A prototype single-port device for pressurized intraperitoneal aerosol chemotherapy. Technical feasibility and local drug distribution

Abstract Purpose: To evaluate the technical feasibility and homogeneity of drug distribution of pressurized intraperitoneal aerosol chemotherapy (PIPAC) based on a novel process of intraperitoneal drug application (multidirectional aerosolization). Methods: This was an in vivo experimental study in pigs. A single-port device was manufactured at the smallest diameter possible for multidirectional aerosolization of the chemotherapeutic drug under positive intraperitoneal pressure. Four domestic pigs were used in the study, one control animal that received multidirectional microjets of 9 mL/sec for 30 min and three animals that received multidirectional aerosolization (pig 02: 9 mL/sec for 30 min; pigs 03 and 04: 3 mL/sec for 15 min). Aerosolized silver nitrate solution was applied for anatomopathological evaluation of intraperitoneal drug distribution. Results: Injection time was able to maintain the pneumoperitoneum pressure below 20 mmHg. The rate of moderate silver nitrate staining was 45.4% for pig 01, 36.3% for pig 02, 36.3% for pig 03, and 72.7% for pig 04. Conclusions: Intra-abdominal drug distribution had a broad pattern, especially in animals exposed to the drug for 30 min. Our sample of only four animals was not large enough to demonstrate an association between aerosolization and a higher silver nitrate concentration in the stained abdominal regions.

Effects of nivolumab in peritoneal carcinamatosis of malign melanoma in mouse model

Abstract Purpose: To evaluate the efficacy of nivolumab and comparison with dacarbazine (DTIC) on peritoneal carcinomatosis of malignant melanoma in mouse model. Methods: Mouse skin melanoma cells was injected under the capsule of the peritoneal surface in the left side of the abdomen. On postoperative day ten, mouses randomised into three groups. Group 1: Control, Group 2: HIPEC (Hyperthermic intraperitoneal chemotherapy) with DTIC and Group 3: HIPEC with Nivolumab. After the sacrification on postoperative day fifteen, peritoneum evaluated macroscopically and histopathologically by using peritoneal regression grading score (PRGS). Results: In the 15th day exploration, all animals developed extensive intraperitoneal tumor growth in Group 1. In Group 2 and Group 3 median tumor size was 0.7±0.3cm and 0.3±0.2cm respectively (p: 0.023). Peritoneal carcinomatosis index (PCI) were significantly lower in Group 3 than other groups (p: 0.019). The lowest total tumor nodules in group 3 was 4 ± 2. The PGRS score was found significantly lower in Group 3 than other groups (p: 0.03). Lymphocytic response rate was found higher in the Group 3. Conclusions: It has been found that nivolumab significantly better than DTIC on peritoneal metastases of malign melanoma in mouse models. Nivolumab treatment gives promising results with pathological evidence in the treatment of metastatic disease of malignant melanoma.

The potential efficacy of Survanta (r) and Seprafilm (r) on preventing intra-abdominal adhesions in rats

ABSTRACT PURPOSE: To investigate the potential efficacy of beractant (Survanta(r)) and Seprafilm(r) on the prevention of postoperative adhesions. METHODS: Forty Wistar-albino female rats were used. The rats were randomly allocated into four groups of 10 rats each as control group (CG), beractant group (BG), Seprafilm(r) group (SG), and combined group (COG). All rats underwent cecal abrasion via midline laparotomy. Before abdominal closure, isotonic saline, beractant, Seprafilm, and combined agents were intraperitoneally administered. Adhesions were classified macroscopically with Canbaz Scoring System on postoperative day 10. Ceacum was resected for histopathological assessment. RESULTS: Macroscopic adhesion scores were significantly lower in BG, SG, and COG than CG (p<0.05); (45%, 15%, 25%, and 15%; respectively). Histopathological assessment revealed a reduced inflammation and fibrosis score in the study groups than CG (p<0.05). In BG, adhesion development, inflammation and fibrosis scores were lower than SG; however, it was not statistically significant. CONCLUSIONS: Intra-abdominal application of beractant is significantly effective for the prevention of adhesion formation with no adverse effect by covering the whole peritoneal mesothelium with excellent gliding properties in a rat model. The combination of both agents is also effective in reducing adhesion formation, however, not superior to single beractant application.

Evaluation of peritoneal endometriosis treatment using intralesional acetylsalicylic acid injection in rabbits

PURPOSE: To investigate the efficacy of intralesional 20% aspirin injection for treatment of experimental peritoneal endometriosis. Methods: Peritoneal endometriosis was experimentally induced in forty adult nulligravid female rabbits. On day 30 post-endometriosis induction, rabbits were randomly divided to assess early (10 days) and late (20 days) effects of intralesional injection of physiological saline solution (control groups) in comparison to intralesional injection of 20% bicarbonate aspirin solution (experimental groups) as follows: control group 1 (10 days, n=10); control group 2 (20 days, n=10); experimental group 3 (10 days, n=10); experimental group 4 (20 days, n=10). Resected tissues, including endometriosis foci, were qualitatively (general morphology and signs of inflammatory cells infiltrate, necrosis and apoptosis) and quantitatively (remaining endometriosis area) assessed by histopathological analysis. Results: Extensive necrosis, hemorrhage, apoptosis, and fibrosis were observed in the experimental groups 3 and 4. Groups 1 and 2 presented typical endometrial tissue cysts, respectively. Groups 3 and 4 showed sparse endometrial tissue foci and no endometrial tissue, respectively. Quantitative analysis revealed that aspirin-treated groups 3 and 4 had significantly (p<0.05) smaller remaining endometriosis area, compared to control groups 1 and 2. Conclusion: Intralesional 20% aspirin injection caused total destruction of peritoneal endometriosis foci in rabbits.

Histological features of peritoneal lavage with ropivacaine in rats with fecal peritonitis / Características histológicas da lavagem peritoneal com ropivacaína em ratos com peritonite fecal

PURPOSE: To evaluate the histological features in lungs, peritoneum and liver of rats subjected to fecal peritonitis and treated with peritoneal lavage with 0.2 percent ropivacaine. METHODS: Twenty Wistar rats were subjected to laparotomy 6 h after the fecal peritonitis induction with autogenous stool. Rats were randomly distributed into 4 groups: I - (n=5) Control, no treatment; II - (n=5) Drying of the abdominal cavity; III - (n=5) Abdominal cavity lavage with 3 ml 0.9 percent saline solution and drying; and IV - (n=5) Abdominal cavity lavage with 3 ml 0.2 percent ropivacaine and drying. The animals that died underwent necropsy, and the surviving ones were subjected to euthanasia on the 11th day post-surgery. Fragments of liver, lungs and peritoneum were removed for histological evaluation. RESULTS: The animals that received peritoneal lavage (groups III and IV) showed greater survival than the drying and control groups. Lavage with ropivacaine prevented death during the observed period. Peritoneal lavage with ropivacaine maintained the architecture of the lung, peritoneum and liver without any important histological alterations. The histopathological findings analyzed correlated with greater survival of group IV. CONCLUSION: Treatment of fecal peritonitis in rats with peritoneal lavage using 0.2 percent ropivacaine demonstrated a reduction in histopathological alterations related to inflammatory response and sepsis.

OBJETIVO: Avaliar os aspectos histopatológicos em pulmões, peritônios e fígados de ratos submetidos à peritonite fecal e tratados com lavagem peritoneal com ropivacaína a 0,2 por cento. MÉTODOS: Utilizou-se 20 ratos Wistar, submetidos à laparotomia 6 horas após a indução de peritonite fecal com fezes autógenas, distribuídos aleatoriamente em quatro grupos: I- (n=5) Controle, nenhum tratamento; II- (n=5) Enxugamento da cavidade abdominal; III- (n=5) Lavagem da cavidade abdominal com 3 ml de solução salina 0,9 por cento e enxugamento ; IV- (n=5) Lavagem da cavidade abdominal com 3 ml de ropivacaína a 0,2 por cento e enxugamento. Os animais que morreram foram necropsiados e os sobreviventes foram eutanasiados no 11º dia do pós-operatório. Retirou-se fragmentos do fígado, pulmões e do peritônio dos animais para estudo histopatológico. RESULTADOS: Os animais que receberam lavagem peritoneal (grupos III e IV) apresentaram maior sobrevida que os grupos enxugamento e controle. A lavagem com ropivacaína impediu o óbito no período avaliado. A lavagem peritoneal com ropivacaína manteve a arquitetura do pulmão, peritônio e fígado sem alterações histológicas importantes. Os achados histopatológicos analisados foram condizentes com o maior tempo de sobrevida no grupo IV. CONCLUSÃO: A lavagem peritoneal com ropivacaína a 0,2 por cento no tratamento da peritonite fecal em ratos demonstrou reduzir as alterações histopatológicas relacionados à resposta inflamatória e sepse.

Evaluation of peritoneal adhesions formation and tissue response to polypropylene - poli (2-hydroxyethyl methacrylate)-(polyHEMA) implant on rats' abdominal wall / Avaliação da formação de aderências peritoneais e da resposta tecidual ao implante de poli (2-hidroxietil dimetacrilato)-(poliHEMA) na parede abdominal de ratos

PURPOSE: To verify if the composit poli (2-hydroxyethyl methacrylate)-PolyHEMA/polypropylene mesh implanted in the female rat's abdominal wall could be suitable for the prevention of peritoneal adhesions, and for the evaluation of the tecidual response produced by this biomaterial. METHODS: Polypropylene meshes (Group PP, n=20) and polypropylene meshes coated with a layer of poli (2-hydroxyethyl methacrylate)-PolyHEMA (Group PH, n=20) were implanted on the abdominal wall of Wistar female rats. Ten animals from each group were submitted to euthanasia at 15 and 30 days of the postoperative period. RESULTS: The animals from the group PP presented visceral adhesions on the mesh surface, which was not observed in the ones from group PH. At the histopathological examination foreign body response was observed in both groups, whilst there was a greater intensity of inflammatory response in group PH on both moments. CONCLUSION: The poli (2-hydroxyethyl methacrylate) polyHEMA hydrogel associated to polypropylene mesh reduces visceral adhesion formation in rats, although it may be associated to greater inflammatory reaction.

OBJETIVO: Verificar se compósito poli 2-hidroxietil dimetacrilato (PoliHEMA) / tela de polipropileno implantado na parede abdominal de ratas seria adequado para prevenção de aderências peritoneais e avaliar a resposta tecidual desencadeada por este biomaterial. MÉTODOS: Foram implantadas telas de polipropileno - Grupo PP (n=20) e telas de polipropileno revestidas por uma camada de poli 2 (hidroxietil dimetacrilato)-PolyHEMA - Grupo PH (n=20) na parede abdominal de ratas da linhagem Wistar. Dez animais de cada grupo foram submetidos à eutanásia aos 15 e 30 dias de pós-operatório. RESULTADOS: Os animais do grupo PP apresentaram aderências viscerais na superfície da tela, o que não foi observado nos do grupo PH. Observou-se no exame histopatológico resposta tipo corpo estranho nos dois grupos sendo que no grupo PH houve maior intensidade de resposta inflamatória nos dois momentos. CONCLUSÃO: O hidrogel de poliHEMA quando associado à tela de polipropileno reduz a formação de aderências viscerais em ratos, embora possa estar associado à reação inflamatória mais intensa.

Histopathologic evaluation of the peritoneum exposed to heat shock: experimental study in rats

PURPOSE: To evaluate histopathologic alterations of the peritoneum exposed to heat shock. METHODS: Sixty rats were randomly distributed into 6 groups: Heat Shock (HS), High Temperature (HT), Body Temperature (BT), Temperature 0oC (TZ), Sham (SH) and Control (CG) with 10 animals each. The peritoneal cavity of animals from groups HS, HT, BT and TZ was irrigated with NaCl solution 0.9 percent at temperatures 50°C, 0°C, 50°C, 37°C and 0°C, respectively. For animals from group SH, the procedures were simulated and those from group CG, laparotomy and biopsies were conducted. Twenty-four hours later, biopsies of the peritoneum for exams under light and electronic microscopy were performed. RESULTS: Edema was found in groups HS 80 percent, HT 60 percent, BT 30 percent TZ 70 percent, SH 40 percent and CG 30 percent. Vascular congestion was found in groups HS 20 percent, HT 30 percent, BT 10 percent and TZ 20 percent. Erythrocyte extravasation was found in groups HT 60 percent and SH 10 percent. Mesothelium destruction was found in 100 percent of specimens from groups HS, HT, BT, TZ, SH and CG 90 percent. Necrosis was found in groups HS 30 percent, HT 20 percent and BT 10 percent. The mean peritoneal thickness ranged from 42.26 μm (TZ) to 26.42 μm (CG). CONCLUSION: The heat shock caused no deaths, but promoted significant peritoneal edema without affecting the other histopathologic indicatives.

OBJETIVO: Avaliar alterações histopatológicas do peritônio exposto a choque térmico. MÉTODOS: Sessenta ratos foram distribuídos aleatoriamente em seis grupos: Choque Térmico (CT), Temperatura Elevada (TE), Temperatura 0°C (TZ) Sham (SH) e Controle (GC) com 10 animais. A cavidade peritoneal dos animais dos grupos CT, TE, TC e TZ foi irrigada com solução de NaCl 0,9 por cento nas temperaturas, 50°C e 0°C, 50°C, 37°C e 0°C, respectivamente. Nos animais do grupo SH foram simulados os procedimentos e nos do GC laparotomia e biópsias. Depois de 24 horas foram realizadas biópsias do peritônio para exames sob microscopia de luz e eletrônica. RESULTADOS: Edema foi encontrado nos grupos CT 80 por cento, TE 60 por cento, TC 30 por cento, TZ 70 por cento, SH 40 por cento e GC 30 por cento. Congestão vascular foi encontrada nos grupos CT 20 por cento, TE 30 por cento, TC 10 por cento e TZ 20 por cento. Extravasamento de hemácias foi encontrado nos grupos TE 60 por cento e SH 10 por cento. Destruição de mesotélio foi encontrada em 100 por cento dos espécimes dos grupos CT, TE, TC, TZ, SH e no grupo GC 90 por cento. Necrose foi encontrada nos grupos CT 30 por cento, TE 20 por cento e TC 10 por cento. A espessura média do peritônio variou de 42,26 μm (TZ) a 26,42 μm (GC). CONCLUSÃO: O choque térmico não causou óbitos, mas promoveu edema peritoneal significante sem alterar os demais indicadores histopatológicos.

Experimental ophitoxemia produced by the opisthoglyphous lora snake (Philodryas olfersii) venom

Várias serpentes da família Colubridae produzem secrecões orais venenosas. Neste trabalho, foi estudado o veneno coletado da presa posterior da serpente opistóglifa venezuelana Philodryas olfersii. Deferentes proteínas estavam presentes no veneno, sendo caracterizadas pela eletroforese de proteínas (SDS-PAGE) a 20%. A secrecão mostrou atividade proteolítica (gelatinase) a qual foi parcialmente purificada em uma coluna de intercâmbio iônico (mono Q2). Adicionalmente, a atividade hemorrágica do veneno de Philodryas olfersii foi demonstrada em embriões de galinha, pele e peritônio de rato. Os sintomas neurológicos foram demonstrados em camundongos inoculados com veneno de Philodryas olfersii. Em conclusão, o veneno da Philodryas olfersii mostrou atividade proteolítica, hemorrágica, e neurotóxica, assim aumentando o interesse na elevada acão tóxica do veneno da Philodryas olfersii.

Hypertonic glucose solution 10 percent - 25 percent on the mesenterium and peritoneum of the rat: macroscopic and microscopic study

OBJETIVO: Investigar as alterações macroscópicas e microscópicas do mesentério e do peritônio parietal quando se administra a solução aquosa de glicose hipertônica a 10% e a 25% na cavidade peritoneal de rato.MÉTODOS: 90 ratos fêmeas (n=90), adultos, "Wistar", jovens, com peso variando de 180 a 250 gramas foram divididos em 3 sub-grupos (A, B e C) contendo cada um 30 animais com procedimentos idênticos, diferindo apenas no período de observação. Os números de 1 a 30 constituem o grupo A ou grupo-controle (NaCl 0,9%), os números de 31 a 60 constituem o grupo B ou grupo-glicose a 10% e os números de 61 a 90 constituem o grupo C ou grupo- glicose a 25%. Realizando-se posteriormente laparotomia com incisão mediana longitudinal de pele a 2 cm abaixo do processo Xiphoideus sterni, estendendo-se por 3 cm caudalmente na linha média ventral. A escolha do procedimento a ser realizado para introdução na cavidade peritoneal de 2 ml de uma solução de cloreto de sódio 0,9% (controle), de glicose hipertônica a 10% e de glicose hipertônica a 25%. Em períodos correspondentes às 6h, 24h e 48h de pós-operatório, os animais de cada grupo foram reoperados, sendo realizada avaliação macroscópica e microscópica além dos registros das alterações histológicas do mesentério e peritônio parietal.RESULTADOS: Na microscopia do mesentério observou-se que 30 animais (33,4%) apresentaram linfonodos hiperplásicos; 6 animais (6,6%) com fibrose reacional; 10 animais (11,1%) com intensa congestão vascular; 16 animais (17,8%) com inflamação crônica inespecífica; 28 casos (31,1%) sem alteração. A microscopia do peritônio revelou 6 casos com fibrose reacional (3,3%) 174 casos (96,7%) sem alteração histológica. CONCLUSÃO: As soluções de glicose a 10% e a 25% não causam necrose tecidual quando introduzidas na cavidade peritoneal. O processo reacional inflamatório é de igual intensidade tecidual comparando-se ao uso da solução de NaCl a 0,9%.

Efecto de diferentes antimicrobianos administrados por vía intraperitoneal sobre la membrana peritoneal / Effect of different antimicrobial agents administered intraperitoneally on the peritoneal membrane

Objetivos: en este estudio se evaluó el efecto de los antimicrobianos sobre el peritoneo al ser administrado por vía intraperitoneal en un modelo exprerimental con ratas. Material y métodos: se emplearon ratas Wistar a las cuales, bajo técnicas asépticas, a nivel de la línea media abdominal, se les administró por vía intraperitoneal, por un periodo de diez días, uno de los siguientes agentes: clindamicina, cloramfenicol, gentamicina, ciprofloxacina, metronidazol o cefotaxima. Al final del periodo de observación los animales fueron sacrificados y se evaluó la presencia de adherencias; también se tomaron biopsias de peritoneo para estudio histopatológico. Resultados: se observó la presencia de adherencias; también se tomaron biopsias de peritoneo para estudio histopatológico. Resultados: se observó la presencia de adherencias principalmente en los grupos que recibieron gentamicina y metronidazol, pero sin que hubiera diferencias estadísticamente significativas al compararlos con el grupo control. El estudio histopatológico evidenció que la respuesta del peritoneno se caracterizó por una reacción inflamatoria leve y focal. Conclusiones: la administración de antimicrobianos por vía intraperitoneal condicionó un infiltrado inflamatorio leve y focal, y no favorecieron la formación de adherencias