Impact of pneumoperitoneum on intra-abdominal microcirculation blood flow: an experimental randomized controlled study of two insufflator models during transanal total mesorectal excision : An experimental randomized multi-arm trial with parallel treatment design.

OBJECTIVE: To compare changes in microcirculation blood flow (MCBF) between pulsatile and continuous flow insufflation. Transanal total mesorectal excision (TaTME) was developed to improve the quality of the resection in rectal cancer surgery. The AirSeal IFS® insufflator facilitates the pelvic dissection, although evidence on the effects that continuous flow insufflation has on MCBF is scarce. METHODS: Thirty-two pigs were randomly assigned to undergo a two-team TaTME procedure with continuous (n = 16) or pulsatile insufflation (n = 16). Each group was stratified according to two different pressure levels in both the abdominal and the transanal fields, 10 mmHg or 14 mmHg. A generalized estimating equations (GEE) model was used. RESULTS: At an intra-abdominal pressure (IAP) of 10 mmHg, continuous insufflation was associated with a significantly lower MCBF reduction in colon mucosa [13% (IQR 11;14) vs. 21% (IQR 17;24) at 60 min], colon serosa [14% (IQR 9.2;18) vs. 25% (IQR 22;30) at 60 min], jejunal mucosa [13% (IQR 11;14) vs. 20% (IQR 20;22) at 60 min], renal cortex [18% (IQR 15;20) vs. 26% (IQR 26;29) at 60 min], and renal medulla [15% (IQR 11;20) vs. 20% (IQR 19;21) at 90 min]. At an IAP of 14 mmHg, MCBF in colon mucosa decreased 23% (IQR 14;27) in the continuous group and 28% (IQR 26;31) in the pulsatile group (p = 0.034). CONCLUSION: TaTME using continuous flow insufflation was associated with a lower MCBF reduction in colon mucosa and serosa, jejunal mucosa, renal cortex, and renal medulla compared to pulsatile insufflation.

Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model.

Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after circulatory death (DCD) liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug tissue plasminogen activator (TPA) as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to 1 hour of cardiac arrest (CA) and divided among 3 groups: no pre-arrest heparinization nor TPA during postmortem regional perfusion; no pre-arrest heparinization but TPA given during regional perfusion; and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled 1 hour after CA, fibrin deposition was not detected, even when heparin was not given prior to arrest. Although it was not useful to prevent microvascular clot formation, pre-arrest heparin did offer cytoprotective effects during CA and beyond, reflected in improved flows during regional perfusion and better biochemical, functional, and histological parameters during posttransplantation follow-up. In conclusion, this study demonstrates the lack of impact of TPA use in porcine DCD liver transplantation and adds to the controversy over whether the use of TPA in human DCD liver transplantation really offers any protective effect. On the other hand, when it is administered prior to CA, heparin does offer anti-inflammatory and other cytoprotective effects that help improve DCD liver graft quality. Liver Transplantation 24 665-676 2018 AASLD.

Effect of transgastric natural orifice transluminal endoscopic surgery peritoneoscopy on abdominal organ microcirculation: an experimental controlled study.

BACKGROUND AND AIMS: On-demand insufflation during endoscopic peritoneoscopy causes wide variations in intra-abdominal pressure. Its effects on splanchnic microcirculation may differ from those of steady intra-abdominal pressure, because pressure characteristics affect crucial intravascular hemodynamic forces--pressure and shear--adapting flow to local metabolic needs. Our aim was to assess the effect of natural orifice transluminal endoscopic surgery (NOTES) peritoneoscopy on splanchnic microcirculatory blood flow. METHODS: Twenty-one swine were randomized to the following: cholecystectomy by transgastric NOTES (n = 8), cholecystectomy by standard laparoscopy (Lap) (n = 8), and a sham group (n = 5). During NOTES, CO2 was manually insufflated with a maximum allowed pressure of 30 mm Hg. In the Lap group, intra-abdominal pressure was maintained at 14 mm Hg. Systemic hemodynamics were measured, and microcirculatory blood flow was quantified by using colored microspheres. RESULTS: Mean intra-abdominal pressure was lower in NOTES than in the Lap group (P = .038). In both groups, cardiac index and preload remained unchanged, whereas systemic vascular resistances increased over time, with a lesser increase in the Lap group (2-way analysis of variance; P = .041). In pneumoperitoneum groups, microcirculatory blood flow decreased similarly in the renal medulla, stomach, small bowel, colon, and mesocolon by 30%, 45%, 34%, 32%, and 37%, respectively. In NOTES, there was a greater microcirculatory blood flow decrease in the renal cortex (NOTES 41% vs Lap 35%; P = .044) and mesentery (NOTES 44% vs Lap 38%; P = .041). CONCLUSIONS: These findings suggest that both types of pneumoperitoneum have similar physiologic effects on microcirculatory blood flow. However, on-demand pneumoperitoneum (NOTES group) caused a greater microcirculatory blood flow decrease in areas with low metabolic needs, redistributing blood flow toward metabolically active areas.

Pretreatment with endothelium-derived nitric oxide synthesis modulators on gastrointestinal microcirculation during NOTES: an experimental study.

BACKGROUND AND STUDY AIMS: On-demand endoscopic insufflation during natural orifice transluminal endoscopic surgery (NOTES) adversely affects microcirculatory blood flow (MBF), even with low mean intra-abdominal pressure, suggesting that shear stress caused by time-varying flow fluctuations has a great impact on microcirculation. As shear stress is inversely related to vascular diameter, nitric oxide (NO) production acts as a brake to vasoconstriction. OBJECTIVE: To assess whether pretreatment by NO synthesis modulators protects gastrointestinal MBF during transgastric peritoneoscopy. METHODS: Fourteen pigs submitted to cholecystectomy by endoscope CO2 insufflation for 60 min were randomized into 2 groups: (1) 150 mg/kg of N-acetyl cysteine (NAC, n = 7) and (2) 4 ml/kg of hypertonic saline 7.5 % (HS, n = 7), and compared to a non-treated NOTES group (n = 7). Five animals made up a sham group. Colored microspheres were used to assess changes in MBF. RESULTS: The average level of intra-abdominal pressure was similar in all groups (9 mmHg). In NOTES group microcirculation decrease compared with baseline was greater in renal cortex, mesocolon, and mesentery (41, 42, 44 %, respectively, p < 0.01) than in renal medulla, colon, and small bowel (29, 32, 34, respectively, p < 0.05). NAC avoided the peritoneoscopy effect on renal medulla and cortex (4 and 14 % decrease, respectively) and reduced the impact on colon and small bowel (20 % decrease). HS eliminated MBF changes in colon and small bowel (14 % decrease) and modulated MBF in renal medulla and cortex (19 % decrease). Neither treatment influenced mesentery MBF decrease. CONCLUSIONS: Both pretreatments can effectively attenuate peritoneoscopy-induced deleterious effects on gastrointestinal MBF.

Transient hyperglycemia during liver transplantation does not affect the early graft function.

UNLABELLED: Background and rationale for the study. Hyperglycemia after graft reperfusion is a consistent finding in liver transplantation (LT) that remains poorly studied. We aim to describe its appearance in LT recipients of different types of grafts and its relation to the graft function. MATERIAL & METHODS: 436 LT recipients of donors after brain death (DBD), donors after cardiac death (DCD), and familial amyloidotic polyneuropathy (FAP) donors were reviewed. Serum glucose was measured at baseline, during the anhepatic phase, after graft reperfusion, and at the end of surgery. Early graft dysfunction (EAD) was assessed by Olthoff criteria. Caspase-3, IFN-γ, IL1ß, and IL6 gene expression were measured in liver biopsy. RESULTS: The highest increase in glucose levels after reperfusion was observed in FAP LT recipients and the lowest in DCD LT recipients. Glucose level during the anhepatic phase was the only modifiable predictive variable of hyperglycemia after reperfusion. No relation was found between hyperglycemia after reperfusion and EAD. However, recipients with the highest glucose levels after reperfusion tended to achieve the best glucose control at the end of surgery and those who were unable to control the glucose value after reperfusion showed EAD more frequently. The highest levels of caspase-3 were found in recipients with the lowest glucose values after reperfusion. In conclusion, glucose levels increased after graft reperfusion to a different extent according to the donor type. Contrary to general belief, transient hyperglycemia after reperfusion does not appear to impact negatively on the liver graft function and could even be suggested as a marker of graft quality.

Clinical markers of the hypercoagulable state by rotational thrombelastometry in obese patients submitted to bariatric surgery.

BACKGROUND: Metabolic and inflammatory disturbances associated with obesity are considered important trigger factors for venous thromboembolism (VTE). Identification of clinical markers indicating a hypercoagulability state could define a group of high-risk patients in the surgical setting. This study aimed to identify these markers using rotational thrombelastometry (ROTEM) analysis, an established method for hemostasis testing that can detect hyperfunctional stages of the clotting process. METHODS: From June to December 2010, this study investigated 109 consecutive obese patients (28 women and 22 men, mean age 46 years, body mass index 46.6 ± 7 kg/m(2)) with no history of VTE who were candidates for bariatric surgery. Preoperative clinical and metabolic characteristics and ROTEM analysis were recorded. Hypercoagulable risk was defined when patients showed a clot strength (G) of ≥11 dynes/cm(2). RESULTS: Of the 109 patients, 20 (18%) were hypercoagulable according to ROTEM analysis. Metabolic/inflammatory biomarkers such as leptin, C-reactive protein, fibrinogen levels, and platelet count were significantly higher in the high-risk patients. In the multivariate analysis, fibrinogen was an independent predictor of G ≥ 11 dynes/cm(2) [odds ratio (OR) 2.92, 95 % confidence interval (CI) 1.80-5.21, p = 0.023]. After adjustment to other data, only waist circumference affected the prediction [OR 4.42, 95 % CI 2.27-6.71, p = 0.009]. Receiver operating characteristic curve analysis showed that 3.95 g/l was the best cutoff point for fibrinogen predictability (sensitivity 100 %, specificity 41%). CONCLUSION: A hypercoagulability state in obese patients is associated with central obesity and high fibrinogen levels, which should be considered clinical hallmarks of this state. More aggressive perioperative prophylaxis for VTE should be recommended when these hallmarks are present in obese patients.

Stroke volume response to liver graft reperfusion stress in cirrhotic patients.

INTRODUCTION: In patients with advanced cirrhosis, stressful stimuli may reveal a silent reduced cardiac performance. During liver transplantation (LT), graft reperfusion strongly stresses the heart and may unmask latent myocardial dysfunction. AIM: The objective of this study was to assess heart response to acutely increased preload after liver graft reperfusion and correlate this response with preoperative data and outcome. METHODS: Preoperative clinical, echocardiographic, and hemodynamic data, and patient outcome were retrospectively recorded for 235 liver recipients who had no known cardiac disease. Myocardial dysfunction was defined as less than 10 % increase of stroke volume after graft reperfusion (non-responder). RESULTS: We found 84 (35.7 %) non-responder patients. The non-responders showed higher Model for end-stage liver disease scores (p = 0.046), left atrial diameter (LAD) (p = 0.040), hepatic vein pressure gradient (p = 0.055), and hyperdynamic state than responders. The percentages of patients with hyponatremia (p = 0.048) and alcohol etiology (p = 0.025) were also higher among non-responders. Independent predictors of inadequate cardiac response in the multivariate analysis were low preoperative systemic vascular resistance (SVRI) [odds ratio (OR) 3.09, 95 % CI 1.15-4.82; p = 0.027] and enlargement of LAD (OR 2.08, 95 % CI 1.49-2.74; p = 0.044). Non-response was associated with higher rates of early cardiovascular events [hazard ratio (HR) 2.84, 95 % CI 1.09-4.22; p = 0.039] and higher length of intensive care unit stay (p = 0.038). No differences were found in 1-year survival rates. CONCLUSIONS: Latent cardiac dysfunction among LT recipients, considered to be abnormal stroke volume response to unclamping of portal vein, is very prevalent. SVRI and LAD were independent predictors of inadequate responses. This condition deserves special attention since it may aggravate the early postoperative course of LT.

Importance of the temporary portocaval shunt during adult living donor liver transplantation.

Adult living donor liver transplantation (aLDLT) is associated with surgical risks for the donor and with the possibility of small-for-size syndrome (SFSS) for the recipient, with both events being of great importance. An excessively small liver graft entails a relative increase in the portal blood flow during reperfusion, and this factor predisposes the recipient to an increased risk of SFSS in the postoperative period, although other causes related to recipient, graft, and technical factors have also been reported. A hemodynamic monitoring protocol was used for 45 consecutive aLDLT recipients. After various hemodynamic parameters before reperfusion were analyzed, a significant correlation between the temporary portocaval shunt flow during the anhepatic phase and the portal vein flow (PVF) after reperfusion of the graft (R(2) = 0.3, P < 0.001) was found, and so was a correlation between the native liver portal pressure and PVF after reperfusion (R(2) = 0.21, P = 0.007). The identification of patients at risk for excessive portal hyperflow will allow its modulation before reperfusion. This could favor the use of smaller grafts and ultimately lead to a reduction in donor complications because it would allow more limited hepatectomies to be performed.

Prospective randomized trial of the effect of octreotide on pancreatic juice output after pancreaticoduodenectomy in relation to histological diagnosis, duct size and leakage.

BACKGROUND: Octreotide is generally administered based on the surgeon's interpretation of perceived risk for pancreatic fistula at the time of pancreaticoduodenectomy (PD). METHODS: A single-institution, prospective randomized trial was conducted between April 2009 and December 2011 involving 62 PD patients who were randomized to receive octreotide (100 µg subcutaneously every 8 h; n = 32) or placebo (n = 30). Pancreatic juice output was measured after the operation using a catheter inserted into the pancreatic duct. Postoperative complications were recorded. RESULTS: No significant differences in median output were found between the octreotide (82.5 ml) and placebo (77.5 ml) groups (P = 0.538). Median total output was significantly lower in patients with adenocarcinoma compared with those with periampullary tumours (P = 0.004) and in patients with a duct diameter of >5 mm compared with those with a duct diameter of <5 mm (P = 0.001). There were no significant differences in overall morbidity between the octreotide and placebo groups (P = 0.819). Grade B pancreatic fistula (International Study Group for Pancreatic Fistula) was observed in two and three patients in the octreotide and placebo groups, respectively. CONCLUSIONS: Morbidity did not differ significantly between the groups. This study did not demonstrate an inhibitory effect of octreotide on exocrine pancreatic secretion. Based on these results, the routine use of octreotide after PD cannot be recommended.

An assessment of thromboelastometry to monitor blood coagulation and guide transfusion support in liver transplantation.

BACKGROUND: Rotation thromboelastometry (TEM) has been proposed as a convenient alternative to standard coagulation tests in guiding the treatment of coagulopathy during orthotopic liver transplantation (OLT). This study was aimed at assessing the value of TEM in monitoring blood coagulation and guide transfusion support in OLT. STUDY DESIGN AND METHODS: Standard coagulation and TEM (EXTEM and FIBTEM) tests were performed at four preestablished intraoperative time points in 236 OLTs and prospectively recorded in a dedicated database together with the main operative and transfusion data. Transfusion thresholds were based on standard coagulation tests. Spearman's rank correlation (ρ), linear regression, and receiver operating characteristic curves were used when appropriate. RESULTS: EXTEM maximum clot firmness (MCF(EXTEM)) was the TEM variable that best correlated with the platelet (PLT) and fibrinogen levels (ρ = 0.62 and ρ = 0.69, respectively). MCF(FIBTEM) correlated with fibrinogen level (ρ = 0.70). EXTEM clot amplitude at 10 minutes (A10(EXTEM)) was a good linear predictor of MCF(EXTEM) (R(2) =0.93). The cutoff values that best predicted the transfusion threshold for PLTs and fibrinogen were A10(EXTEM) = 35 mm and A10(FIBTEM) = 8 mm. At these values, the negative and positive predictive accuracies of TEM to predict the transfusion thresholds were 95 and 27%, respectively. CONCLUSION: A10(EXTEM) is an adequate TEM variable to guide therapeutic decisions during OLT. Patients with A10(EXTEM) of greater than 35 mm are unlikely to bleed because of coagulation deficiencies, but using A10(EXTEM) of not more than 35 mm as the sole transfusion criterion can lead to unnecessary utilization of PLTs and fibrinogen-rich products.

Decompression of the portal bed and twice-baseline portal inflow are necessary for the functional recovery of a "small-for-size" graft.

BACKGROUND: In partial liver transplant, a reduction in the intrahepatic vascular bed produces a rise in the portal vein flow and the portal venous pressure gradient, leading to endothelial and, thereby, hepatocellular injury and death in a process known as "small-for-size" (SFS) syndrome. OBJECTIVE: To demonstrate that a calibrated portocaval shunt prevents superfluous inflow in a porcine model of SFS transplant. METHODS: Donor pigs (15-20 kg) underwent 70% hepatectomy. In 2 groups, a 6 mm (S6) (n = 6) or 12 mm (S12) (n = 6) Gore-Tex shunt was placed between the portal vein and infrahepatic inferior vena cava. In a third group, no portocaval shunt was placed (SFS) (n = 17). Grafts were stored for 5 hours at 4°C and then transplanted into recipients (30-35 kg). RESULTS: Five-day survival was 29% in SFS, 100% in S6, and 0 in S12. Postreperfusion portal vein flow was 4-, 2-, and 1-times flow at baseline in SFS, S6, and S12, respectively. With respect to portal venous pressure gradient, both the 6- and 12-mm shunts effectively decompressed the portal bed. Aspartate aminotransferase and bilirubin rose and the Quick prothrombin time fell in all animals after reperfusion but improved significantly by day 5 in S6. Serum levels of endothelin-1 remained elevated in SFS and S12 but returned to baseline by 12 hours in S6: 2.76 (2.05-4.08) and 2.04 (1.97-2.12) versus 0.43 (0.26-0.50) pg/mL, respectively (P < 0.05 for both comparisons). CONCLUSIONS: A calibrated portocaval shunt that maintains portal vein flow about twice its baseline value produces a favorable outcome after SFS liver transplantation, avoiding endothelial injury due to portal hyperperfusion or to hypoperfusion because of excess shunting.

Superior preservation of DCD livers with continuous normothermic perfusion.

OBJECTIVE: Unexpected donation after cardiac death (DCD) donors suffer cardiac arrest suddenly and are maintained with normothermic extracorporeal membrane oxygenation (NECMO) while consent for donation is obtained. The objective of this study was to determine whether ex vivo normothermic machine perfusion (NMP) improves upon the benefits of NECMO in a large-animal model of unexpected DCD liver transplant. METHODS: Donor pigs underwent 90-minute cardiac arrest and were divided in to 3 groups. In the first, livers were preserved immediately with cold storage (CS, n = 6). In the other 2 groups, donors underwent 60-minute NECMO followed by CS (NECMO+CS, n = 6) or NMP (NECMO+NMP, n = 6). After 4-hour preservation, livers were transplanted into recipient pigs. RESULTS: Five-day survival was 0 in CS, 83% in NECMO+CS, and 100% in NECMO+NMP. After reperfusion, injury, and inflammatory markers rose significantly among CS grafts, all of which developed primary nonfunction. Sixty minutes of NECMO, however, resulted in only 1 death, whereas NECMO followed by NMP led to no deaths and significant improvements in injury, inflammation, and synthetic function in comparison to NECMO and CS. CONCLUSION: Although 60 minutes recuperative NECMO is better than CS alone, NMP improves further on NECMO and may have a role in preserving DCD livers in the clinical setting.

Optimizing cost-effectiveness in perioperative care for liver transplantation: a model for low- to medium-income countries.

Although liver transplantation (LT) is a highly effective treatment, it has been considered too costly for publicly funded health systems in many countries with low to medium average incomes. However, with economic growth and improving results, some governments are reconsidering this position. Cost-effectiveness data for LT are limited, especially in perioperative care, and the techniques and costs vary widely between centers without overt differences in outcomes. Anesthesiologists working in new programs find it difficult to determine which modalities are essential, which are needed only in exceptional circumstances, and which may be omitted without effects on outcomes. We investigated key elements of preoperative evaluations, intraoperative management, and early postoperative care that might significantly affect costs in order to develop a best-value approach for new programs in resource-limited health systems. We identified all modalities of care commonly used in anesthesia and perioperative care for adult LT along with their costs. Those considered to be universally accepted as minimum requirements for safe care were excluded from the analysis, and so were those considered to be safe and low-cost, even when evidence of efficacy was lacking. The remaining items were, therefore, those with uncertain or context-restricted value and significant costs. A systematic review of the published evidence, practice surveys, and institutional guidelines was performed, and the evidence was graded and summarized. With respect to costs and benefits, each modality was then cited as strongly recommended, recommended or optional, or no recommendation was made because of insufficient evidence. Sixteen modalities, which included preoperative cardiovascular imaging, venovenous bypass, pulmonary artery catheterization, high-flow fluid warming devices, drug therapies for hemostasis, albumin, cell salvage, anesthetic drugs, personnel (staffing) requirements, and early extubation, were assessed. Only high-flow fluid warming was strongly recommended. The recommended modalities included preoperative echocardiography, cell salvage, tranexamic acid and early extubation. Six others were rated optional, and there was insufficient evidence for 5 modalities. We conclude that some costly techniques and treatments can be omitted without adverse effects on outcomes.

Step-by-step guide for a simplified model of porcine orthotopic liver transplant.

BACKGROUND: Based on similar anatomy, physiology, and size to humans, pigs provide an excellent means for studying new therapies related to orthotopic liver transplant (OLT). Techniques that have been described to date, however, are unnecessarily complex and increase the likelihood of morbidity and adverse outcome. MATERIALS AND METHODS: Male outbred weanling pigs underwent OLT according to our procedure, with a short anhepatic time (<20 min) and without veno-venous bypass or vasoactive substances during the anhepatic phase. Vascular anastomoses were performed identical to the clinical setting, and a simple stented choledochocholedochostomy was created. RESULTS: The authors have performed this procedure 130 times using four transplant models: standard, whole-liver (n = 10), small-for-size (n = 48), donor after cardiac death (n = 44), and donor adenoviral gene transfection (n = 28). The average cold ischemic and anhepatic times were 302 ± 43 and 17 ± 3 min, respectively. Hypotension was successfully treated with intravenous fluids. In all cases, the recipient survived the operation and was extubated. Survival to the end follow-up varied according to the model and was 56% (73/130) for all cases. At autopsy or euthanasia, no vascular thrombosis or outflow obstruction was found. Survival was 100% for pigs transplanted with standard, whole-liver grafts (n = 10). In this group, AST and bilirubin rose during the first 24 h after graft reperfusion, while the Quick prothrombin time (QPT) fell. By the fifth postoperative day, these parameters had returned to baseline. CONCLUSIONS: This model is straightforward and reproducible and offers surgeons and researchers the opportunity to perform OLT studies under clinically relevant conditions.

Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy.

Liver resection treats primary and secondary liver tumors, though clinical applicability is limited by the remnant liver mass and quality. Herein, major hepatic resections were performed in pigs to define changes associated with sufficient and insufficient remnants and improve liver-specific outcomes with somatostatin therapy. Three experimental groups were performed: 75% hepatectomy (75H), 90% hepatectomy (90H), and 90% hepatectomy + somatostatin (90H + SST). Animals were followed for 24 h (N = 6) and 5 d (N = 6). After hepatectomy, portal pressure gradient was higher in 90H versus 75H and 90H + SST (8 (3-13) mmHg vs. 4 (2-6) mmHg and 4 (2-6) mmHg, respectively, p < 0.001). After 24 h, changes were observed in 90H associated with stellate cell activation and collapse of sinusoidal lumen. Collagen chain type 1 alpha 1 mRNA expression was higher, extracellular matrix width less, and percentage of collagen-staining areas greater at 24 h in 90H versus 75H and 90H + SST. After 5 d, remnant liver mass was higher in 75H and 90H + SST versus 90H, and Ki-67 immunostaining was higher in 90H + SST versus 75H and 90H. As well, more TUNEL-staining cells were observed in 90H versus 75H and 90H + SST at 5 d. Perioperative somatostatin modified portal pressure, injury, apoptosis, and stellate cell activation, stemming changes related to hepatic fibrogenesis seen in liver remnants not receiving treatment.

The use of beta-adrenergic drugs improves hepatic oxygen metabolism in cirrhotic patients undergoing liver resection.

BACKGROUND & AIMS: Hepatic resection is associated with hemodynamic and oxygen metabolism disturbances of the residual liver resulting from liver regeneration. In underlying liver disease, the remnant liver responds inadequately to increased energy demands leading to a less efficient recovery process. The aim of this study was to assess the effect of vasoactive drugs on hepatic oxygen metabolism and hemodynamics in cirrhotic patients that have undergone liver resection. METHODS: Thirty patients were randomly allocated to receive peri-operatively low doses (4 microg/kg/min) of dopamine (DaG, n=10), dobutamine (DbG, n=10) or saline (CG, n=10). Hepatic hemodynamics, hepatic oxygen metabolism and lactate uptakes were evaluated before drug administration and at the time of abdominal closure. Post-operative liver function and outcome were recorded. RESULTS: The peri-operative use of vasoactive drugs preserved total hepatic blood flow and hepatic compliance, even increasing in patients who received Db, whereas those parameters decreased in CG after liver resection. At this time, oxygen delivery and consumption decreased in CG patients, but were unchanged when vasoactive drugs were used. In all groups, lactate uptake decreased sharply and only DbG showed positive lactate extraction capacity. The peak of post-operative bilirubin, which resumed baseline values more quickly in DbG, inversely correlated with intra-operative hepatic compliance and hepatic oxygen extraction. CONCLUSION: Low doses of vasoactive drugs, especially dobutamine, improved hepatic oxygen supply and uptake preserving immediate function of the remnant cirrhotic liver.

Portal hyperperfusion: mechanism of injury and stimulus for regeneration in porcine small-for-size transplantation.

Understanding the pathogenesis of small-for-size (SFS) syndrome is critical to expanding the applicability of partial liver transplantation. We aimed to characterize its acute presentation and association with alterations in hepatic hemodynamics, microstructure, and regeneration in a porcine model. Eighteen SFS liver transplants were performed. Donors underwent 70% hepatectomy. Partial grafts were implanted into larger recipients. Whole liver transplants were also performed (n = 6). Recipients were followed until death or for 5 days. Hemodynamics were measured, and tissue was sampled intraoperatively and at the study end. Serum was sampled regularly during follow-up. Seventeen SFS transplants and 6 whole liver transplants were included. SFS grafts represented 23.2% (19.3%-25.3%) of the recipients' standard liver volume. The survival rate was 29% and 100% in the SFS and whole liver groups, respectively. The portal venous flow, pressure gradient, and resistance were significantly higher in recipients of SFS grafts versus whole livers after portal and arterial reperfusion. Arterial flow as a percentage of the total liver blood flow was significantly lower after reperfusion in SFS grafts and remained so when measured again after 5 days. Markers of endothelial cell injury increased soon after reperfusion, and those of hepatocellular injury increased later; both predicted the appearance of either graft failure or histological recovery. Proliferative activity peaked earlier and higher among nonsurvivors in the SFS group. Surviving grafts demonstrated a slower but maintained rise in regenerative activity, although metabolic activity failed to improve. In SFS transplantation in the acute setting, portal hyperperfusion is a stimulus for regeneration but may simultaneously cause irreparable endothelial injury. This porcine model not only helps to elucidate the inciting factors in SFS pathogenesis but also offers a clinically relevant means to study its prevention.

The influence of the explant technique on the hemodynamic profile during sequential domino liver transplantation in familial amyloid polyneuropathy patients.

Familial amyloidotic polyneuropathy (FAP) patients present adrenergic cardiac input blockade secondary to amyloid deposits and sympathetic neuropathy. Consequently, their capacity to compensate for hemodynamic changes is limited. To avoid hemodynamic disturbances in sequential liver transplants, a standard procedure with venovenous bypass or inferior vena cava preservation is contemplated. The aim of this study was to evaluate the impact of both techniques on the hemodynamic management and outcome of patients affected by FAP and scheduled for a domino liver transplantation program. We evaluated 36 FAP patients. Venovenous bypass was performed for 20 patients (the venovenous bypass group), whereas the vena cava preservation technique was used for the remaining 16 patients (the cava preservation group). The time that elapsed from FAP diagnosis to liver transplantation was 3.2 +/- 2.7 years. Peripheral neuropathy was present in all patients, autonomic dysfunction was present in 71%, and cardiac involvement was present in 69%. Renal and gastrointestinal manifestations were reported in 19% and 53% of patients, respectively. The 1-, 3-, and 5-year survival rates were 97%, 93%, and 93%, respectively. Intraoperative hemodynamic and cardiac disorders, need for vasoactive drugs, blood loss, and transfusion requirements were recorded. Postoperative outcome and cardiac and renal complications were also recorded. No significant differences in disease severity or demographic characteristics were observed. Among all the variables studied, only the total ischemia time and time in surgery were significantly longer in the venovenous bypass group patients (P < or = 0.05). During the postoperative period, the incidence of minor cardiovascular events, incidence of acute renal dysfunction, and outcomes were similar in the 2 groups. In conclusion, either preservation of the vena cava or the standard technique with venovenous bypass can be safely used in FAP patients during liver transplantation. Liver Transpl 15:869-875, 2009. (c) 2009 AASLD.

Hybrid vaginal MA-NOS sleeve gastrectomy: technical note on the procedure in a patient.

BACKGROUND: Standard sleeve gastrectomy for the morbidly obese is feasible and safe using the hybrid transvaginal minilaparoscopic-assisted natural orifice surgery (MA-NOS) with available laparoscopic/endoscopic instruments and technology as illustrated by this technical report on a female patient. METHODS: The intervention was a transvaginal sleeve gastrectomy in a 67-year-old woman who was hypertensive, noninsulin-dependent with diabetes with morbid obesity (BMI, 37). Operative field view was maintained at all times with a gastroscope introduced through a transvaginal trocar. The surgeon positioned himself at the right side of the patient using a 2-mm needle port/mini-grasper placed in the left upper quadrant for traction of the greater curvature of the stomach. A 12-mm umbilical trocar was used as the port for insertion of the LigaSure device used for division of the short gastric vessels and the Endo-GIA stapler for creation of the gastric tube. The first assistant used a second mini-grasper for liver retraction and stomach positioning. The resected stomach was retrieved through the vagina. There were no intraoperative complications. The operative time was 150 minutes. RESULTS: The advantages of minimally invasive surgery seemed to be enhanced with this hybrid laparoscopic approach. Postoperative course was uneventful. All component steps of a laparoscopic sleeve gastrectomy (LSG) were reproduced. The patient was discharged on the third postoperative day. CONCLUSIONS: Transvaginal hybrid MA-NOS sleeve gastrectomy is both feasible and safe. The hybrid technique ensured safety during the performance of the procedure. MA-NOS is a potential option to avoid abdominal incisions and related complications for the laparoscopic resection of large intra-abdominal organs. Combined hybrid laparoscopic NOS for humans is currently a safe and reliable approach for major surgery through the NOS approach in female patients. Hybrid surgery allows controlled implementation of NOS techniques in clinical practice, providing a stepwise progression to the pure NOS approach once the appropriate technology has been developed. Additionally, it is the best way to stimulate the active development and evaluation of the underpinning technologies and instruments for these novel endoscopic surgical approaches. Appropriate clinical indications for these new procedures are yet to be defined. LSG is associated with short-term excess weight loss and resolution of comorbidities comparable to those obtained with other restrictive procedures. The performance of sleeve gastrectomy is an option in selected patients undergoing bariatric surgical treatment, particularly in the super obese and those who are considered high risk because of comorbid disease.