O objetivo do presente trabalho foi avaliar o valor diagnóstico e o impacto na modificação da conduta terapêutica do ultra-som intra-operatório (UIO) na cirurgia por neoplasia de fígado, vias biliares e pâncreas, comparando-se achados da avaliação pré-operatória de rotina com métodos de imagem convencionais (tomografia computadorizada e ressonância magnética) com achados obtidos por meio da exploração cirúrgica (inspeção e palpação). Foram analisados, retrospectivamente, exames realizados em 49 pacientes, sendo 15 portadores de neoplasia hepática secundária; 14, de neoplasia hepática primária; 14, de tumor neuroendócrino pancreático e seis de neoplasia cística pancreática. No grupo de pacientes com neoplasia hepática e de vias biliares, a TC identificou 65% dos tumores; a exploração cirúrgica, 69,5% e o UIO, 95,2%. Houve mudança da conduta, em decorrência dos achados do UIO, em 34,4% dos pacientes. No grupo de tumores neuroendócrinos pancreáticos, a TC identificou corretamente 44,4% dos tumores; a RM, 60,9%; a exploração cirúrgica com palpação, 72,7% e o UIO, 100%. Houve mudança de conduta em 42,9% dos pacientes. No grupo de neoplasia cística, o UIO não acrescentou informação adicional relevante em relação à TC e à RM, exceto no paciente com neoplasia papilífera intraductal. Apesar do grande avanço nos métodos de avaliação por imagem pré-operatórios e mesmo com toda a expertise do cirurgião, os resultados mostram que o UIO modifica positivamente o planejamento cirúrgico em um número significativo de pacientes, devendo, portanto fazer parte integrante da avaliação intra-operatória dos pacientes candidatos à ressecção hepática por neoplasia primária ou secundária e da cirurgia de neoplasia endócrina pancreática / Intraoperative sonography (IOU) is an imaging modality that has been showing rapid growth in the last decade that can has a variety of applications in different surgical specialities, particularly in abdominal surgery. The purpose of this study was to analyze the use o IOU in the setting of surgery for liver, biliary and pancreatic malignancies. To achieve that, the findings of routine preoperative state-of the-art imaging modalities (CT and MRI) and the findings of surgical exploration (inspection and palpation) were compared to those of IOU. The impact of IOU on preoperative plans based on CT and MRI and on management after surgical exploration were studied as well 49 patients were retrospectively studied. Of those 15 had metastatic liver disease and 14 primary liver cancer; 14 had pancreatic neuroendocrine tumours and 6 had cystic pancreatic neoplasms. In the group of hepatic and biliary malignancies CT identified 65% of the tumours, surgical exploration identified 69.5% and IOU 95.2% (including 3 false positives). IOU determined a change in management in 34.4% of the patients. In the group of pancreatic neuroendocrine tumours the rates of identification were 27.3% for CT, 60.9% for MRI, 72.7% for surgical exploration and 100% for IOU, with an alteration in surgical plans in 42.9% of patients after IOU. In the case of patients with cystic pancreatic neoplasia, IOUS did not add any relevant additional information in relation to CT or MRI, with exception to one patient that had a papiliferous intraductal neoplasia. In spite of the great advances on preoperatory imaging modalities and of the possibility of direct surgical exploration, IOU has shown that it positively modifies surgical planning. For that reason, it should be included as an essential adjunct in the intraoperatory evaluation of patients with pancreatic endocrine neoplasia and of candidates for hepatic resection in cases of primary and secondary malignancies

The Relationship Between Central Venous Catheter and Post-operative Complications in Patients Undergoing Hepatic Resection David C. O’Connor, Ph.D., DNAP, CRNA A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2018 Dissertation Chair: Clarence J. Biddle, Ph.D., CRNA Hepatic resection is indicated for primary and secondary malignancies. Use of a low central venous pressure technique is associated with decreased blood loss in these cases. This technique has evolved; central venous catheters and high dose morphine are no longer used, and patients are extubated earlier. The purpose of this study is to assess a relationship between these changes and outcomes. Central venous pressure has fallen out of favor as an accurate fluid measurement. Central venous catheters are associated with many complications. Outcomes in patients undergoing hepatic resection have improved over 20 years at one high volume institution. Guided by Donabedian’s theory of measuring outcomes, a non-randomized, non-experimental, retrospective, cohort design was conducted. The independent variables were intraoperative insertion of a central venous catheter, use of morphine, and time of extubation. The dependent variables were superficial and deep wound infections, number and severity of complications. The population sample is patients who submitted to partial hepatectomy at Memorial Sloan Kettering Cancer Center from 2007-2016. Data was obtained from hepatobiliary and anesthesia databases at Memorial Sloan Kettering Cancer Center. Data of 2518 from a possible 3903 patients were analyzed with chi square, univariate, Poisson and multivariate regressions. Univariate analysis for presence of CVC was significant for 90-day mortality (p 0.013). Use of morphine was significant for superficial wound infection (p 0.035), and a decrease in complications (p <.001). Amount of morphine was associated with fewer severe complications (p <.001). Incidental findings included a relationship between gender, total amount of fluids and number of segments resected. The significance of CVC with 90-day mortality was eliminated with stepwise multivariate regression. The findings support the change in anesthetic practice with clinical significance. Incidental findings regarding fluids and segments are supported in the literature. Future research should include goal directed fluid therapy and investigation of the relationship between gender and outcomes.

O objetivo do presente trabalho foi avaliar o valor diagnóstico e o impacto na modificação da conduta terapêutica do ultra-som intra-operatório (UIO) na cirurgia por neoplasia de fígado, vias biliares e pâncreas, comparando-se achados da avaliação pré-operatória de rotina com métodos de imagem convencionais (tomografia computadorizada e ressonância magnética) com achados obtidos por meio da exploração cirúrgica (inspeção e palpação). Foram analisados, retrospectivamente, exames realizados em 49 pacientes, sendo 15 portadores de neoplasia hepática secundária; 14, de neoplasia hepática primária; 14, de tumor neuroendócrino pancreático e seis de neoplasia cística pancreática. No grupo de pacientes com neoplasia hepática e de vias biliares, a TC identificou 65% dos tumores; a exploração cirúrgica, 69,5% e o UIO, 95,2%. Houve mudança da conduta, em decorrência dos achados do UIO, em 34,4% dos pacientes. No grupo de tumores neuroendócrinos pancreáticos, a TC identificou corretamente 44,4% dos tumores; a RM, 60,9%; a exploração cirúrgica com palpação, 72,7% e o UIO, 100%. Houve mudança de conduta em 42,9% dos pacientes. No grupo de neoplasia cística, o UIO não acrescentou informação adicional relevante em relação à TC e à RM, exceto no paciente com neoplasia papilífera intraductal. Apesar do grande avanço nos métodos de avaliação por imagem pré-operatórios e mesmo com toda a expertise do cirurgião, os resultados mostram que o UIO modifica positivamente o planejamento cirúrgico em um número significativo de pacientes, devendo, portanto fazer parte integrante da avaliação intra-operatória dos pacientes candidatos à ressecção hepática por neoplasia primária ou secundária e da cirurgia de neoplasia endócrina pancreática / Intraoperative sonography (IOU) is an imaging modality that has been showing rapid growth in the last decade that can has a variety of applications in different surgical specialities, particularly in abdominal surgery. The purpose of this study was to analyze the use o IOU in the setting of surgery for liver, biliary and pancreatic malignancies. To achieve that, the findings of routine preoperative state-of the-art imaging modalities (CT and MRI) and the findings of surgical exploration (inspection and palpation) were compared to those of IOU. The impact of IOU on preoperative plans based on CT and MRI and on management after surgical exploration were studied as well 49 patients were retrospectively studied. Of those 15 had metastatic liver disease and 14 primary liver cancer; 14 had pancreatic neuroendocrine tumours and 6 had cystic pancreatic neoplasms. In the group of hepatic and biliary malignancies CT identified 65% of the tumours, surgical exploration identified 69.5% and IOU 95.2% (including 3 false positives). IOU determined a change in management in 34.4% of the patients. In the group of pancreatic neuroendocrine tumours the rates of identification were 27.3% for CT, 60.9% for MRI, 72.7% for surgical exploration and 100% for IOU, with an alteration in surgical plans in 42.9% of patients after IOU. In the case of patients with cystic pancreatic neoplasia, IOUS did not add any relevant additional information in relation to CT or MRI, with exception to one patient that had a papiliferous intraductal neoplasia. In spite of the great advances on preoperatory imaging modalities and of the possibility of direct surgical exploration, IOU has shown that it positively modifies surgical planning. For that reason, it should be included as an essential adjunct in the intraoperatory evaluation of patients with pancreatic endocrine neoplasia and of candidates for hepatic resection in cases of primary and secondary malignancies

Contemporary hepatobiliary surgery practice must accurately assess operative risk in increasingly elderly populations with greater co-morbidity. Current methods fail to identify patients at high risk of postoperative complications. Cardiopulmonary exercise testing (CPET) derived anaerobic threshold (AT) and ventilatory equivalence of carbon dioxide (VE/VCO2) are validated predictors of postoperative outcome in major intra-abdominal surgery and outperform contemporary tools of risk evaluation. Despite evidence of improved in-hospital postoperative survival in large centres offering complex curative hepatobiliary surgery, morbidity remains high and long-term survival in the high-risk subset remains poor. This thesis investigated the role of validated CPET-derived markers in predicting perioperative outcomes for a high-risk hepatobiliary surgery population. It was also utilised to study the impact of malignant obstructive jaundice on peripheral oxygen extraction. In a prospective cohort of high-risk patients undergoing liver resection, an AT of 9.9 ml O2/kg/min predicted in-hospital mortality and long-term survival. Below this threshold, AT was 100% sensitive and 75.9% specific for in-hospital mortality (PPV 19%, NPV 100%). Long-term survival below the threshold of 9.9 was significantly worse when compared to those above (mortality HR 1.81). The VE/VCO2 was the most significant predictor of postoperative complications and a threshold of 34.5 provided 84% specificity and 47% sensitivity (PPV 76%, NPV 60%). Amongst the high-risk pancreaticoduodenectomy patients, VE/VCO2 was the single most predictive marker of in-hospital postoperative mortality with an AUC of 0.850 (p=0.020); a threshold value 41 was 75% sensitive and 94.6% specific (PPV 50%, NPV 98.1%). The VE/VCO2 41 was also the only predictor of poor long-term survival (HR 1.90). Notably, AT, Revised Cardiac Risk Index and Glasgow Prognostic Score did not predict outcome after pancreaticoduodenectomy. Patients with malignant obstructive jaundice, evaluated for peripheral oxygen extraction using CPET, showed lower mean peak oxygen consumption (peak VO2) at 63±17.4% of the predicted value. This was noted in absence of any significant pre-existing cardiopulmonary disease and normal respiratory reserve. Normal patterns of oxygen extraction were seen at rest, during incremental work rate and peak exercise levels. Levels of oxygen partial pressure and saturation exceeded baseline values after exercise signifying normal microcirculatory responses. Thus, aerobic capacity was limited by dysfunction in delivery (cardiac output) rather than oxygen extraction. CPET provides useful prognostic adjuncts for early and long-term outcomes in the high-risk patients undergoing major hepatobiliary surgery. These findings provide useful tools for perioperative optimisation of the high-risk patient and plan appropriate level of postoperative care to address mortality and morbidity after surgery.

Le carcinome hépatocellulaire (CHC) est un cancer très fréquent - au 5ème rang de l’échelon mondial - dont l’incidence ne cesse d’augmenter. Lié aux maladies chroniques du foie (hépatite C, syndrome métabolique et, le plus souvent, cirrhose), il représente désormais un véritable problème de santé publique. C’est la nature du foie sous-jacent qui détermine les modalités de sa prise en charge. Lorsque le foie ne présente pas de maladie chronique (foie sain), on se trouve généralement devant une tumeur déjà évoluée; dans ce cas on a recours essentiellement à la résection hépatique. Lorsque le foie présente une maladie chronique (foie pathologique), qu’il s’agisse de fibrose, cirrhose ou hépatite, c’est le stade tumoral au moment du diagnostic qui oriente le choix du traitement ; à part la transplantation, limitée dans ses indications, les options thérapeutiques comportent la résection hépatique, la destruction par voie sous-cutanée (radio fréquence) et un traitement par voie artérielle (chimioembolisation). Cependant, ces traitements à visée curative, ne peuvent être envisagés actuellement que dans 30% des cas. Notre travail porte uniquement sur la résection hépatique. Partout disponible, cette intervention chirurgicale représente en effet le traitement de référence dans la prise en charge du CHC. Nous nous appuyons sur une vaste enquête nationale qui, développée sur une période de 15 ans – de 1990 à 2005 – à partir de 23 centres de chirurgie, à porté sur plus de 2590 dossiers de patients. Grâce à ces données de base, particulièrement précieuses par leur nombre et leur précisions, nous avons tenté de donner une image panoramique des pratiques (indications, techniques opératoires) et des résultats (survie, récidive, morbidité, mortalité) de la résection hépatique pour CHC en France. Il s’agit de la plus grande étude multicentrique chirurgicale menée sur le CHC en France à ce jour. On a classé 102 paramètres dans 6 groupes de données ont été colligés pour chaque malade inclus dans l’étude: Terrain, Bilan préopératoire, Chirurgie, Anatomopathologie, Morbidité et traitements adjuvants et Evolution. Au total, cette enquête a permis de recueillir une somme considérable de données dont l’analyse multivariée avait pour l’objectif d’aboutir à des critères prédictifs de mortalité opératoire et de survie après résection sur foie sain et pathologique. Cette analyse a confirmé le développent et la qualité de la chirurgie hépatique en France. Aussi, l’analyse a montré que la résection hépatique est un traitement efficace du CHC sur foie sain et pathologique. Ces résultats et leur implication pour l’approche multidisciplinaire en cancérologie contribueront à améliorer les connaissances et la prise en charge du CHC. Finalement, à coté de la transplantation hépatique, limitée par ses indications restreintes et la pénurie de greffons, la résection du CHC occupe une place importante qui doit continuer de croître du fait de ses bons résultats et de l’augmentation constante de l’incidence du CHC / Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, and the third most common cause of cancer-related death. It is a major health problem worldwide, which represents the most prevalent primary liver cancer and constitutes the third most frequent cause of cancer-related deaths. The major risk factor for HCC is cirrhosis. All types of cirrhosis predispose to HCC, but the incidence is particularly high in persistent infection with hepatitis B (HBV) and hepatitis C (HCV) and in alcoholic liver disease. The clinical presentation and management of HCC depends on whether the liver is cirrhotic and whether there is underlying viral hepatitis. Therapeutic options fall into four main categories (1) surgical interventions, including tumor resection and liver transplantation, (2) percutaneous interventions, including ethanol injection and radiofrequency thermal ablation, (3) transarterial interventions, including embolisation and chemoembolisation and (4) drugs as well as gene and immune therapies. Potentially curative therapies are tumor resection, liver transplantation, and percutaneous interventions that can result in complete responses and improved survival in a high proportion of patients. Liver resection offers the greatest impact on survival when patients do not meet transplantation criteria and this is considered as the optimal treatment for HCC. The objective of this thesis, based on a retrospective survey, was to give an overview on conditions of realization and the results of the resection of HCC in France, in the period from 1990-2005. All the French centers of excellence in the hepatobiliary surgery were contacted and most of them accepted to participate. All the contacted units were essentially localized in University Clinical Centers, all of them experts in hepatic surgery and most of them were centers for liver transplantation. More than 2590 cases with hepatic resection were collected in this study. The file consisted of 102 questions and contained following headings: demographic data, underlined liver pathology, circumstances of diagnosis, imaging, evaluation of underlined liver pathology: biological, morphological, histological, preparation for resection: neoadjuvant treatment of the tumor, portal embolization, surgical intervention: approach, clamping, vascular control, nature and the extent of the exeresis, anatomic or non-anatomic features, histopathological analysis of the removed tissues, results: mortality, morbidity, recurrence, survival, lost from analysis. In total, this survey enabled us to collect a considerable sum of data in order to give a more precise overview on predictive criteria of per operative mortality and survival, as well as recurrence rates, after the resection of normal and pathological livers. It confirmed the development and the quality of the hepatic surgery in France

Objective: The primary aim of this study was to assess patients’ preferences between radiofrequency ablation (RFA) versus hepatic resection (HR) for the treatment of small hepatocellular carcinomas (HCC). Methods: Decision analysis was performed by using probability trade-off (PTO) technique to elicit patients’ preferences and the strength of their decisions. Results: The vast majority of the study population preferred RFA over HR (70% vs. 30%, p=0.001). Their initial choice changed if 5-year survival benefit after surgery was at least 14% superior to RFA and if the 3-year disease-free survival advantage was at least 13% better than ablation. Conclusions: The results of this study suggest that fully informed cirrhotic patients would prefer RFA if diagnosed with early stage HCC even if able to undergo surgery.

Objective: The primary aim of this study was to assess patients’ preferences between radiofrequency ablation (RFA) versus hepatic resection (HR) for the treatment of small hepatocellular carcinomas (HCC). Methods: Decision analysis was performed by using probability trade-off (PTO) technique to elicit patients’ preferences and the strength of their decisions. Results: The vast majority of the study population preferred RFA over HR (70% vs. 30%, p=0.001). Their initial choice changed if 5-year survival benefit after surgery was at least 14% superior to RFA and if the 3-year disease-free survival advantage was at least 13% better than ablation. Conclusions: The results of this study suggest that fully informed cirrhotic patients would prefer RFA if diagnosed with early stage HCC even if able to undergo surgery.

Lowering of central venous pressure in hepatic surgery is nowadays widely recommended and used procedure. Low central venous pressure anesthesia is associated with decreased blood loss and improved clinical outcome. There are several approaches how to reach low central venous pressure. Till now none of them is recommended as superior in terms of patient safety and clinical outcome. Concurrently there is still debate if to use the low central venous pressure anesthesia principle or if it could be replaced with a principle of anesthesia with high stroke volume variation (or another dynamic preload parameter) with the use of a more sophisticated hemodynamic monitoring method. Results of our study didn't show any significant difference between two approaches used for reduction of central venous pressure, but suggest that the principle of low central venous pressure anesthesia could be possibly replaced by the principle of high stroke volume variation anesthesia which presumes the use of advanced hemodynamic monitoring. KEYWORDS Hepatic resection, central venous pressure, Pringle maneuver, hemodynamics, hemodynamic monitoring, fluid therapy, anesthesia

Las técnicas ablativas basadas en energía por radiofrecuencia (RF) se emplean con el fin de lograr un calentamiento seguro y localizado en el tejido biológico. En los últimos años ha habido un rápido crecimiento en el número de nuevos procedimientos médicos que hacen uso de dichas técnicas, lo cual ha ido acompañado de la aparición de nuevos diseños de electrodos y protocolos de aplicación de energía. Sin embargo, existen todavía muchas incógnitas sobre el verdadero comportamiento electro-térmico de los aplicadores de energía, así como de la interacción energía-tejido en aplicaciones concretas. El principal propósito de esta Tesis Doctoral es adquirir un mejor conocimiento de los fenómenos eléctricos y térmicos involucrados en los procesos de calentamiento de tejidos biológicos mediante corrientes de RF. Esto permitirá, por un lado, mejorar la eficacia y seguridad de las técnicas actualmente empleadas en la clínica en campos tan diferentes como la cirugía cardiaca, oncológica o dermatológica; y por otro, sugerir mejoras tecnológicas para el diseño de nuevos aplicadores. La Tesis Doctoral combina dos metodologías ampliamente utilizadas en el campo de la Ingeniería Biomédica, como son el modelado computacional (matemático) y la experimentación (ex vivo e in vivo). En cuanto al área cardiaca, la investigación se ha centrado, por una parte, en mejorar la ablación intraoperatoria de la fibrilación auricular por aproximación epicárdica, es decir, susceptible de ser realizada de forma mínimamente invasiva. Para ello, se ha estudiado mediante modelos matemáticos un sistema de medida de la impedancia epicárdica como método de valoración de la cantidad de grasa previo a la ablación. Por otra parte, se ha estudiado cómo mejorar la ablación de la pared ventricular por aproximación endocárdica-endocárdica (septo interventricular) y endocárdica-epicárdica (pared libre del ventrículo). Con este objetivo, se han comparado mediante modelado por computador la eficacia de los modos de ablación bipolar y unipolar en términos de la transmuralidad de la lesión en la pared ventricular. En lo que respecta al área de cirugía oncológica, la investigación se ha centrado en la resección hepática asistida por RF. Las técnicas de calentamiento por RF deberían ser capaces de minimizar el sangrado intraoperatorio y sellar vasos y ductos mediante la creación de una necrosis coagulativa por calentamiento. Si este calentamiento se produce en las cercanías de grandes vasos, existe un problema potencial de daño a la pared de dicho vaso. En este sentido, se ha evaluado con modelos matemáticos y experimentación in vivo si el efecto del flujo de sangre dentro de un gran vaso es capaz de proteger térmicamente su pared cuando se realiza una resección asistida por RF en sus cercanías. Además, se ha realizado un estudio computacional y experimental ex vivo e in vivo del comportamiento electro-térmico de aplicadores de RF bipolares internamente refrigerados, puesto que representan una opción más segura frente a los monopolares en la medida en que las corrientes de RF fluyen casi exclusivamente por el tejido biológico situado entre ambos electrodos. Respecto al área dermatológica, la investigación se ha centrado en mejorar el tratamiento de enfermedades o desórdenes del tejido subcutáneo (tales como lipomatosis, lipedema, enfermedad de Madelung y celulitis) mediante el estudio teórico de la dosimetría correcta en cada caso. Para ello, se han evaluado los efectos eléctricos, térmicos y termo-elásticos de dos estructuras diferentes de tejido subcutáneo durante el calentamiento por RF, y se ha cuantificado el daño térmico producido en ambas estructuras tras dicho calentamiento / González Suárez, A. (2014). Computational Models and Experimentation for Radiofrequency-based Ablative Techniques [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/36502 / TESIS

Lowering of central venous pressure in hepatic surgery is nowadays widely recommended and used procedure. Low central venous pressure anesthesia is associated with decreased blood loss and improved clinical outcome. There are several approaches how to reach low central venous pressure. Till now none of them is recommended as superior in terms of patient safety and clinical outcome. Concurrently there is still debate if to use the low central venous pressure anesthesia principle or if it could be replaced with a principle of anesthesia with high stroke volume variation (or another dynamic preload parameter) with the use of a more sophisticated hemodynamic monitoring method. Results of our study didn't show any significant difference between two approaches used for reduction of central venous pressure, but suggest that the principle of low central venous pressure anesthesia could be possibly replaced by the principle of high stroke volume variation anesthesia which presumes the use of advanced hemodynamic monitoring. KEYWORDS Hepatic resection, central venous pressure, Pringle maneuver, hemodynamics, hemodynamic monitoring, fluid therapy, anesthesia