Peritoneal Albumin Dialysis as a Novel Approach for Liver Support: Study in a Porcine Model of Acute Hepatic Failure.

Artificial liver support gained considerable interest in recent years due to the development of various albumin dialysis systems, which prolong survival of some patients with acute liver failure (ALF). Τhis study aims to examine the role of peritoneal albumin dialysis in a postoperative ALF model. ALF was induced in 14 female Landrace pigs by a combination of major liver resection (70-75% of total parenchyma) and ischemic-reperfusion injury on the liver remnant. Animals were randomly divided in two groups (n = 7 each). Both were monitored for 12 h of reperfusion and received peritoneal dialysis for 6 h, beginning 6 h after reperfusion. The albumin group received an albumin-rich solution and the control group received albumin-free solution. The control group gradually developed intracranial hypertension, whereas, in the albumin group, rise in the intracranial pressure was substantially attenuated (P < 0.01, t = 12 h). Albumin-treated animals had significantly lower levels of ammonia (P < 0.01), total bile acids (P < 0.01), free fatty acids (P < 0.05), lactate (P < 0.01), and total bilirubin (P < 0.05). Liver malondialdehyde and protein carbonyl were significantly reduced (P = 0.007 and P = 0.001 at t = 12 h) after albumin dialysis. Results suggest that this method may become a useful adjunct in the management of ALF, thus, justifying further study.

Non-functioning pancreatic endocrine tumors: eleven-year experience in a single institute.

PURPOSE: Non-functioning pancreatic endocrine tumors (NF-PETs) comprise the majority of pancreatic endocrine tumors. We present our experience from the management of 18 patients with NF-PET. METHODS: From May 2002 to June 2013, 18 patients were admitted in our hospital for the management of NF-PETs. We analyzed their clinical presentation, preoperative evaluation, surgical and postoperative management and the outcome. RESULTS: The tumor was located in the pancreatic head in 13 (72%) patients and in the body and tail of the pancreas in the remaining 5 (28%). Four patients (22%) had stage IIIa, 7 (39%) stage IIIb and 7 (39%) stage IV. Twelve (67%) patients with pancreatic head tumor underwent pancreatoduodenectomy (PD). In one case (5%), the tumor was deemed unresectable and the remaining 5 (28%) patients underwent distal pancreatectomy and splenectomy (DPSP). Four (22%) patients with unilobar metastatic liver disease underwent hemihepatectomy or segmentectomy. Perioperative mortality was 0%. Postoperatively, all stage IV patients received peptide receptor radionuclide treatment (PRRT). The 5-year overall survival rate was 61%, with a median survival of 71 months, whereas the 5-year overall survival rate after diagnosis of hepatic metastases was 45%. CONCLUSION: Surgical resection is the gold standard for the treatment of NF-PETs. A formal resection appears to be the standard procedure when malignancy is verified or suspected. Aggressive surgery should be undertaken in patients with locally advanced or metastatic NF-PETs, as it may prolong survival. In stage IV patients, intra-arterial PRRT, after super-selective catheterization of the hepatic artery, is a promising therapeutic modality.

Pancreatic injury after major hepatectomy: a study in a porcine model.

PURPOSE: The aim of this study was to investigate the pathophysiology of pancreatitis after major hepatectomy. METHODS: The study used ten female pigs. Three served as sham animals (sham group) and were killed after laparotomy to obtain normal tissue samples. Seven animals were subjected to major hepatectomy (70-75%), using the Pringle maneuver for 150 min, after constructing a portacaval side-to-side anastomosis (hepatectomy group). Duration of reperfusion was 24 h. RESULTS: Pancreatic tissue sampled 24 h after reperfusion had increased necrosis and edema in comparison to sham group and to tissue sampled at 12 h. Tissue malondialdehyde (MDA) did not differ significantly between samples at 12 and 24 h but was increased in the hepatectomy group in comparison to sham animals. Percentage increase in portal MDA content during reperfusion was greater at 12 h of reperfusion in comparison to the increase after 24 h. Portal pressure increased significantly after 12 h of reperfusion. Serum amylase and C-peptide increased during reperfusion in comparison to baseline levels. CONCLUSIONS: The findings suggest that intraoperative portal congestion is not the only cause of the development of pancreatitis after major hepatectomy. The oxidative markers suggest that reactive oxygen species produced during vascular control may be responsible as well.

Two cases of primary splenic hydatid cyst in Greece.

Cystic disease of the spleen is an uncommon entity in general population. Most cases result from parasitic infection by Echinococcus granulosus, a form called splenic hydatid disease (SHD), with a reported frequency of 0.5-6.0% within abdominal hydatidosis. On the contrary, an isolated splenic involvement of hydatid disease is very uncommon even in endemic regions. Two cases of primary SHD managed with open and laparoscopic radical surgery in our department are reported herein. Primary SHD is a rare entity with non-specific symptoms underlying clinical suspicion by the physician for prompt diagnosis. Surgical treatment is the mainstay therapy, while laparoscopic approach when feasible is safe, offering the advantages of laparoscopic surgery.

The combined effect of erythropoietin and granulocyte macrophage colony stimulating factor on liver regeneration after major hepatectomy in rats.

BACKGROUND: The liver presents a remarkable capacity for regeneration after hepatectomy but the exact mechanisms and mediators involved are not yet fully clarified. Erythropoietin (EPO) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) have been shown to promote liver regeneration after major hepatectomy.Aim of this experimental study is to compare the impact of exogenous administration of EPO, GM-CSF, as well as their combination on the promotion of liver regeneration after major hepatectomy. METHODS: Wistar rats were submitted to 70% major hepatectomy. The animals were assigned to 4 experimental groups: a control group (n = 21) that received normal saline, an EPO group (n = 21), that received EPO 500 IU/kg, a GM-CSF group (n = 21) that received 20 mcg/kg of GM-CSF and a EPO+GMCSF group (n = 21) which received a combination of the above. Seven animals of each group were killed on the 1st, 3rd and 7th postoperative day and their remnant liver was removed to evaluate liver regeneration by immunochemistry for PCNA and Ki 67. RESULTS: Our data suggest that EPO and GM-CSF increases liver regeneration following major hepatectomy when administered perioperatively. EPO has a more significant effect than GM-CSF (p < 0.01). When administering both, the effect of EPO seems to fade as EPO and GM-CSF treated rats have decreased regeneration compared to EPO administration alone (p < 0.01). CONCLUSION: EPO, GM-CSF and their combination enhance liver regeneration after hepatectomy in rats when administered perioperatively. However their combination has a weaker effect on liver regeneration compared to EPO alone. Further investigation is needed to assess the exact mechanisms that mediate this finding.

Pancreatic intraductal papillary mucinous neoplasm masquerading as ampullary adenoma: a diagnostic puzzle.

Intraductal papillary mucinous neoplasm (IPMN) is the most common pancreatic cystic lesion, remaining mostly asymptomatic. An atypical presentation of such a lesion, initially thought to be an ampullary adenoma, is presented herein. A 78-year-old white male with painless jaundice was treated in a tertiary hospital. Imaging and endoscopic investigations pointed towards an ampullary adenoma obstructing and causing dilatation of both bile and pancreatic ducts. Endoscopic papillectomy was carried out and histology revealed tubulovillous adenoma. Follow-up duodenoscopy 3 months later showed a recurrent lesion with mucous leaking from the pancreatic duct. Cytology revealed mucin-rich atypical cells, consistent with main-duct IPMN. Pancreatoduodenectomy was performed, finally revealing main-duct IPMN protruding through Vater's ampulla. Cystic pancreatic lesions are increasingly found and IPMN is the most common of these. On the other hand, the management of ampullary adenomas has been revolutionized by endoscopic treatment and the advent of endoscopic papillectomy, with expanding indications. Meticulous clinical and imaging work up of these patients is essential to avoid suboptimal treatment. IPMN should be included in the differential diagnosis of ampullary adenomas, especially in the presence of a grossly dilated pancreatic duct.

Does vascular occlusion in liver resections predispose to recurrence of malignancy in the liver remnant due to ischemia/reperfusion injury? A comparative retrospective cohort study.

BACKGROUND: Severe ischemic changes of the liver remnant after hepatectomy could expedite tumor recurrence on the residual liver. Our study aimed at assessing the effect of warm ischemic/reperfusion (I/R) injuries on surgery-to-local recurrence interval and patient overall survival, during major hepatectomies under inflow and outflow vascular control. METHODS: One hundred and eighteen patients were subjected to liver resection under total inflow and outflow vascular clamping and were assigned as study group. These individuals were retrospectively matched to 112 counterparts, who underwent liver surgery applying inflow and outflow vascular clamping only of the segment harboring the tumor, sparing the liver remnant from any I/R injury (control group). The two cohorts were compared regarding recurrence-free survival and overall survival. RESULTS: Reversible I/R injuries of the liver remnant subjected to vascular clamping were manifested, with increase of AST values at postoperative day 2 in the study group, as compared to the control group (603 ± 270 U/L vs. 450 ± 290 U/L, p < 0.001), reversing to normal by day 7. Recurrence-free survival and overall survival were no significantly different between the two groups (log rank statistic p = 0.298 and 0.639, respectively). CONCLUSION: Reversible I/R injuries of the liver remnant do not seem to be implicated in the precipitation of local malignant recurrence or in shorter long-term survival, in comparison to a technique sparing the residual liver of I/R injury. This retrospective cohort study was registered at clinicaltrials.gov under unique identifying number: NCT04257240.

Novel Endoscopic Management of Eroding Laparoscopic Adjustable Gastric Band: A Case Series.

Complications of laparoscopic adjustable gastric bands include migration and slippage of the band, dilation of the proximal gastric pouch, troublesome gastroesophageal reflux symptoms, and erosion of the stomach. The latter occurs in 0.6-12.7% of cases and necessitates removal of the band. Several open and laparoscopic surgical techniques have been described for band extraction, while fully endoscopic techniques have emerged and proven safe. Three cases of eroding gastric bands treated in a single center with fully endoscopic removal of the band are analyzed in this study. Novel use of the duodenoscope and endoscopic retrograde cholangiopancreatography instruments and accessories is described, in order to perform endoscopic division of the plastic band and retraction through the mouth. All three cases were successfully treated utilizing this novel technique. Gastric wall erosion from the band has nonspecific symptoms and various predisposing factors. Removal of the foreign material is required. Endoscopic procedures are effective in 77-92% of cases, avoiding general anaesthesia with low surgical morbidity. As a result patients are discharged early resolving quicker to a normal diet.

Effects of endoscopic sphincterotomy on biliary epithelium: a case-control study.

AIM: To study the long-term effects of endoscopic sphincterotomy on biliary epithelium. METHODS: This is a prospective case-control study. A total of 25 patients with a median age of 71 years (range 49-89 years) and prior endoscopic sphincterotomy (ES) for benign disease formed the first group. The median time from ES was 42 mo (range 8-144 mo). Another 25 patients with a median age of 76 years (range 44-94 mo) and similar characteristics who underwent current endoscopic retrograde cholangiopancreatography (ERCP) and ES for benign disease formed the second group (control group). Brush cytology of the biliary tree with p53 immunocytology was performed in all patients of both groups. ERCPs and recruitment were conducted at the Endoscopic Unit of Aretaieion University Hospital and Tzaneio Hospital, Athens, from October 2006 to June 2010. RESULTS: No cases were positive or suspicious for malignancy. Epithelial atypia was higher in the first group (32% vs. 8% in the second group, P = 0.034). Acute cholangitis and previous biliary operation rates were also higher in the first group (acute cholangitis, 60% vs. 24% in the second group, P = 0.01; previous biliary operation, 76% vs. 24% in the second group, P = 0.001). Subgroup analysis showed that previous ES was the main causal factor for atypia, which was not related to the time interval from the ES (P = 0.407). Two patients (8%) with atypia in the first group were p53-positive. CONCLUSION: ES causes biliary epithelial atypia that represents mostly reactive/proliferative rather than premalignant changes. The role of p53 immunoreactivity in biliary atypia needs to be further studied.

Desferrioxamine Attenuates Pancreatic Injury after Major Hepatectomy under Vascular Control of the Liver: Experimental Study in Pigs.

Introduction. Pancreatic injury can manifest after major hepatectomy under vascular control. The main mechanism involved seems to be remote oxidative injury due to "spillage" of reactive oxygen species and cytokines from the liver. The aim of this study is to evaluate the role of desferrioxamine in the prevention of pancreatic injury following major hepatectomy. Methods. Twelve Landrace pigs were subjected to a combination of major hepatectomy (70-75%), using the Pringle maneuver for 150 minutes, after constructing a porta-caval side-to-side anastomosis. The duration of reperfusion was 24 hours. Animals were randomly divided into a control group (n = 6) and a desferrioxamine group (DFX, n = 6). DFX animals were treated with continuous IV infusion of desferrioxamine 100 mg/kg. Pancreatic tissue injury, c-peptide and amylase concentrations, and pancreatic tissue oxidative markers were evaluated. Results. Desferrioxamine-treated animals showed decreased c-peptide levels, decreased acinar cell necrosis, and decreased tissue malondialdehyde levels 24 hours after reperfusion compared with the control group. There was no difference in portal pressure or serum amylase levels between the groups. Conclusions. Desferrioxamine seems to attenuate pancreatic injury after major hepatectomy under vascular control possibly by preventing and reversing production and circulation of oxidative products.

Ischemic preconditioning attenuates lactate release by the liver during hepatectomies under vascular control: a case-control study.

BACKGROUND: We have previously demonstrated lactate release by the liver itself in hepatectomies performed under selective hepatic vascular exclusion. We hypothesized that ischemic preconditioning applied in this setting might lead to a reduction of hepatic lactate production. METHODS: Twenty-one patients underwent hepatectomy under inflow and outflow occlusion combined with ischemic preconditioning (IP group, n = 21). These patients were matched 1:1 with patients subjected to the same technique of hepatectomy under vascular occlusion without ischemic preconditioning (control group, n = 21). The transhepatic lactate gradient (hepatic vein-portal vein) was calculated before liver dissection and 60 min post-reperfusion. RESULTS: In the control group, the transhepatic lactate gradient before liver resection was negative indicating consumption by the liver. After 60 min post-reperfusion, this gradient became positive, indicating net lactate production by the liver (0.2 ± 0.3 vs. -0.3 ± 0.2 mmol/L, P < 0.001). In the IP group, the liver consumed lactate both before resection and 60 min post-reperfusion (gradients -0.2 ± 1.1 and -0.1 ± 0.6 mmol/L, respectively). The magnitude of lactate release by the liver correlated with systemic hyperlactatemia post-reperfusion and 24 h postoperatively (r(2) = 0.54, P < 0.001 and r(2) = 0.67, P < 0.001, respectively). Significant correlations between the transhepatic lactate gradient post-reperfusion and peak postoperative AST as well as the apoptotic response of the liver remnant were also demonstrated (r(2) = 0.72, P < 0.001 and r(2) = 0.66, P < 0.001, respectively). CONCLUSION: The microcirculatory derangement and cellular aerobic metabolism breakdown elicited by ischemia-reperfusion insults can be prevented with hepatoprotective measures such as ischemic preconditioning. The transhepatic lactate gradient could act as a monitoring and prognostic tool of the efficacy of ischemic preconditioning.

Evaluation of ischemia-reperfusion liver injury by near-infrared spectroscopy in an experimental swine model: the effect of desferoxamine.

INTRODUCTION: Ischemia-reperfusion (I-R) injury has long been regarded a primary factor for the physiological dysfunction that can occur following major liver resection performed under vascular control. The aim of our study was to assess the effect of treatment with desferoxamine (DFO), a potent antioxidative agent, monitoring the I-R injury on a porcine model of major hepatectomy. MATERIALS AND METHODS: Twelve female pigs were allocated to control (n = 6) and DFO groups (n = 6) and underwent 30 min of liver ischemia, during which a ≥30% hepatectomy was performed, followed by six hours of postoperative monitoring. The DFO group animals were preconditioned with a continuous iv solution of DFO to a total dose of 100 mg/kg during their postoperative period. Liver remnants (≈70% of initial liver volume) were evaluated by means of infrared spectroscopy, serum lactate measurement of the systemic, portal and hepatic vein blood, and by immunohistochemical assessment of apoptosis in consecutive liver biopsies. RESULTS: DFO group demonstrated considerably faster restoration of tissue oxygenation (92.33% vs. 80%, p < .05) and serum lactate values (1.23 mmol/l vs. 2.27 mmol/l, p < .05). Moreover, apoptosis as estimated by TUNEL and caspase-3 staining was significantly lower in the DFO group (0.06% vs. 1.17% and 1.17% vs. 2%, respectively, p < .05). The severity of the I-R injury showed a linear correlation to the restoration of tissue oxygenation, as estimated by infrared-spectroscopy (r(2) = 0.81, p < .01). CONCLUSION: Iron chelation with DFO appears to attenuate I-R injury of the liver remnant following hepatectomy, as reflected by faster restoration of tissue oxygenation and lower apoptotic activity.

An ongoing dispute in the management of severe pancreatic fistula: Pancreatospleenectomy or not?

The aim of this manuscript is to review controversies in managing severe pancreatic fistula after pancreatic surgery. Significant progress in surgical technique and perioperative care has reduced the mortality rate of pancreatic surgery. However, leakage of the pancreatic stump still accounts for the majority of surgical complications after pancreatic resection. Various strategies have been employed in order to manage pancreatic fistula. Nonetheless high grade pancreatic fistula evokes controversy in relation to the choice of treatment. A Medline search was performed, with regard to conservative treatment options versus completion pancreatectomy for the management of pancreatic fistula grade C. Pancreatic fistula rates remain unchanged with an incidence ranging from 5%-20% and this is considered as the most important cause of postoperative death. Many authors claim that completion pancreatectomy has probably lost its role in favour of interventional radiology procedures, while others believe that completion pancreatectomy continues to have a place in the management of patients with severe clinical deterioration after pancreatic fistula who do not respond to non-surgical interventions. There is no agreement on the best clinical management of severe pancreatic fistula after pancreatic surgery. Completion pancreatectomy is reserved for patients not improving with conventional measures.

Transhepatic lactate gradient in relation to liver ischemia/reperfusion injury during major hepatectomies.

Hepatectomies performed under selective hepatic vascular exclusion are associated with a series of events culminating in ischemia/reperfusion injury, a state that shares common characteristics with situations known to result in global or regional hyperlactatemia. Accordingly, we sought to determine whether lactate is released by the liver during hepatic resections performed under blood flow deprivation and what relation this has to a possible systemic hyperlactatemic state. After ethical approval, 14 consecutive patients with resectable liver tumors subjected to hepatectomy under inflow and outflow occlusion of the liver were studied. Lactate concentrations were assessed in simultaneously drawn arterial, portal venous, and hepatic venous blood before liver dissection and 50 minutes postreperfusion. Moreover, the transhepatic lactate gradient (hepatic vein - portal vein) was calculated to see if there was net production or consumption of lactate. Before hepatic dissection, the transhepatic lactate gradient was negative, suggesting consumption by the liver. Fifty minutes after reperfusion, this gradient became significantly positive, demonstrating release of lactate by the liver (0.12 +/- 0.31 vs. -0.38 +/- 0.30 mmol/L, P < 0.05). The magnitude of lactate release correlated with systemic arterial lactate levels at the same time point (r(2) = 0.63, P < 0.001). A weaker but significant correlation was demonstrated between the transhepatic lactate gradient postreperfusion and systemic arterial lactate levels 24 hours postoperatively (r(2) = 0.41, P = 0.013). A strong correlation between the transhepatic lactate gradient postreperfusion and peak postoperative aspartate aminotransferase values was also demonstrated (r(2) = 0.73, P < 0.001). The liver becomes a net producer of lactate in hepatectomies performed under blood flow deprivation. This lactate release can explain some of the systemic hyperlactatemia seen in this context and relates to the extent of ischemia/reperfusion injury.