[Portal vein embolization prior to major hepatectomy: A multidisciplinary approach for advanced liver tumors in Chile]. / Embolización portal previo a hepatectomía mayor: Experiencia multidisciplinaria en tumores hepáticos avanzados en Chile.

BACKGROUND: One of the main limitations to achieving a complete tumor resection in patients with technically resectable liver tumors is the presence of a small future liver remnant (FLR). Portal vein embolization (PVE) allows hypertrophy of the non-embolized lobe, reducing the risk of postoperative liver failure. AIM: To describe the experience of portal embolization prior to hepatectomy and its effectiveness in converting advanced unresectable liver tumors into resectable tumors. METHODS: Non-concurrent cohort study. All patients who underwent PVE before hepatectomy between 2016 and 2020 in our center were included. Demographic and diagnostic variables, pre and post-PVE volumes, perioperative variables, and global and disease-free survival were analyzed. RESULTS: Nineteen patients were included. Median age 66 (54-72) years and 57.9% (n= 11) were women. Bilateral metastases were present in 78.9% (n= 15). Sixteen patients (84.2%) received neoadjuvant chemotherapy. One patient (5.3%) had a complication after PVE. The median time between embolization and volumetry was 5.3 weeks (4.7-7.1). Median FLR before and after PVE were 19.8% (16.2-27.7) and 30% (25.2-40.5), respectively. The median percentage of hypertrophy was 48% (40.4-76.5). Fifteen patients (78.9%) underwent hepatectomy. Significant complications occurred in 26.6% (n= 4); among them, three patients (20%) presented postoperative liver failure. CONCLUSIONS: PVE is safe and effective in promoting FLR hypertrophy in the presence of chemotherapy, allowing patients with advanced liver tumors to undergo surgery with curative intent.

A new approach for the acquisition of trauma surgical skills: an OSCE type of simulation training program.

BACKGROUND: Worldwide, trauma-related deaths are one of the main causes of mortality. Appropriate surgical treatment is crucial to prevent mortality, however, in the past decade, general surgery residents' exposure to trauma cases has decreased, particularly since the COVID-19 pandemic. In this context, accessible simulation-based training scenarios are essential. METHODS: A low-cost, previously tested OSCE scenario for the evaluation of surgical skills in trauma was implemented as part of a short training boot camp for residents and recently graduated surgeons. The following stations were included bowel anastomosis, vascular anastomosis, penetrating lung injury, penetrating cardiac injury, and gastric perforation (laparoscopic suturing). A total of 75 participants from 15 different programs were recruited. Each station was videotaped in high definition and assessed in a remote and asynchronous manner. The level of competency was assessed through global and specific rating scales alongside procedural times. Self-confidence to perform the procedure as the leading surgeon was evaluated before and after training. RESULTS: Statistically significant differences were found in pre-training scores between groups for all stations. The lowest scores were obtained in the cardiac and lung injury stations. After training, participants significantly increased their level of competence in both grading systems. Procedural times for the pulmonary tractotomy, bowel anastomosis, and vascular anastomosis stations increased after training. A significant improvement in self-confidence was shown in all stations. CONCLUSION: An OSCE scenario for training surgical skills in trauma was effective in improving proficiency level and self-confidence. Low pre-training scores and level of confidence in the cardiac and lung injury stations represent a deficit in residency programs that should be addressed. The incorporation of simulation-based teaching tools at early stages in residency would be beneficial when future surgeons face extremely severe trauma scenarios.

Validity Argument for a Simulation-Based Objective Structured Clinical Examination Scenario for Evaluation of Surgical Skills in Trauma.

BACKGROUND: Trauma is one of the main causes of death globally, and appropriate surgical care is crucial to impact mortality. However, resident-performed trauma cases have diminished in the last 10 years. Simulation-based tools have proven to be effective to evaluate practical skills in a variety of settings. However, there is a lack of evidence regarding proper validation of trauma surgery models. OBJECTIVE: The aim of this study was to evaluate under a contemporary validity framework, an objective structured clinical evaluation (OSCE) scenario for the assessment of basic and advanced surgical skills in trauma and emergency surgery. METHODS: An OSCE-type simulation assessment program was developed incorporating six stations representing basic and advanced surgical skills that are essential in trauma surgery. Each station was designed using ex-vivo animal tissue. The stations included basic knots and sutures, bowel resection and anastomosis, vascular end-to-end anastomosis, lung injury repair, cardiac injury repair, and laparoscopic suturing. Eight postgraduate year 2 (PY-2), eight recently graduated surgeons (RGS), and 3 experts were recruited, and their performance was blindly assessed by experts using the validated general rating scale OSATS (Objective Structured Assessment of Technical Skills) as well as the time taken to complete the procedure. RESULTS: Significant differences were identified among groups. The average OSATS score was 82 for the PY2 group, 113 for the RGS group, and 147 for the experts (P < 0.01). The average procedural time to complete all the stations was 98 minutes for the PY2 group, 68 minutes for the RGS group, and 35 minutes for the expert surgeons (P < 0.01). CONCLUSION: An OSCE scenario designed using ex-vivo tissue met 4 out of 5 criteria of the Messick validity framework: content, relation to other variables, response process and consequences of the test. The results show it is a valid strategy for the evaluation of practical skills in trauma surgery.

The Miami International Evidence-based Guidelines on Minimally Invasive Pancreas Resection.

OBJECTIVE: The aim of this study was to develop and externally validate the first evidence-based guidelines on minimally invasive pancreas resection (MIPR) before and during the International Evidence-based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR) meeting in Miami (March 2019). SUMMARY BACKGROUND DATA: MIPR has seen rapid development in the past decade. Promising outcomes have been reported by early adopters from high-volume centers. Subsequently, multicenter series as well as randomized controlled trials were reported; however, guidelines for clinical practice were lacking. METHODS: The Scottisch Intercollegiate Guidelines Network (SIGN) methodology was used, incorporating these 4 items: systematic reviews using PubMed, Embase, and Cochrane databases to answer clinical questions, whenever possible in PICO style, the GRADE approach for assessment of the quality of evidence, the Delphi method for establishing consensus on the developed recommendations, and the AGREE-II instrument for the assessment of guideline quality and external validation. The current guidelines are cosponsored by the International Hepato-Pancreato-Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Asian-Pacific Hepato-Pancreato-Biliary Association, the European-African Hepato-Pancreato-Biliary Association, the European Association for Endoscopic Surgery, Pancreas Club, the Society of American Gastrointestinal and Endoscopic Surgery, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology. RESULTS: After screening 16,069 titles, 694 studies were reviewed, and 291 were included. The final 28 recommendations covered 6 topics; laparoscopic and robotic distal pancreatectomy, central pancreatectomy, pancreatoduodenectomy, as well as patient selection, training, learning curve, and minimal annual center volume required to obtain optimal outcomes and patient safety. CONCLUSION: The IG-MIPR using SIGN methodology give guidance to surgeons, hospital administrators, patients, and medical societies on the use and outcome of MIPR as well as the approach to be taken regarding this challenging type of surgery.

[Current situation of pediatric liver transplantation in Chile. Inequities associated with the MELD/PELD prioritization system]. / Situación actual del trasplante hepático pediátrico por hepatopatías crónicas en Chile: Inequidades asociadas a la priorización por sistema MELD/PELD.

BACKGROUND: The Chilean allocation system for liver transplantation (LT) uses the MELD/PELD score to prioritize candidates on the waiting list. AIM: To assess if the Chilean allocation system for LT is equitable for pediatric candidates compared to their adult counterparts. MATERIAL AND METHODS: We used the Public Health Institute's registry between October 2011 and December 2017. We analyzed candidates with chronic hepatic diseases listed for LT. The primary outcome was the cadaveric liver transplantation (CLT) rate. Secondary outcomes were death or disease progression in the waiting list and living donor liver transplant (LDLT) rate. RESULTS: We analyzed 122 pediatric and 735 adult candidates. Forty one percent of pediatric candidates obtained a CLT compared to 48% of adults (p = NS). Among patients aged under two years of age, the access to CLT on the waiting list there was 28% of CLT, compared to 48% in adults (p = 0.001). Fifty-seven percent of candidates aged under two years were listed for cholestatic diseases, obtaining a CLT in 18% and requiring a LDLT in 49%. The median time in the waiting list for CLT was 5.9 months in pediatric candidates and 5.1 in adults, while the median time to death in the waiting list was 2.8 and 5.6 months, respectively. The mortality rate at one year in candidates under two years old was 38.1% compared to 32.5% in adults. CONCLUSIONS: Pediatric candidates with chronic liver diseases, especially under two years of age, have greater access difficulties to CLT than adults. Half of the pediatric candidates die on the waiting list before three months. The mortality among candidates under two years of age in the waiting list is excessively high.

Fellows perspective of HPB training in Latin America.

BACKGROUND: Currently, no standards for HPB training exist in Latin America. The aim of this work is to evaluate fellows' experience of HPB training and the areas of opportunity to improve. METHODS: A 35 points survey was developed and distributed among fellows from dedicated HPB training programs in Latin America. The survey was applied by direct phone call (37%) or web based (63%), to fellows graduated between 2010 and 2014, from 7 different programs. RESULTS: Thirty-nine fellows from Argentina, Brazil, Chile and México were considered with a response rate of 82% (32/39). Most fellows (90%) shared cases with more than one co-fellow. Scrubbing with chief residents ocurred to 60% of fellows; only 14% of fellows noted having a primary surgeon role in more than 70% of cases. Median number of major hepatectomies during training was 15 (1-100), Whipple procedures 6 (1-40), and major bile duct repair 20 (1-80). Limited funding was the main reason to avoid HPB programs outside the country of origin. CONCLUSION: HPB training in Latin America requires more operative volume and autonomy. Financial burden is the main limitation to pursue training overseas. A multinational fellowship that takes advantage of each center may overcome differences in volume and type of cases.

Safe implementation of minimally invasive pancreas resection: a systematic review.

BACKGROUND: Minimally invasive pancreas resection (MIPR) has been expanding in the past decade. Excellent outcomes have been reported, however, safety concerns exist. The aim of this study was to define prerequisites for performing MIPR with the objective to guide safe implementation of MIPR into clinical practice. METHODS: This systematic review was conducted as part of the 2019 Miami International Evidence-Based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR). PubMed, Embase and Cochrane databases were searched for literature concerning the implementation of MIPR between 1946 and November 2018. Quality assessment was according to The Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: Overall, 1150 studies were screened, of which 32 studies with 8519 patients were included in this systematic review. Training programs for minimally invasive distal pancreatectomy, laparoscopic pancreatoduodenectomy and robotic pancreatoduodenectomy have been described with acceptable outcomes during the learning curve and improved outcomes after training. Learning curve studies have revealed an association between growing experience and improving perioperative outcomes. In addition, the association between higher center volume and lower mortality and morbidity has been reported by several studies. CONCLUSION: When embarking on MIPR, it is recommended to participate in a dedicated training program, to assure a sufficient volume, especially when implementing minimally invasive pancreatoduodenectomy, (20 procedures recommended annually), and prospectively collect and closely monitor outcomes for continuous quality assessment, this can be achieved through institutional databases and participation in national or international registries.

Portal Angiogenesis in Chronic Liver Disease Patients Correlates with Portal Pressure and Collateral Formation.

BACKGROUND/AIMS: One hallmark of chronic liver disease in patients with portal hypertension is the formation of portal-systemic collaterals in which angiogenesis has a fundamental role. We studied patients with chronic liver disease undergoing liver transplantation to correlate levels of circulating angiogenic factors in portal and peripheral circulation with portal pressure and portal-systemic collaterals. METHODS: Sixteen patients who underwent liver transplantation were enrolled. During transplant surgery, we determined portal venous pressure and portal-systemic collateral formation. We determined angiogenics mediator levels in systemic and portal plasma. Peripheral plasma from healthy donors was measured as controls. RESULTS: Vascular endothelial growth factor (VEGF)-R1 and 2, Ang-1 and 2, Tie2, FGF- 1 and 2, CD163, PDGFR-ß, PDGFsRα, PDGF-AB and BB, CD163, TGF-ß VASH-1 levels were significantly different in the controls in comparison to cases. Significantly decreased portal venous levels of Ang-1, FGF-1, PDGF-AB/BB, and CC were observed in patients with higher portal pressure. Peripheral VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation. While peripheral VEGF-R1 was higher in patients with severe collateral formation. For portal circulation, VEGF, Ang-1, -pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation Conclusions: Angiogenesis factors correlated with portal pressure and collateral formation and different patterns of circulating angiogenesis mediators were found in peripheral and portal blood of patients with chronic liver disease. These results support the importance of angiogenic pathways in cirrhosis and portal hypertension and highlight areas for further study to identify clinically useful noninvasive markers of portal pressure and collateral formation.

Accuracy of the BAR score in the prediction of survival after liver transplantation.

INTRODUCTION AND AIM: The Balance of Risk (BAR) Score, a simple scoring system that combines six independent donor and recipient variables to predict outcome after liver transplantation (LT), was validated in a large U.S./European cohort of patients. This study aims to assess the performance of the BAR score to predict survival after liver transplantation and determine the factors associated with short and long-term survival in Latin-American patients. MATERIAL AND METHODS: A retrospective cohort study was performed in 194 patients [112 (55.4%) males; mean age 52±14 years] who underwent 202 LT during the period 2003-2015. Demographic, clinical, pathological and surgical variables, as well as mortality and survival rates, were analyzed. The BAR score was investigated through a receiver operating characteristics (ROC) curve with the calculation of the area under the curve (AUC) to evaluate the predictive score power for 3-month, 1 and 5-year mortality in a matched donor-recipient cohort. Youden index was calculated to identify optimal cutoff points. RESULTS: The AUC of BAR score in predicting 3-month, 1-year and 5-year mortality were 0.755 (CI95% 0.689-0.812), 0.702 (CI95% 0.634-0.764) and 0.610 (CI95% 0.539-0.678) respectively. The best cut-off point was a BAR score ≥15 points. In the multivariate analysis BAR score <15 was associated with higher survival rates at 3 months and 1 and 5-years. CONCLUSIONS: BAR score <15 points is an independent predictor of better short and long-term survival in Latin-American patients undergoing LT. The BAR scoring system has an adequate diagnostic capacity allowing to predict 3 and 12-month mortality.

[Liver transplantation: development, learning curve and results after the first 300 cases]. / Trasplante hepático: evolución, curva de aprendizaje y resultados después de los primeros 300 casos.

BACKGROUND: Liver transplantation (LT) is an option for people with liver failure who cannot be cured with other therapies and for some people with liver cancer. AIM: To describe, and analyze the first 300 LT clinical results, and to establish our learning curve. MATERIAL AND METHODS: Retrospective cohort study with data obtained from a prospectively collected LT Program database. We included all LT performed at a single center from March 1994 to September 2017. The database gathered demographics, diagnosis, indications for LT, surgical aspects and postoperative courses. We constructed a cumulative summation test for learning curve (LC-CUSUM) using 30-day post-LT mortality. Mortality at 30 days, and actuarial 1-, and 5-year survival rate were analyzed. RESULTS: A total of 281 patients aged 54 (0-71) years (129 women) underwent 300 LT. Ten percent of patients were younger than 18 years old. The first, second and third indications for LT were non-alcoholic steatohepatitis, chronic autoimmune hepatitis and alcoholic liver cirrhosis, respectively. Acute liver failure was the LT indication in 51 cases (17%). The overall complication rate was 71%. Infectious and biliary complications were the most common of them (47 and 31% respectively). The LC-CUSUM curve shows that the first 30 patients corresponded to the learning curve. The peri-operative mortality was 8%. Actuarial 1 and 5-year survival rates were 82 and 71.4%, respectively. CONCLUSIONS: Outcome improvement of a LT program depends on the accumulation of experience after the first 30 transplants and the peri-operative mortality directly impacted long-term survival.

Incidental versus non-incidental gallbladder cancer: index cholecystectomy before oncologic re-resection negatively impacts survival in T2b tumors.

BACKGROUND: Conflicting data exists whether non-oncologic index cholecystectomy (IC) leading to discovery of incidental gallbladder cancer (IGBC) negatively impacts survival. This study aimed to determine whether a subgroup of patients derives a disadvantage from IC. METHODS: Patients with IGBC and non-IGBC treated at an academic USA and Chilean center during 1999-2016 were compared. Patients with T1, T4 tumor or preoperative jaundice were excluded. T2 disease was classified into T2a (peritoneal-side tumor) and T2b (hepatic-side tumor). Disease-specific survival (DSS) and its predictors were analyzed. RESULTS: Of the 196 patients included, 151 (77%) had IGBC. One hundred thirty-six (90%) patients of whom 118 (87%) had IGBC had T2 disease. Three-year DSS rates were similar between IGBC and non-IGBC for all patients. However, for T2b patients, 3-year survival rate was worse for IGBC (31% vs 85%; p = 0.019). In multivariate analysis of T2 patients, predictors of poor DSS were hepatic-side tumor hazard ratio [HR], 2.9; 95% CI, 1.6-5.4; p = 0.001) and N1 status (HR, 2.4; 95% CI, 1.6-3.6; p < 0.001). CONCLUSIONS: Patients with T2b gallbladder cancer specifically benefit from a single operation. These patients should be identified preoperatively and referred to hepatobiliary center.

[Liver transplantation in a patient with human immunodeficiency virus (HIV). Case report]. / Trasplante hepático exitoso en un paciente portador del Virus de la Inmunodeficiencia Humana (VIH).

Abstrac: Before the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus (HIV) were considered as having an absolute contraindication for liver transplantation (LT). Considering the increased life expectancy in HIV positive patients under HAART and the improvements in the management of graft recipients, these patients are now suitable for carrying out transplants in selected cases. We report a 26 years old HIV positive male who developed acute liver failure possibly caused by drug induced liver injury who underwent a successful liver transplantation.

Simulation-trained junior residents perform better than general surgeons on advanced laparoscopic cases.

BACKGROUND: Multiple simulation training programs have demonstrated that effective transfer of skills can be attained and applied into a more complex scenario, but evidence regarding transfer to the operating room is limited. OBJECTIVE: To assess junior residents trained with simulation performing an advanced laparoscopic procedure in the OR and compare results to those of general surgeons without simulation training and expert laparoscopic surgeons. METHODS: Experimental study: After a validated 16-session advanced laparoscopy simulation training program, junior trainees were compared to general surgeons (GS) with no simulation training and expert bariatric surgeons (BS) in performing a stapled jejuno-jejunostomy (JJO) in the OR. Global rating scale (GRS) and specific rating scale scores, operative time and the distance traveled by both hands measured with a tracking device, were assessed. In addition, all perioperative and immediate postoperative morbidities were registered. RESULTS: Ten junior trainees, 12 GS and 5 BS experts were assessed performing a JJO in the OR. All trainees completed the entire JJO in the OR without any takeovers by the BS. Six (50 %) BS takeovers took place in the GS group. Trainees had significantly better results in all measured outcomes when compared to GS with considerable higher GRS median [19.5 (18.8-23.5) vs. 12 (9-13.8) p < 0.001] and lower operative time. One morbidity was registered; a patient in the trainees group was readmitted at postoperative day 10 for mechanical ileus that resolved with medical treatment. CONCLUSION: This study demonstrated transfer of advanced laparoscopic skills acquired through a simulated training program in novice surgical residents to the OR.

Allowing New Opportunities in Advanced Laparoscopy Training Using a Full High-Definition Training Box.

INTRODUCTION: Simulated laparoscopy training is limited by its low-quality image. A high-definition (HD) laparoscopic training box was developed under the present necessity of simulating advanced surgery. OBJECTIVE: To describe and test a new HD laparoscopic training box for advanced simulation training. METHODS: We describe the features and image quality of the new training box. The simulator was tested and then evaluated by a group of 76 expert surgeons using a 4-item questionnaire. To assess the effectiveness of training using this simulation box, 15 general surgery residents were trained to perform a laparoscopic jejuno-jejunostomy in a validated simulation program. They were assessed with objective rating scales before and after the training program, and their results were compared with that of experts. RESULTS: The training box was assembled using high-density fiberglass shaped as an insufflated abdomen. It has an adapted full-HD camera with a LED-based illumination system. A manually self-regulated monopod attached to the camera enables training without assistance. Of the expert surgeons who answered the questionnaire, 91% said that the simulation box had a high-quality image and that it was very similar to real laparoscopy. All residents trained improved their rating scores significantly when comparing their initial versus final assessment ( P < .001). Their performance after completing the training in the box was similar to that of experts ( P > .2). CONCLUSIONS: This novel laparoscopic training box presents a high-resolution image and allows training different types of advanced laparoscopic procedures. The simulator box was positively assessed by experts and demonstrated to be effective for laparoscopy training in resident surgeons.

Effects of dexmedetomidine and esmolol on systemic hemodynamics and exogenous lactate clearance in early experimental septic shock.

BACKGROUND: Persistent hyperlactatemia during septic shock is multifactorial. Hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation together with impaired lactate clearance have been implicated. An excessive adrenergic response could contribute to persistent hyperlactatemia and adrenergic modulation might be beneficial. We assessed the effects of dexmedetomidine and esmolol on hemodynamics, lactate generation, and exogenous lactate clearance during endotoxin-induced septic shock. METHODS: Eighteen anesthetized and mechanically ventilated sheep were subjected to a multimodal hemodynamic/perfusion assessment including hepatic and portal vein catheterizations, total hepatic blood flow, and muscle microdialysis. After monitoring, all received a bolus and continuous infusion of endotoxin. After 1 h they were volume resuscitated, and then randomized to endotoxin-control, endotoxin-dexmedetomidine (sequential doses of 0.5 and 1.0 µg/k/h) or endotoxin-esmolol (titrated to decrease basal heart rate by 20 %) groups. Samples were taken at four time points, and exogenous lactate clearance using an intravenous administration of sodium L-lactate (1 mmol/kg) was performed at the end of the experiments. RESULTS: Dexmedetomidine and esmolol were hemodynamically well tolerated. The dexmedetomidine group exhibited lower epinephrine levels, but no difference in muscle lactate. Despite progressive hypotension in all groups, both dexmedetomidine and esmolol were associated with lower arterial and portal vein lactate levels. Exogenous lactate clearance was significantly higher in the dexmedetomidine and esmolol groups. CONCLUSIONS: Dexmedetomidine and esmolol were associated with lower arterial and portal lactate levels, and less impairment of exogenous lactate clearance in a model of septic shock. The use of dexmedetomidine and esmolol appears to be associated with beneficial effects on gut lactate generation and lactate clearance and exhibits no negative impact on systemic hemodynamics.

Pediatric liver transplantation in Latin America: Where do we stand?

LT started in LA in 1968, and pediatric LT records are available starting in the 1990s. Currently, eight countries perform pediatric LT in LA. Registries by national organizations fail to report robust data on pediatric LT. The aim of this paper was to report on the pediatric LT activity in LA. Data were gathered retrospectively through information available in the national registries websites and from local centers. Of the eight countries that report pediatric LT activity, Brazil, Argentina, Mexico, and Colombia have adequate registries of the numbers of LT performed. These countries concentrate most of the activity for pediatric LT. A total of 4593 pediatric LT were reported in LA. Websites for national organizations do not provide open data on post-transplant survival rates or waiting list mortality. The information herein is based on reports by local centers. Overall, survival from select centers is similar to that reported on North American and European registries, between 80 and 90% in the first year post-transplant. In conclusion, pediatric LT activity is growing in LA, especially in Brazil and Argentina. However, the lack of an appropriate LA registry restricts the assessment of quality and therefore restricts interventions aimed at quality improvements in different regions.

Impairment of exogenous lactate clearance in experimental hyperdynamic septic shock is not related to total liver hypoperfusion.

INTRODUCTION: Although the prognostic value of persistent hyperlactatemia in septic shock is unequivocal, its physiological determinants are controversial. Particularly, the role of impaired hepatic clearance has been underestimated and is only considered relevant in patients with liver ischemia or cirrhosis. Our objectives were to establish whether endotoxemia impairs whole body net lactate clearance, and to explore a potential role for total liver hypoperfusion during the early phase of septic shock. METHODS: After anesthesia, 12 sheep were subjected to hemodynamic/perfusion monitoring including hepatic and portal catheterization, and a hepatic ultrasound flow probe. After stabilization (point A), sheep were alternatively assigned to lipopolysaccharide (LPS) (5 mcg/kg bolus followed by 4 mcg/kg/h) or sham for a three-hour study period. After 60 minutes of shock, animals were fluid resuscitated to normalize mean arterial pressure. Repeated series of measurements were performed immediately after fluid resuscitation (point B), and one (point C) and two hours later (point D). Monitoring included systemic and regional hemodynamics, blood gases and lactate measurements, and ex-vivo hepatic mitochondrial respiration at point D. Parallel exogenous lactate and sorbitol clearances were performed at points B and D. Both groups included an intravenous bolus followed by serial blood sampling to draw a curve using the least squares method. RESULTS: Significant hyperlactatemia was already present in LPS as compared to sham animals at point B (4.7 (3.1 to 6.7) versus 1.8 (1.5 to 3.7) mmol/L), increasing to 10.2 (7.8 to 12.3) mmol/L at point D. A significant increase in portal and hepatic lactate levels in LPS animals was also observed. No within-group difference in hepatic DO2, VO2 or O2 extraction, total hepatic blood flow (point D: 915 (773 to 1,046) versus 655 (593 to 1,175) ml/min), mitochondrial respiration, liver enzymes or sorbitol clearance was found. However, there was a highly significant decrease in lactate clearance in LPS animals (point B: 46 (30 to 180) versus 1,212 (743 to 2,116) ml/min, P < 0.01; point D: 113 (65 to 322) versus 944 (363 to 1,235) ml/min, P < 0.01). CONCLUSIONS: Endotoxemia induces an early and severe impairment in lactate clearance that is not related to total liver hypoperfusion.

Gastrointestinal neuroendocrine tumor with unresectable liver metastases: an example of multimodal therapeutic approach.

Gastrointestinal neuroendocrine tumors (NET) frequently present with unresectable hepatic metastases, which poses a barrier for curative treatment. Resection of the primary tumor and subsequent orthotopic liver transplantation (OLT) has been proposed as a treatment approach but available data in this regard is limited. We present a clinical case of an otherwise asymptomatic 44-yo man complaining of abdominal pain and dyspepsia that was diagnosed of a 10 cm duodenal tumor with multiple hepatic metastases. A CT-guided biopsy confirmed a NET. He underwent first a Whipple's procedure, and then was listed for liver transplantation. During the waiting time a multimodal therapeutic approach was used including the use of radioactive 177lutetium-labeled somatostatin analogues, long-acting somastostatin analogues and antiangiogenic antibodies (bevacizumab) in order to keep neoplastic disease under control. Two years after Whipple's procedure and given disease stability he underwent OLT with an uneventful postoperative evolution. Patient condition and graft function are optimal after a 4-year follow-up period with no evidence of recurrence. This case report underscores how a multimodal approach involving careful patient selection, resective surgery as well as use of somatostatin analogues and antiangiogenic biological therapy followed by liver transplantation can achieve excellent long-term results in this difficult patient population.

Gallbladder cancer: expert consensus statement.

An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists was convened on 15 January 2014 to review current evidence on the management of gallbladder carcinoma in order to establish practice guidelines. In summary, within high incidence areas, the assessment of routine gallbladder specimens should include the microscopic evaluation of a minimum of three sections and the cystic duct margin; specimens with dysplasia or proven cancer should be extensively sampled. Provided the patient is medically fit for surgery, data support the resection of all gallbladder polyps of >1.0 cm in diameter and those with imaging evidence of vascular stalks. The minimum staging evaluation of patients with suspected or proven gallbladder cancer includes contrasted cross-sectional imaging and diagnostic laparoscopy. Adequate lymphadenectomy includes assessment of any suspicious regional nodes, evaluation of the aortocaval nodal basin, and a goal recovery of at least six nodes. Patients with confirmed metastases to N2 nodal stations do not benefit from radical resection and should receive systemic and/or palliative treatments. Primary resection of patients with early T-stage (T1b-2) disease should include en bloc resection of adjacent liver parenchyma. Patients with T1b, T2 or T3 disease that is incidentally identified in a cholecystectomy specimen should undergo re-resection unless this is contraindicated by advanced disease or poor performance status. Re-resection should include complete portal lymphadenectomy and bile duct resection only when needed to achieve a negative margin (R0) resection. Patients with preoperatively staged T3 or T4 N1 disease should be considered for clinical trials of neoadjuvant chemotherapy. Following R0 resection of T2-4 disease in N1 gallbladder cancer, patients should be considered for adjuvant systemic chemotherapy and/or chemoradiotherapy.