Case report of mannose-binding lectin (MBL) deficiency and postoperative sepsis and coagulopathy in a patient following total pancreatectomy for chronic pancreatitis.

CONTEXT: Complement plays a central role against infection and coordinates the activity of coagulation and fibrinolysis. In this report we present a patient that underwent total pancreatectomy experienced sepsis, coagulopathy and bleeding that endangered the postoperative course. CASE REPORT: A sixty-five-year-old woman underwent total pancreatectomy for intractable pain without islet transplant, this patient was diagnosed as AP and MBL deficient from a blood test performed preoperatively. On the postoperative course she experienced severe haemorrhages and sepsis for 3 weeks postoperatively. An analysis of serial perioperative serum samples conducted which showed further depletion of the alternate and MBL complement pathway without restoration to baseline levels. CONCLUSION: This is the first reported case of alternative and mannose-binding lectin pathways depletion associated with major postoperative bleeding and sepsis following pancreatic surgery. Future research should examine the relationship between complement pathways activity and postoperative complications in order to possibly introduce it as a preoperative screening and possible replacement therapy prior to any major surgical intervention.

The development of a multiorgan ex vivo perfused model: results with the porcine liver-kidney circuit over 24 hours.

We already developed an ex vivo liver-kidney model perfused for 6 h in which the kidney acted as a homeostatic organ to improve the circuit milieu compared to liver alone. In the current study, we extended the multiorgan perfusions to 24 h to evaluate the results and eventual pitfalls manifesting with longer durations. Five livers and kidneys were harvested from female pigs and perfused over 24 h. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. The primary end point of the study was the evaluation of the organ functions as gathered from biochemical and acid-base parameters. In the combined liver-kidney circuit, the organs survived and maintained an acceptable homeostasis for different lengths of time, longer for the liver (up to 19-23 h of perfusions) than the kidney (9-13 h of perfusions). Furthermore, glucose and creatinine values decreased significantly over time (from the 5th and 9th hour of perfusion onward). The addition of a kidney to the perfusion circuit improved the biochemical environment by removing excess products from ongoing metabolic processes. The consequence is a more physiological milieu that could improve results from future experimental studies. However, it is likely that long perfusions require some nutritional support over the hours to maintain the organ's vitality and functionality throughout the experiments.

Staging laparoscopy for hilar cholangiocarcinoma in 100 patients.

PURPOSE: Accurate preoperative radiological staging of hilar cholangiocarcinoma remains difficult, and a number of patients are found to have irresectable advanced tumours or occult metastases at exploration. Staging laparoscopy can improve the detection of irresectable disease, avoiding unnecessary laparotomy. This study examines the role of staging laparoscopy in hilar cholangiocarcinoma, with a focus on yield over different time periods and identification of preoperative factors increasing the risk of irresectable disease. METHODS: Retrospective case note review of all patients undergoing staging laparoscopy for radiologically resectable hilar cholangiocarcinoma, identified from the hepatobiliary multidisciplinary team database, was performed. RESULTS: One hundred consecutive patients underwent staging laparoscopy between 1998 and 2011. Of these, 34 patients were found to be irresectable due to metastatic disease, and 11, due to extensive local disease. Fifty patients proceeded to exploratory laparotomy following staging laparoscopy, and 36 % (18/50) of whom were found to have irresectable disease: 12 patients due to advanced local disease and 6 patients due to metastases. The overall yield of laparoscopy was 45 %, and the accuracy was 71 %. There was no significant difference in age, preoperative bilirubin, neutrophil/lymphocyte ratio, Ca19-9 levels or T stage between patients with resectable disease and with irresectable disease on laparoscopy. There was also no change in the yield of laparoscopy over time, despite advances in radiological imaging. CONCLUSION: In this series, staging laparoscopy avoided unnecessary laparotomy in 45 % of patients with radiologically resectable hilar cholangiocarcinoma. No factor was able to predict positive yield, and therefore, all patients with potentially resectable hilar cholangiocarcinoma should undergo staging laparoscopy.

Histological changes during extracorporeal perfusions of the porcine liver: implications for temporary support during acute liver failures.

Ex vivo perfused porcine livers have been used for temporary support during acute liver failure. The aim of this study was to assess both the histological changes and temporal pattern of the changes that occur during extracorporeal liver perfusions and to correlate these with factors that may influence them. Five porcine livers were harvested, preserved in cold ice and reperfused for 6 h in an extracorporeal circuit using autologous normothermic blood. Tissue biopsies were collected hourly. The Ishak score was used to quantify hepatic necrosis, and immunohistochemistry was used to evaluate apoptosis and regeneration. Liver weight, perfusion parameters, arterial blood gases and blood samples were also collected. The Ishak score peaked immediately before and 4 h after the start of reperfusion. Scattered necrosis, microvesicular steatotic vacuolization, sinusoidal dilatation and red cell extravasation were present. Anion gap acidosis was associated with the Ishak score. An inverse correlation was present between liver regeneration and necrosis, and between liver weight and regeneration. No changes were observed for apoptosis. Among the inflammatory cytokines evaluated, interleukin-6 and -8 levels increased significantly during the perfusions. Hepatic necrosis was always present during the extracorporeal perfusions, followed a definite pattern and was inversely correlated with regeneration. Apoptosis did not increase over baseline levels. The meaning of these findings and their correlation with clinical outcomes during acute hepatic failures deserve further investigation.

Reduction in circulating pro-angiogenic and pro-inflammatory factors is related to improved outcomes in patients with advanced pancreatic cancer treated with gemcitabine and intravenous omega-3 fish oil.

BACKGROUND: Pancreatic cancer is a rapidly progressive disease which is often only amenable to palliative treatment. Few patients respond to palliative chemotherapy, so surrogate markers indicating which patients are likely to respond to treatment are required. There is a well-established link between pro-inflammatory circulating cytokines and growth factors (CAF), and the development of neoplasia. Agents that may modulate these factors are of interest in developing potential novel therapeutic applications. METHODS: As part of a single-arm phase II trial in patients with advanced pancreatic cancer (APC) treated with gemcitabine and intravenous (i.v.) omega-3 rich lipid emulsion (n-3FA), serum samples were analysed for 14 CAF using a multiplex cytokine array. Baseline serum concentrations were correlated with overall (OS) and progression-free survival (PFS), and changes in concentration correlated with time and outcomes for CAF responders were analysed. RESULTS: Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) concentrations reduced significantly with treatment over time. Low baseline interleukin (IL)-6 and -8 were correlated with improved OS. PDGF responders showed a tendency towards improved OS and FGF responders a significantly improved PFS. DISCUSSION: Treatment with gemcitabine plus i.v. n-3FA may reduce concentrations of CAF which may be associated with an improved outcome. Baseline IL-6 and -8 may be surrogate markers for outcome in patients with APC treated with this regimen.

Addition of a kidney to the normothermic ex vivo perfused porcine liver model does not increase cytokine response.

The addition of a kidney to the ex vivo liver perfused model may facilitate the circuit homeostatic balance of important biochemical parameters (i.e. pH changes, urea and creatinine, or glucose levels) but might also increase the inflammatory reaction produced. In this study, we compared the production of various cytokines between liver-kidney and liver-alone circuits. Seven livers were harvested from female pigs and perfused for 6 h. In five additional experiments, a kidney was also harvested and connected in parallel. Blood samples for interleukins (IL) 1, 2, 4, 6, 8, 10, and 12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were collected before perfusion and at hours 1, 2, 4 and 6 postperfusion. In the combined liver-kidney circuit, a significant increase was present only for IL-6 and IL-8, but this did not differ significantly from those recorded in the liver-alone circuit. All other cytokines were not modified from baseline levels. The addition of a kidney to the perfusion circuit does not stimulate a greater inflammatory reaction than that of the liver alone and therefore further confirms the safety of the experimental setups in view of more delicate experiments requiring strict homeostatic conditions.

The porcine hepatic arterial supply, its variations and their influence on the extracorporeal perfusion of the liver.

BACKGROUND: Variations in the porcine hepatic vasculature may contribute to the outcome of experiments based on liver perfusion models. We studied the hepatic artery (HA), variations of its branches, and the correlation with the resultant perfusion. MATERIALS AND METHODS: Nineteen animals were used. After 6 h of perfusion, dissection of the HA and its branches was conducted up to the insertion in the liver parenchyma. Data about the macroscopic appearance of lobes and the pattern of branching were recorded. RESULTS: In all cases, the HA bifurcated into two constant branches, one for the LL/LM lobes (further divided in two vessels for each lobe) and one for the RM lobe. Five main patterns were identified involving vessels for the RL and the CL lobes. Two variations produced complete and uniform perfusion of the entire liver in all cases, while in the remaining cases, only part of them were completely perfused. CONCLUSIONS: Some variants of the porcine HA and its branches are associated with the risk of incomplete perfusion if the perfusion cannula placement does not take the individual hepatic arterial anatomy into account. Understanding of the hepatic arteries branching patterns is essential when ex vivo perfusion models are being established.

Effects of hypoxia due to isovolemic hemodilution on an ex vivo normothermic perfused liver model.

BACKGROUND: The liver has a complex hormonal and nervous control mechanism leading to difficulty in the interpretations of its responses to chronic hypoxia. Theoretically an ex vivo perfused model of the liver should, by dissociating the organ from the extrinsic regulatory mechanisms, allow a better and unequivocal analysis of changes obtained. MATERIALS AND METHODS: Twelve livers were harvested from female pigs and perfused for 6 h. Hypoxia was produced by means of isovolemic hemodilution with hemoglobin and hematocrit reduced to 40% of the baseline value. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. Every hour, physiological parameters (arterial/portal venous pressures and flows) were measured and blood samples were collected for the analysis of hemoglobin, red blood cells, hematocrit, lactate, glucose, albumin, alanine aminotransferase, alkaline phosphatase, and total bilirubin, arterial and venous blood gases. The arterio-venous oxygen and carbon dioxide differences, and the hepatic metabolic rate for oxygen, were also calculated. Primary endpoint of the study was the glucose response of the liver to acute hypoxia. Secondary endpoints were eventual changes of markers for hepatic viability and functionality. RESULTS: Most parameters showed significant variability during the first h of perfusion but subsequently normalized and remained stable at baseline values for the following 5 h. A strong and significant hyperglycemic response was present throughout the experiment (P < 0.001). Lactate rose steadily throughout the study period and after 6 h of perfusion there was a significant deviation from initial values (P < 0.05). Albumin did not change significantly throughout the study although a trend towards decreasing values was observed (Friedman test, P = NS). After an initial rise in levels of alanine transaminase and alkaline phosphatase following perfusion (P < 0.01), values remained constant without any further increase. CONCLUSIONS: Following reperfusion in an ex vivo model, the liver reacts to low oxygen concentrations mobilizing glycogen deposits. This mechanism depends on an intrinsic sensibility of hepatocytes to hypoxia, as demonstrated by the ex vivo liver perfusion. These findings improve our knowledge in organ preservation for liver transplantation.

Laparoscopic pancreatic surgery: a review of present results and future prospects.

Pancreatic surgery is still associated with a relatively high morbidity and mortality compared with other specialties. This is a result of the complex nature of the organ, the difficult access as a result of the retroperitoneal position and the number of technically challenging anastomoses required. Nevertheless, the past two decades have witnessed a steady improvement in morbidity and a decrease in mortality achieved through alterations of technique (particularly relating to the pancreatic anastomoses) together with hormonal manipulation to decrease pancreatic secretions. Recently minimally invasive pancreatic surgery has been attempted by several centres around the world which has stimulated considerable interest in this approach. The majority of the cases attempted have been distal pancreatectomies, because of the more straightforward nature of the resection and the lack of a pancreatic ductal anastomosis, but more recently reports of laparoscopic pancreaticoduodenectomy have started to appear. The reports of the series to date have been difficult to interpret and although the results are claimed to be equivalent or better than those associated with a traditional approach a careful examination of the literature and comparison with the best results previously reported does not presently support this. In the present review we examined all the reports of pancreatic procedures performed laparoscopically and compared the results with those previously achieved at open surgery.

Normothermic perfusion of ischaemic porcine kidneys: an evaluation of ex vivo function and endothelin receptor antagonism.

BACKGROUND: Non-heart-beating donors suffer a period of warm ischaemia (WI) injury, resulting in higher rates of delayed graft function compared with heart-beating donors. Endothelin is believed to play a pathophysiological role in the intense vasospasm associated with WI. This study aimed to investigate renal function using normothermic perfusion and potential therapeutic intervention with endothelin receptor antagonism. METHODS: Porcine kidneys, subjected to varying periods of in situ WI (<10, 30 and 60 minutes), underwent normothermic machine perfusion with a perfluorodecalin perfusate. Intrarenal vascular resistance (IRR) was measured throughout perfusion, and urine and perfusate biochemical analysis was performed after 1 and 3 hours. Endothelin receptor antagonism was tested by administration of BQ-123 and BQ-788. RESULTS: Initial IRR during perfusion increased with WI. IRR reduced to similar levels in all WI groups after 90 minutes of perfusion, but subsequently rose after 150 minutes. BQ-123 considerably increased the initial IRR; however, it abolished the rise seen towards the end of perfusion. BQ-788 had little effect. Renal metabolism and function deteriorated with increasing WI. Perfusion had adverse effects on renal function and metabolism. Endothelin receptor antagonism had little effect on renal function. CONCLUSIONS: This study suggests that ex vivo assessment after normothermic perfusion correlates with warm ischaemic damage. However, endothelin receptor antagonism does not ameliorate the rise in IRR or renal function after kidneys are subjected to a warm ischaemic insult.

A case of liver metastasis from an oncocytoma with a focal area of chromophobe renal cell carcinoma: a wolf in sheep's clothing.

In 2004, the World Health Organization classified the renal oncocytomas as benign neoplasms of the kidney. There are reports of subtypes of renal tumors, with similar histological morphology to oncocytoma, but with malignant potential, one of these tumors is the eosinophilic variant of chromophobe renal cell carcinoma. It is important to characterize the histological features and the subtype of tumor, as this predicts biological behavior and cancer-specific survival rate. A rare case of a liver metastasis from a focal area of eosinophilic variant of chromophobe renal cell carcinoma mixed in oncocytoma in a 69-year-old woman is reported. Although some renal tumors may contain oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma histology, caution should be exercised while diagnosing oncocytomas in needle biopsies as there may be unsampled area of chromophobe carcinoma which has a potential for metastatic spread representing a wolf in sheep's clothing.

Hepatic microwave ablation: a review of the histological changes following thermal damage.

Microwave (MW) ablation therapy is a local treatment by which tumours are destroyed by coagulation from the passage of MWs into cells. The aim of this review is to examine histological results obtained from preclinical and clinical studies. A literature search was undertaken for all studies focusing on MW therapy and in which lesions were excised for a complete histopathological examination after treatment. Two main zones were described after ablative therapy (central and transitional). Both corresponded to specific microscopic characteristics and evolved over time in a precise manner. No viable cells even up to 6 cm in diameter were demonstrated in 93% of lesions after treatment. Microwave therapy is a reliable technique under a variety of clinical situations. Future investigations are needed to compare MW with other ablative techniques to identify factors that influence the effectiveness of the various techniques and to determine specific indications.

Delayed necrotizing acalculous cholecystitis after multiple trauma.

This is a case report of a necrotizing acalculous cholecystitis 7 weeks after multiple orthopedic trauma successfully treated by operative intervention.

Relaxation of the criteria for day surgery laparoscopic cholecystectomy.

BACKGROUND: For day case laparoscopic cholecystectomy programmes, studies suggest that overnight admission may be predicted by the following factors: gall bladder wall thickness, patient age over 55 years and previous sphincterotomy. This study investigated the effect of relaxing selection for a day surgery laparoscopic cholecystectomy programme, by removing these factors from the exclusion criteria. METHODS: Between September 2002 and April 2003, patients for elective laparoscopic cholecystectomy were considered for day surgery subject to standard criteria. For the initial part of the programme, patients were additionally excluded according to the risk factors mentioned above. RESULTS: Thirty-three patients underwent intended day case procedures. The first 16 were selected according to the more rigorous criteria. The latter 17 were significantly older, with a significantly higher incidence of gall bladder wall thickening. There were seven admissions, three in the former part of the study and four in the latter. CONCLUSION: The exclusion criteria described are not necessary for a good same-day discharge rate.

Hepatectomy for metastatic noncolorectal gastrointestinal, breast and testicular tumours.

BACKGROUND: The indications for hepatectomy for colorectal or neuroendocrine metastases are becoming clear with increasing experience reported. For other primary diseases, however, the overall number of cases is relatively small, and it is more difficult to derive clear guidelines. This paper reviews the reported experience of hepatectomy for metastases from non-colorectal gastrointestinal primary cancers, breast cancer and testicular teratoma. The aim is to determine for each whether and under what circumstances hepatectomy is indicated. METHODS: A Medline search was used to identify papers reporting hepatectomy for metastases from non-colorectal gastrointestinal carcinomas, breast carcinomas and testicular teratomas. The data collected included the primary disease, the number of cases reported, the survival post-hepatectomy and any prognostic factors associated with outcome. RESULTS: Of the gastrointestinal malignancies, hepatectomy for gastric metastases yields a 5-year survival, roughly half that reported for colorectal disease, and further elucidation of prognostic factors would be desirable. Results were poor for other gastrointestinal malignancies. Good results were reported for breast and testicular teratoma. CONCLUSION: Of the non-colorectal gastrointestinal primaries, at present only hepatectomy for gastric metastases can be cautiously recommended. For nongastrointestinal primaries, hepatic metastases probably represent widespread dissemination even if occult, and therefore, hepatectomy may only be of use when effective adjuvant treatments are available.

How much liver resection is too much?

BACKGROUND: Hepatic failure occurring after liver resection carries a poor prognosis and is a complication dreaded by surgeons. Inadequate reserve in the remaining parenchyma leads to a steady decrease in liver function, inability to regenerate, and progression to liver failure. For this reason, many methods to quantify functional hepatic reserve have been developed. METHODS: This article reviews the main methods used in the assessment of hepatic reserve in patients undergoing hepatectomy and their use in operative decision making. RESULTS: A range of methods to categorically quantify the functional reserve of the liver have been developed, ranging from scoring systems (such as the Child-Pugh classification) to tests assessing complex hepatic metabolic pathways to radiological methods to assess functional reserve. However, no one method has or is ever likely to emerge as a single measure with which to dictate safe limits of resectability. CONCLUSIONS: In the future, the role of residual liver function assessment may be of most benefit in the routine stratification of risk, thus enabling both patient consent to be obtained and surgical procedure to be performed, with full information and facts regarding operative risks. However, there is no one single test that remains conclusively superior.

A randomized controlled trial investigating the effects of parenteral fish oil on survival outcomes in critically ill patients with sepsis: a pilot study.

INTRODUCTION: Death from sepsis in the intensive care unit (ITU) is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with ω-3 has been demonstrated to attenuate the effects of uncontrolled inflammation and may be clinically beneficial. METHOD: A randomized control trial investigating the effects of parenteral ω-3 was carried out. Consecutive patients diagnosed with sepsis were entered into the study and randomized to receive either parenteral ω-3 or standard medical care only. The primary outcome measure was a reduction in organ dysfunction using the Sequential Organ Failure Assessment (SOFA) score as a surrogate marker. The secondary outcome measures were mortality, length of stay, mean C-reactive protein (CRP), and days free of organ dysfunction/failure. RESULTS: Sixty patients were included in the study. The baseline demographics were matched for the two cohorts. Patients treated with parenteral ω-3 were associated with a significant reduction in new organ dysfunction (Δ-SOFA 2.2 ± 2.2 vs. 1.0 ± 1.5, P = .005 and maximum-SOFA 10.1 ± 4.2 vs. 8.1 ± 3.2, P = .041) and maximum CRP (186.7 ± 78 vs. 141.5 ± 62.6, P = .019). There was no significant reduction in the length of stay between cohorts. Patients treated with ω-3 in the strata of less severe sepsis had a significant reduction in mortality (P = .042). CONCLUSION: The treatment of critically ill septic patients with parenteral ω-3 is safe. It is associated with a significant reduction in organ dysfunction. It may be associated with a reduction in mortality in patients with less severe sepsis.

A comparison of renal preservation by cold storage and machine perfusion using a porcine autotransplant model.

BACKGROUND: Pulsatile machine perfusion offers theoretical advantages as a method of preserving kidneys before transplantation. This may be particularly the case for organs taken from non-heart-beating donors (NHBD), but there is still a lack of data to support this view. The aim of this study was to compare the effectiveness of static cold storage in ice (CS) and hypothermic pulsatile machine perfusion (MP) as methods of renal transplant preservation. METHODS: Groups of large white pigs (n=5) underwent left nephrectomy after warm ischemic times (WIT) of 0 or 30 min. Kidneys were preserved by CS or by cold (3degrees-8degreesC) MP for 24 hr. The left kidney was then autotransplanted into the right iliac fossa and an immediate right nephrectomy was performed. Renal function was assessed daily for 14 days. RESULTS: Fourteen-day animal survival rates for 0 and 30 min WIT were four of five and one of five after both CS and MP. In the zero WIT groups, there was improved recovery of renal function after MP (area under the creatinine curve, 4,722+/-2,496 [MP] vs. 8,849+/-2,379 [CS]; P<0.05). MP did not improve renal function after 30 min of WIT (mean daily area under the creatinine curve, 1,077+/-145 [MP] vs. 1,049+/-265 [CS]). CONCLUSIONS: In this model, MP improved 24-hr preservation of kidneys not subjected to warm ischemia (heart-beating donor model), but there was no evidence that MP was a better method of preservation than CS for kidneys exposed to 30 min of WIT (NHBD model).

Ite Boerema--surgeon and engineer with a double-Dutch legacy to medical technology.

Ite Boerema, 1902-1978: a Dutchman with a brilliant academic surgical career, and war hero, decorated for resistance to the Germans in World War II. As a man who regarded surgery as "engineering in medicine," we still feel his legacy in medical technology today, specifically with regard to his work on esophageal anastomoses and hyperbaric oxygen therapy. This biography places his major contributions to medicine in context of the man himself and of contemporary medicine.

Artificial liver support: potential to retard regeneration?

HYPOTHESIS: The concept of an "artificial liver" has been in development for over 40 years. Such devices aim to temporarily assume metabolic and excretory functions of the liver, with removal of potentially hepatotoxic substances, thereby clinically stabilizing patients and preventing deterioration while awaiting transplantation. If sufficient numbers of viable hepatocytes remain, regeneration and subsequent recovery of innate liver function may occur. However, these devices have not yet become part of routine clinical use. Much less is known regarding the effect such devices have, if any, on circulating cytokines and growth factors and the subsequent effects on the regenerating liver. If these devices remove or reduce factors known to promote regeneration, is the rate of regeneration retarded? Conversely, does the incorporation of hepatocytes into bioartificial support systems confer an advantage through the production of growth-promoting factors from these cultured hepatocytes?Data Sources, Extraction, and STUDY SELECTION: Data were obtained using PubMed search for reports involving liver support, extracorporeal circuits, dialysis, growth factors, and cytokines. Those reports specifically looking at the effect of artificial liver support on cytokines and growth factors are discussed. CONCLUSIONS: There is a paucity of information on the key events and substances involved in hepatic regeneration. In addition, there is a potential impact of liver support devices on the regeneration of substances associated with hepatic regeneration. Further study is needed.