenal vein; bile duct cirrhosis) through rapid collateral vessel recruitment to circumvent vessel occlusion. Thereby, medication BPC 157 regimens were administered as a single challenge before and during ischemia or, alternatively, at various time points during reperfusion. ----- Aim: To introduce BPC 157 therapy against pringle maneuver-damage. ----- Methods: In deeply anesthetised rats, the portal triad was clamped up for 30 min. Rats then underwent reperfusion for either 15 min or 24 h. Medication [(10 µg, 10 ng/kg) regimens, administered as a single challenge] picked (a) ischemia, PTO period [at 5 min before (ip) or at 5 or 30 min of ligation time (as a bath to PTO)] or (b) reperfusion, post-PTO period [at 1 or 15 min (bath during surgery) or 24 h (ip) reperfusion-time]. We provided gross, microscopy, malondialdehyde, serum enzymes, electrocardiogram, portal, caval, and aortal pressure, thrombosis and venography assessments. ----- Results: BPC 157 counteracts electrocardiogram disturbances (increased P wave amplitude, S1Q3T3 QRS pattern and tachycardia). Rapidly presented vascular pathway (portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left ileal vein-inferior caval vein) as the adequate shunting immediately affected disturbed haemodynamics. Portal hypertension and severe aortal hypotension during PTO, as well as portal and caval hypertension and mild aortal hypotension in reperfusion and refractory ascites formation were markedly attenuated (during PTO) or completely abrogated (reperfusion); thrombosis in portal vein tributaries and inferior caval vein or hepatic artery was counteracted during portal triad obstruction PTO. Also, counteraction included the whole vicious injurious circle [i.e., lung pathology (severe capillary congestion), liver (dilated central veins and terminal portal venules), intestine (substantial capillary congestion, submucosal oedema, loss of villous architecture), splenomegaly, right heart (picked P wave values)] regularly perpetuated in ischemia and progressed by reperfusion in Pringle rats. ----- Conclusion: BPC 157 resolves pringle maneuver-damage in rats, both for ischemia and reperfusion