ROBOTIC ASSISTED VERSUS LAPAROSCOPIC DISTAL PANCREATECTOMY: A RETROSPECTIVE STUDY.

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) is associated with less blood loss and faster functional recovery. However, the benefits of robotic assisted distal pancreatectomy (RDP) over laparoscopic distal pancreatectomy (LDP) are unknown. AIMS: To compare RDP versus LDP for surgical treatment of benign lesions, pre-malignant and borderline malignant pancreatic neoplasias. METHODS: This is a retrospective study comparing LDP with RDP. Main outcomes were overall morbidity and overall costs. Secondary outcomes were pancreatic fistula (PF), infectious complications, readmission, operative time (OT) and length of hospital stay (LOS). RESULTS: Thirty patients submitted to LDP and 29 submitted to RDP were included in the study. There was no difference regarding preoperative characteristics. There was no difference regarding overall complications (RDP - 72,4% versus LDP - 80%, p=0,49). Costs were superior for patients submitted to RDP (RDP=US$ 6,688 versus LDP=US$ 6,149, p=0,02), mostly due to higher costs of surgical materials (RDP=US$ 2,364 versus LDP=1,421, p=0,00005). Twenty-one patients submitted to RDP and 24 to LDP developed pancreatic fistula (PF), but only 4 RDP and 7 LDP experienced infectious complications associated with PF. OT (RDP=224 min. versus LDP=213 min., p=0.36) was similar, as well as conversion to open procedure (1 RDP and 2 LDP). CONCLUSIONS: The postoperative morbidity of robotic distal pancreatectomy is comparable to laparoscopic distal pancreatectomy. However, the costs of robotic distal pancreatectomy are slightly higher.

Robotic assisted versus laparoscopic distal pancreatectomy: a retrospective study / Pancreatectomia distal robótica versus laparoscópica: um estudo retrospectivo

ABSTRACT BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) is associated with less blood loss and faster functional recovery. However, the benefits of robotic assisted distal pancreatectomy (RDP) over laparoscopic distal pancreatectomy (LDP) are unknown. AIMS: To compare RDP versus LDP for surgical treatment of benign lesions, pre-malignant and borderline malignant pancreatic neoplasias. METHODS: This is a retrospective study comparing LDP with RDP. Main outcomes were overall morbidity and overall costs. Secondary outcomes were pancreatic fistula (PF), infectious complications, readmission, operative time (OT) and length of hospital stay (LOS). RESULTS: Thirty patients submitted to LDP and 29 submitted to RDP were included in the study. There was no difference regarding preoperative characteristics. There was no difference regarding overall complications (RDP - 72,4% versus LDP - 80%, p=0,49). Costs were superior for patients submitted to RDP (RDP=US$ 6,688 versus LDP=US$ 6,149, p=0,02), mostly due to higher costs of surgical materials (RDP=US$ 2,364 versus LDP=1,421, p=0,00005). Twenty-one patients submitted to RDP and 24 to LDP developed pancreatic fistula (PF), but only 4 RDP and 7 LDP experienced infectious complications associated with PF. OT (RDP=224 min. versus LDP=213 min., p=0.36) was similar, as well as conversion to open procedure (1 RDP and 2 LDP). CONCLUSIONS: The postoperative morbidity of robotic distal pancreatectomy is comparable to laparoscopic distal pancreatectomy. However, the costs of robotic distal pancreatectomy are slightly higher.

RESUMO RACIONAL: A pancreatectomia distal minimamente invasiva (PDMI) está associada a menos perda sanguínea e recuperação funcional mais rápida, no entanto, os benefícios da pancreatectomia distal robótica (PDR) são desconhecidos quando comparada a pancreatectomia distal laparoscópica (PDL). OBJETIVOS: Comparar PDR versus PDL no tratamento cirúrgico de lesões benignas, neoplasias pancreáticas malignas, pré-malignas e limítrofes. MÉTODOS: Estudo retrospectivo comparando PDL com PDR. Os desfechos primários avaliados foram morbidade e custos hospitalares. Os desfechos secundários foram fístula pancreática (FP), complicações infecciosas, readmissão, tempo cirúrgico e tempo de internação hospitalar (TIH). RESULTADOS: Trinta pacientes submetidos a PDL e 29 submetidos a PDR foram incluídos no estudo. Não houve diferença em relação às características pré-operatórias. Não houve diferença em relação às complicações gerais (PDL - 72,4% versus PRD - 80%, p=0,49). Os custos foram superiores para PDR (PDR=US$ 6688 versus PDL=US$ 6149, p=0,02), principalmente devido aos custos mais elevados de materiais cirúrgicos (PDR=US$ 2364 versus PDL=1421, p=0,00005). Vinte e um pacientes submetidos a PDR e 24 submetidos a PDL desenvolveram fístula pancreática (PF), no entanto, apenas 4 submetidos PDR e 7 a PDL apresentaram complicações infecciosas associadas a FP. O tempo cirúrgico (PDR=224 min. versus PDL=213 min., p=0,36) e a conversão para cirurgia aberta (1 PDR e 2 PDL) não tiveram diferença estatística. CONCLUSÕES: A morbidade pós operatória da pancreatectomia distal robótica é comparável à pancreatectomia distal laparoscópica. Entretando, os custos da pancreatectomia distal robótica são mais elevados.

Insights of Outcome after Resection of Small Nonfunctioning Neuroendocrine Pancreatic Tumors.

BACKGROUND: The incidence of small nonfunctioning neuroendocrine pancreatic tumors (NF-PNETs) has been increasing systematically in the last few decades. Surgical resection was once considered the treatment of choice but has been questioned in the direction of a more conservative approach for selected patients. Our aim was to analyze the outcome of surgical resection of small (≤3cm) NF-PNETs. METHODS: We retrospectively evaluated 14 patients with sporadic NF-PNETs who underwent pancreatic resection. Data were collected from patients' medical records. RESULTS: Of the 14 patients included, 35.71% were men, and the average age was 52.36 ± 20.36 years. Comorbidities were present in 92.86% of the cases. The incidence of postoperative complications was 42.86%, the 30-day mortality was zero, and the length of follow-up was 3.31 ± 3.0 years. The results of pathological evaluations revealed WHO grade I in 42.86% of cases, II in 21.43%, and neuroendocrine carcinoma in 35.71%. The median tumor size was 1.85cm (range, 0.5-3cm), and 2 cases had synchronous metastasis. The median TNM stage was IIa (range, I-IV). The disease-free and patient survival rates were 87.5% and 100% at 3 years and 43.75% and 75% at 10 years, respectively. The tumor pathological grade was significantly higher in head tumors than body-tail tumors, but there were no differences with respect to tumor size and TNM staging. CONCLUSION: A surgical approach to treat small sporadic NF-PNETs is safe with low mortality and high patient survival. Based on these data, small pancreatic head tumors can be more aggressive, suggesting that surgical resection is still the best option to treat small nonfunctioning PNETS. Thus, conservative treatment should be indicated very cautiously for only cases with absolute contraindications for surgery.

Long Term Follow-up Results of Surgical Management of Chronic Pancreatitis.

Background: Chronic pancreatitis is a progressive loss of exocrine and endocrine pancreatic function. Surgical procedures are required in cases of intractable pain, biliary obstruction or intestinal obstruction, complications from pseudocysts, or pancreatic fistulae. Objective: To assess the outcomes after surgical management of chronic pancreatitis, in a long-term follow-up. Methods: Patients that underwent surgical management of chronic pancreatitis,from 2006 to 2017, were reviewed. Demographics and complications of the procedures were recorded. Visual analogue pain scale was used for pain control evaluation. The 12-Item Short-Form Health Survey questionnaire was used for quality of life assessment. Results: Sixty-five patients were included in the study. Mean follow-up was 60.26 months. Twenty patients underwent lateral pancreatojejunostomy, 22 to Roux-en-Y cystojejunostomy, 7 to transgastric cyst-gastrostomy,1 to Frey procedure, 4 to hepaticojejunostomy, 1 to Frey procedure and hepaticojejunostomy, 1 to lateral pancreatojejunostomy and cyst-gastrostomy, 7 to lateral pancreatojejunostomy and hepaticojejunostomy and 2 to cystojejunostomy and hepaticojejunostomy. No cases of perioperative deaths were recorded. A Pancreatic fistula was found in 5 cases, and all of them followed non-operative management. Of the 65 patients included in the study, 39 answered the questionnaires. Mean scores on SF-12, physical and mental scales were respectively 42.72 +- 10.76 and 49.84 +- 11.75. Conclusion: Surgical management of chronic pancreatitis is safe, with low mortality and morbidity rates. These procedures are effective in assuaging pain and in providing good quality of life.

Advanced age does not increase morbidity in pancreaticoduodenectomy.

BACKGROUND: Due to rising life expectancy of population, very complex surgical procedures such as pancreaticoduodenectomy (PD), are more commonly being performed in elderly patients. The objective of this study was to evaluate the safety of PD in patients older than 75 years old and the risk factors associated with severe complications. METHODS: Patients who underwent PD for periampullary tumors were retrospectively reviewed and divided into two groups, A (<75 years) and B (>75 years). The primary endpoint was severe postoperative complications (Clavien 3 or greater). Secondary endpoints were mortality and any complications. RESULTS: Ninety consecutive patients underwent PD for periampullary tumors in the studied period, 70 in group A and 20 in group B. Clinical and pathological characteristics of both groups were equivalents except for age. There were no difference regarding the incidence of severe complications (17% vs. 10%, P=0.72) or all complications (50% vs. 50%, P>0.999). Although mortality was greater in group A (8.6% vs. 0%), it was not statistically significant (P=0.333). On multivariate analyses, only male sex, obesity and American Society of Anesthesiology Score of 3 or 4 were associated with severe postoperative complications. CONCLUSIONS: Poor clinical status, obesity and male gender are associated with severe complications in PD, but not age greater than 75 years, therefore PD can be considered safe in elderly patients and age itself should not be a contraindication for PD.

PRELIMINARY RESULTS OF TOPICAL HEPATIC HYPOTHERMIA IN A MODEL OF LIVER ISCHEMIA/REPERFUSION INJURY IN RATS.

BACKGROUND: Ischemia/reperfusion causes organ damage but it is mandatory in hepatic transplantation, trauma and other complex liver surgeries, when Pringle maneuver is applied to minimize bleeding during these procedures. It is well known that liver ischemia/reperfusion leads to microcirculatory disturbance and cellular injury. In this setting hypothermia is known to reduce oxygen demand, lowering intracellular metabolism. OBJECTIVE:: To evaluate the effects of hypothermia in liver ischemia/reperfusion injury, using a new model of topic isolated liver hypothermia. METHODS: We used male Wistar rats weighting about 250 grams, kept in ad libitum feeding regime and randomly divided into two groups of nine animals: 1) Normothermic group, rats were submitted to normothermic ischemia of the median and left hepatic lobes, with subsequent resection of right and caudate lobes during liver reperfusion; and 2) Hypothermic group, rats were submitted to liver ischemia under hypothermia at 10°C. Liver ischemia was performed for 45 minutes. The animals were euthanized 48 hours after liver reperfusion for blood and liver tissue sampling. RESULTS: The transaminases analyses showed a significant decrease of AST and ALT in Hypothermic group (P<0.01) compared to Normothermic group (1403±1234 x 454±213 and 730±680 x 271±211 U/L, respectively). Histology showed severe necrosis in 50% and mild necrosis in 50% of cases in Normothermic group, but severe necrosis in 10% and mild or absent necrosis 90% of the cases in hypothermic group. CONCLUSION:: A simplified model of liver ischemia/reperfusion that simulates orthotopic liver autotransplantion was demonstrated. Topical hypothermia of isolated hepatic lobules showed liver protection, being a viable and practical method for any kind of in vivo liver preservation study.

Resultados preliminares de hipotermia tópica do fígado em modelo de isquemia/reperfusão hepática em ratos / Preliminary results of topical hepatic hypothermia in a model of liver ischemia/reperfusion injury in rats

ABSTRACT BACKGROUND Ischemia/reperfusion causes organ damage but it is mandatory in hepatic transplantation, trauma and other complex liver surgeries, when Pringle maneuver is applied to minimize bleeding during these procedures. It is well known that liver ischemia/reperfusion leads to microcirculatory disturbance and cellular injury. In this setting hypothermia is known to reduce oxygen demand, lowering intracellular metabolism. OBJECTIVE: To evaluate the effects of hypothermia in liver ischemia/reperfusion injury, using a new model of topic isolated liver hypothermia. METHODS We used male Wistar rats weighting about 250 grams, kept in ad libitum feeding regime and randomly divided into two groups of nine animals: 1) Normothermic group, rats were submitted to normothermic ischemia of the median and left hepatic lobes, with subsequent resection of right and caudate lobes during liver reperfusion; and 2) Hypothermic group, rats were submitted to liver ischemia under hypothermia at 10°C. Liver ischemia was performed for 45 minutes. The animals were euthanized 48 hours after liver reperfusion for blood and liver tissue sampling. RESULTS The transaminases analyses showed a significant decrease of AST and ALT in Hypothermic group (P<0.01) compared to Normothermic group (1403±1234 x 454±213 and 730±680 x 271±211 U/L, respectively). Histology showed severe necrosis in 50% and mild necrosis in 50% of cases in Normothermic group, but severe necrosis in 10% and mild or absent necrosis 90% of the cases in hypothermic group. CONCLUSION: A simplified model of liver ischemia/reperfusion that simulates orthotopic liver autotransplantion was demonstrated. Topical hypothermia of isolated hepatic lobules showed liver protection, being a viable and practical method for any kind of in vivo liver preservation study.

RESUMO CONTEXTO: A isquemia/reperfusão leva a grave lesão de órgãos, mas ocorre obrigatoriamente no transplante hepático, no trauma e em outras cirurgias hepáticas complexas, quando a manobra de Pringle é aplicada com o intuito de minimizar o sangramento durante os procedimentos. É bem conhecido que a isquemia/reperfusão do fígado leva a distúrbios microcirculatórios e lesões celulares. Neste cenário, a hipotermia é conhecida por reduzir a demanda de oxigênio, diminuindo o metabolismo intracelular. OBJETIVO: Avaliar os efeitos da hipotermia na lesão de isquemia/reperfusão hepática utilizando-se um novo modelo de hipotermia isolada do fígado. MÉTODOS: Utilizaram-se ratos Wistar do sexo masculino com peso aproximado de 250 gramas, mantidos em regime de alimentação ad libitum e divididos aleatoriamente em dois grupos de nove animais: 1) Grupo Normotérmico - os ratos foram submetidos a isquemia normotérmica dos lobos hepáticos mediano e esquerdo, com posterior ressecção dos lobos direito e caudado durante a reperfusão hepática; e 2) Grupo Hipotérmico - os ratos foram submetidos a isquemia hepática sob hipotermia a 10°C. A isquemia hepática foi realizada durante 45 minutos. Os animais foram sacrificados 48 horas após a reperfusão hepática para coleta de sangue e tecido hepático para análise. RESULTADOS: As transaminases AST e ALT apresentaram diminuição significativa no grupo Hipotérmico (P<0,01) em relação ao grupo Normotérmico (1403±1234 x 454±213 e 730±680 x 271±211 U/L, respectivamente). A histologia mostrou necrose grave em 50% e necrose leve em 50% dos casos no grupo Normotérmico, porém, necrose grave em 10% e necrose leve ou ausente em 90% dos casos no grupo Hipotérmico. CONCLUSÃO: Foi demonstrado modelo simplificado de isquemia/reperfusão do fígado que simula o autotrasplante de fígado. A hipotermia tópica dos lóbulos hepáticos isolados mostrou proteção do fígado a ischemia/reperfusão, sendo um método viável e prático para qualquer tipo de estudo de preservação hepática in vivo.

MINIMALLY INVASIVE SURGERY FOR PSEUDOPAPILLARY NEOPLASM OF THE PANCREAS.

BACKGROUND: Solid pseudopapillary pancreatic neoplasia is usually a large well-circumscribed pancreatic mass, with cystic and solid areas more frequently found in young women. It is a benign pancreatic neoplasia in most cases, therefore minimally invasive surgery could be an interesting approach. AIM: Evaluate the results of minimally invasive surgery for this neoplasia. METHODS: Patients with this tumor who underwent minimally invasive pancreatectomies between 2009 and 2015 in a single institution, were analyzed regarding demographic, clinical-pathological futures, post-operative morbidity and disease-free survival. RESULTS: All were women, and their median age was 39 (18-54) years. Two patients with tumor in the head of the pancreas underwent laparoscopic pancreaticoduodenectomy, and another one underwent laparoscopic enucleation. Two patients with tumor in the neck underwent central pancreatectomy. Distal pancreatectomies were performed in the other five, one with splenic preservation. None required blood transfusion or conversion to open surgery. Two (20%) developed clinical relevant pancreatic fistulas, requiring readmission. Median length of postoperative hospital stay was five days (2-8). All resection margins were negative. Patients were followed for a median of 38 months (14-71), and there was no recurrence. CONCLUSIONS: Minimally invasive surgery for solid pseudopapillary pancreatic neoplasia is feasible for tumors in different locations in the pancreas. It was associated with acceptable morbidity and respected the oncologic principles for treatment.

RACIONAL: Tumores sólidos pseudopapilíferos do pâncreas são em geral massas circunscritas, com componentes sólidos e císticos, mais frequentemente encontrados em mulheres jovens. Na maioria dos casos, são neoplasias benignas e portanto, a abordagem minimamente invasiva pode ser considerada vantajosa. OBJETIVO: Avaliar os resultados das pancreatectomias laparoscópicas em pacientes com esses tumores. MÉTODOS: Foram avaliados pacientes submetidos à pancreatectomias minimamente invasivas em um única instituição. Foram analisadas variáveis demográficas, clinicopatológicas, complicações pós-operatórias e sobrevida. RESULTADOS: Todos os pacientes eram mulheres e a idade mediana foi de 39 (18-54) anos. Duas pacientes com tumores na cabeça do pâncreas foram submetidas à duodenopancreatectomia e outra à enucleação. Duas pacientes com tumores no colo do pâncreas realizaram pancreatectomia central. Outras cinco com neoplasias no corpo e cauda foram submetidas à pancreatectomia distal, uma delas com preservação do baço. Nenhuma necessitou de conversão para laparotomia. Houve duas fístulas pancreáticas clinicamente relevantes (20%). O tempo mediano de internação foi de cinco (2 a 8) dias e duas pacientes foram reinternadas (20%). Todas as margens de ressecção foram negativas e após seguimento mediano de 38 (14-71) semanas, todas estavam livres de doença. CONCLUSÃO: As ressecções pancreáticas minimamente invasivas de tumores sólidos pseudopapilíferos são factíveis para tumores em diferentes localizações no pâncreas, com morbidade aceitável obedecendo-se os princípios oncológicos para o tratamento dessas neoplasias.

Evaluation of microvessel density and p53 expression in pancreatic adenocarcinoma.

OBJECTIVE: To evaluate the prognostic significance of microvessel density and p53 expression in pancreatic cancer. METHODS: Between 2008 and 2012, 49 patients with pancreatic adenocarcinoma underwent resection with curative intention. The resected specimens were immunohistochemically stained with anti-p53 and anti-CD34 antibodies. Microvessel density was assessed by counting vessels within ten areas of each tumoral section a highpower microscope. RESULTS: The microvessel density ranged from 21.2 to 54.2 vessels/mm2. Positive nuclear staining for p53 was found in 20 patients (40.6%). The overall median survival rate after resection was 24.1 months and there were no differences in survival rates related to microvessel density or p53 positivity. Microvessel density was associated with tumor diameter greater than 3.0 cm and with R0 resection failure. CONCLUSIONS: Microvessel density was associated with R1 resection and with larger tumors. p53 expression was not correlated with intratumoral microvessel density in pancreatic adenocarcinoma.

Evaluation of microvessel density and p53 expression in pancreatic adenocarcinoma

OBJECTIVE: To evaluate the prognostic significance of microvessel density and p53 expression in pancreatic cancer. METHODS: Between 2008 and 2012, 49 patients with pancreatic adenocarcinoma underwent resection with curative intention. The resected specimens were immunohistochemically stained with anti-p53 and anti-CD34 antibodies. Microvessel density was assessed by counting vessels within ten areas of each tumoral section a highpower microscope. RESULTS: The microvessel density ranged from 21.2 to 54.2 vessels/mm2. Positive nuclear staining for p53 was found in 20 patients (40.6%). The overall median survival rate after resection was 24.1 months and there were no differences in survival rates related to microvessel density or p53 positivity. Microvessel density was associated with tumor diameter greater than 3.0 cm and with R0 resection failure. CONCLUSIONS: Microvessel density was associated with R1 resection and with larger tumors. p53 expression was not correlated with intratumoral microvessel density in pancreatic adenocarcinoma.

Minimally invasive surgery for pseudopapillary neoplasm of the pancreas / Cirurgia minimamente invasiva para tratamento da neoplasia pseudopapilar do pâncreas

ABSTRACT Background: Solid pseudopapillary pancreatic neoplasia is usually a large well-circumscribed pancreatic mass, with cystic and solid areas more frequently found in young women. It is a benign pancreatic neoplasia in most cases, therefore minimally invasive surgery could be an interesting approach. Aim: Evaluate the results of minimally invasive surgery for this neoplasia. Methods: Patients with this tumor who underwent minimally invasive pancreatectomies between 2009 and 2015 in a single institution, were analyzed regarding demographic, clinical-pathological futures, post-operative morbidity and disease-free survival. Results: All were women, and their median age was 39 (18-54) years. Two patients with tumor in the head of the pancreas underwent laparoscopic pancreaticoduodenectomy, and another one underwent laparoscopic enucleation. Two patients with tumor in the neck underwent central pancreatectomy. Distal pancreatectomies were performed in the other five, one with splenic preservation. None required blood transfusion or conversion to open surgery. Two (20%) developed clinical relevant pancreatic fistulas, requiring readmission. Median length of postoperative hospital stay was five days (2-8). All resection margins were negative. Patients were followed for a median of 38 months (14-71), and there was no recurrence. Conclusions: Minimally invasive surgery for solid pseudopapillary pancreatic neoplasia is feasible for tumors in different locations in the pancreas. It was associated with acceptable morbidity and respected the oncologic principles for treatment.

RESUMO Racional: Tumores sólidos pseudopapilíferos do pâncreas são em geral massas circunscritas, com componentes sólidos e císticos, mais frequentemente encontrados em mulheres jovens. Na maioria dos casos, são neoplasias benignas e portanto, a abordagem minimamente invasiva pode ser considerada vantajosa. Objetivo: Avaliar os resultados das pancreatectomias laparoscópicas em pacientes com esses tumores. Métodos: Foram avaliados pacientes submetidos à pancreatectomias minimamente invasivas em um única instituição. Foram analisadas variáveis demográficas, clinicopatológicas, complicações pós-operatórias e sobrevida. Resultados: Todos os pacientes eram mulheres e a idade mediana foi de 39 (18-54) anos. Duas pacientes com tumores na cabeça do pâncreas foram submetidas à duodenopancreatectomia e outra à enucleação. Duas pacientes com tumores no colo do pâncreas realizaram pancreatectomia central. Outras cinco com neoplasias no corpo e cauda foram submetidas à pancreatectomia distal, uma delas com preservação do baço. Nenhuma necessitou de conversão para laparotomia. Houve duas fístulas pancreáticas clinicamente relevantes (20%). O tempo mediano de internação foi de cinco (2 a 8) dias e duas pacientes foram reinternadas (20%). Todas as margens de ressecção foram negativas e após seguimento mediano de 38 (14-71) semanas, todas estavam livres de doença. Conclusão: As ressecções pancreáticas minimamente invasivas de tumores sólidos pseudopapilíferos são factíveis para tumores em diferentes localizações no pâncreas, com morbidade aceitável obedecendo-se os princípios oncológicos para o tratamento dessas neoplasias.

Pentoxifylline enhances the protective effects of hypertonic saline solution on liver ischemia reperfusion injury through inhibition of oxidative stress.

BACKGROUND: Liver ischemia reperfusion (IR) injury triggers a systemic inflammatory response and is the main cause of organ dysfunction and adverse postoperative outcomes after liver surgery. Pentoxifylline (PTX) and hypertonic saline solution (HTS) have been identified to have beneficial effects against IR injury. This study aimed to investigate if the addition of PTX to HTS is superior to HTS alone for the prevention of liver IR injury. METHODS: Male Wistar rats were allocated into three groups. Control rats underwent 60 minutes of partial liver ischemia, HTS rats were treated with 0.4 mL/kg of intravenous 7.5% NaCl 15 minutes before reperfusion, and HPTX group were treated with 7.5% NaCl plus 25 mg/kg of PTX 15 minutes before reperfusion. Samples were collected after reperfusion for determination of ALT, AST, TNF-alpha, IL-6, IL-10, mitochondrial respiration, lipid peroxidation, pulmonary permeability and myeloperoxidase. RESULTS: HPTX significantly decreased TNF-alpha 30 minutes after reperfusion. HPTX and HTS significantly decreased ALT, AST, IL-6, mitochondrial dysfunction and pulmonary myeloperoxidase 4 hours after reperfusion. Compared with HTS only, HPTX significantly decreased hepatic oxidative stress 4 hours after reperfusion and pulmonary permeability 4 and 12 hours after reperfusion. CONCLUSION: This study showed that PTX added the beneficial effects of HTS on liver IR injury through decreases of hepatic oxidative stress and pulmonary permeability.

Liver resection for the treatment of post-cholecystectomy biliary stricture with vascular injury.

AIM: To report experience with liver resection in a select group of patients with postoperative biliary stricture associated with vascular injury. METHODS: From a prospective database of patients treated for benign biliary strictures at our hospital, cases that underwent liver resections were reviewed. All cases were referred after one or more attempts to repair bile duct injuries following cholecystectomy (open or laparoscopic). Liver resection was indicated in patients with Strasberg E3/E4 (hilar stricture) bile duct lesions associated with vascular damage (arterial and/or portal), ipsilateral liver atrophy/abscess, recurrent attacks of cholangitis, and failure of previous hepaticojejunostomy. RESULTS: Of 148 patients treated for benign biliary strictures, nine (6.1%) underwent liver resection; eight women and one man with a mean age of 38.6 years. Six patients had previously been submitted to open cholecystectomy and three to laparoscopic surgery. The mean number of surgical procedures before definitive treatment was 2.4. All patients had Strasberg E3/E4 injuries, and vascular injury was present in all cases. Eight patients underwent right hepatectomy and one underwent left lateral sectionectomy without mortality. Mean time of follow up was 69.1 mo and after long-term follow up, eight patients are asymptomatic. CONCLUSION: Liver resection is a good therapeutic option for patients with complex postoperative biliary stricture and vascular injury presenting with liver atrophy/abscess in which previous hepaticojejunostomy has failed.

Penetrance of functioning and nonfunctioning pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 in the second decade of life.

CONTEXT: Data are scarce on the penetrance of multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-PETs) and insulinomas in young MEN1 patients. A potential positive correlation between tumor size and malignancy (2-3 cm, 18%; >3 cm, 43%) has greatly influenced the management of MEN1 adults with NF-PETs. OBJECTIVE: The aim of the study was to estimate the penetrance of NF-PETs, insulinomas, and gastrinomas in young MEN1 carriers. DESIGN: The data were obtained from a screening program (1996-2012) involving 113 MEN1 patients in a tertiary academic reference center. PATIENTS: Nineteen MEN1 patients (aged 12-20 y; 16 patients aged 15-20 y and 3 patients aged 12-14 y) were screened for NF-PETs, insulinomas, and gastrinomas. METHODS: Magnetic resonance imaging/computed tomography and endoscopic ultrasound (EUS) were performed on 10 MEN1 carriers, magnetic resonance imaging/computed tomography was performed on five patients, and four other patients underwent an EUS. RESULTS: The overall penetrance of PETs during the second decade of life was 42% (8 of 19). All eight PET patients had NF-PETs, and half of those tumors were multicentric. One-fifth of the screened patients (21%; 4 of 19) harbored at least one large tumor (>2.0 cm). Insulinoma was detected in two NF-PET patients (11%) at the initial screening; gastrinoma was not present in any cases. Six of the 11 (54%) screened patients aged 15-20 years who underwent an EUS had NF-PETs. Potential false-positive EUS results were excluded based on EUS-guided biopsy results, the reproducibility of the NF-PET findings, or the observation of increased tumor size during follow-up. Distal pancreatectomy and the nodule enucleation of pancreatic head tumors were conducted on three patients with large tumors (>2.0 cm; T2N0M0) that were classified as grade 1 neuroendocrine tumors (Ki-67<2%). CONCLUSIONS: Our data demonstrated high penetrance of NF-PETs in 15- to 20-year-old MEN1 patients. The high percentage of the patients presenting consensus criteria for surgery for NF-PET alone or NF-PET/insulinoma suggests a potential benefit for the periodic surveillance of these tumors in this age group.

HOXB7 mRNA is overexpressed in pancreatic ductal adenocarcinomas and its knockdown induces cell cycle arrest and apoptosis.

BACKGROUND: Human homeobox genes encode nuclear proteins that act as transcription factors involved in the control of differentiation and proliferation. Currently, the role of these genes in development and tumor progression has been extensively studied. Recently, increased expression of HOXB7 homeobox gene (HOXB7) in pancreatic ductal adenocarcinomas (PDAC) was shown to correlate with an invasive phenotype, lymph node metastasis and worse survival outcomes, but no influence on cell proliferation or viability was detected. In the present study, the effects arising from the knockdown of HOXB7 in PDAC cell lines was investigated. METHODS: Real time quantitative PCR (qRT-PCR) (Taqman) was employed to assess HOXB7 mRNA expression in 29 PDAC, 6 metastatic tissues, 24 peritumoral tissues and two PDAC cell lines. siRNA was used to knockdown HOXB7 mRNA in the cell lines and its consequences on apoptosis rate and cell proliferation were measured by flow cytometry and MTT assay respectively. RESULTS: Overexpression of HOXB7 mRNA was observed in the tumoral tissues and in the cell lines MIA PaCa-2 and Capan-1. HOXB7 knockdown elicited (1) an increase in the expression of the pro-apoptotic proteins BAX and BAD in both cell lines; (2) a decrease in the expression of the anti-apoptotic protein BCL-2 and in cyclin D1 and an increase in the number of apoptotic cells in the MIA PaCa-2 cell line; (3) accumulation of cell in sub-G1 phase in both cell lines; (4) the modulation of several biological processes, especially in MIA PaCa-2, such as proteasomal ubiquitin-dependent catabolic process and cell cycle. CONCLUSION: The present study confirms the overexpression of HOXB7 mRNA expression in PDAC and demonstrates that decreasing its protein level by siRNA could significantly increase apoptosis and modulate several biological processes. HOXB7 might be a promising target for future therapies.

Surgical site infections in liver transplant recipients in the model for end-stage liver disease era: an analysis of the epidemiology, risk factors, and outcomes.

In recipients of liver transplantation (LT), surgical site infection (SSIs) are among the most common types of infection occurring in the first 60 days after LT. In 2007, the Model for End-Stage Liver Disease (MELD) scoring system was adopted as the basis for prioritizing organ allocation. Patients with higher MELD scores are at higher risk for developing SSIs as well as other health care-associated infections. However, there have been no studies comparing the incidence of SSIs in the pre-MELD era with the incidence in the period since its adoption. Therefore, the objectives of this study were to evaluate the incidence, etiology, epidemiology, and outcomes of post-LT SSIs in those 2 periods and to identify risk factors for SSIs. We evaluated all patients who underwent LT over a 10-year period (2002-2011). SSI cases were identified through active surveillance. The primary outcome measure was an SSI during the first 60 days after LT. Risk factors were analyzed via logistic regression, and 60-day survival rates were evaluated via Cox regression. We evaluated 543 patients who underwent LT 597 times. The SSI rates in the 2002-2006 and 2007-2011 periods were 30% and 24%, respectively (P = 0.21). We identified the following risk factors for SSIs: retransplantation, the transfusion of more than 2 U of blood during LT, dialysis, cold ischemia for >400 minutes, and a cytomegalovirus infection. The overall 60-day survival rate was 79%. Risk factors for 60-day mortality were retransplantation, dialysis, and a longer surgical time. The use of the MELD score modified the incidence and epidemiology of SSIs only during the first year after its adoption. Risks for SSIs were related more to intraoperative conditions and intercurrences after LT than to a patient's status before LT.

Clinical spectrum and therapeutic approach to hepatocellular injury in patients with hyperthyroidism.

Liver dysfunction in patients with hyperthyroidism includes abnormalities associated with the effects of thyroid hormone excess, those secondary to drug-induced liver injury, and changes resulting from concomitant liver disease. Our goal was to describe clinical, biochemical, and histopathological patterns in patients suffering from hyperthyroidism and concomitant liver dysfunction and to propose an algorithm of procedures to facilitate diagnosis and management of such cases. This study describes seven patients with liver biochemistry abnormalities detected after diagnosis of hyperthyroidism and one with undiagnosed decompensated hyperthyroidism and acute hepatitis. Two patients showed autoantibody reactivity which, together with liver histology, suggested the diagnosis of classic autoimmune hepatitis. Three patients experienced hepatotoxicity induced by propylthiouracil, the manifestations of which ranged from a benign course after drug withdrawal in one, a longstanding course in another suggesting drug-induced autoimmune hepatitis, and a more severe clinical condition with acute liver failure in a third patient, requiring liver transplantation. The three remaining patients showed no precipitating factors other than thyroid hyperactivity itself. They could be interpreted as having a thyroid storm with different clinical presentations. In conclusion, this series of patients illustrates the most frequent patterns of hepatocellular damage associated with hyperthyroidism and provides an algorithm for their diagnosis and treatment.

Pentoxifylline improves liver regeneration through down-regulation of TNF-α synthesis and TGF-ß1 gene expression.

AIM: To investigate the mechanism of pentoxifylline (PTX) improvement in liver regeneration. RESULTS: Rats were randomized into 4 groups: Control rats; Sham - sham-operation rats; Saline - 70% hepatectomy plus saline solution; PTX - 70% hepatectomy plus PTX. At 2 and 6 h after hepatectomy, aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) serum and hepatic tissue levels were determined. Tumor growth factor (TGF)-ß1 gene expression in liver tissue was evaluated 24 h after hepatectomy by quantitative reverse transcriptase polymerase chain reaction analysis. Proliferation was analyzed by mitotic index and proliferating cell nuclear antigen (PCNA) staining 48 h after hepatectomy. RESULTS: TNF-α and IL-6 serum levels increased at 2 and 6 h after hepatectomy. At 2 h after hepatectomy serum PTX was reduced but not hepatic levels of TNF-α and IL-6. A decrease in liver TGF-ß1 gene expression and an increase in mitotic index and PCNA after hepatectomy were observed in the PTX treatment group in comparison to the saline group. CONCLUSION: PTX improves liver regeneration by a mechanism related to down regulation of TNF-α production and TGF-ß1 gene expression.

Transduodenal endosonography-guided biliary drainage and duodenal stenting for palliation of malignant obstructive jaundice and duodenal obstruction.

CONTEXT: Endosonography-guided biliary drainage has been used over the last few years as a salvage procedure when endoscopic retrograde cholangiopancreatography fails. Malignant gastric outlet obstruction may also be present in these patients. We report the results of both procedures during the same session in patients with duodenal and biliary obstruction due to malignant disease. METHODS: A retrospective review from a prospective collected database. RESULTS: Technical success was achieved in all five patients; however, only three patients experienced relief of jaundice and gastric outlet obstruction. CONCLUSIONS: Endosonography-guided biliary drainage and duodenal stenting in the same session is feasible. However, severe complications may limit the procedure. This is a challenging procedure and should be done by experts with special attention to patient's selection.