Tissular growth factors profile after teduglutide administration on an animal model of intestinal anastomosis.

BACKGROUND: Teduglutide is an enterotrophic analogue of glucagon-like peptide-2, with an indirect and poorly understood mechanism of action, approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the response of tissue growth factors to surgical injury and teduglutide administration on an animal model of intestinal anastomosis. METHODS: Wistar rats (n = 59) were distributed into four groups: "ileal resection" or "laparotomy", each one subdivided into "postoperative teduglutide administration" or "no treatment"; and sacrificed at the third or the seventh day, with ileal sample harvesting. Gene expression of insulin-like growth factor 1 (Igf1), vascular endothelial growth factor a (Vegfa), transforming growth factor ß1 (Tgfß1), connective tissue growth factor (Ctgf), fibroblast growth factor 2 (Fgf2), fibroblast growth factor 7 (Fgf7), epidermal growth factor (Egf), heparin-binding epidermal-like growth factor (Hbegf), platelet-derived growth factor b (Pdgfb) and glucagon-like peptide 2 receptor (Glp2r)was studied by real-time polymerase chain reaction. RESULTS: Upregulation of Fgf7, Fgf2, Egf, Vegfaand Glp2rat the third day and of Pdgfat the seventh day was verified in the perianastomotic segment. Teduglutide administration was associated with higher fold-change of relative gene expression of Vegfa(3.6 ± 1.3 vs.1.9 ± 2.0, p = 0.0001), Hbegf(2.2 ± 2.3 vs. 1.1 ± 0.9, p = 0.001), Igf1(1.6 ± 7.6 vs. 0.9 ± 0.7, p = 0.002) and Ctgf(1.1 ± 2.1 vs. 0.6 ± 2.0, p = 0.013); and lower fold-change of Tgfß1, Fgf7and Glp2r. CONCLUSIONS: Those results underscore the recognized role of Igf1and Hbegfas molecular mediators of the effects of teduglutide and suggest that other humoral factors, like Vegfand Ctgf, may also be relevant in the perioperative context. Induction of Vegfa, Igf1and Ctgfgene expressions might indicate a favorable influence of teduglutide on the intestinal anastomotic healing.

Tissular growth factors profile after teduglutide administration on an animal model of intestinal anastomosis / Perfil tisular de factores de crecimiento postadministración de teduglutida en un modelo animal de anastomosis intestinal

Background: Teduglutide is an enterotrophic analogue of glucagon-like peptide-2, with an indirect and poorly understood mechanism of action, approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the response of tissue growth factors to surgical injury and teduglutide administration on an animal model of intestinal anastomosis. Methods: Wistar rats (n = 59) were distributed into four groups: "ileal resection" or "laparotomy", each one subdivided into "postoperative teduglutide administration" or "no treatment"; and sacrificed at the third or the seventh day, with ileal sample harvesting. Gene expression of insulin-like growth factor 1 (Igf1), vascular endothelial growth factor a (Vegfa), transforming growth factor β1 (Tgfβ1), connective tissue growth factor (Ctgf), fibroblast growth factor 2 (Fgf2), fibroblast growth factor 7 (Fgf7), epidermal growth factor (Egf), heparin-binding epidermal-like growth factor (Hbegf), platelet-derived growth factor b (Pdgfb) and glucagon-like peptide 2 receptor (Glp2r)was studied by real-time polymerase chain reaction. Results: Upregulation of Fgf7, Fgf2, Egf, Vegfaand Glp2rat the third day and of Pdgfat the seventh day was verified in the perianastomotic segment. Teduglutide administration was associated with higher fold-change of relative gene expression of Vegfa (3.6 ± 1.3 vs.1.9 ± 2.0, p = 0.0001), Hbegf (2.2 ± 2.3 vs. 1.1 ± 0.9, p = 0.001), Igf1 (1.6 ± 7.6 vs. 0.9 ± 0.7, p = 0.002) and Ctgf (1.1 ± 2.1 vs. 0.6 ± 2.0, p = 0.013); and lower fold-change of Tgfβ1, Fgf7and Glp2r. Conclusions: Those results underscore the recognized role of Igf1and Hbegfas molecular mediators of the effects of teduglutide and suggest that other humoral factors, like Vegfand Ctgf, may also be relevant in the perioperative context. Induction of Vegfa, Igf1and Ctgfgene expressions might indicate a favorable influence of teduglutide on the intestinal anastomotic healing (AU)

Introducción: teduglutida es un análogo intestinotrofico do peptido-2 similar al glucagon, con un mecanismo de acción indirecto y poco conocido, aprobado para la rehabilitación del síndrome de intestino corto. Este estudio propone analizar la respuesta de los factores de crecimiento tisulares a la agresión quirúrgica y a la administración de teduglutida en un modelo animal de anastomosis intestinal. Métodos: ratones Wistar (n = 59) fueron distribuidos en cuatro grupos: "resección ileal" o "laparotomia", cada uno subdividido en "administración post-operatoria de teduglutida" o "sin tratamiento"; y sacrificados en el tercero o el séptimo dia, con recogida de muestras ileales. La expresión genica de Igf1, Vegfa, Tgfβ1, Ctgf, Fgf2, Fgf7, Egf, Hbegf, Pdgfb y Glp2r fue analizada por qRT-PCR. Resultados: en el segmento perianastomotico se verifico una sobrerregulacion de Fgf7, Fgf2, Egf, Vegfa y Glp2r al tercer dia y de Pdg al séptimo día. La administración de teduglutida se asoció con mayor cambio de la expresión génica relativa de Vegfa (3.6 ± 1.3 vs. 1.9 ± 2.0, p = 0.0001), Hbegf (2.2 ± 2.3 vs. 1.1 ± 0.9, p = 0.001), Igf1 (1.6 ± 7.6 vs. 0.9 ± 0.7, p = 0.002) y Ctgf (1.1 ± 2.1 vs. 0.6 ± 2.0, p = 0.013); y menor cambio de Tgfβ1, Fgf7 y Glp2r. Conclusiones: estos resultados refuerzan el reconocido papel de Igf1 y Hbegf como mediadores moleculares de los efectos de la teduglutida y sugieren que otros factores humorales, como Vegf y Ctgf, también pueden ser relevantes en el contexto perioperatorio. La inducción de las expresiones de los genes Vegfa, Igf1 y Ctgf podría indicar una influencia favorable de teduglutida en la cicatrización anastomotica intestinal (AU)

Intestinal Epithelial Stem Cells: Distinct Behavior After Surgical Injury and Teduglutide Administration.

BACKGROUND: Previous studies suggest that intestinal epithelial stem cells (IESC), critical drivers of homeostasis and regeneration, include two subpopulations: crypt-based columnar and "position +4" stem cells, identified by Lgr5 and Bmi1 biomarkers, respectively. Teduglutide is an enterotrophic counterpart of glucagon-like peptide 2. This study aimed to investigate the response of putative IESC to surgical injury and teduglutide administration on an animal model of intestinal resection and anastomosis. METHODS: Wistar rats (n = 59) were distributed into four groups: "Ileal Resection" versus "Laparotomy", subsequently subdivided into "Postoperative Teduglutide Administration" versus "No Treatment"; and sacrificed at third or seventh days, with ileal sample harvesting. Flow cytometry was used to analyze epithelial stem cells with monoclonal antibodies against Lgr5, Bmi1 and also CD44, CD24, CD166, and Grp78 surface markers. RESULTS: Surgical trauma induced an increase of epithelial stem cells population at third day (9.0 ± 0.3 versus 5.7 ± 0.3%, p = 0.0001), which was more intense and involved all subpopulations after ileal resection. At seventh day, teduglutide was significantly associated with higher proportion of Lgr5+/Bmi1- cells (5.8 ± 0.1 versus 2.9 ± 0.3%, p = 0.005) and, on the contrary, lower percentage of Lgr5-/Bmi1+ cells (0.03 ± 0.01 versus 1.9 ± 0.1%, p = 0.049) after ileal resection; and higher proportion of Lgr5+/Bmi1+ cells (1.7 ± 0.1 versus 1.1 ± 0.2%, p = 0.028) after isolated laparotomy. After surgery, Lgr5+/Bmi1- and Lgr5-/Bmi1+ subpopulations demonstrated an inverse correlation and both correlated negatively with Grp78 labeling index. Lgr5-/Bmi1+ and CD44+/CD24low/CD166+/Grp78+ cells proportions exhibited a high grade positive correlation. CONCLUSION: Those observations support the existence of two epithelial stem cells subpopulations with distinct behavior after surgical injury and teduglutide treatment.

Intestinal inflammatory and redox responses to the perioperative administration of teduglutide in rats.

PURPOSE:: To investigate the inflammatory and redox responses to teduglutide on an animal model of laparotomy and intestinal anastomosis. METHODS:: Wistar rats (n=62) were allocated into four groups: "Ileal Resection and Anastomosis" vs. "Laparotomy", each one split into "Postoperative Teduglutide Administration" vs. "No Treatment"; and euthanized at the third or the seventh day. Ileal and blood samples were recovered at the baseline and at the euthanasia. Flow cytometry was used to study the inflammatory response (IL-1α, MCP-1, TNF-α, IFN-γ and IL-4 levels), oxidative stress (cytosolic peroxides, mitochondrial reactive species, intracellular glutathione and mitochondrial membrane potential) and cellular viability and death (annexin V/propidium iodide double staining). RESULTS:: Postoperative teduglutide treatment was associated with higher cellular viability index and lower early apoptosis ratio at the seventh day; higher cytosolic peroxides level at the third day and mitochondrial overgeneration of reactive species at the seventh day; higher tissue concentration of IL-4 and lower local pro-to-anti-inflammatory cytokines ratio at the seventh day. CONCLUSION:: Those findings suggest an intestinal pro-oxidative and anti-inflammatory influence of teduglutide on the peri-operative context with a potential interference in the intestinal anastomotic healing.

Teduglutide effects on gene regulation of fibrogenesis on an animal model of intestinal anastomosis.

BACKGROUND: Teduglutide is an enterotrophic analog of glucagon-like peptide 2 approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the effects of teduglutide administration on the gene regulation of fibrogenesis during the intestinal anastomotic healing on an animal model. METHODS: Wistar rats (n = 62) were assigned into four groups: "Ileal Resection and Anastomosis" or "Laparotomy," each one subdivided into "Postoperative Teduglutide Administration" or "No Treatment," and sacrificed at the third or at the seventh days, with ileal sample harvesting. Gene expression of matrix components and remodeling factors (matrix metalloproteinases [Mmp] and tissue inhibitors of metalloproteinases [Timp]) and growth factors was studied by real-time polymerase chain reaction. Net collagen deposition was assessed through the Collagen-to-Mmp-to-Timp ratio of fold change of relative gene expression. RESULTS: Gene expression profiles revealed a balance toward net degradation of collagen at the third day of the intestinal anastomotic healing. Teduglutide appeared to be associated with an overall accumulation of collagen at the third day of the anastomotic repair, attributable to the upregulation of Collagen type 1 alpha 1, Collagen type 3 alpha 1, and Collagen type 4 alpha 1, Timp1, and Timp2 and downregulation of Mmp13 and to a net degradation of collagen at the seventh day, derived from repression of Collagen type 3 alpha 1, Collagen type 5 alpha 1 and Timp1 expression. CONCLUSIONS: Teduglutide appeared to be associated with a favorable influence on fibrogenesis at the third day of the intestinal anastomotic repair and to a trend to fibrolysis at the seventh day.

Intestinal inflammatory and redox responses to the perioperative administration of teduglutide in rats

Abstract Purpose: To investigate the inflammatory and redox responses to teduglutide on an animal model of laparotomy and intestinal anastomosis. Methods: Wistar rats (n=62) were allocated into four groups: "Ileal Resection and Anastomosis" vs. "Laparotomy", each one split into "Postoperative Teduglutide Administration" vs. "No Treatment"; and euthanized at the third or the seventh day. Ileal and blood samples were recovered at the baseline and at the euthanasia. Flow cytometry was used to study the inflammatory response (IL-1α, MCP-1, TNF-α, IFN-γ and IL-4 levels), oxidative stress (cytosolic peroxides, mitochondrial reactive species, intracellular glutathione and mitochondrial membrane potential) and cellular viability and death (annexin V/propidium iodide double staining). Results: Postoperative teduglutide treatment was associated with higher cellular viability index and lower early apoptosis ratio at the seventh day; higher cytosolic peroxides level at the third day and mitochondrial overgeneration of reactive species at the seventh day; higher tissue concentration of IL-4 and lower local pro-to-anti-inflammatory cytokines ratio at the seventh day. Conclusion: Those findings suggest an intestinal pro-oxidative and anti-inflammatory influence of teduglutide on the peri-operative context with a potential interference in the intestinal anastomotic healing.

Glutaminemia prognostic significance in critical surgical patients. An analysis of plasma aminogram profile / Significado pronóstico de la glutaminemia en pacientes quirúrgicos críticos. Análisis del perfil del aminograma plasmático

Background: Glutamine depletion is common in the critically-ill patients. Glutaminemia lower than 420 μmol/l has been considered as an independent predictive factor of mortality, but the indications for exogenous glutamine supplementation remain controversial. This study intends to determine the glutaminemia profile in critical surgical patients and to investigate its correlation with the severity indexes and the prognosis. Methods: A prospective study of 28 adult critical surgical patients was performed. Plasma amino acid concentrations were quantified, by ion exchange chromatography, at the moment of admission and at the first and third days, and compared with those of 11 reference healthy individuals. Severity indexes and parameters of prognosis were registered. Results: In critical surgical patients, mean glutaminemia at admission was lower than that of control individuals (385.1 ± 123.1 versus 515 ± 57.9 μmol/l, p = 0.002) and decreased until the third day (p = 0.042). Prevalence of severe hypoglutaminemia (< 420 μmol/l) at admission was 64.3%. Baseline glutaminemia correlated with the Simplified Acute Physiology Score II (SAPS II score) (Pearson’s correlation coefficient r = -39.4%, p = 0.042), and it was lower in cases of erythrocytes transfusion (339.9 ± 78.8 versus 454.9 ± 148.8 μmol/l, p = 0.013). Glutaminemia at the third day correlated with the duration of invasive ventilation support (r = -65%, p = 0 .012) and ICU stay (r = -66.5%, p = 0.009). Glutaminemia below 320 μmol/l, observed in 25% of the patients, was associated with higher in-hospital mortality (42.9 versus 19%, statistically not significant [n.s.]) and lower actuarial survival (212.1 ± 77.9 versus 262.3 ± 32.4 days, n.s.). Conclusions: Those results underscore the relevance of hypoglutaminemia as an adverse predictive factor in the critical surgical patients. Determination of glutaminemia may contribute to a better definition of the indications for glutamine supplementation (AU)

Introducción: la hipoglutaminemia es común en los pacientes críticos, pero las indicaciones para la suplementación con glutamina exógena siguen siendo controvertidas. Este estudio pretende determinar el perfil de glutaminemia en pacientes quirúrgicos críticos e investigar su correlación con los índices de gravedad y el pronóstico. Métodos: se realizó un estudio prospectivo de 28 pacientes quirúrgicos críticos adultos. Las aminoacidemias se cuantificaron mediante cromatografía de intercambio iónico en el momento del ingreso y en el primer y tercer día, y se compararon con las de 11 individuos sanos. Se registraron índices de gravedad y de pronóstico. Resultados: en pacientes quirúrgicos críticos, la glutaminemia media en el ingreso fue inferior a la de los controles (385,1 ± 123,1 versus 515 ± 57,9 μmol/l, p = 0,002) y disminuyó hasta el tercer día (p = 0,042). La prevalencia de hipoglutaminemia severa (< 420 μmol/l) en el ingreso fue de 64,3%. La glutaminemia basal se correlacionó con el SAPS II (r = -39,4%, p = 0,042), y fue menor en los casos de transfusión de eritrocitos (339,9 ± 78,8 versus 454,9 ± 148,8 μmol/l, p = 0,013). La glutamina al tercer día se correlacionó con la duración de la ventilación invasiva (r = -65%, p = 0,012) y de la estancia en la UCI (r = -66,5%, p = 0,009). La glutaminemia < 320 μmol/l, observada en el 25% de los pacientes, se asoció con mayor mortalidad hospitalaria (42,9 versus 19%, n.s.) y menor supervivencia actuarial (212,1 ± 77,9 versus 262,3 ± 32,4 días, n.s.). Conclusiones: estos resultados refuerzan la importancia de hipoglutaminemia como un factor predictivo adverso en los pacientes quirúrgicos críticos. La determinación de glutaminemia puede contribuir a una mejor definición de las indicaciones para la suplementación (AU)

Intestinal dysfunction in the critical trauma patients - An early and frequent event.

BACKGROUND: Small-bowel dysfunction exerts a relevant prognostic impact in the critically ill patients. Citrullinemia has been used in the evaluation of the intestinal function and it is considered an objective parameter of the functional enterocyte mass. Present study proposes to determine the intestinal dysfunction prevalence and the citrullinemia kinetic profile in severe trauma patients and to investigate its correlation with severity indicators and clinical outcome. METHODS: A prospective study including 23 critical trauma patients was performed. Aminoacidemias were quantified, by ion exchange chromatography, at the admission and at the first and third days. Severity and outcome parameters were registered. RESULTS: In severe trauma patients, severe hypocitrullinemia (< 20 µmol/L) prevalence at admission was high (69.6%) and mean citrullinemia was low (19.5 ± 11.1 µmol/L). Baseline citrullinemia was inversely and significantly correlated with shock index (r = -55.1%, p = 0.008) and extent of invasive ventilation support (r = -42.7%, p = 0.042). Citrullinemia < 13.7 µmol/L at admission, observed in 17.4% of patients, was associated with higher shock index (1.27 ± 0.10 versus 0.75 ± 0.18, p = 0.0001) and longer duration of invasive ventilation support (20.3 ± 7 versus 11.2 ± 7.1 days, p = 0.029) and intensive care unit stay (22 ± 5.9 versus 12.2 ± 8.8 days, p = 0.048). A citrullinemia decrease in the first day after admittance superior to 12.7% constituted a significant predictive factor of in-hospital mortality (75 versus 14.3%, p = 0.044; odds ratio = 7.8; accuracy = 65.2%; specificity = 92.3%; negative predictive value = 85.7%] and lower actuarial survival (69.8 ± 41.6 versus 278.1 ± 37.4 days, p = 0.034). CONCLUSIONS: Those results confirm the high prevalence and the prognostic relevance of hypocitrullinemia, considered a biomarker of enterocyte dysfunction, in severe trauma patients.

Intestinal dysfunction in the critical trauma patients - An early and frequent event / Disfunción intestinal en los traumatizados críticos. Un suceso precoz y frecuente

Background: Small-bowel dysfunction exerts a relevant prognostic impact in the critically ill patients. Citrullinemia has been used in the evaluation of the intestinal function and it is considered an objective parameter of the functional enterocyte mass. Present study proposes to determine the intestinal dysfunction prevalence and the citrullinemia kinetic profi le in severe trauma patients and to investigate its correlation with severity indicators and clinical outcome. Methods: A prospective study including 23 critical trauma patients was performed. Aminoacidemias were quantified, by ion exchange chromatography, at the admission and at the first and third days. Severity and outcome parameters were registered. Results: In severe trauma patients, severe hypocitrullinemia (< 20 μmol/L) prevalence at admission was high (69.6%) and mean citrullinemia was low (19.5 ± 11.1 μmol/L). Baseline citrullinemia was inversely and significantly correlated with shock index (r = -55.1%, p = 0.008) and extent of invasive ventilation support (r = -42.7%, p = 0.042). Citrullinemia < 13.7 μmol/L at admission, observed in 17.4% of patients, was associated with higher shock index (1.27 ± 0.10 versus 0.75 ± 0.18, p = 0.0001) and longer duration of invasive ventilation support (20.3 ± 7 versus 11.2 ± 7.1 days, p = 0.029) and intensive care unit stay (22 ± 5.9 versus 12.2 ± 8.8 days, p = 0.048). A citrullinemia decrease in the first day after admittance superior to 12.7% constituted a significant predictive factor of in-hospital mortality (75 versus 14.3%, p = 0.044; odds ratio = 7.8; accuracy = 65.2%; specificity = 92.3%; negative predictive value = 85.7%] and lower actuarial survival (69.8 ± 41.6 versus 278.1 ± 37.4 days, p = 0.034). Conclusions: Those results confirm the high prevalence and the prognostic relevance of hypocitrullinemia, considered a biomarker of enterocyte dysfunction, in severe trauma patients (AU)

Introducción: la disfunción intestinal ejerce un importante impacto pronóstico en los pacientes críticamente enfermos. La citrulinemia se ha utilizado en la evaluación de la función intestinal. El presente estudio propone determinar la prevalencia de la disfunción intestinal y el perfil cinético de la citrulinemia en enfermos con trauma grave e investigar su correlación con la gravedad y la evolución clínica. Métodos: se realizó un estudio prospectivo incluyendo 23 pacientes traumatizados críticos. Las aminoacidemias se cuantificaron, mediante cromatografía de intercambio iónico, en la admisión y en el primer y tercer días. Se registraron los parámetros de gravedad y evolución clínica. Resultados: la prevalencia de la hipocitrulinemia grave (< 20 μmol/L) en la admisión fue alta (69,6%) y citrulinemia media fue baja (19,5 ± 11,1 μmol/L). La citrulinemia basal se correlacionó con el índice de choque (r = -55,1%, p = 0,008) y la duración de asistencia ventilatoria invasiva (r = -42,7%, p = 0,042). La citrulinemia < 13,7 μmol/L en la admisión se asoció con mayor índice de choque (1,27 ± 0,1 versus 0,75 ± 0,18, p = 0,0001) y mayor duración de ventilación invasiva (20,3 ± 7 versus 11,2 ± 7,1 días, p = 0,029) y hospitalización en la unidad de cuidados intensivos (22 ± 5,9 versus 12,2 ± 8,8 días, p = 0,048). La disminución de la citrulinemia en el primer día superior al 12,7% fue un factor predictor signifi cativo de mortalidad hospitalaria (75 versus 14,3%, p = 0,044; odds ratio = 7,8; precisión = 65,2%; especificidad = 92,3%; valor predictivo negativo = 85,7%] y menor supervivencia actuarial (69,8 ± 41,6 versus 278,1 ± 37,4 días, p = 0,034). Conclusiones: estos resultados confirman la alta prevalencia y la importancia pronóstica de la hipocitrulinemia, biomarcador de disfunción enterocitaria, en los pacientes con trauma severo (AU)

Argininemia and plasma arginine bioavailability - predictive factors of mortality in the severe trauma patients?

BACKGROUND: Arginine is an amino acid determinant in the metabolic, immune and reparative responses to severe trauma. The present study aims to determine argininemia and plasma arginine bioavailability (PAB) in critical trauma patients and to analyze its correlation with prognosis. METHODS: A prospective study of 23 critical trauma patients was undertaken. Aminoacidemias were determined, by ion exchange chromatography, at admission and in the first and third days and compared with those of 11 healthy individuals. PAB was calculated. Severity indexes and outcome parameters were recorded. RESULTS: Values of argininemia, citrullinemia and ornithinemia at the admission were significantly lower than those of the controls (arginine: 41.2 ± 20.6 versus 56.1 ± 11.9 µmol/L, P = 0.034). Hipoargininemia (<60 µmol/L) prevalence was 82.6 %. Mean PAB was 62.4 ± 25.6 %. Argininemia < 26 µmol/L constituted a significant predictive factor of in-hospital mortality [n = 4 (17.4 %); 75 versus 15.8 %, P = 0.04; odds ratio = 4.7; accuracy = 87 %] and lower actuarial survival (63.5 ± 43.9 versus 256.1 ± 33.3 days, P = 0.031). PAB <42 % [n = 6 (26.1 %)] was associated with higher lactacidemia levels (P = 0.033), higher in-hospital mortality (66.7 versus 11.8 %, P = 0.021; odds ratio = 5.7, accuracy = 82.6 %) and lower actuarial survival (87.2 ± 37.5 versus 261.4 ± 34.7 days, n.s.). Probability of in-hospital mortality was inversely and significantly related with PAB [61.8 ± 8.8 % (95 % CI 50.8-72.7) when PAB <41 % and 2.8 ± 1.9 % (95 % CI 1.9-8.3) when PAB > 81 %, P = 0.0001]. Charlson's index ≥1, APACHE II ≥19.5, SOFA ≥7.5, and glutaminemia < 320 µmol/L were also predictive factors of actuarial survival. CONCLUSIONS: Those results confirm the high prevalence of arginine depletion in severe trauma patients and the relevance of argininemia and PAB as predictive factors of mortality in this context.

Locally advanced adenocarcinoma of the rectum presenting with necrotising fasciitis of the perineum: successful management with early aggressive surgery and multimodal therapy.

Colorectal cancer is a common malignant neoplasm and its treatment usually involves surgery associated, in some cases, depending on the staging, with chemoradiotherapy. Necrotising fasciitis of the perineum is a highly lethal infection of the perineum, perirectal tissues and genitals, requiring emergency surgical debridement, broad-spectrum antibiotics and control of sepsis. We present the case of a 59-year-old man with necrotising fasciitis of the perineum as the first clinical manifestation of locally advanced adenocarcinoma of the rectum, in which successful management consisted of early and aggressive surgical debridement, followed by multimodal therapy with curative intent. 2 years and 6 months after surgery the patient is well, with no evidence of local or systemic relapse.

Solitary necrotic nodule of the liver: a very challenging diagnosis!

Solitary necrotic nodule of the liver is a rare entity of unknown aetiology. We describe the case of a 59-year-old woman reporting sporadic right upper quadrant pain. An abdominal CT scan revealed a liver nodule located in segment 4. The complementary investigation was unable to identify the neoplastic lesion, and its surgical resection was performed, with an uneventful recovery. Pathological examination revealed a 'solitary necrotic nodule of the liver.' The patient remains asymptomatic and free of recurrence 3 years after surgery. This case corroborates that despite the advances in liver imaging and biopsy, liver nodules are sometimes a diagnostic challenge; quite often, only its surgical resection allows a definitive diagnosis.

Hepatectomy and liver regeneration: from experimental research to clinical application.

BACKGROUND: The mechanisms and kinetics of hepatic growth have continuously been investigated. This study concerns liver regeneration in animal and patients who underwent partial hepatectomy evaluated by the hepatic extraction fraction (HEF) calculated through radioisotopic methods. METHODS: Thirty normal Wistar rats were submitted to an 85% hepatectomy, and 95 patients with primary and secondary liver tumours were included. In animal study, the liver regeneration kinetics was assessed by HEF using 99mTc-mebrofenin, the ratio liver/bodyweight and by using bromodeoxyuridine deoxyribonucleic acid incorporation. In patient study, the liver regeneration was evaluated by calculation of HEF before surgery, 5 and 30 days after hepatectomy. RESULTS: In animal, we verified a positive correlation between HEF kinetics and liver/bodyweight ratio or hepatocyte proliferation evaluated by bromodeoxyuridine deoxyribonucleic acid staining after 85% hepatectomy. In the clinical arm, no statistical differences of the HEF before hepatectomy, 5 and 30 days after hepatectomy, were observed. CONCLUSIONS: Our results support the view that human liver regeneration commences early, is fast, non-anatomical and functionally complete 5 days after hepatectomy. The fast functional liver regeneration may have a high clinical impact particularly concerning the post-operative oncological therapeutic approaches.

Study of hepatocellular function in the murine model following hepatic artery selective clamping.

PURPOSE: To investigate the impact of selective hepatic artery clamping (SHAC) in hepatocellular function. METHODS: Three groups of Wistar male rats were subjected to SHAC ischemia period of 60min: Group A continuous SHAC were subjected to SHAC ischemia period of 60min, Group B intermittent SHAC of 30min with 5min of reperfusion and Group C intermittent SHAC of 15min with 5min of reperfusion. Animals without SHAC were included-Group D. To evaluate hepatocellular function blood markers and hepatic extraction function (HEF) using 99mTc-mebrofenin were performed before and after surgery. Flow cytometry was used to analyze oxidative stress and cell viability. RESULTS: A mortality rate of 7.6% in Group A was observed. HEF maintained normal values between the groups. Flow cytometry demonstrated no significant differences between the groups in viability, type of cell death as well as in the production of reactive oxygen species. CONCLUSIONS: The selective hepatic artery clamping compared to other clamping techniques results on increased cell viability and decreased hepatocyte death. The SHAC is a potential alternative to decrease per-operative bleeding while maintaining hepatocellular function.

Study of hepatocellular function in the murine model following hepatic artery selective clamping

PURPOSE: To investigate the impact of selective hepatic artery clamping (SHAC) in hepatocellular function. METHODS: Three groups of Wistar male rats were subjected to SHAC ischemia period of 60min: Group A continuous SHAC were subjected to SHAC ischemia period of 60min, Group B intermittent SHAC of 30min with 5min of reperfusion and Group C intermittent SHAC of 15min with 5min of reperfusion. Animals without SHAC were included-Group D. To evaluate hepatocellular function blood markers and hepatic extraction function (HEF) using 99mTc-mebrofenin were performed before and after surgery. Flow cytometry was used to analyze oxidative stress and cell viability. RESULTS: A mortality rate of 7.6% in Group A was observed. HEF maintained normal values between the groups. Flow cytometry demonstrated no significant differences between the groups in viability, type of cell death as well as in the production of reactive oxygen species. CONCLUSIONS: The selective hepatic artery clamping compared to other clamping techniques results on increased cell viability and decreased hepatocyte death. The SHAC is a potential alternative to decrease per-operative bleeding while maintaining hepatocellular function.

Haemoptysis and left upper quadrant abdominal pain: an unusual presentation of partial thoracic migration of an adjustable gastric band's tube.

Laparoscopic gastric banding is considered the safest bariatric procedure, holding satisfactory long-term weight loss results, low rates of early complications and negligible mortality. Long-term follow-up are showing a high prevalence of late complications. We describe the case of a 40-year-old female patient, with a medical history of laparoscopic gastric banding, admitted in the emergency department complaining of haemoptysis, left upper quadrant abdominal pain and a slight tachycardia. After an exhaustive clinical evaluation with laboratorial and radiological assessments, diagnosis of partial thoracic migration of the band's tube was established. Despite the unusual clinical setting, this case emphasises the necessity of awareness for the potential long-term complications of gastric banding either from primary or secondary care providers.

Hepatic extraction fraction: interest of its quantification in patients with hepatic tumours.

BACKGROUND/AIMS: This prospective study aimed to estimate the usefulness of the hepatic extraction fraction (HEF) in the context of the pre- and postoperative evaluation of patients with hepatic tumours. METHODOLOGY: Seventy patients with colorectal metastases (n=25), hepatocellular carcinoma (n=25), cholangiocellular carcinoma (n=6), gastric cancer metastases (n=5), hemangioma (n=5) and others (n=4) were included. Thirty patients underwent hepatectomy. Child-Pugh score, prothrombin, albumin, ALT, AST, AF, LDH, total, direct and indirect bilirubin, platelet number as well as the HEF were evaluated in the preoperative period and one month after hepatectomy. RESULTS: Preoperative evaluation of HEF values between Child-Pugh A (93.6±17.3%) and Child-Pugh B/C (n=13; 58.1±28.6%) demonstrated significant differences (p=0.001). We found a high negative correlation between the preoperative HEF and ALT (p<0.001), AST (p<0.001), AF (p<0.001), TB (p<0.001), IB (p<0.001) and DB (p<0.001), and also a high positive correlation between the preoperative HEF and albumin (p<0.001) or prothrombin (p<0.01). All operated patients had a normal HEF and a positive correlation between the postoperative HEF and albumin (p<0.05) at one month after surgery. CONCLUSIONS: The HEF allows a dynamic evaluation of hepatocellular function, which is not possible with other clinical, biological and radiological methods.